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Abstract The central nervous system (CNS) comprises a diverse range of brain cell types with distinct functions and gene expression profiles. Although single-cell RNA sequencing (scRNA-seq) provides new insights into the brain cell atlases, integrating large-scale CNS scRNA-seq data still encounters challenges due to the complexity and heterogeneity among CNS cell types/subtypes. In this study, we introduce a self-supervised contrastive learning method, called scCM, for integrating large-scale CNS scRNA-seq data. scCM brings functionally related cells close together while simultaneously pushing apart dissimilar cells by comparing the variations of gene expression, effectively revealing the heterogeneous relationships within the CNS cell types/subtypes. The effectiveness of scCM is evaluated on 20 CNS datasets covering 4 species and 10 CNS diseases. Leveraging these strengths, we successfully integrate the collected human CNS datasets into a large-scale reference to annotate cell types and subtypes in neural tissues. Results demonstrate that scCM provides an accurate annotation, along with rich spatial information of cell state. In summary, scCM is a robust and promising method for integrating large-scale CNS scRNA-seq data, enabling researchers to gain insights into the cellular and molecular mechanisms underlying CNS functions and diseases.

Background: Spontaneous intracerebral hemorrhage (ICH) is associated with alarmingly high rates of disability and mortality, and current therapeutic options are suboptimal. A critical component of ICH pathology is the initiation of a robust inflammatory response, often termed “cytokine storm,” which amplifies the secondary brain injury following the initial hemorrhagic insult. The precise sources and consequences of this cytokine-driven inflammation are not fully elucidated, necessitating further investigation. Methods: To address this knowledge gap, our study conducted a comprehensive cytokine profiling using Luminex® assays, assessing 23 key cytokines. We then employed single-cell RNA sequencing and spatial transcriptomics at three critical time points post-ICH: the hyperacute, acute, and subacute phases. Integrating these multimodal analyses allowed us to identify the cellular origins of cytokines and elucidate their mechanisms of action. Results: Luminex® cytokine assays revealed a significant upregulation of IL-6 and IL-1β levels at the 24-h post-ICH time point. Through the integration of scRNA-seq and spatial transcriptomics in the hemorrhagic hemisphere of rats, we observed a pronounced activation of cytokine-related signaling pathways within the choroid plexus. Initially, immune cell presence was sparse, but it surged 24 h post-ICH, particularly in the choroid plexus, indicating a substantial shift in the immune microenvironment. We traced the source of IL-1β and IL-6 to endothelial cells, establishing a link to pyroptosis. Endothelial pyroptosis post-ICH induced the production of IL-1β and IL-6, which activated microglial polarization characterized by elevated expression of Msr1, Lcn2, and Spp1 via the NF-κB pathway in the choroid plexus. Furthermore, we identified neuronal populations undergoing apoptosis, mediated by the Lcn2-SLC22A17 pathway in response to IL-1β and IL-6 signaling. Notably, the inhibition of pyroptosis using VX-765 significantly mitigated neurological impairments. Conclusions: Our study provides evidence that endothelial pyroptosis, characterized by the release of IL-1β and IL-6, triggers microglial polarization through NF-κB pathway activation, ultimately leading to microglia-mediated neuronal apoptosis in the choroid plexus post-ICH. These findings suggest that targeted therapeutic strategies aimed at mitigating endothelial cell pyroptosis and neutralizing inflammatory cytokines may offer neuroprotection for both microglia and neurons, presenting a promising avenue for ICH treatment.

Background: Craniopharyngiomas have a high recurrence rate and a poor prognosis, and the key methods for reducing recurrences are unknown. The aim of this study was to explore the key points of microscopic or endoscopic transsphenoidal surgery used to treat infradiaphragmatic craniopharyngiomas. Methods: We reviewed the medical records of patients with infradiaphragmatic craniopharyngiomas who were admitted to Peking Union Medical College Hospital between 2011 and 2018. Results: When considering tumor location, all 34 patients had intrasellar tumors, with 19 of them exhibiting suprasellar extensions. Of the 34 patients, 24 patients underwent resection under the microscope and the remaining 10 patients underwent transsphenoidal endoscopic surgery. Gross total tumor resection was achieved in 16 patients. Twelve patients underwent invaded sellar diaphragm resection, while the remaining 22 patients were not. Cerebrospinal fluid leaks occurred during surgery in 18 patients. Visual acuity improved in two patients. After an average follow-up of 31.1 months, 13 patients experienced tumor recurrence. The short term recurrence rate in the sellar diaphragm resection group was significantly lower compared to the non-resected group (P

Abstract Intracerebral hemorrhage (ICH) poses a formidable challenge in stroke management, with limited therapeutic options, particularly in the realm of immune‐targeted interventions. Clinical trials targeting immune responses post‐ICH have encountered setbacks, potentially attributable to the substantial cellular heterogeneity and intricate intercellular networks within the brain. Here, we present a pioneering investigation utilizing single‐cell RNA sequencing and spatial transcriptome profiling at hyperacute (1 h), acute (24 h), and subacute (7 days) intervals post‐ICH, aimed at unraveling the dynamic immunological landscape and spatial distributions within the cerebral tissue. Our comprehensive analysis revealed distinct cell differentiation patterns among myeloid and lymphocyte populations, along with delineated spatial distributions across various brain regions. Notably, we identified a subset of lymphocytes characterized by the expression of Spp1 and Lyz2, termed macrophage‐associated lymphocytes, which exhibited close interactions with myeloid cells. Specifically, we observed prominent interactions between Lgmn+Macro‐T cells and microglia through the spp1–cd44 pathway during the acute phase post‐ICH in the choroid plexus. These findings represent a significant advancement in our understanding of immune cell dynamics at single‐cell resolution across distinct post‐ICH time points, thereby laying the groundwork for exploring critical temporal windows and informing the development of targeted therapeutic strategies.

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

Abstract Protein aggregate species play a pivotal role in the pathology of various degenerative diseases. Their dynamic changes are closely correlated with disease progression, making them promising candidates as diagnostic biomarkers. Given the prevalence of degenerative diseases, growing attention is drawn to develop pragmatic and accessible protein aggregate species detection technology. However, the performance of current detection methods is far from satisfying the requirements of extensive clinical use. In this review, we focus on the design strategies, merits, and potential shortcomings of each class of detection methods. The review is organized into three major parts: native protein sensing, seed amplification, and intricate program, which embody three different but interconnected methodologies. To the best of our knowledge, no systematic review has encompassed the entire workflow, from the molecular level to the apparatus organization. This review emphasizes the feasibility of the methods instead of theoretical detection limitations. We conclude that high selectivity does play a pivotal role, while signal compilation, multilateral profiling, and other patient‐oriented strategies (i.e. less invasiveness and assay speed) are also important.

PurposeNo multi-center radiomics models have been built to predict delayed remission (DR) after transsphenoidal surgery (TSS) in Cushing’s disease (CD). The present study aims to build clinical and radiomics models based on data from three centers to predict DR after TSS in CD.MethodsA total of 122 CD patients from Peking Union Medical College Hospital, Xuanwu Hospital, and Fuzhou General Hospital were enrolled between January 2000 and January 2019. The T1-weighted gadolinium-enhanced MRI images and clinical data were used as inputs to build clinical and radiomics models. The regions of interest (ROI) of MRI images were automatically defined by a deep learning algorithm developed by our team. The area under the curve (AUC) of receiver operating characteristic (ROC) curves was used to evaluate the performance of the models. In total, 10 machine learning algorithms were used to construct models.ResultsThe overall DR rate is 44.3% (54/122). According to multivariate Logistic regression analysis, patients with higher BMI and lower postoperative cortisol levels are more likely to achieve a higher rate of delayed remission. Among the 10 models, XGBoost achieved the best performance among all models in both clinical and radiomics models with AUC values of 0.767 and 0.819 respectively. The results from SHAP value and LIME algorithms revealed that postoperative cortisol level (PoC) and BMI were the most important features associated with DR.ConclusionRadiomics models can be built as an effective noninvasive method to predict DR and might be useful in assisting neurosurgeons in making therapeutic plans after TSS for CD patients. These results are preliminary and further validation in a larger patient sample is needed.

