Glymphatic abnormality in systemic lupus erythematosus detected by diffusion tensor image analysis along the perivascular space.

OBJECTIVES: This study aimed to evaluate the activity of the glymphatic system in systemic lupus erythematosus (SLE) by a diffusion-based method termed "Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS)", and examined its correlations with morphological changes in the brain. METHODS: In this cross-sectional study, forty-five female patients with SLE and thirty healthy controls (HCs) were included. Voxel-based and surface-based morphometric analyses were performed to examine T1 weighted images, and diffusion tensor images were acquired to determine diffusivity along the x-, y-, and z-axes in the plane of the lateral ventricle body. The ALPS-index was calculated. The differences in values between SLE patients and HC group were compared using the independent samples t test or Mann-Whitney U test. For the correlations between the ALPS-index and brain morphological parameters, partial correlation analysis and Pearson's correlation analysis were conducted. RESULTS: SLE patients showed lower values for the ALPS-index in left (1.543 ± 0.141 vs 1.713 ± 0.175, p < 0.001), right (1.428 ± 0.142 vs 1.556 ± 0.139, p < 0.001) and whole (1.486 ± 0.121 vs 1.635 ± 0.139, p < 0.001) brain compared with the HC group. The reduced ALPS-index showed significant positive correlations with gray matter loss. CONCLUSION: The non-invasive ALPS-index could serve as a sensitive and effective neuroimaging biomarker for individually quantifying glymphatic activity in patients with SLE. Glymphatic system abnormality may be involved in the pathophysiologic mechanism underlying central nervous system damage in SLE patients.

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.

Double pituitary adenomas: report of two cases and systematic review of the literature.

Objective: Double pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical remission after surgery is an important challenge in DPA management. This study aims to analyze independent prognostic factors in DPA patients and summarize clinical experiences to prevent surgical failure. Methods: Two cases of DPA patients with Cushing's disease diagnosed and surgically treated at Peking Union Medical College Hospital are reported. A literature review was performed on the online database Pubmed, and 57 DPA patients from 22 retrieved articles were included. Demographic characteristics, endocrine manifestations, diagnostic methods, tumor size, and immunohistochemical features of 59 patients were analyzed. Binary logistic regression models were used to identify independent prognostic factors affecting postoperative biochemical remission. Results: Among 59 DPA patients, the mean ± SD age was 43.64 ± 14.42 years, with 61.02% being female (n = 36). The most common endocrine manifestations were Cushing's syndrome (23/59, 38.98%) and acromegaly (20/59, 33.90%). The most prevalent immunohistochemical types were ACTH-immunopositive (31/118, 26.27%) and GH-immunopositive (31/118, 26.27%) tumors. Microadenomas (<1cm) were the most frequent in terms of tumor size (62/92, 67.39%). The detection rate for double lesions on 3.0T MRI was 50.00% (14/28), which significantly higher than 1.5T MRI (P = 0.034). Univariate analysis revealed that female, Cushing's syndrome and only single lesion detected by surgical exploration were associated with significantly worse prognosis (P<0.05). Multivariate analysis identified double lesion detected by surgical exploration (OR = 0.08, P = 0.003) and contiguous type tumor (OR = 0.06, P = 0.017) as independent protective factors for DPA patients. Conclusions: The double lesion detected by surgical exploration is independently associated with a better prognosis for DPA patients. Comprehensive intraoperative exploration are crucial measures to avoid missing causative lesions.

Systemic lupus erythematosus-related brain abnormalities in the default mode network and the limbic system: A resting-state fMRI meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an immune-mediated and multi-systemic disease which may affect the nervous system, causing neuropsychiatric SLE (NPSLE). Recent neuroimaging studies have examined brain functional alterations in SLE. However, discrepant findings were reported. This meta-analysis aims to identify consistent resting-state functional abnormalities in SLE. METHODS: PubMed and Web of Science were searched to identify candidate resting-state functional MRI studies assessing SLE. A voxel-based meta-analysis was performed using the anisotropic effect-size version of the seed-based d mapping (AES-SDM). The abnormal intrinsic functional patterns extracted from SDM were mapped onto the brain functional network atlas to determine brain abnormalities at a network level. RESULTS: Twelve studies evaluating fifteen datasets were included in this meta-analysis, comprising 572 SLE patients and 436 healthy controls (HCs). Compared with HCs, SLE patients showed increased brain activity in the bilateral hippocampus and right superior temporal gyrus, and decreased brain activity in the left superior frontal gyrus, left middle temporal gyrus, bilateral thalamus, left inferior frontal gyrus and right cerebellum. Mapping the abnormal patterns to the network atlas revealed the default mode network and the limbic system as core neural systems commonly affected in SLE. LIMITATIONS: The number of included studies is relatively small, with heterogeneous analytic methods and a risk of publication bias. CONCLUSIONS: Brain functional alterations in SLE are predominantly found in the default mode network and the limbic system. These findings uncovered a consistent pattern of resting-state functional network abnormalities in SLE which may serve as a potential objective neuroimaging biomarker.

Hippocampal amide proton transfer values are associated with cerebral small vessel disease imaging markers and total burden: a community-based cross-sectional study.

