Integrating network pharmacology and transcriptomic omics reveals that akebia saponin D attenuates neutrophil extracellular traps-induced neuroinflammation via NTSR1/PKAc/PAD4 pathway after intracerebral hemorrhage.

Neutrophils and their production of neutrophil extracellular traps (NETs) significantly contribute to neuroinflammation and brain damage after intracerebral hemorrhage (ICH). Although Akebia saponin D (ASD) demonstrates strong anti-inflammatory activities and blood-brain barrier permeability, its role in regulating NETs formation and neuroinflammation following ICH is uncharted. Our research focused on unraveling the influence of ASD on neuroinflammation mediated by NETs and the mechanisms involved. We found that increased levels of peripheral blood neutrophils post-ICH are correlated with worse prognostic outcomes. Through network pharmacology, we identified ASD as a promising therapeutic target for ICH. ASD administration significantly improved neurobehavioral performance and decreased NETs production in neutrophils. Furthermore, ASD was shown to upregulate the membrane protein NTSR1 and activate the cAMP signaling pathway, confirmed through transcriptome sequencing, western blot, and immunofluorescence. Interestingly, the NTSR1 inhibitor SR48692 significantly nullified ASD's anti-NETs effects and dampened cAMP pathway activation. Mechanistically, suppression of PKAc via H89 negated ASD's anti-NETs effects but did not affect NTSR1. Our study suggests that ASD may reduce NETs formation and neuroinflammation, potentially involving the NTSR1/PKAc/PAD4 pathway post-ICH, underlining the potential of ASD in mitigating neuroinflammation through its anti-NETs properties.

A long-term prognosis study of human USP8-mutated ACTH-secreting pituitary neuroendocrine tumours.

OBJECTIVE: Somatic variants in the ubiquitin-specific protease 8 (USP8) gene are the most common genetic cause of Cushing disease. We aimed to explore the relationship between clinical outcomes and USP8 status in a single centre. DESIGN, PATIENTS AND MEASUREMENTS: We investigated the USP8 status in 48 patients with pituitary corticotroph tumours. A median of 62 months of follow-up was conducted after surgery from November 2013 to January 2015. The clinical, biochemical and imaging features were collected and analysed. RESULTS: Seven USP8 variants (p.Ser718Pro, p.Ser719del, p.Pro720Arg, p.Pro720Gln, p.Ser718del, p.Ser718Phe, p.Lys713Arg) were identified in 24 patients (50%). USP8 variants showed a female predominance (100% vs. 75% in wild type [WT], p = .022). Patients with p.Ser719del showed an older age at surgery compared to patients with the p.Pro720Arg variant (47- vs. 24-year-olds, p = .033). Patients with p.Pro720Arg showed a higher rate of macroadenoma compared to patients harbouring the p.Ser718Pro variant (60% vs. 0%, p = .037). No significant differences were observed in serum and urinary cortisol and adrenocorticotropin hormone (ACTH) levels. Immediate surgical remission (79% vs. 75%) and long-term hormone remission (79% vs. 67%) were not significantly different between the two groups. The recurrence rate was 21% (4/19) in patients harbouring USP8 variants and 13% (2/16) in WT patients. Recurrence-free survival presented a tendency to be shorter in USP8-mutated individuals (76.7 vs. 109.2 months, p = .068). CONCLUSIONS: Somatic USP8 variants accounted for 50% of the genetic causes in this cohort with a significant female frequency. A long-term follow-up revealed a tendency toward shorter recurrence-free survival in USP8-mutant patients.

Phase 1 study of safety and preliminary efficacy of intranasal transplantation of human neural stem cells (ANGE-S003) in Parkinson's disease.

BACKGROUND: Intranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial. METHODS: This was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy. RESULTS: 7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels. CONCLUSIONS: Treatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation.

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.

Noncancerous disease-targeting AIEgens.

