Multi-center application of a convolutional neural network for preoperative detection of cavernous sinus invasion in pituitary adenomas.

OBJECTIVE: Cavernous sinus invasion (CSI) plays a pivotal role in determining management in pituitary adenomas. The study aimed to develop a Convolutional Neural Network (CNN) model to diagnose CSI in multiple centers. METHODS: A total of 729 cases were retrospectively obtained in five medical centers with (n = 543) or without CSI (n = 186) from January 2011 to December 2021. The CNN model was trained using T1-enhanced MRI from two pituitary centers of excellence (n = 647). The other three municipal centers (n = 82) as the external testing set were imported to evaluate the model performance. The area-under-the-receiver-operating-characteristic-curve values (AUC-ROC) analyses were employed to evaluate predicted performance. Gradient-weighted class activation mapping (Grad-CAM) was used to determine models' regions of interest. RESULTS: The CNN model achieved high diagnostic accuracy (0.89) in identifying CSI in the external testing set, with an AUC-ROC value of 0.92 (95% CI, 0.88-0.97), better than CSI clinical predictor of diameter (AUC-ROC: 0.75), length (AUC-ROC: 0.80), and the three kinds of dichotomizations of the Knosp grading system (AUC-ROC: 0.70-0.82). In cases with Knosp grade 3A (n = 24, CSI rate, 0.35), the accuracy the model accounted for 0.78, with sensitivity and specificity values of 0.72 and 0.78, respectively. According to the Grad-CAM results, the views of the model were confirmed around the sellar region with CSI. CONCLUSIONS: The deep learning model is capable of accurately identifying CSI and satisfactorily able to localize CSI in multicenters.

SIRT1-Mediated HMGB1 Deacetylation Suppresses Neutrophil Extracellular Traps Related to Blood-Brain Barrier Impairment After Cerebral Venous Thrombosis.

Cerebral venous thrombosis (CVT) is a neurovascular disease with recently increasing incidence. Aseptic inflammatory responses play an important role in the pathology of CVT. Recent studies report that neutrophil extracellular traps (NETs) are major triggers of thrombosis and inflammation in stroke, but their effect on brain injury in CVT requires further validation. In this study, two CVT animal models were used to simulate superior sagittal sinus thrombosis and cortical vein thrombosis. The effects of brain tissue infiltration of NETs and the molecular mechanisms associated with NET formation were deeply explored in combination with proteomics, histology, and serology. The results showed that the cortical vein thrombosis model could be combined with more severe blood-brain barrier (BBB) disruption and showed more severe cerebral hemorrhage. Decreased Sirtuin 1 (SIRT1) expression promotes high mobility group box 1 (HMGB1) acetylation, causing increased cytosolic translocation and extracellular release, and HMGB1 can promote NET formation and recruitment. In addition, corticocerebral accumulation of NETs contributes to BBB damage. This establishes a vicious cycle between BBB damage and NET accumulation. SIRT1 mediated-HMGB1 deacetylation may play a critical role in attenuating BBB damage following CVT. This study employed a combined validation using models of venous sinus thrombosis and cortical vein thrombosis to investigate the deacetylation role of SIRT1, aiming to offer new insights into the pathological mechanisms of brain injury following CVT.

Identification of cholesterol metabolism-related subtypes in nonfunctioning pituitary neuroendocrine tumors and analysis of immune infiltration.