Abstract Malignant tumors pose a serious risk to human health. Ascorbic acid (AA) has potential for tumor therapy; however, the mechanism underlying the ability of AA to selectively kill tumor cells remains unclear. AA can cause redox disequilibrium in tumor cells, resulting in the release of abundant reactive oxygen species, represented by hydrogen peroxide (H2O2). Therefore, the detection of H2O2 changes can provide insight into the selective killing mechanism of AA against tumor cells. In this work, inspired by the ion‐exchange mechanism in coral formation, a flexible H2O2 sensor (PtNFs/CoPi@CC) is constructed to monitor the dynamics of H2O2 in the cell microenvironment, which exhibits excellent sensitivity and spatiotemporal resolution. Moreover, the findings suggest that dehydroascorbic acid (DHA), the oxidation product of AA, is highly possible the substance that actually acts on tumor cells in AA therapy. Additionally, the intracellular redox disequilibrium and H2O2 release caused by DHA are positively correlated with the abundance and activity of glucose transporter 1 (GLUT1). In conclusion, this work has revealed the potential mechanism underlying the ability of AA to selectively kill tumor cells through the construction and use of PtNFs/CoPi@CC. The findings provide new insights into the clinical application of AA.

Metastatic PitNETs are a rare life-threatening condition with poor prognosis and documentation. Due to the scarce literature and lack of precise treatment, we hope to better characterise PitNET using the next-generation whole exon sequencing (WES) and RNA sequencing. This case study outlines a 54 years-old man and a 52 years-old woman who were both diagnosed with PitNET and analysis of peripheral blood and tumours were performed by WES and RNA sequencing. Analysis showed that DICER1 mutations in precancerous lesions and LAG3 overexpression were significant in aiding the prognosis and diagnosis of PitNETs. The first case with overexpressed LAG3 and DICER1 mutation died 26 months later, and the second case with LAG3 overexpression achieved partial remission. This study revealed that heightened expression of LAG3 offered promising targets for ICI and mutations in DICER1 could provide markers for effective diagnosis and prognosis.

IntroductionIntracranial germ cell tumors (iGCTs), comprising of germinoma (GE) and non-germinomatous GCT (NGGCT), are a group of heterogenous brain tumors. Immunohistochemical markers, such as placental-like alkaline phosphatase (PLAP), are commonly used in diagnosis but show moderate sensitivity. Organic cation transporter 3/4 (OCT3/4) has been proposed as a novel biomarker for diagnosis and prognosis of iGCTs. This paper aimed to compare OCT3/4 with PLAP as potential immunohistochemical biomarkers in iGCTs diagnosis and clarify the relationship between OCT3/4 and prognosis of patients with iGCTs.MethodsMeta-analyses were performed to estimate pooled percentage point differences in positive rates between OCT3/4 and PLAP, their sensitivities, and correlation between OCT3/4 and prognosis in iGCTs.ResultsNine articles were included representing of 241 patients. A fixed-effects model meta-analysis revealed that OCT3/4s positive rate was 8.6% higher (95% CI, 0.7% lower to 17.9% higher) than that of PLAP. Using fixed-effects models, sensitivities of OCT3/4 as a potential immunohistochemical biomarker in CNS GE and NGGCT were 85% (95% CI, 79% to 89%) and 56% (95% CI, 39% to 71%), respectively. In comparison, PLAP had lower sensitivities in both GE (73%; 95% CI, 64% to 91%) and NGGCT (43%; 95% CI, 27% to 61%). Moreover, OCT3/4 was significantly negatively correlated with 5-year progression free survival in patients with CNS GE (HR = 2.56, 95 % CI 1.47 to 4.44; p = 0.0008). Sensitivity analyses showed similar results.DiscussionThis study provides the first comprehensive assessment of the efficacies of OCT3/4 and PLAP in iGCTs detection and prognosis prediction, indicating OCT3/4 seems to be a more sensitive and reliable immunohistochemical marker in iGCT diagnosis.

Ischemic stroke is a leading cause of long-term disability and a severe social and economic burden. After ischemic stroke, the central nervous system (CNS) microenvironment at the site of injury is often inflammatory and inhibitory, which limits endogenous neurogenesis and regeneration. Current treatments fail to promote recovery in disabled survivors because of the poor regenerative capacity of the CNS, and thus there is an urgent need to develop biomaterials that create a microenvironment that is conducive to neurogenesis. Injectable hydrogels that mimic native properties hold great potential for tissue repair. Hydrogels alone or in combination with other therapeutics can remodel the hostile stroke microenvironment by modulating neuroinflammation to promote exogenous and endogenous regenerative repair processes. In this review, we discuss the pathophysiology and current treatment approaches for brain repair and functional recovery in ischemic stroke, and then provide an overview of the potential of hydrogels in stroke treatment. We also offer our perspective on the clinical translation of hydrogels, with the aim of advancing the ischemic stroke field.

ObjectiveNeuronavigation and classification of craniopharyngiomas can guide surgical approaches and prognostic information. The QST classification has been developed according to the origin of craniopharyngiomas; however, accurate preoperative automatic segmentation and the QST classification remain challenging. This study aimed to establish a method to automatically segment multiple structures in MRIs, detect craniopharyngiomas, and design a deep learning model and a diagnostic scale for automatic QST preoperative classification.MethodsWe trained a deep learning network based on sagittal MRI to automatically segment six tissues, including tumors, pituitary gland, sphenoid sinus, brain, superior saddle cistern, and lateral ventricle. A deep learning model with multiple inputs was designed to perform preoperative QST classification. A scale was constructed by screening the images.ResultsThe results were calculated based on the fivefold cross-validation method. A total of 133 patients with craniopharyngioma were included, of whom 29 (21.8%) were diagnosed with type Q, 22 (16.5%) with type S and 82 (61.7%) with type T. The automatic segmentation model achieved a tumor segmentation Dice coefficient of 0.951 and a mean tissue segmentation Dice coefficient of 0.8668 for all classes. The automatic classification model and clinical scale achieved accuracies of 0.9098 and 0.8647, respectively, in predicting the QST classification.ConclusionsThe automatic segmentation model can perform accurate multi-structure segmentation based on MRI, which is conducive to clearing tumor location and initiating intraoperative neuronavigation. The proposed automatic classification model and clinical scale based on automatic segmentation results achieve high accuracy in the QST classification, which is conducive to developing surgical plans and predicting patient prognosis.

Cystic lesions are common lesions of the sellar region with various pathological types, including pituitary apoplexy, Rathke’s cleft cyst, cystic craniopharyngioma, etc. Suggested surgical approaches are not unique when dealing with different cystic lesions. However, cystic lesions with different pathological types were hard to differentiate on MRI with the naked eye by doctors. This study aimed to distinguish different pathological types of cystic lesions in the sellar region using preoperative magnetic resonance imaging (MRI). Radiomics and deep learning approaches were used to extract features from gadolinium-enhanced MRIs of 399 patients enrolled at Peking Union Medical College Hospital over the past 15 years. Paired imaging differentiations were performed on four subtypes, including pituitary apoplexy, cystic pituitary adenoma (cysticA), Rathke’s cleft cyst, and cystic craniopharyngioma. Results showed that the model achieved an average AUC value of 0.7685. The model based on a support vector machine could distinguish cystic craniopharyngioma from Rathke’s cleft cyst with the highest AUC value of 0.8584. However, distinguishing cystic apoplexy from pituitary apoplexy was difficult and almost unclassifiable with any algorithms on any feature set, with the AUC value being only 0.6641. Finally, the proposed methods achieved an average Accuracy of 0.7532, which outperformed the traditional clinical knowledge-based method by about 8%. Therefore, in this study, we first fill the gap in the existing literature and provide a non-invasive method for accurately differentiating between these lesions, which could improve preoperative diagnosis accuracy and help to make surgery plans in clinical work.