Noncancerous diseases include a wide plethora of medical conditions beyond cancer and are a major cause of mortality around the world. Despite progresses in clinical research, many puzzles about these diseases remain unanswered, and new therapies are continuously being sought. The evolution of bio-nanomedicine has enabled huge advancements in biosensing, diagnosis, bioimaging, and therapeutics. The recent development of aggregation-induced emission luminogens (AIEgens) has provided an impetus to the field of molecular bionanomaterials. Following aggregation, AIEgens show strong emission, overcoming the problems associated with the aggregation-caused quenching (ACQ) effect. They also have other unique properties, including low background interferences, high signal-to-noise ratios, photostability, and excellent biocompatibility, along with activatable aggregation-enhanced theranostic effects, which help them achieve excellent therapeutic effects as an one-for-all multimodal theranostic platform. This review provides a comprehensive overview of the overall progresses in AIEgen-based nanoplatforms for the detection, diagnosis, bioimaging, and bioimaging-guided treatment of noncancerous diseases. In addition, it details future perspectives and the potential clinical applications of these AIEgens in noncancerous diseases are also proposed. This review hopes to motivate further interest in this topic and promote ideation for the further exploration of more advanced AIEgens in a broad range of biomedical and clinical applications in patients with noncancerous diseases.

Photoinduced Nonvolatile Resistive Switching Behavior in Oxygen-Doped MoS2 for a Neuromorphic Vision System.

Controlling resistance by external fields provides fascinating opportunities for the development of novel devices and circuits, such as temperature-field-induced superconductors, magnetic-field-triggered giant magnetoresistance devices, and electric-field-operated flash memories. In this work, we demonstrate a light-triggered nonvolatile resistive switching behavior in oxygen-doped MoS2. The two-terminal devices exhibit stable light-modulated resistive switching characteristics and optically tunable synaptic properties with an on/off ratio of up to 104. The integrated device with crossbar architecture enables simultaneous image sensing, preprocessing, and storage in a single device, thereby increasing the training efficiency and recognition rate of image recognition tasks. This work presents a novel pathway to develop the next generation of light-controlled memory and artificial vision systems for neuromorphic computing.

A machine learning approach for predicting perihematomal edema expansion in patients with intracerebral hemorrhage.

OBJECTIVES: Preventing the expansion of perihematomal edema (PHE) represents a novel strategy for the improvement of neurological outcomes in intracerebral hemorrhage (ICH) patients. Our goal was to predict early and delayed PHE expansion using a machine learning approach. METHODS: We enrolled 550 patients with spontaneous ICH to study early PHE expansion, and 389 patients to study delayed expansion. Two imaging researchers rated the shape and density of hematoma in non-contrast computed tomography (NCCT). We trained a radiological machine learning (ML) model, a radiomics ML model, and a combined ML model, using data from radiomics, traditional imaging, and clinical indicators. We then validated these models on an independent dataset by using a nested 4-fold cross-validation approach. We compared models with respect to their predictive performance, which was assessed using the receiver operating characteristic curve. RESULTS: For both early and delayed PHE expansion, the combined ML model was most predictive (early/delayed AUC values were 0.840/0.705), followed by the radiomics ML model (0.799/0.663), the radiological ML model (0.779/0.631), and the imaging readers (reader 1: 0.668/0.565, reader 2: 0.700/0.617). CONCLUSION: We validated a machine learning approach with high interpretability for the prediction of early and delayed PHE expansion. This new technique may assist clinical practice for the management of neurocritical patients with ICH. KEY POINTS: • This is the first study to use artificial intelligence technology for the prediction of perihematomal edema expansion. • A combined machine learning model, trained on data from radiomics, clinical indicators, and imaging features associated with hematoma expansion, outperformed all other methods.

Concurrent mutations of germline GPR101 and somatic USP8 in a pediatric giant pituitary ACTH adenoma: a case report.