OBJECTIVE: This study aimed to investigate the role of cholesterol metabolism-related genes in nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) invading the cavernous sinus and analyze the differences in immune cell infiltration between invasive and noninvasive NF-PitNETs. METHODS: First, a retrospective analysis of single-center clinical data was performed. Second, the immune cell infiltration between invasive and noninvasive NF-PitNETs in the GSE169498 dataset was further analyzed, and statistically different cholesterol metabolism-related gene expression matrices were obtained from the dataset. The hub cholesterol metabolism-related genes in NF-PitNETs were screened by constructing machine learning models. In accordance with the hub gene, 73 cases of NF-PitNETs were clustered into two subtypes, and the functional differences and immune cell infiltration between the two subtypes were further analyzed. RESULTS: The clinical data of 146 NF-PitNETs were evaluated, and the results showed that the cholesterol (P = 0.034) between invasive and noninvasive NF-PitNETs significantly differed. After binary logistic analysis, cholesterol was found to be an independent risk factor for cavernous sinus invasion (CSI) in NF-PitNETs. Bioinformatics analysis found three immune cells between invasive and noninvasive NF-PitNETs were statistically significant in the GSE169498 dataset, and 34 cholesterol metabolism-related genes with differences between the two groups were obtained 12 hub genes were selected by crossing the two machine learning algorithm results. Subsequently, cholesterol metabolism-related subgroups, A and B, were obtained by unsupervised hierarchical clustering analysis. The results showed that 12 immune cells infiltrated differentially between the two subgroups. The chi-square test revealed that the two subgroups had statistically significance in the invasive and noninvasive samples (P = 0.001). KEGG enrichment analysis showed that the differentially expressed genes were mainly enriched in the neural ligand-receptor pathway. GSVA analysis showed that the mTORC signaling pathway was upregulated and played an important role in the two-cluster comparison. CONCLUSION: By clinical data and bioinformatics analysis, cholesterol metabolism-related genes may promote the infiltration abundance of immune cells in NF-PitNETs and the invasion of cavernous sinuses by NF-PitNETs through the mTOR signaling pathway. This study provides a new perspective to explore the pathogenesis of cavernous sinus invasion by NF-PitNETs and determine potential therapeutic targets for this disease.

Thyroxine changes in COVID-19 pandemic: A systematic review and meta-analysis.

Objective: COVID-19 infection may affect thyroid function. However, changes in thyroid function in COVID-19 patients have not been well described. This systematic review and meta-analysis assess thyroxine levels in COVID-19 patients, compared with non-COVID-19 pneumonia and healthy cohorts during the COVID-19 epidemic. Methods: A search was performed in English and Chinese databases from inception to August 1, 2022. The primary analysis assessed thyroid function in COVID-19 patients, comparing non-COVID-19 pneumonia and healthy cohorts. Secondary outcomes included different severity and prognoses of COVID-19 patients. Results: A total of 5873 patients were enrolled in the study. The pooled estimates of TSH and FT3 were significantly lower in patients with COVID-19 and non-COVID-19 pneumonia than in the healthy cohort (P < 0.001), whereas FT4 were significantly higher (P < 0.001). Patients with the non-severe COVID-19 showed significant higher in TSH levels than the severe (I2 = 89.9%, P = 0.002) and FT3 (I2 = 91.9%, P < 0.001). Standard mean differences (SMD) of TSH, FT3, and FT4 levels of survivors and non-survivors were 0.29 (P= 0.006), 1.11 (P < 0.001), and 0.22 (P < 0.001). For ICU patients, the survivors had significantly higher FT4 (SMD=0.47, P=0.003) and FT3 (SMD=0.51, P=0.001) than non-survivors. Conclusions: Compared with the healthy cohort, COVID-19 patients showed decreased TSH and FT3 and increased FT4, similar to non-COVID-19 pneumonia. Thyroid function changes were related to the severity of COVID-19. Thyroxine levels have clinical significance for prognosis evaluation, especially FT3.

TNF-α Impairs Pericyte-Mediated Cerebral Microcirculation via the NF-κB/iNOS Axis after Experimental Traumatic Brain Injury.

Secondary structural and functional abnormalities of the neurovascular unit are important pathological mechanisms following traumatic brain injury (TBI). The neurovascular unit maintains blood-brain barrier and vascular integrity through interactions among glial cells, pericytes and endothelial cells. Trauma-induced neuroinflammation and oxidative stress may act as initiating factors for pathological damage after TBI, which in turn impairs cerebral microcirculatory function. Studies have shown that the tumor necrosis factor α (TNF-α)/nuclear factor-κB (NF-κB) pathway regulates inflammation and oxidative damage, but its role in pericyte-mediated cerebral microcirculation are currently unknown. Herein, we assessed TNF-α/NF-κB signaling and inducible nitric oxide synthase (iNOS), and the effects of the TNF-α inhibitor infliximab after TBI. Whether pericyte damage is dependent on the TNF-α/NF-κB/iNOS axis was also evaluated to explore the mechanisms underlying disturbances in the microcirculation after TBI. Microglia are activated after TBI to promote inflammatory factors and free radical release, and upregulate NF-κB and iNOS expression. After lipopolysaccharide treatment, the activity of TNF-α/NF-κB/iNOS in BV2 cells was also upregulated. Inhibition of TNF-α using infliximab reduced NF-κB phosphorylation and nuclear translocation and downregulated iNOS expression, which attenuated the inflammation and oxidative damage. Meanwhile, inhibition of TNF-α reversed pericyte marker loss, and improved pericyte function and microcirculation perfusion after TBI. In conclusion, our study suggests that microglia released TNF-α after TBI, which promoted neuroinflammation and oxidative stress by activating downstream NF-κB/iNOS signals, and this led to pericyte-mediated disturbance of the cerebral microcirculation.