ObjectivesThe effects of the key parameters of the inlet duct of a waterjet propulsor on its hydrodynamic performance are studied, providing references for the design of waterjet propulsors. MethodsBased on STAR-CCM+ software, the influence of the axis height and inlet angle of a waterjet inlet duct on its hydrodynamic performance under different intake velocity ratio (IVR) conditions is studied using steady Reynolds-averaged Navier-Stokes equations (RANS) numerical simulation. Numerical uncertainty analysis is carried out according to the international towing tank conference (ITTC) uncertainty analysis procedure. In this paper, the computational domain is discretized with hexahedral structured grids. The set of governing equations is closed using the Realizable k-ε two-layer turbulence model, and the discretization schemes are second-order accurate. The semi-implicit method for pressure linked equations (SIMPLE) algorithm is applied in the pressure-velocity coupling calculation. ResultsThe results show that the numerical uncertainty is less than 4%, indicating that the grids used in this paper yield well-converged and reliable numerical results. ConclusionsThe efficiency of the inlet duct is higher in the range of IVR = 0.7~1.1. For large IVR, the inlet angle should be reduced. For small IVR, the axis height can be appropriately increased to improve the homogeneity of flow at the exit of the inlet duct.

Background: Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare disease, whose pathogenesis remains unclear. Here, we conducted untargeted metabolomics and lipidomics to identify seminal plasma signatures of nCHH, and to study the effect of LH and FSH deficiency on semen. Methods: Twenty-five diagnosed patients with nCHH (HH group) and twenty-three healthy participants (HC group) were enrolled. Laboratory parameters, seminal plasma samples and patients’ medical data were collected. Untargeted metabolomics and lipidomic profiling were performed using mass spectrometry (MS). Results: The metabolomics profiling are altered among patients with nCHH and healthy controls. There are 160 kinds of differential metabolites and the main different lipid species are TAG, PC, SM and PE. Conclusions: The metabolomics profiles in patients with nCHH changed. We hope that this work provides important insights into the pathophysiology of nCHH.

ObjectiveCOVID-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.MethodsA 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.ResultsA 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.ConclusionsCompared 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.

Exosomes are small extracellular vesicles that carry various bioactive molecules including various RNAs that modulate the activities of recipient cells. It has drawn considerable attention as means of cell communication and drug delivery. Exosome plays important role in various tumors, but it is rarely summarized in pituitary adenoma (PA). PA is the second most common primary central nervous system tumor, and its recurrence and persistent postoperative hormone hypersecretion lead to compromised quality of life. How exactly exosomes impact tumor development and hormone secretion is important for the development of this tumor diagnosis and treatment. In this review, we discuss how exosomal RNAs impact PAs and their potential as future clinical therapies. In our literature review, first, we found that exosomal microRNA hsa-miR-1180-3p is a potential early biomarker for NFPAs. Since NFPAs are typically difficult to diagnose, this is an especially important finding. Second, exosomal protein transcripts are potential invasive biomarker, such as MMP1, N-cadherin, CDK6, RHOU, INSM1, and RASSF10. Third, exosomal contents such as hsa-miR-21-5p promote distant bone formation of GHPA patients. Fourth, tumor suppressors in the exosome constitute novel therapeutic application of exosome, including long noncoding RNA (lncRNA) H19, miR-149-5p, miR-99a-3p, and miR-423-5p. This review discusses the possible mechanisms of exosome and their contents in PA and promotes the use of exosomes in both clinical diagnosis and treatment of this tumor.

BackgroundEpidermoid cysts of cavernous sinus (CS) are rare congenital neoplasms of the central nervous system. In previous literature reports, the treatment for CS epidermoid cysts was mainly microsurgical resection, and the surgical methods included simple microsurgery and endoscope-assisted microsurgery. The present case report demonstrates the first case of complete resection of a CS epidermoid cyst by a simple endoscopic endonasal transcavernous (EET) approach.Case presentationA 54-year-old woman presented with chronic persistent headaches and occasional syncope. Brain MRI demonstrated a space-occupying lesion of the left CS, and digital substruction angiography (DSA) showed a small aneurysm at the beginning of the left ophthalmic artery. Thrombotic therapy of carotid–ophthalmic aneurysms was performed first, and the patient underwent resection of the CS lesion secondary. Considering the location of the lesion and the neuroendoscopy technology and experience of the doctor, we made bold innovations and used an EET approach to achieve complete resection of the lesion. The postoperative pathological results were consistent with the characteristics of epidermoid cyst. During the 1-year follow up, the patient showed no apparent signs of recurrence on head MRI.ConclusionEpidermoid cyst of cavernous sinus is a rare benign occupying lesion in cavernous sinus. Reviewing the previous literature, the main treatment is microneurosurgery, and neuroendoscopy is only used as an auxiliary equipment. We present the first case of complete endoscopic resection of CS epidermoid cyst by EET approach according to CARE guidelines, aiming to share the new surgical plan for CS epidermoid cyst and provide more surgical options for this disease for neurosurgery colleagues.

ObjectiveHypothalamic dysfunction (HD) results in various endocrine disorders and is associated with an increased risk of metabolic comorbidities. This study aimed to analyze the clinical characteristics and metabolic abnormalities of adults with HD of various causes.MethodsThis study retrospectively reviewed adults with HD treated at our center between August 1989 and October 2020. Metabolic characteristics of patients were compared to those of age-, sex-matched lean, and body mass index (BMI)-matched controls.ResultsTemperature dysregulation (61.0%) was the most common hypothalamic physiological dysfunction. At least one anterior pituitary hormone deficiency was observed in 50 patients (84.7%), with hypogonadotropic hypogonadism being the most frequently observed. Metabolic syndrome was confirmed in 31 patients (52.5%) and was significantly more prevalent in those with panhypopituitarism or overweight/obesity. Metabolic syndrome (MetS) was significantly more common in patients with HD than in both lean and BMI-matched controls (P < 0.001 and P = 0.030, respectively). Considering the components of MetS, elevated fasting glucose levels were significantly more common in patients with HD than in BMI-matched controls (P = 0.029). Overweight/obesity and panhypopituitarism were significant risk factors for MetS in the multivariate analysis on patients with HD. Moreover, in the multivariate analysis on patients and BMI-matched control, HD was a significant risk factor of MetS (P=0.035, OR 2.919) after adjusted for age, sex and BMI.ConclusionsTemperature dysregulation and hypogonadotropic hypogonadism are the most common physiological and endocrine dysfunctions, respectively. MetS and unfavorable metabolic profiles were prevalent in adults with HD. HD was a significant risk factor of MetS after adjusted for BMI.

Plasmacytoma is a malignant tumor originating from the plasma cells of the bone marrow. Those discovered after a head injury is rare. We report a case of a 48-year-old female who complained of scalp mass without other symptoms after head injury. Meningioma was considered preoperatively based on imaging findings, and surgical resection was performed. Postoperatively, multiple myeloma complicated by skull plasmacytoma was diagnosed by histopathology and systematic examinations in succession. When evaluating a head mass that appeared after a head injury, plasmacytoma should be considered at times. Osteolytic changes and biconvex form on imaging are beneficial to differentiation.