BACKGROUND: Cushing's disease (CD) is rare in pediatric patients. It is characterized by elevated plasma adrenocorticotropic hormone (ACTH) from pituitary adenomas, with damage to multiple systems and development. In recent years, genetic studies have shed light on the etiology and several mutations have been identified in patients with CD. CASE PRESENTATION: A girl presented at the age of 10 years and 9 months with facial plethora, hirsutism and acne. Her vision and eye movements were impaired. A quick weight gain and slow growth were also observed. Physical examination revealed central obesity, moon face, buffalo hump, supra-clavicular fat pads and bruising. Her plasma ACTH level ranged between 118 and 151 pg/ml, and sella enhanced MRI showed a giant pituitary tumor of 51.8 × 29.3 × 14.0 mm. Transsphenoidal pituitary debulk adenomectomy was performed and immunohistochemical staining confirmed an ACTH-secreting adenoma. Genetic analysis identified a novel germline GPR101 (p.G169R) and a somatic USP8 (p. S719del) mutation. They were hypothesized to impact tumor growth and function, respectively. CONCLUSIONS: We reported a rare case of pediatric giant pituitary ACTH adenoma and pointed out that unusual concurrent mutations might contribute to its early onset and large volume.

Functioning gonadotroph adenomas in premenopausal women: clinical and molecular characterization and review of the literature.

PURPOSE: To summary the clinical features of premenopausal women with functioning gonadotroph adenomas (FGAs) and preliminarily explore their molecular characterization. METHODS: 12 premenopausal females with FGAs in our center were retrospectively analyzed. Previously reported cases were also summarized. The patients were clinically divided into FSH- or LH-predominant types according to their preoperative serum FSH/LH ratio. The expressions of related genes in the tumor tissues of female FGAs, non-functioning gonadotroph adenomas (NFGAs), and silent corticotropin adenomas were evaluated by RT-qPCR. RESULTS: Of all the 12 patients with FGAs from our center, 11 (91.7%) were diagnosed as FSH-predominant type, and they all had menstrual disorders, including 9 with spontaneous ovarian hyperstimulation syndrome (sOHSS). Their hormonal profiles showed non-suppressed FSH (12.45 ± 7.34 IU/L) with hyperestrogenemia [median estradiol level 1353.0 pg/mL (636.0, 3535.0)]. The other patient (8.3%) with LH-predominant type mainly manifested with infertility and sustained elevated serum LH without FSH or estradiol increasing. 65 premenopausal FGAs patients were systematic reviewed. 60 patients (92.3%) were FSH-predominant type, including 86.7% presented with menstrual disorders, 16.7% reported infertility, and 98.2% (55/56) showed sOHSS. No sOHSS or hyperestrogenemia were found in the 5 patients (7.7%) with LH-predominant type. Pituitary imaging data revealed macroadenomas and microadenomas accounted for 89.2% and 10.8%, respectively. Of 63 patients (96.9%) who underwent pituitary adenoma resection, 77.8% had complete tumor resection and no recurrence at the last follow-up. The relative expressions of KISS1 mRNA were significantly higher in FGA group than in NFGA group (p = 0.018), and significantly positively correlated with the preoperative serum estradiol levels (p = 0.004). CONCLUSIONS: Different clinical features were observed in premenopausal women with FGAs of FSH- or LH-predominant types. The elevated KISS1 expression in tumor tissues might involve in the secretion function of FGAs.

Validation of perihematomal edema expansion as a new imaging biomarker to predict clinical outcome in patients with intracerebral hemorrhage.