Complex torcular dural arteriovenous fistula leading to cortical venous reflux-induced severe varix and subsequent bilateral cerebral hemispheric hemorrhage: a case report.

Background and importance: Dural arteriovenous fistulas (dAVFs) with cortical venous reflux (CVR) are associated with a higher incidence of intracranial hemorrhage (ICH). We report a rare case of a complex torcular dAVF with severe cortical veins (CV) varix leading to extensive bilateral cerebral hemorrhages. This discovery suggests a potential new subtype of dAVF. The case underscores the necessity of a comprehensive understanding of hemodynamic changes in dAVFs and the importance of considering venous compensatory capacity in treatment. This case challenges existing classifications and treatment strategies for dAVFs, highlighting the need for further research and discussion within the neurosurgical community. Clinical presentation: A 56-year-old male was admitted to the hospital presenting with dizziness, fatigue, and numbness. Brain CT scans revealed extensive bilateral cerebral hemorrhages. Digital subtraction angiography (DSA) identified a complex torcular dAVF. No cerebral sinus venous thrombosis was detected, but a venous variation in the left transverse sinus was observed. Preoperative DSA demonstrated the patient's well-developed venous compensatory ability. Subsequently, the patient underwent transarterial embolization. The patient made a good recovery. Follow-up DSA and MR angiography at 3 months and 1 year post-treatment showed no recurrence. Conclusion: DAVFs are rare lesions, prone to ICH, particularly when CVR is involved. We report a rare case of CVR with severe varix leading to hemorrhagic lesions in both cerebral hemispheres. Our aim is to alert neurosurgical colleagues worldwide to this potential new subtype and to evaluate treatment options, in order to assist those who may encounter such cases in the future.

Perioperative fluctuation and overall evaluation of adenohypophyseal hormone secretion in patients with nonfunctioning pituitary adenoma.

OBJECTIVE: Perioperative adenohypophyseal hormone assessment can improve therapeutic strategies and be used to evaluate the prognosis of pituitary adenomas. An individual hormone level does not entirely reflect the pituitary gland. Thus, this study aimed to analyze perioperative hormonal changes and propose a normalized method to facilitate overall assessment of the adenohypophysis. METHODS: The authors retrospectively analyzed 89 male patients with nonfunctioning pituitary adenoma (NFPA) who underwent transsphenoidal surgery. Preoperative clinical data, imaging data, and perioperative hormone levels of the anterior pituitary gland were evaluated. Hormone values were rescaled using minimum-maximum normalization. The sum of the normalized hormone levels was defined as the total hormonal rate (THR). RESULTS: Preoperative findings indicated correlations among different adenohypophyseal hormones. Luteinizing hormone (p = 0.62) and adrenocorticotropic hormone (p = 0.89) showed no significant changes after surgery, but growth hormone levels increased (p < 0.001). On the contrary, the levels of thyroid-stimulating hormone (p < 0.001), follicle-stimulating hormone (p = 0.02), and prolactin (p < 0.001) decreased. THR indicated a significant postoperative reduction in adenohypophyseal function (p = 0.04). Patients with postoperative hypopituitarism had significantly lower THR than those without (p = 0.003), with an area under the curve of 0.66. For NFPAs that presented with normal preoperative hormone levels, THR was a good clinical predictor of immediate postoperative hypopituitarism, with an area under the curve of 0.74. CONCLUSIONS: The normalized synthesis index of hormones is a novel and clinically valuable method used to reflect adenohypophyseal secretion. Compared with individual hormones, these results indicated that THR can facilitate the analysis of general hormone levels despite various fluctuations in adenohypophyseal hormones. THR may also contribute to the effective prediction of short-term surgery-induced hypopituitarism.

Novel Nomograms to Predict Delayed Hyponatremia After Transsphenoidal Surgery for Pituitary Adenoma.