ObjectiveConvolutional neural network (CNN) is designed for image classification and recognition with a multi-layer neural network. This study aimed to accurately assess sellar floor invasion (SFI) of pituitary adenoma (PA) using CNN.MethodsA total of 1413 coronal and sagittal magnetic resonance images were collected from 695 patients with PAs. The enrolled images were divided into the invasive group (n = 530) and the non-invasive group (n = 883) according to the surgical observation of SFI. Before model training, 100 images were randomly selected for the external testing set. The remaining 1313 cases were randomly divided into the training and validation sets at a ratio of 80:20 for model training. Finally, the testing set was imported to evaluate the model performance.ResultsA CNN model with a 10-layer structure (6-layer convolution and 4-layer fully connected neural network) was constructed. After 1000 epoch of training, the model achieved high accuracy in identifying SFI (97.0 and 94.6% in the training and testing sets, respectively). The testing set presented excellent performance, with a model prediction accuracy of 96%, a sensitivity of 0.964, a specificity of 0.958, and an area under the receptor operator curve (AUC-ROC) value of 0.98. Four images in the testing set were misdiagnosed. Three images were misread with SFI (one with conchal type sphenoid sinus), and one image with a relatively intact sellar floor was not identified with SFI.ConclusionThis study highlights the potential of the CNN model for the efficient assessment of PA invasion.

We attempt to generate a definition of delayed perihematomal edema expansion (DPE) and analyze its time course, risk factors, and clinical outcomes. A multi-cohort data was derived from the Chinese Intracranial Hemorrhage Image Database (CICHID). A non-contrast computed tomography (NCCT) -based deep learning model was constructed for fully automated segmentation hematoma and perihematomal edema (PHE). Time course of hematoma and PHE evolution correlated to initial hematoma volume was volumetrically assessed. Predictive values for DPE were calculated through receiver operating characteristic curve analysis and were tested in an independent cohort. Logistic regression analysis was utilized to identify risk factors for DPE formation and poor outcomes. The test cohort’s Dice scores of lesion segmentation were 0.877 and 0.642 for hematoma and PHE, respectively. Overall, 1201 patients were enrolled for time-course analysis of ICH evolution. A total of 312 patients were further selected for DPE analysis. Time course analysis showed the growth peak of PHE approximately concentrates in 14 days after onset. The best cutoff for DPE to predict poor outcome was 3.34 mL of absolute PHE expansion from 4-7 days to 8-14 days (AUC=0.784, sensitivity=72.2%, specificity=81.2%), and 3.78 mL of absolute PHE expansion from 8-14 days to 15-21 days (AUC=0.682, sensitivity=59.3%, specificity=92.1%) in the derivation sample. Patients with DPE was associated with worse outcome (OR: 12.340, 95%CI: 6.378-23.873, P

Abstract Background Functional gonadotroph adenomas (FGAs) are rare adenomas that most commonly secrete FSH. However, solitary LH-secreting pituitary adenomas are unusual. Case presentation A 30-year-old woman with elevated LH and normal FSH presented with inability to conceive. An MRI revealed an enlarged sella turcica and an intrasellar mass. Treatment with transsphenoidal resection led to normalization of LH and estradiol, as well as successful pregnancy. And we reviewed 6 cases of LH-secreting pituitary adenomas from 1981 to 2020. Conclusions Our case is unique because of the LH-secreting pituitary adenoma without FSH hypersecretion. This case indicates that pituitary adenoma should be considered when other diseases causing infertility have been excluded.

Abstract Background Hippocampal sclerosis (HS) is associated with post-surgery outcome in patients with temporal lobe epilepsy (TLE), and an automated method that quantifies HS severity is still lacking. Here, we aim to propose an MRI-based HS index (HSI) that integrates hippocampal volume and FLAIR signal to measure the severity of HS. Methods Forty-two pre-surgery TLE patients were included retrospectively, with T1-weighted (T1W) and FLAIR images acquired from each subject. Two experienced neurosurgeons (W.D. and C.S.) and one neurologist (Q.L.) rated HS severity with a four-class grading scale (normal, mild, moderate and severe) based on both hippocampal volume loss and increased FLAIR signal. A consensus of HS severity for each subject was made by voting among the three visual rating results. Regarding the automatic quantification, the hippocampal volume was quantified by AccuBrain on T1W image, and the FLAIR signal of hippocampus was calculated as the mean intensity of hippocampal region on the FLAIR image (normalized by the mean intensity of gray matter). To fit the HSI from visual rating, we applied ordinal regression with the voted visual rating as the dependent variable, and hippocampal volume and FLAIR signal as the independent variables. The HSI was calculated by weighting the predicted probabilities of the four-class grading scales from ordinal regression. Results The intra-class correlation coefficient (single measure) of the three raters was 0.806. The generated HSI was significantly correlated with the visual rating scales of the three raters (W.D.: 0.823, Q.L.: 0.817, C.S.: 0.717). HSI scores well differentiated the different HS categories as defined by the agreed HS visual rating (normal vs. mild: p

ObjectiveClival chordoma is a locally aggressive tumor with low metastatic potential. In the past decade, endoscopic endonasal approach (EEA) for clival chordoma has had a higher resection rate and a lower morbidity rate than transcranial approaches. Here, we present our initial single-center experience after EEA of clival chordomas.Patients and methodsThis study retrospectively analyzed 17 consecutive patients with clival chordoma who received EEA in our department between March 2015 and September 2021. The operation was performed by a single surgeon with EEA. The clinical and pathological characteristics were analyzed along with the surgical outcomes and complications.ResultsA total of 17 consecutive patients with clival chordoma received EEA with a median follow-up of 29.2 months (range 1-79). Gross total resection (GTR) was performed in 7 cases (41%), subtotal resection (STR) in 7 case (41%) and partially resection (PR) in 3 cases (18%). Cerebrospinal fluid leakage occurred in 2 cases (12%) and meningitis developed in 3 patients (18%) which were all successfully treated with intravenous antibiotics without any complications. There were no perioperative deaths or new focal neurological deficits postoperatively. Four in 7 patients with STR have had radiotherapy while the other three chose to be monitored. Till the last follow-up, three patients in STR group who received radiotherapy (3 in 4) had no tumor regrowth, while one in STR group with radiotherapy (1 in 4) showed tumor progression. Two patients in STR group without radiotherapy (2 in 3) showed stable tumor while the left one (1 in 3) showed tumor progression. One patient in the PR group died of tumor progression 2 years postoperation and the other one showed tumor progression and died of lung cancer 1 year postoperation. In addition, 1 in 7 patients with GTR had tumor recurrence in situ after 10 months and developed surgical pathway seeding in the spinal canal in C1 after 16 months. No recurrence occurred in the other 6 cases with GTR during the follow-up.ConclusionAlthough more cases are needed, our case series showed EEA is a safe and reliable method for clival chordoma with high resection rates and low morbidity rates. GTR without tumor residuum would improve the outcome.