OBJECTIVES: The use of hematoma expansion (HE) in intracerebral hemorrhage (ICH) patients is limited due to its low sensitivity. Perihematomal edema (PHE) has been considered an important marker of secondary brain injury after ICH. Enrolling PHE expansion to redefine traditional ICH expansion merits exploration. MATERIALS AND METHODS: This study analyzed a cohort of patients with spontaneous ICH. The hematoma and PHE were manually segmented. Logistic regression analysis was utilized to identify risk factors for poor outcomes. Receiver operating characteristic curve analysis was performed to calculate the predictive values of PHE expansion and HE. Poor neurological outcome was defined as a modified Rankin Scale score of 4-6 at 90 days. RESULTS: Overall, 223 target patients were enrolled in the study. Multivariable analysis showed the larger PHE expansion is the independent risk factors for poor prognosis. The predictive value of absolute PHE expansion (AUC=0.776, sensitivity=67.9%, specificity=77.0%) was higher than that of absolute HE (AUC=0.573, sensitivity=41.7%, specificity=87.1%) and HE (>6 ml) (AUC=0.594, sensitivity=23.8%, specificity=95.0%). The best cutoff for early absolute/relative PHE expansion resulting in a poor outcome was 5.96 ml and 31%. CONCLUSIONS: Early PHE expansion was associated with a poor outcome, characterized by a better predictive value than HE.

Predictors of Immediate Remission after Surgery in Cushing's Disease Patients: A Large Retrospective Study from a Single Center.

OBJECTIVE: Transsphenoidal surgery (TSS) is the first-line treatment of patients with Cushing's disease (CD). However, biochemical remission rates after TSS for CD vary from 59 to 95%, and the predictors of surgical outcomes remain unclear. The aim of this study was to identify the predictors of early outcomes in patients with CD treated with TSS. METHODS: The clinical features and outcomes of CD patients who underwent TSS between February 2000 and September 2019 at the Peking Union Medical College Hospital were collected from medical records and analyzed. Uni- and multivariate odds ratio (OR) analyses were performed to identify the predictors of early outcomes in patients with CD. RESULTS: A total of 1,045 patients were included. The median age at TSS was 34.0 years (IQR 26.0-45.0), with a female:male ratio of 4.2:1 (844/201). The median duration of symptoms was 46.0 months (IQR 24.0-72.0). After surgery, the overall postoperative immediate remission rate was 73.3%, and 26.7% of patients had persistent hypercortisolism. Univariate analysis demonstrated that the number of operations was correlated with a lower immediate remission rate (OR 0.393, 95% CI 0.266-0.580, p = 0.000), as was tumor size (OR 0.462, 95% CI 0.334-0.639, p = 0.000), the duration of disease (OR 0.996, 95% CI 0.993-0.999, p = 0.003), and preoperative ACTH concentration (0.998, 95% CI 0.996-0.999, p = 0.003). Cavernous sinus invasion has also been identified as an important factor associated with a lower immediate remission rate (OR 0.275, 95% CI 0.166-0.456, p = 0.000). No correlations were detected between the immediate outcomes and age, gender, BMI, the combination of a low- and high-dose dexamethasone suppression test, preoperative morning serum cortisol level, or 24-h urinary free cortisol level (all p > 0.05). The results of multivariate analysis were similar to those of univariate analysis. Preoperative ACTH ≤67.35 ng/L predicted remission with 60.9% sensitivity and 49.5% specificity (AUC 0.553; p = 0.008). A cutoff of ≤64.5 months for disease duration predicted immediate remission with 40.5% sensitivity and 71.0% specificity (AUC 0.552; p = 0.01). CONCLUSION: Early outcomes of TSS in CD patients can be predicted by factors including the number of operations, duration of disease, tumor invasion, tumor size, and preoperative ACTH concentration. These predictors can be used to improve the perioperative management of CD patients.

A Chinese Case of X-Linked Acrogigantism and Systematic Review.