Objective: This study aimed to develop a nomogram of clinical variables and magnetic resonance imaging scans to predict delayed hyponatremia after transsphenoidal surgery for pituitary adenoma. Methods: Patients who underwent transsphenoidal surgery for pituitary adenoma in Fuzong Clinical Medical College of Fujian Medical University between January 2012 and December 2020 were retrospectively investigated. Medical records, MRI findings, and laboratory examination results were recorded as candidate variable predictors of delayed hyponatremia. A nomogram to predict delayed hyponatremia was formulated based on the multivariable model of risk factors. The predictive accuracy and discriminative ability of the nomogram were assessed using the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analyses. The model underwent prospective validation in three medical centers with patients who underwent transsphenoidal surgery for pituitary adenoma between January 2021 and February 2022. Results: The model that incorporated the postoperative length of "measurable pituitary stalk," pituitary stalk deviation angle difference, postoperative diabetes insipidus, sinking depth of diaphragma sellae, and blood sodium level on the second postoperative day was developed and presented as the nomogram of the training cohort. The nomogram achieved area under the ROC curve (AUCs) of 0.806 and 0.849 for the training cohort and the testing cohort, respectively, and displayed good calibration. Decision curve analysis showed that the nomogram was clinically useful when the threshold probability was 13-96%. Conclusions: We developed a nomogram to evaluate the individualized prediction of delayed hyponatremia after transsphenoidal surgery for pituitary adenomas.

Cerebral venous hemodynamic responses in a mouse model of traumatic brain injury.

Traumatic brain injury (TBI) is a serious public health problem that endangers human health and is divided into primary and secondary injuries. Previous work has confirmed that changes in cerebral blood flow (CBF) are related to the progression of secondary injury, although clinical studies have shown that CBF monitoring cannot fully and accurately evaluate disease progression. These studies have almost ignored the monitoring of venous blood flow; however, as an outflow channel of the cerebral circulation, it warrants discussion. To explore the regulation of venous blood flow after TBI, the present study established TBI mouse models of different severities, observed changes in cerebral venous blood flow by laser speckle flow imaging, and recorded intracranial pressure (ICP) after brain injury to evaluate the correlation between venous blood flow and ICP. Behavioral and histopathological assessments were performed after the intervention. The results showed that there was a significant negative correlation between ICP and venous blood flow (r = -0.795, P < 0.01), and both recovered to varying degrees in the later stages of observation. The blood flow changes in regional microvessels were similar to those in venous, and the expression of angiogenesis proteins around the impact area was significantly increased. In conclusion, this study based on the TBI mouse model, recorded the changes in venous blood flow and ICP and revealed that venous blood flow can be used as an indicator of the progression of secondary brain injury.

Microscopic Transsphenoidal Resection of Giant Pituitary Adenomas: Analysis of the Factors Limiting the Degree of Resection in 73 Cases.

Purpose: To analyze the risk factors affecting the gross-total resection of giant pituitary adenomas using a transsphenoidal approach under a microscope to provide a reference basis for formulating an appropriate surgical strategy. Methods: The clinical data of patients who underwent microscopic transsphenoidal resection of giant pituitary adenomas in a single center from January 2011 to December 2020 were retrospectively analyzed. Based on magnetic resonance imaging and surgical records, the predictive factors affecting the gross-total resection of giant pituitary adenomas under microscopy were determined through univariate and multivariate analyses. Results: A total of 73 patients with giant pituitary adenomas underwent transsphenoidal microsurgery. Gross-total resection was performed in 19 cases (26%), subtotal resection in 31 cases (42%), partial resection in 21 cases (29%), and the degree of resection was <50% in only two cases (3%). After binary logistic analysis, it was found that it was more difficult to completely remove giant pituitary adenomas with a Knosp grade 3-4 [odds ratio (OR) = 0.214, 95% confidence interval (CI): 0.05-0.917; P = 0.038], greater proportion of tumor suprasellar volume (odds ratio = 0.937, 95% confidence interval: 0.898-0.978; P = 0.003), and intraoperative evidence of invasion of the cavernous sinus (odds ratio = 0.187, 95% CI: 0.039-0.898; P = 0.036). Conclusion: It is difficult to remove a giant pituitary adenoma invading the cavernous sinus completely with a higher degree of invasion of the suprasellar region using microscopic transsphenoidal surgery. The combined application of multiple surgical methods can help to improve the degree of resection during a single operation.

Change in cephalocaudal tumor cavity diameter after transsphenoidal surgery is a predictor of diabetes insipidus in pituitary adenoma.