ObjectivesConvolutional neural network (CNN) is a deep-learning method for image classification and recognition based on a multi-layer NN. In this study, CNN was used to accurately assess cavernous sinus invasion (CSI) in pituitary adenoma (PA).MethodsA total of 371 patients with PA were enrolled in the retrospective study. The cohort was divided into the invasive (n = 102) and non-invasive groups (n = 269) based on surgically confirmed CSI. Images were selected on the T1-enhanced imaging on MR scans. The cohort underwent a fivefold division of randomized datasets for cross-validation. Then, a tenfold augmented dataset (horizontal flip and rotation) of the training set was enrolled in the pre-trained Resnet50 model for transfer learning. The testing set was imported into the trained model for evaluation. Gradient-weighted class activation mapping (Grad-CAM) was used to obtain the occlusion map. The diagnostic values were compared with different dichotomizations of the Knosp grading system (grades 0-1/2-4, 0-2/3a-4, and 0-3a/3b-4).ResultsBased on Knosp grades, 20 cases of grade 0, 107 cases of grade 1, 82 cases of grade 2, 104 cases of grade 3a, 22 cases of grade 3b, and 36 cases of grade 4 were recorded. The CSI rates were 0%, 3.7%, 18.3%, 37.5%, 54.5%, and 88.9%. The predicted accuracies of the three dichotomies were 60%, 74%, and 81%. The area under the receiver operating characteristic (AUC-ROC) of Knosp grade for CSI prediction was 0.84; the cutoff was 2.5 with a Youden value of 0.62. The accuracies of the CNN model ranged from 0.80 to 0.96, with AUC-ROC values ranging from 0.89 to 0.98. The Grad-CAM saliency maps confirmed that the region of interest of the model was around the sellar region.ConclusionsWe constructed a CNN model with a high proficiency at CSI diagnosis. A more accurate CSI identification was achieved with the constructed CNN than the Knosp grading system.

Purpose: Pituitary adenomas (PAs) are the second most common intracranial neoplasms. Total surgical resection was extremely important for curing PAs, whereas tumor stiffness has gradually become the most critical factor affecting the resection rate in PAs. We aimed to investigate the molecular mechanisms of tumor stiffening and explore novel medications to reduce stiffness for improving surgical remission rates in PA patients.Methods: RNA sequencing, whole-genome bisulfite sequencing, and whole exome sequencing were applied to identify transcriptomic, epigenomic, and genomic underpinnings among 11 soft and 11 stiff PA samples surgically resected from patients at Peking Union Medical College Hospital (PUMCH). GH3 cell line and xenograft PA model was used to demonstrate therapeutic effect of sunitinib, and atomic force microscopy (AFM) was used to detect the stiffness of tumors.Results: Tumor microenvironment analyses and immunofluorescence staining indicated endothelial cells (ECs) and cancer-associated fibroblasts (CAFs) were more abundant in stiff PAs. Weighted gene coexpression network analysis identified the most critical stiffness-related gene (SRG) module, which was highly correlated with stiff phenotype, ECs and CAFs. Functional annotations suggested SRGs might regulate PA stiffness by regulating the development, differentiation, and apoptosis of ECs and CAFs and related molecular pathways. Aberrant DNA methylation and m6A RNA modifications were investigated to play crucial roles in regulating PA stiffness. Somatic mutation analysis revealed increased intratumoral heterogeneity and decreased response to immunotherapy in stiff tumors. Connectivity Map analysis of SRGs and pRRophetic algorithm based on drug sensitivity data of cancer cell lines finally determine sunitinib as a promising agent targeting stiff tumors. Sunitinib inhibited PA growth in vitro and in vivo, and also reduced tumor stiffness in xenograft PA models detected by AFM.Conclusion: This is the first study investigating the underlying mechanisms contributing to the stiffening of PAs, and providing novel insights into medication therapy for stiff PAs.

BackgroundMost of pituitary adenomas (PAs) are slow-growing benign tumors which can be cured or controlled by conventional therapies, including surgery, medical treatment or radiotherapy. A small set of PAs, usually known as aggressive PAs or refractory PAs, present with more aggressive behavior and lead to poorer prognosis than classical PAs.MethodsWe retrospectively analyzed the clinical and pathological characteristics of 44 patients who were diagnosed with refractory PAs by a multidisciplinary team (MDT). All the patients’ demographic characteristics, radiological findings, Knosp grade, treatment details and clinical outcomes were abstracted from the medical records. Additionally, 44 patients with nonrefractory PAs (NRPAs) matched for age and gender were selected to serve as the control group.ResultsDespite using all combined treatments including surgery, radiotherapy and conventional medical treatments, all the refractory PAs showed tumor progression or hormone hypersecretion which caused increased morbidity and mortality and remained challenging to management. Compared with those of the non-refractory PAs, the tumor size, invasive rate and tumor growth rate (TGR) were significantly higher in the refractory PAs. TGR >2.2% per month may be considered as a preoperative indicator of refractoriness. The Ki-67 index in the refractory PAs were all ≥3%. EGFR, but not MMP2 or MMP9, was significantly overexpressed in refractory PAs compared with the corresponding levels in nonrefractory PAs.ConclusionRefractory PAs are unresponsive to surgery, radiotherapy and conventional medical treatments with a poor prognosis. Moreover, a TGR ≥2.2% per month, Ki-67 index ≥3% and EGFR overexpression may be independent predictors of clinical refractoriness.

ObjectiveTranssphenoidal surgery (TSS) is the first-line treatment for corticotroph adenomas. Although most corticotroph adenomas are noninvasive microadenomas, a small subset of them invading cavernous sinus (CS) is notoriously difficult to manage. The aim of this study was to evaluate the surgical outcome of corticotroph adenomas with CSI from a single center.Patients and MethodsThe clinical features and outcomes of CD patients who underwent TSS between January 2000 and September 2019 at Peking Union Medical College Hospital were collected from medical records. The clinical, endocrinological, radiological, histopathological, and surgical outcomes, and a minimum 12-month follow-up of patients with corticotroph adenomas invading CS were retrospectively reviewed.ResultsEighty-six patients with corticotroph adenomas invading CS were included in the study. The average age at TSS was 37.7 years (range, 12 to 67 years), with a female-to-male ratio of 3.1:1 (65/21). The median duration of symptoms was 52.6 months (range, 1.0 to 264 months). The average of maximum diameter of tumor was 17.6 mm (range, 4.5–70 mm). All included 86 patients underwent TSS using a microscopic or an endoscopic approach. Gross total resection was achieved in 63 patients (73.3%), subtotal resection was attained in 18 (20.9%), and partial resection was achieved in 5 (5.8%). After surgery, the overall postoperative immediate remission rate was 48.8% (42/86); 51.2% (44/86) of patients maintained persistent hypercortisolism. In 42 patients with initial remission, 16.7% (7/42) experienced a recurrence. In these patients with persistent disease and recurrent CD, data about further treatment were available for 30 patients. Radiotherapy was used for 15 patients, and 4 (26.7%) of them achieved biochemical remission. Repeat TSS was performed in 5 patients, and none achieved remission. Medication was administered in 4 patients, and one of them obtained disease control. Adrenalectomy was performed in 6 patients, and 5 (83.3%) achieved biochemical remission. At the last follow-up, 10 of 30 patients (33.3%) were in remission, and 20 patients still had persistent disease.The remission rate in corticotroph adenomas with cavernous sinus invasion (CSI) that underwent gross total resection and first TSS was significantly higher than that in patients undergoing subtotal resection, partial resection, and a second TSS (all p < 0.05). However, there was no significant difference in the remission rate between patients with different tumor sizes, Knosp grades, and surgical approaches (p > 0.05).ConclusionThe management of corticotroph adenomas with CSI remain a therapeutic challenge due to incomplete resection of invasive and/or a large adenoma. With the application of multiple techniques, approximately half of the patients could achieve gross total resection and biochemical remission via TSS by experienced neurosurgeons. The extent of tumor resection and the number of operations were associated with surgical remission rate in corticotroph adenomas with CSI. If the remission was not achieved by surgery, other treatments including radiotherapy, medical therapy, and even bilateral adrenalectomy are required.