INTRODUCTION: This study described a Chinese case of X-linked acrogigantism (X-LAG) and summarized the characteristics and treatment of all reported cases. METHODS: Clinical materials and biological samples from a 5-year and 2-month-old female due to "growth acceleration for 4 years" were collected. Array comparative genomic hybrid (aCGH) and further verification were performed. All X-LAG cases from the PubMed and Web of Science databases were collected and summarized with available data. RESULTS: The patient presented accelerating growth since 1 year, and her height reached 134.6 cm (+5.24 standard deviation score [SDS]) when she was 5-year and 2-month old. She also had coarsening facial features, snoring, and acral enlargement. Growth hormone (GH) was not suppressed by the glucose-GH inhibition test, and insulin-like growth factor 1 (IGF-1) and prolactin (PRL) levels were elevated. Pituitary MRI revealed a pituitary enlargement with a maximum diameter of 22.3 mm. Octreotide imaging indicated the presence of a pituitary adenoma. The tumor shrank slightly after 3 courses of somatostatin analog but without clinical or biochemical remissions, of which the GH nadir value was 9.4 ng/mL, and IGF-1 was elevated to 749 ng/mL. Therefore, she underwent transsphenoidal surgery. Immunohistochemistry showed GH-positive and PRL-positive cells in the pituitary adenoma. Xq26.3 microduplication of the patient's germline DNA was identified by aCGH. Of all 35 reported cases, females accounted for 71.43%. There were 93.10% and 53.83% patients with hyperprolactinemia and hyperinsulinemia, respectively. Pathology showed that 75.00% of cases were adenomas. Ninety percent of cases had germline variants. The clinical and biochemical remission rates were 78.26% and 82.61%, respectively. However, the rate of complication occurrence during therapy reached 80%. CONCLUSION: It is important to recognize the possibility of X-LAG when a child under 2-year old presents overgrowth. Early diagnosis and treatment are of great importance for better treatment efficacy and clinical outcome.

Guideline conformity to the Stupp regimen in patients with newly diagnosed glioblastoma multiforme in China.

Aims: To determine how consistently Chinese glioblastoma multiforme (GBM) patients were treated according to the Stupp regimen. Patients and methods: The proportion of treatments conforming to the Stupp regimen and reasons for nonconformity were evaluated in 202 newly diagnosed GBM patients. Results: Only 15.8% of GBM patients received treatments compliant with the Stupp regimen. The main deviations were temozolomide dosages >75 mg/m2 (58/120; 48.3%) and treatment durations <42 days (84/120; 70.0%) in the concomitant phase and temozolomide dosages <150 mg/m2 (89/101; 88.1%) in the maintenance phase. Median overall survival (27.09 vs 18.21 months) and progression-free survival (14.27 vs 12.10 months) were longer in patients who received Stupp regimen-compliant treatments. Conclusion: Increased conformity to the Stupp regimen is needed for GBM patients in China.

Lay abstract In 2005 the European Organization for Research and Treatment of Cancer 26981 study led to US FDA approval for the use of temozolomide in combination with radiotherapy to treat glioblastoma multiforme (GBM). The Stupp regimen consists of fractionated focal irradiation in daily fractions of 2 Gy given 5 days/week for 6 weeks (a total of 60 Gy), plus concomitant daily temozolomide (75 mg/m²/day, 7 days/week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150­200 mg/m²/day for 5 days during each 28-day cycle). In 2012 the Chinese guidelines for the diagnosis and treatment of glioma of the CNS recommended the Stupp regimen as first-line therapy for newly diagnosed GBM. In the present study, compliance of GBM treatments with the Stupp regimen in 28 Chinese centers from 2012­2016 was evaluated. Only 15.8% of GBM patients received treatments compliant with the Stupp regimen. The main deviations related to temozolomide dosages and treatment durations in the concomitant and maintenance phases. Median overall survival (27.09 vs 18.21 months) and progression-free survival (14.27 vs 12.10 months) were longer in patients who received Stupp regimen-compliant treatments.

Successful pregnancy after operation in an infertile woman caused by luteinizing hormone-secreting pituitary adenoma: case report and literature review.

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.

Integrated multi-omics profiling of nonfunctioning pituitary adenomas.