OBJECTIVE: To assess the factors influencing the development of diabetes insipidus after transsphenoidal surgery for pituitary adenomas. METHODS: We retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent transsphenoidal surgery. The pituitary gland was assessed using a 3.0 T magnetic resonance imaging, and the predictors of postoperative diabetes insipidus were determined through univariate and multivariate analyses. RESULTS: A total of 212 eligible patients with pituitary adenomas were included; 82 (38.7%) cases developed postoperative diabetes insipidus while 130 cases (61.3%) did not. Diabetes insipidus was transient in 80 (37.7%) patients and permanent in 2 (0.9%) patients. The results of logistic regression analyses showed that the change in cephalocaudal tumor cavity diameter after transsphenoidal surgery was associated with the occurrence of postoperative diabetes insipidus. CONCLUSIONS: Change in cephalocaudal tumor cavity diameter after transsphenoidal surgery may play an important role in predicting diabetes insipidus onset in patients with a pituitary adenoma.

A novel rat model for cerebral venous sinus thrombosis: verification of similarity to human disease via clinical analysis and experimental validation.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare neurovascular disorder with highly variable manifestations and clinical courses. Animal models properly matched to the clinical form of CVST are necessary for elucidating the pathophysiology of the disease. In this study, we aimed to establish a rat model that accurately recapitulates the clinical features of CVST in human patients. METHODS: This study consisted of a clinical analysis and animal experiments. Clinical data for two centres obtained between January 2016 and May 2021 were collected and analysed retrospectively. In addition, a Sprague-Dawley rat model of CVST was established by inserting a water-swellable rubber device into the superior sagittal sinus, following which imaging, histological, haematological, and behavioural tests were used to investigate pathophysiological changes. Principal component analysis and hierarchical clustering heatmaps were used to evaluate the similarity between the animal models and human patients. RESULTS: The imaging results revealed the possibility of vasogenic oedema in animal models. Haematological analysis indicated an inflammatory and hypercoagulable state. These findings were mostly matched with the retrospective clinical data. Pathological and serological tests further revealed brain parenchymal damage related to CVST in animal models. CONCLUSIONS: We successfully established a stable and reproducible rat model of CVST. The high similarity between clinical patients and animal models was verified via cluster analysis. This model may be useful for the study of CVST pathophysiology and potential therapies.

Predictive Factors for Early-Onset Seizures in Patients With Cerebral Venous Sinus Thrombosis.

Seizures are reported to be important factors contributing to poor prognosis in patients with cerebral venous sinus thrombosis (CVST). However, the predictive factors for concurrent early onset seizures in patients with CVST remain unclear. To identify the predictive factors of early seizures in patients with CVST, this study retrospectively evaluated the clinical data of patients diagnosed with CVST at two centers from January 2011 to December 2020 and analyzed the relationship between admission characteristics and early onset seizures. A total of 112 CVST patients (63 men and 49 women; mean age 39.82 ± 15.70 years) were enrolled in this study, of whom 34 (30.36%) had seizures. For patients with seizures, cerebral hemorrhage, cortical vein thrombosis, anterior superior sagittal sinus (SSS) thrombosis, middle SSS thrombosis, CVST score, modified Rankin Scale, National Institute of Health Stroke Scale (NIHSS) score, neutrophil percentage, and D-dimer level were more severe than those without seizures. Logistic regression analysis showed that cerebral hemorrhage (P = 0.002), anterior SSS thrombosis (P = 0.003), NIHSS score ≥5 (P = 0.003), and D-dimer ≥0.88 mg/L (P = 0.004) were all significant predictive factors of early-onset seizures in CVST patients. Combining the four factors further improved the predictive capability with an area under the curve of 0.871 (95% confidence interval = 0.803-0.939). Further large-scale prospective studies are required to confirm these findings.

Predictive factors for delayed hyponatremia after transsphenoidal surgery in patients with pituitary adenomas.