Electrohydrodynamic jet (E-jet) printing has broad application prospects in the preparation of flexible electronics and optical devices. Ejection cycle time and droplet size are two key factors affecting E-jet-printing quality, but due to the complex process of E-jet printing, it remains a challenge to establish accurate relationships among ejection cycle time and droplet diameter and printing parameters. This paper develops a model based on random forest regression (RFR) for E-jet-printing prediction. Trained with 72 groups of experimental data obtained under four printing parameters (voltage, nozzle-to-substrate distance, liquid viscosity, and liquid conductivity), the RFR model achieved a MAPE (mean absolute percent error) of 4.35% and an RMSE (root mean square error) of 0.04 ms for eject cycle prediction, as well as a MAPE of 2.89% and an RMSE of 0.96 μm for droplet diameter prediction. With limited training data, the RFR model achieved the best prediction accuracy among several machine-learning models (RFR, CART, SVR, and ANN). The proposed prediction model provides an efficient and effective way to simultaneously predict the ejection cycle time and droplet diameter, advancing E-jet printing toward the goal of accurate, drop-on-demand printing.

PurposeStudies on hyperprolactinemia and hypopituitarism in acromegaly are limited. We aimed to analyze the preoperative status, postoperative alterations, and correlated factors of hyperprolactinemia and hypopituitarism in acromegaly patients.MethodsThis is a single-center cohort study with long-term follow-up. We prospectively enrolled 529 acromegaly patients. Hyperprolactinemia and hypopituitarism were evaluated by testing hypothalamus-pituitary-end organ (HPEO) axes hormones before and after surgery.ResultsHyperprolactinemia (39.1%) and hypopituitarism (34.8%) were common in acromegaly. The incidences of axis-specific hypopituitarism varied (hypogonadism, 29.7%; hypothyroidism, 5.9%; adrenal insufficiency, 5.1%), and multiple HPEO axes dysfunction was diagnosed in 5.3% of patients. Patients with preoperative hyperprolactinemia [hazard ratio (HR)=1.39 (1.08-1.79); p=0.012], hypogonadism [HR=1.32 (1.01-1.73); p=0.047], and hypothyroidism [HR=3.49 (1.90-6.44); p

Pituitary adenomas (PAs) are a group of tumors with complex and heterogeneous clinical manifestations. Early accurate diagnosis, individualized management, and precise prediction of the treatment response and prognosis of patients with PA are urgently needed. Artificial intelligence (AI) and machine learning (ML) have garnered increasing attention to quantitatively analyze complex medical data to improve individualized care for patients with PAs. Therefore, we critically examined the current use of AI and ML in the management of patients with PAs, and we propose improvements for future uses of AI and ML in patients with PAs. AI and ML can automatically extract many quantitative features based on massive medical data; moreover, related diagnosis and prediction models can be developed through quantitative analysis. Previous studies have suggested that AI and ML have wide applications in early accurate diagnosis; individualized treatment; predicting the response to treatments, including surgery, medications, and radiotherapy; and predicting the outcomes of patients with PAs. In addition, facial imaging-based AI and ML, pathological picture-based AI and ML, and surgical microscopic video-based AI and ML have also been reported to be useful in assisting the management of patients with PAs. In conclusion, the current use of AI and ML models has the potential to assist doctors and patients in making crucial surgical decisions by providing an accurate diagnosis, response to treatment, and prognosis of PAs. These AI and ML models can improve the quality and safety of medical services for patients with PAs and reduce the complication rates of neurosurgery. Further work is needed to obtain more reliable algorithms with high accuracy, sensitivity, and specificity for the management of PA patients.

Background: Endogenous Cushing's syndrome (CS), also called hypercortisolism, leads to a significant increase in mortality due to excessive cortisol production, which is mainly due to cardiovascular disease. CS complicated with cardiomyopathies, which is a rare and severe condition, has rarely been reported in the literature.Objective: To investigate the clinical characteristics of CS complicated with cardiomyopathies, we retrospectively reviewed the clinical manifestations, laboratory results, cardiac imaging results and prognosis to further understand the diagnosis, treatment, and management of these cases.Methods: The clinical data of patients diagnosed with CS complicated with cardiomyopathies obtained from discharge sheets from Peking Union Medical College Hospital from January 1986 to August 2021 were collected. Case reports of CS complicated with cardiomyopathies were retrieved from PubMed. In addition, Cushing's disease (CD) patients without cardiomyopathies were collected as controls to compare the clinical features.Results: A total of 19 cases of CS complicated with cardiomyopathies and cases of CD without cardiomyopathies (n = 242) were collected. The causes of CS included pituitary adenoma (n = 8, 42.11%), adrenal adenoma (n = 7, 36.84%), ectopic adrenocorticotropic hormone (ACTH) tumor (n = 2, 10.53%) and unclear causes (n = 2, 10.53%) in the CS complicated with cardiomyopathies group. The types of cardiomyopathies were dilated cardiomyopathies (n = 15, 78.94%) and hypertrophic cardiomyopathies (n = 4, 21.05%). The serum sodium concentration was significantly higher [145.50 (140.50–148.00) mmol/L vs. 141.00 (140.00–143.00) mmol/L], while the serum potassium concentration was significantly lower [2.70 (2.40–3.60) mmol/L] vs. 3.90 (3.50–4.20 mmol/L)] in the CS complicated with cardiomyopathies group compared to the CD patients without cardiomyopathies. There were no significant differences between the CS complicated with cardiomyopathies group and the CD patients without cardiomyopathies in the serum cortisol concentration and 24-h urine free cortisol, but a significant difference in the adrenocorticotropic hormone level [109.00 (91.78–170.30) pg/ml vs. 68.60 (47.85–110.00) pg/ml]. Twelve/16 (75.0%) patients showed significant improvement or even a complete healing of the heart structure and function after remission of hypercortisolemia after treatment with CS.Conclusions: CS complicated with cardiomyopathies is a very rare clinical entity, in which cortisol plays an important role and it can be greatly improved after remission of hypercortisolemia.

PurposeCushing’s disease (CD) is a rare disease that contributes to 70–80% hypercortisolemia, which presents similarities and differences between pediatric and adult patients, and even between male and female patients. However, the comparative study of CD between different age groups and different genders is still insufficient. The aim of the study is to make a systematic comparison to reveal the gender differences in children and adult patients of CD, helping clinicians to provide optimal treatment for different groups of patients.MethodsWe conducted a retrospective research consisting of 30 pediatric and 392 adult CD patients in a single center in Peking Union Medical College Hospital. All 422 patients showed symptoms related to hypercortisolism and received adenoma excision surgery in the department of neurosurgery between 2014 and 2020.ResultsFor the accuracy of diagnosis, the sensitivity of BIPSS at baseline in pediatric patients was lower than in adults (75 vs. 91%, P = 0.054) but increased greatly after desmopressin stimulation (94 vs. 95%). However, the accuracy of lateralization for BIPSS was not preferred for prediction. As for clinical manifestations, growth retardation, weight gain, hirsutism, and acne were more prevalent for children, while for adults, hypertension, osteopenia, glucometabolic disorder, easy bruising, hair loss, and weight loss were more frequently seen. As previously reported, we observed a significant difference between the male prevalence of pediatric and adult patients (50 vs. 17%, P < 0.001), which was possibly caused by the more severe and earlier onset of a series of symptoms. Gender-related comparison showed greater morbidity of nephrolithiasis, hypokalemia, hypertension, easy bruising, osteopenia, and striae for male patients, while irregular menses, hirsutism, and hair loss were more common for female patients. Further analysis showed that the secretory activity of the PA axis was higher for males, presenting as the more remarkable alteration of laboratory parameters and contributing to the more severe clinical manifestations. For patients treated with transsphenoidal pituitary surgery (TSS), the immediate prognosis could be predicted by operation history, invasiveness, Ki-67, and information provided by MRI, including tumor size and Knosp grading. However, we still lack methods to predict long-term prognosis.ConclusionsOur study is the first detailed and systematic comparison between pediatric and adult CD patients. Further exploration of the impact of CD on different genders reveals a more severe and probably an earlier-onset pattern of CD for male patients.