PURPOSE: Genetic and epigenetic alterations are involved in pituitary adenoma pathogenesis, however the molecular basis of proliferative nonfunctioning pituitary adenomas (NFPAs) remains unclear. Here, we analyzed integrated multi-omics profiling including copy number variation (CNV), DNA methylation and gene expression of 8 NFPAs. METHODS: We collected 4 highly proliferative (hpNFPA, Ki-67 ≥ 3) and 4 lowly proliferative (Ki-67 ≤ 1) NFPAs, and comprehensively assessed CNV, DNA methylation, and gene expression by Illumina HumanMethylation450 BeadChip and Affymetrix GeneChip PrimeView Human Gene Expression Array. We performed Ingenuity Pathway Analysis (IPA) for differentially expressed genes to illustrate aberrant pathways and delineated protein-protein networks of selected key genes in dysregulated pathways. RESULTS: Aberrant arm level CNV, dysregulated DNA methylation, and associated impacts on gene expressions were observed in 2 early occurring hpNFPAs. Chromosomal losses were associated with attenuated expression of DNA methyltransferases, further altering global methylation in these 2 samples. Correlation analysis between DNA methylation and gene expression in 8 NFPAs indicates methylation in promoter and gene body regions are both involved in gene regulation. IPA showed PPARα/RXRα, dopamine receptor signaling, cAMP-mediated signaling, and calcium signaling were all activated, while p38 MAPK and ERK5 signaling were inhibited in hpNFPAs. Moreover, selected key gene networks in hpNFPAs exhibited concurrent methylation status and expression levels of adenylate cyclase genes, G protein subunits, HLA genes, CXCL12, and CCL2. CONCLUSION: This study presents comprehensive multi-omics views of CNV, DNA methylation, and gene expression in 8 NFPAs. Pathway analysis and network maps of key genes provide clues to elucidate the molecular basis of hpNFPA.

Diagnostic value of Knosp grade and modified Knosp grade for cavernous sinus invasion in pituitary adenomas: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to examine the reliability of existing Knosp grade (KG) and modified KG for cavernous sinus invasion (CSI). METHODS: A thorough search of literature from 1993 to 2020 in six databases was performed. Studies that reported the intraoperative confirmation of CSI using KG and/or modified KG were included. The pooled estimates were calculated by meta-analysis with a bivariate mixed-effect model and the assessment of heterogeneity with I2 statistic. RESULTS: The final search yielded 12 eligible studies, which enrolled 3006 patients assessed with KG and 1315 patients assessed with modified KG. The results of the area under the receiver operating characteristic curve showed the good discriminative abilities of grades 2-4 (0.90), 3-4 (0.86) and 3B-4 (0.91) in predicting CSI. Grade 3A showed a remarkably lower CSI rate (44% versus 81%) and incomplete resection rate (26% versus 52%) than grade 3B. Grades 0 and 1 showed a low CSI rate. CSI and incomplete resection rates in grade 2 (30% and 21%, respectively) were close to those in grade 3A. CONCLUSIONS: Modifying the KG improved its prognostic role in CSI and gross total resection. However, these grading systems cannot be used as the group standard for invasive and non-invasive pituitary adenomas (PAs) because of the weak reliability of the scale's middle grades (grades 2 and 3A). Authors of future PA studies should consider reporting KG as high (grades 3B and 4), medium (grades 2 and 3A) and low (grades 0 and 1) to optimise the application of the scale.

Clinical profiles of silent corticotroph adenomas compared with silent gonadotroph adenomas after adopting the 2017 WHO pituitary classification system.