Objective: The aim of this study was to evaluate the incidence and duration of delayed hyponatremia and to assess the factors influencing the development of delayed hyponatremia after transsphenoidal surgery (TSS) in pituitary adenomas. Methods: We retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of delayed hyponatremia. Results: Of the 285 patients with pituitary adenoma who underwent microscopic TSS, 44 (15.4%) developed postoperative-delayed hyponatremia and 241 (84.6%) did not. The onset of delayed hyponatremia occurred an average of 5.84 days post-surgery and persisted for an average of 5.36 days. Logistic regression analysis showed the highest risk of delayed hyponatremia in patients with significant change in tumor cavity height (odds ratio (OR), 1.158; 95% CI, 1.062, 1.262; P = 0.001), preoperative hypothalamus-pituitary-thyroid axis hypofunction (OR, 3.112; 95% CI, 1.481, 6.539; P = 0.003), and significant difference in blood sodium levels before and 2 days after TSS (OR, 1.101; 95% CI, 1.005, 1.206; P = 0.039). Conclusions: Preoperative hypothyroidism, difference in blood sodium levels before and 2 days after TSS, and the change in tumor cavity height after TSS played important roles in predicting postoperative-delayed hyponatremia onset in patients with pituitary adenomas.

Machine-Learning Prediction of Postoperative Pituitary Hormonal Outcomes in Nonfunctioning Pituitary Adenomas: A Multicenter Study.

Objective: No accurate predictive models were identified for hormonal prognosis in non-functioning pituitary adenoma (NFPA). This study aimed to develop machine learning (ML) models to facilitate the prognostic assessment of pituitary hormonal outcomes after surgery. Methods: A total of 215 male patients with NFPA, who underwent surgery in four medical centers from 2015 to 2021, were retrospectively reviewed. The data were pooled after heterogeneity assessment, and they were randomly divided into training and testing sets (172:43). Six ML models and logistic regression models were developed using six anterior pituitary hormones. Results: Only thyroid-stimulating hormone (p < 0.001), follicle-stimulating hormone (p < 0.001), and prolactin (PRL; p < 0.001) decreased significantly following surgery, whereas growth hormone (GH) (p < 0.001) increased significantly. The postoperative GH (p = 0.07) levels were slightly higher in patients with gross total resection, but the PRL (p = 0.03) level was significantly lower than that in patients with subtotal resection. The optimal model achieved area-under-the-receiver-operating-characteristic-curve values of 0.82, 0.74, and 0.85 in predicting hormonal hypofunction, new deficiency, and hormonal recovery following surgery, respectively. According to feature importance analyses, the preoperative levels of the same type and other hormones were all important in predicting postoperative individual hormonal hypofunction. Conclusion: Fluctuation in anterior pituitary hormones varies with increases and decreases because of transsphenoidal surgery. The ML models could accurately predict postoperative pituitary outcomes based on preoperative anterior pituitary hormones in NFPA.

The Difference Between Preoperative and Postoperative Pituitary Stalk Deviation Angles Can Predict Delayed Hyponatremia After Transsphenoidal Surgery.

OBJECTIVE: Our aim was to assess the factors influencing the development of delayed hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of the difference between preoperative and postoperative pituitary stalk deviation angles on delayed hyponatremia. METHODS: A retrospective study was performed on the clinical data of patients with pituitary adenomas who were treated with TSS at a single institution. On the basis of the observation of indicators such as pituitary stalk deviation angle and length of "measurable pituitary stalk" on magnetic resonance imaging, we determined the predictors of postoperative delayed hyponatremia through univariate and multivariate analyses. RESULTS: Microscopic TSS was performed in 422 patients with pituitary adenoma, of whom 66 experienced postoperative delayed hyponatremia. Logistic regression analysis showed that the risk of delayed hyponatremia was greater for patients with a large difference between preoperative and postoperative pituitary stalk deviation angle (odds ratio = 1.040, 95% confidence interval: 1.018-1.051; P < 0.001) and a large difference in the "measurable pituitary stalk" (odds ratio = 1.128, 95% confidence interval: 1.011-1.258; P = 0.032), and patients with high blood sodium on the second day after surgery have a lower probability of developing delayed hyponatremia. CONCLUSIONS: This study is the first to suggest the important role of the difference between preoperative and postoperative pituitary stalk deviation angles in predicting the development of delayed hyponatremia after TSS for pituitary adenomas.

Diaphragma sellae sinking can predict the onset of hyponatremia after transsphenoidal surgery for pituitary adenomas.