BackgroundBasal ganglia germ cell tumors (BGGCTs) represent an extremely rare subset of tumors about which little is known. Some patients suffer from tumor dissemination, such as sellar involvement. This study aimed to evaluate the independent prognostic risk factors of patients with BGGCTs with or without sellar involvement.MethodsSixteen patients were diagnosed with BGGCTs at Peking Union Medical College Hospital from January 2000 to December 2020. A literature review was performed on the online databases Medline and PubMed, and 76 cases in the 19 retrieved articles were identified at the same time. The data regarding biochemical tests, radiological examinations, and outcomes during follow-up were analyzed.ResultsOf 92 patients in this study, seven patients were clinically diagnosed as germinomas, with the remaining 85 patients receiving surgery. Fifty-two patients suffered from multifocal lesions or tumor dissemination. The patients with BGGCTs demonstrated a significant male predilection. The patients with delayed diagnosis more likely had cognitive disturbance (p = 0.028), mental disturbance (p = 0.047), and diabetes insipidus (p = 0.02). Multivariate analysis demonstrated that the independent poor prognostic risk factors of patients with BGGCTs were delayed diagnosis [odd ratio (OR) 2.33; 95% CI 1.02–5.31], focal radiotherapy (OR 4.00; 95% CI 1.69–9.49), and non-pure germinoma (OR 4.64; 95% CI 1.76–12.22).ConclusionsThe delayed diagnosis, focal radiotherapy, and non-pure germinoma were associated with a poorer prognosis for patients with BGGCTs with or without sellar involvement.

Optic nerve hemangioblastoma is a very rare benign tumor with only 39 reported cases by now. It appears to be hyperintense on T2-weighted images with a significant enhancement on contrast scans, which are similar to glioma and meningioma. Due to the lack of specificity in MRI manifestations, optic nerve hemangioblastoma is often misdiagnosed. To provide new insights into differential diagnosis of optic nerve hemangioblastoma, we report for the first time an optic nerve hemangioblastoma case employing advanced magnetic resonance techniques including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, and magnetic resonance angiography (MRA). In addition, we have collected all reported optic nerve hemangioblastoma cases and reviewed their neuroimaging findings by MRI and angiography. Our results show that solid-type tumor is the dominant form of optic nerve hemangioblastoma and extensive edema is widely observed. These findings are surprisingly contrary to manifestations of cerebellar hemangioblastoma. Besides the structural features, quantitative indexes including ADC and relative cerebral blood volume (rCBV) ratio, which are significantly elevated in cerebellar hemangioblastoma, may also shed a light on the preoperative diagnosis of hemangioblastoma of optic nerve. Finally, we discuss the critical neuroimaging features in the differential diagnosis between optic nerve hemangioblastoma from optic pathway glioma and optic nerve sheath meningioma.

BackgroundMcCune-Albright syndrome is a rare disorder characterized by fibrous dysplasia, café au lait skin spots, and hyperfunctioning endocrinopathies. The coexistence of precocious puberty and growth hormone excess in McCune-Albright syndrome is rare. Both conditions can manifest as accelerated growth, and treatments can be more challenging for such patients. This study aimed to describe the clinical manifestations of combined GH excess and PP in the context of McCune-Albright syndrome and analyze the clinical features and treatments of these patients.MethodClinical data from 60 McCune-Albright syndrome patients from Peking Union Medical College Hospital were obtained. The demographic characteristics, growth hormone, insulin-like growth factor-1, prolactin, alkaline phosphatase, and sex hormone levels; growth velocity; and bone age data were obtained. The growth velocity Z-score, bone age over chronological age ratio, and predicted adult height Z-score were calculated before and after treatment. Published studies and case reports were systemically searched, and data on demographic, clinical, and biochemical characteristics and treatment outcomes were obtained.ResultsWe reviewed seven patients among 60 McCune-Albright syndrome patients at Peking Union Medical College Hospital (5 female) and 39 patients (25 female) from the published literature. Six of the seven patients from Peking Union Medical College Hospital and half of the patients from the published studies were pediatric patients. These patients had increased growth velocity Z-scores and bone age over chronological age ratios. After good control of both conditions, the growth velocity Z-score and bone age over chronological age ratio decreased significantly, and the predicted adult height Z-score increased. The final heights and predicted adult height Z-scores were not impaired in patients with gigantism. All the patients had craniofacial fibrous dysplasia associated with optic and otologic complications.ConclusionMcCune-Albright syndrome with growth hormone excess and precocious puberty is more common in girls. Patients have accelerated linear growth and advanced skeletal age, and early and good control of both conditions leads to a reduced growth velocity and stabilized bone age. The predicted adult and final heights are not negatively affected when growth hormone excess is diagnosed in pediatric patients.

ObjectiveNo 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.MethodsA 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.ResultsOnly 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.ConclusionFluctuation 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.

Intracerebral hemorrhage (ICH) has one of the worst prognoses among patients with stroke. Surgical measures have been adopted to relieve the mass effect of the hematoma, and developing targeted therapy against secondary brain injury (SBI) after ICH is equally essential. Numerous preclinical and clinical studies have demonstrated that perihematomal edema (PHE) is a quantifiable marker of SBI after ICH and is associated with a poor prognosis. Thus, PHE has been considered a promising therapeutic target for ICH. However, the findings derived from existing studies on PHE are disparate and unclear. Therefore, it is necessary to classify, compare, and summarize the existing studies on PHE. In this review, we describe the growth characteristics and relevant underlying mechanism of PHE, analyze the contributions of different risk factors to PHE, present the potential impact of PHE on patient outcomes, and discuss the currently available therapeutic strategies.

BackgroundNo existing machine learning (ML)-based models use free text from electronic medical records (EMR) as input to predict immediate remission (IR) of Cushing’s disease (CD) after transsphenoidal surgery.PurposeThe aim of the present study is to develop an ML-based model that uses EMR that include both structured features and free text as input to preoperatively predict IR after transsphenoidal surgery.MethodsA total of 419 patients with CD from Peking Union Medical College Hospital were enrolled between January 2014 and August 2020. The EMR of the patients were embedded and transformed into low-dimensional dense vectors that can be included in four ML-based models together with structured features. The area under the curve (AUC) of receiver operating characteristic curves was used to evaluate the performance of the models.ResultsThe overall remission rate of the 419 patients was 75.7%. From the results of logistic multivariate analysis, operation (p < 0.001), invasion of cavernous sinus from MRI (p = 0.046), and ACTH (p = 0.024) were strongly correlated with IR. The AUC values for the four ML-based models ranged from 0.686 to 0.793. The highest AUC value (0.793) was for logistic regression when 11 structured features and “individual conclusions of the case by doctor” were included.ConclusionAn ML-based model was developed using both structured and unstructured features (after being processed using a word embedding method) as input to preoperatively predict postoperative IR.