PURPOSE: Silent corticotroph adenomas (SCAs) can be redefined according to the 2017 World Health Organization pituitary classification system with the introduction of T­PIT, a transcription factor. We studied the clinical features of these redefined SCAs. METHODS: We compared 112 patients with SCAs and 198 patients with silent gonadotroph adenomas (SGAs) who underwent surgery from January 2019 to May 2020. RESULTS: The prevalence of SCAs increased from 21.3 to 30.2% under the new classification rules. T-PIT-positive, adrenocorticotropic hormone-negative SCAs and T-PIT-positive, adrenocorticotropic hormone-positive SCAs exhibited similar clinical features. SCAs exhibited significant female preponderance (90.2% vs. 29.8%, P < 0.0001); more frequent invasion (36.6% vs. 7.6%, P < 0.0001), especially multiple-site invasion (P < 0.0001); and marked cystic changes on imaging compared with SGAs (54.5% vs. 19.2%, P < 0.0001). SCAs had a softer tumor consistency (89.2% vs. 61.1%, P < 0.0001). Gross total resection was achieved in 66.1% of SCAs and 66.2% of SGAs (P > 0.9999). The overall recurrence/progression rates of SCAs and SGAs were 9.8% and 6.6% at 14.1 and 13.5 months of follow-up, respectively (P = 0.3765). The proportion of patients with more than two recurrences requiring multiple surgeries and radiation was similar between SCAs and SGAs (7.1% vs. 3.0%, P = 0.1514). However, multiple recurrences of SCAs affected younger patients than SGAs (39.0 vs. 53.5 years, P = 0.0433). CONCLUSIONS: The prevalence of SCAs increased with the introduction of T-PIT. SCAs and SGAs exhibited comparable size and recurrence/progression rates, but SCAs showed increased invasion and more marked cystic change. Aggressive SCAs tended to affect younger patients. Close long-term monitoring for SCA recurrence/progression is required.

Experience of Ectopic Adrenocorticotropin Syndrome: 88 Cases With Identified Causes.

OBJECTIVE: Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare cause of Cushing's syndrome and diagnosis and management remain challenging. The aim of this study was to present the clinical spectrum of a group of EAS cases in a single center to explore better management strategies. METHODS: A retrospective study was conducted to identify 88 confirmed EAS cases at our hospital from 1984 to 2019. The clinical, biochemical, imaging, and pathological features were analyzed. RESULTS: Of the 88 eligible patients with EAS, 38 (43.2%) cases of pulmonary neuroendocrine tumors (NETs) and a larger number of thymic/mediastinal NETs (29 cases, 33%) were identified. The clinical and biological features of EAS and Cushing's disease overlapped but were more severe in EAS. Inferior petrosal sinus sampling (97.4%) and computed tomography (85.4%) provided the highest positive diagnostic accuracy. Computed tomography is also a useful tool to identify tumors in chest cavity compared with nonchest lesions (91.2% vs 57.1%). Although a greater tumor size (4.54 cm vs 1.44 cm) and higher rate of insuppressible high-dose dexamethasone suppression test (83.3% vs 51.5%) were found in thymic/mediastinum NETs than in pulmonary NETs, the level of hormone production had no difference. CONCLUSION: EAS had more common and severe clinical presentations than Cushing's disease, and multiple imaging approaches are required for reliable diagnosis. A higher proportion of thymic/mediastinal NETs was found in our study. For patients without a certain tumor source, long-term follow-up and further evaluations are needed.

Assessing the Evolution of Intracranial Hematomas by using Animal Models: A Review of the Progress and the Challenges.

Stroke has become the second leading cause of death in people aged higher than 60 years, with cancer being the first. Intracerebral hemorrhage (ICH) is the most lethal type of stroke. Using imaging techniques to evaluate the evolution of intracranial hematomas in patients with hemorrhagic stroke is worthy of ongoing research. The difficulty in obtaining ultra-early imaging data and conducting intensive dynamic radiographic imaging in actual clinical settings has led to the application of experimental animal models to assess the evolution of intracranial hematomas. Herein, we review the current knowledge on primary intracerebral hemorrhage mechanisms, focus on the progress of animal studies related to hematoma development and secondary brain injury, introduce preclinical therapies, and summarize related challenges and future directions.

Multiple myeloma complicated by skull plasmacytoma discovered after head injury.

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.