PURPOSE: Sinking of the diaphragma sellae (DS) may stretch the pituitary stalk, which in turn impairs neurohypophyseal function; thus, it may play a role in the development of postoperative hyponatremia. We aimed to assess the factors influencing the development of hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of DS sinking on hyponatremia. METHODS: After applying the inclusion and exclusion criteria, we retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. The pituitary gland was scanned using a 3.0-T magnetic resonance imaging, and sagittal and coronal images were acquired. We evaluated the following: preoperative and postoperative hypothalamus‒pituitary‒thyroid axis function, hypothalamus‒pituitary‒adrenal axis function, intra-operative cerebrospinal fluid leaks, diabetes insipidus, hyponatremia, time from the day of surgery to the day of discharge, and time of hyponatremia onset. RESULTS: Of the 460 patients who had microscopic TSS for pituitary adenoma, 83 experienced postoperative hyponatremia. Hyponatremia occurred approximately 5.25 days postoperatively and persisted for 5.54 days. The lowest average blood sodium level was 123.9 mEq/L, which occurred at 7.49 days after surgery. Logistic regression analysis showed that the risk of hyponatremia was greater for patients with a significant DS sinking depth, a large pituitary stalk deviation angle difference, and a longer postoperative "measurable pituitary stalk". The difference in blood sodium levels between pre-TSS and 2 days post-TSS was also an independent predictor of postoperative hyponatremia onset. CONCLUSION: DS sinking plays an important role in predicting hyponatremia onset after TSS for pituitary adenomas.

Outcomes of Preinjury Use of Statins in Patients with Traumatic Brain Injury: A Systematic Review and Meta-analysis.

BACKGROUND: No completely effective pharmacotherapies have been developed to improve the outcomes of traumatic brain injury (TBI). Given the reporting of cohort studies suggesting that preinjury statin use may reduce TBI-associated mortality, this study aimed to evaluate the effects of statin use in patients with TBI. METHODS: This study was performed according to the PRISMA guidelines. The PubMed, Embase, Cochrane Central, Web of Science, and China National Knowledge Infrastructure databases were searched from inception until April 13, 2021, using a search strategy that included 2 main terms: "statins" and "traumatic brain injury." The outcomes were mortality, hospital length of stay, and intensive care unit length of stay, which were evaluated using a random-effects model and represented by the pooled risk ratio with 95% confidence intervals. RESULTS: The search results identified 7 eligible studies, with a total of 111,935 patients with brain injury. Preinjury statin use in patients with TBI was associated with a significantly decreased risk of mortality compared with that in nonusers (risk ratio, 0.75; 95% confidence interval, 0.59-0.94; I2 = 53%). Subgroup analysis showed that statin withdrawal might increase mortality. Sensitivity analysis showed that the results were stable and robust. CONCLUSIONS: Preinjury statin use may contribute to mortality reduction in patients with TBI, whereas statin withdrawal might increase mortality. In clinical management, statin use should not be discontinued after TBI.

Identification of differentially expressed microRNAs and the potential of microRNA-455-3p as a novel prognostic biomarker in glioma.

Glioma is an aggressive central nervous system malignancy. MicroRNAs (miRNAs/miRs) have been reported to be involved in the tumorigenesis of numerous types of cancer, including glioma. The present study aimed to identify the differentially expressed miRNAs in glioma, and further explore the clinical value of miR-455-3p in patients with glioma. GEO2R was used for the identification of the differentially expressed miRNAs according to the miRNA expression profiles obtained from the Gene Expression Omnibus database. OncomiR was used to analyze the relationship of miRNAs with the survival outcomes of the patients with glioma. A total of 108 patients with glioma were recruited to examine the expression levels of miR-455-3p and further explore its clinical value. The bioinformatics analysis results suggested that a total of 64 and 48 differentially expressed miRNAs were identified in the GSE90603 and GSE103229 datasets, respectively. There were 12 miRNAs in the overlap of the two datasets, of which three were able to accurately predict overall cancer survival, namely hsa-miR-7-5p, hsa-miR-21-3p and hsa-miR-455-3p. In patients with glioma, miR-455-3p was determined to be significantly upregulated (P<0.001). Additionally, patients with high miR-455-3p expression had significantly lower 5-year overall survival than those with low miR-455-3p expression (log-rank test, P=0.001). Cox regression analysis further determined that miR-455-3p was an independent prognostic indicator for overall survival in patients with glioma (hazard ratio=2.136; 95% CI=1.177-3.877; P=0.013). In conclusion, the present study revealed a series of miRNAs with potential functional roles in the pathogenesis of glioma, and provides findings that indicate miR-455-3p as a promising biomarker for the prognosis of glioma.