ContextTraditionally, low-dose dexamethasone suppression test (LDDST) was used to confirm the diagnosis of Cushing’s syndrome (CS), and high-dose dexamethasone suppression test (HDDST) was used to differentiate Cushing’s disease (CD) and ectopic adrenocorticotropin (ACTH) syndrome (EAS), but some studies suggested that HDDST might be replaced by LDDST. For the differential diagnosis of CS, dexamethasone suppression test was usually combined with other tests such as bilateral petrosal sinus sampling (BIPSS) and pituitary magnetic resonance imaging, but the optimal pathway to incorporate these tests is still controversial.ObjectivesTo develop an optimized pathway for the differential diagnosis of CD and EAS based on LDDST.Design and SettingSingle-center retrospective study (2011–2019).PatientsTwo hundred sixty-nine CD and 29 EAS patients with pathological diagnosis who underwent consecutive low- and high-dose DST.ResultsFor the differential diagnosis of CD and EAS, the area under curve (AUC) of LDDST using urine free cortisol (0.881) was higher than that using serum cortisol (0.685) (p < 0.001) in head-to-head comparison among a subgroup of 108 CD and 10 EAS. The AUC of LDDST (0.883) was higher than that of HDDST (0.834) among all the included patients. With the cutoff of

In this article, we present a 31-year-old female who presented with intermittent headache and oligomenorrhea of over 10 years’ duration. Imaging revealed a large suprasellar mass with sellar extension. The patient underwent an endoscopic endonasal trans-sphenoidal surgery to resection of the mass. Clinical, radiological, and operative findings from this patient were initially considered to be Rathke’s cleft cyst (RCC). However, postoperative histological examinations revealed a mature cystic teratoma. No radiotherapy was performed after surgery. At the most recent follow-up, approximately 1 year later, the patient is doing well with no headache and no recurrence of the teratoma.

Pituitary metastasis is an unusual situation in clinical practice, while the incidence is increasing with age. Breast cancer for women and lung cancer for men were the most frequent primary origins of pituitary metastasis. Diagnosing asymptomatic patients with unknown primary malignant origin is difficult, thus pituitary metastasis may be diagnosed as primary pituitary adenoma. Here, we report a case of a 65-year-old patient with visual changes and diabetes insipidus, showing an extensive mass in the sellar region which was initially thought to be a primary pituitary adenoma. Patient corticotropic deficits were corrected, and transnasal transsphenoidal surgery was adopted, leading to total tumor resection. Tumor texture during surgical procedure was similar to that of pituitary adenoma. However, the histopathological and immunohistochemistry results suggested it as a pituitary metastasis from lung neuroendocrine tumor. Postoperative chest CT scan confirmed a pulmonary mass consistent with primary neoplasm. Abdominal CT further detected multiple metastases in liver, pancreas, and colon. Despite intensive treatment, the patient continued to show decreased level of consciousness due to cachexia, resulting in death 1 week after surgery. This case highlights the importance of differential diagnosis of invasive lesions of the sellar region, especially in individuals over 60 years of age with diabetes insipidus.

BackgroundPrimary pituitary lymphoma (PPL) is an extremely rare disease with poor prognosis. Although PPL has been shown to be different from classical primary central nervous system lymphoma because of the embryological origin of structures, individual and precise treatment of PPL remains unknown.MethodsA 61-year-old man and a 65-year-old woman both diagnosed with primary pituitary diffuse large B cell lymphoma underwent genetic analysis of cerebrospinal fluid and tumor tissue by next generation sequencing.ResultsIn the first case, partial remission was achieved following R²-MTX chemotherapy. In the other case with TP53 mutation and BCL6-LPP fusion, disease progressed although different chemotherapy regimens were given.ConclusionThe gene mutation of TP53 and BCL6 may be identified as a marker responsible for prognostic difference in patients with PPL. Genetic analysis may provide a novel approach for precise management and prognosis prediction.

BackgroundDiagnosing the well-known concomitant Rathke’s cleft cyst (RCC) and differentiating it from other sellar lesions are difficult because RCC is and other sellar lesions are closely related and represent a continuum from simple RCCs to more complex lesions. The purpose of this study is to better understand the adeno- and neurohypophysis adjacent to the par intermedia remnants and their role in the origin of the coexistence of these two distinct tumor neoplasias; to assess the incidence in different age groups; to categorize the pathohistological subtype, which can be incorporated in predictive/prognostic models; and finally, to evaluate the current evidence on collision tumors of the sellar embryonic remnant tract in terms of their biological behavior and pathology.MethodsUtilizing the PubMed database, data were collected from 1920 to 2019. Information about demographics, clinical characteristics, and age was summarized and analyzed by using univariable and multivariable models. The same cell type was observed regardless of whether the tumor was only one type or mixed types, and their histologic patterns were assessed.ResultsThe incidence rates were similar among patients stratified into three age subgroups: 40–49 years (24.57%), 50–59 years (19.54%), and older than 60 years (22.98%). We found that various types of sellar lesions, namely, squamous metaplasia (SM) + goblet cells (GC) (HR 46.326), foamy macrophages (FM) (HR 39.625), epithelial cells and multinucleated giant cells or cholesterin (EM) (HR 13.195), a cavernous portion of the right internal carotid artery (CP-ICA) (HR 9.427), epithelial cells with ciliated cuboidal (EC-CC) (HR 8.456), were independently associated with RCC pathological status. These divergent AUCs (0.848 for Hypo as RCC, 0.981 for RCC co PA, 0.926 for CD and CP co RCC) and subtypes of PA (HR 4.415, HR 2.286), Hypo (HR 3.310), CD and CP (HR 2.467), EC and DC and PG and SGR (HR 1.068), coexisting with the risk of a comorbid RCC lesion, may reflect the etiologic heterogeneity of coderivation and the different effects of some risk factors on tumor subtypes. Our analyses suggested that the greatest accuracy was observed for the pituitary adenoma subtype, with an AUC of 0.981 (95% confidence interval [CI]: 0.959–1.005), while the poorest accuracy was observed for aneurysms, with an AUC of 0.531 (95% CI: 0.104–0.958). We separately analyzed and confirmed the above results. Sensitivity analysis revealed no evidence of systematic bias due to missing data.ConclusionThis study showed that the histopathological changes in patients with sellar embryonic remnant-associated collision tumors showed highly consistent epithelial cell replacement (renewal) (ciliated columnar epithelium to ciliated squamous epithelium to squamous epithelium) or accumulation, and the RCC cyst wall was similar in structure to the tracheobronchial airway epithelium, with progenitor cell characteristics. The collision accuracy between RCC and other tumors (PAs, craniopharyngioma, chordoma, etc.) is different; these characteristics constitute the theoretical basis for the postmigration development of the pharyngeal bursa.

IgG4-related inflammatory pseudotumors are very uncommon and are characterized histologically by the presence of inflammatory swellings with increasing IgG4-positive plasma cells and lymphocytes infiltrating the tissues. As reports of intracranial IgG4-related pseudotumors are very rare, we report a case of an IgG4-related inflammatory pseudotumor involving the clivus mimicking meningioma. A 46-year-old male presented with intermittent headache for 2 years and a sudden onset of dysphagia and dysphonia of 7 days’ duration along with lower limb weakness. Enhanced magnetic resonance imaging (MRI) of the skull base revealed an isointense signal on T1- and T2-weighted images from an enhanced mass located at the middle of the upper clivus region, for which a meningioma was highly suspected. Then, an endoscopic transsphenoidal approach was adopted and the lesion was partially resected, as the subdural extra-axial lesion was found to be very tough and firm, exhibiting fibrous scarring attaching to the brain stem and basal artery. After the surgery, brain stem and posterior cranial nerve decompression was achieved, and the patient’s symptoms, such as dysphagia, dysphonia and lower limb weakness, improved. Pathological findings showed many IgG4-positive plasma cells and lymphocytes surrounded by collagen-rich fibers. The patient was sent to the rheumatology department for further glucocorticoids after the diagnosis of an IgG4-related inflammatory pseudotumor was made. This case highlights the importance of considering IgG4-related inflammatory pseudotumors as a differential diagnosis in patients with lesions involving the clivus presenting with a sudden onset of symptoms of dysphagia and dysphonia along with lower limb weakness when other more threatening causes have been excluded. IgG4-related inflammatory pseudotumors are etiologically enigmatic and unpredictable, and total resection might not be warranted. Glucocorticoids are usually the first line of treatment after diagnosis.