Background: Neurodegeneration has been suggested to be associated with cerebral small vessel disease (CSVD). The association between different CSVD imaging markers and the extent of neurodegeneration could be indirectly confirmed by examining the relationship between CSVD imaging markers and the hippocampal amide proton transfer (APT) values. The associations between hippocampal APT values with CSVD imaging markers and CSVD total load need to be further validated. The aim of this study was to investigate potential variations in hippocampal APT values among individuals with CSVD imaging markers and varying degrees of CSVD total burden. Methods: A cross-sectional study (retrospective analysis of prospectively-acquired data) was conducted at Nanxishan Hospital of Guangxi Zhuang Autonomous Region. From May 2020 to June 2021, 165 individuals (age, 40-76 years; male/female, 103/62) were included in this study. The inclusion criteria for the participants were as follows: The presence of lacunar infarction (LI), and/or cerebral microbleed (CMB); moderate-to-severe enlarged perivascular space (EPVS) (>20); deep white matter hyperintensity (WMH) > Fazekas 2 or periventricular WMH > Fazekas. The exclusion criteria comprised the following: History of craniocerebral operation; Cases with significant pathology incidentally identified during magnetic resonance (MR) scan; Drug or alcohol abuse. The differences of hippocampal APT values between CSVD imaging makers presence or absence groups and different CSVD total burden groups were compared using independent t-test and one-way analysis of variance (ANOVA). The correlations between APT values and CSVD imaging markers were analyzed using Pearson correlation analysis. A mediation analysis model was used to investigate the mediating effect of the hippocampal APT values in the association between CSVD total loads and Montreal Cognitive Assessment (MoCA) score was assessed. Results: The hippocampal APT values among different CSVD total load groups were significantly different (P<0.001). The hippocampal APT values were significantly different between the imaging markers presence and absence groups. The P values for the LI, WMH EPVS, and CMB presence or absence groups were <0.001, <0.001, 0.034, and 0.002, respectively. The hippocampal APT values were significantly correlated with CMB (P<0.01), LI (P<0.01) and WMH (P<0.01). The mediation models demonstrated that the APT values of the hippocampus partially mediated the association between CSVD total load and MoCA score, the proportion of mediation attributable was calculated as 17.50%. Conclusions: Hippocampal APT values were associated with CSVD imaging markers and total burden. Hippocampal APT values may serve as a biomarker for the early detection of neurodegeneration in CSVD patients.

Amide proton transfer imaging has added value for predicting extraprostatic extension in prostate cancer patients.

Background: Prostate cancer invades the capsule is a key factor in selecting appropriate treatment methods. Accurate preoperative prediction of extraprostatic extension (EPE) can help achieve precise selection of treatment plans. Purpose: The aim of this study is to verify the diagnostic efficacy of tumor size, length of capsular contact (LCC), apparent diffusion coefficient (ADC), and Amide proton transfer (APT) value in predicting EPE. Additionally, the study aims to investigate the potential additional value of APT for predicting EPE. Method: This study include 47 tumor organ confined patients (age, 64.16 ± 9.18) and 50 EPE patients (age, 61.51 ± 8.82). The difference of tumor size, LCC, ADC and APT value between groups were compared. Binary logistic regression was used to screen the EPE predictors. The receiver operator characteristic curve analysis was performed to assess the diagnostic performance of variables for predicting EPE. The diagnostic efficacy of combined models (model I: ADC+LCC+tumor size; model II: APT+LCC+tumor size; and model III: APT +ADC+LCC+tumor size) were also analyzed. Results: APT, ADC, tumor size and the LCC were independent predictors of EPE. The area under the curve (AUC) of APT, ADC, tumor size and the LCC were 0.752, 0.665, 0.700 and 0.756, respectively. The AUC of model I, model II, and model III were 0.803, 0.845 and 0.869, respectively. The cutoff value of APT, ADC, tumor size and the LCC were 3.65%, 0.97×10-3mm2/s, 17.30mm and 10.78mm, respectively. The sensitivity/specificity of APT, ADC, tumor size and the LCC were 76%/89.4.0%, 80%/59.6%, 54%/78.9%, 72%/66%, respectively. The sensitivity/specificity of model I, Model II and Model III were 74%/72.3%, 82%/72.5% and 84%/80.9%, respectively. Data conclusion: Amide proton transfer imaging has added value for predicting EPE. The combination model of APT balanced the sensitivity and specificity.

Investigating the relationship between intracranial atherosclerotic plaque remodelling and diabetes using high-resolution vessel wall imaging.

BACKGROUND: Intracranial atherosclerosis, a leading cause of stroke, involves arterial plaque formation. This study explores the link between plaque remodelling patterns and diabetes using high-resolution vessel wall imaging (HR-VWI). AIM: To investigate the factors of intracranial atherosclerotic remodelling patterns and the relationship between intracranial atherosclerotic remodelling and diabetes mellitus using HR-VWI. METHODS: Ninety-four patients diagnosed with middle cerebral artery or basilar artery atherosclerosis were enrolled. Their basic clinical data were collected, and HR-VWI was performed. The vascular area at the plaque (VAMLN) and normal reference vessel (VAreference) were delineated and measured using image postprocessing software, and the Remodelling index (RI) was calculated. According to the value of the RI, the patients were divided into a positive remodelling (PR) group, intermediate remodelling (IR) group, negative remodelling (NR) group, PR group and non-PR (N-PR) group. RESULTS: The PR group exhibited a higher prevalence of diabetes and serum cholesterol levels than the IR and NR groups [45.2%, 4.54 (4.16, 5.93) vs 25%, 4.80 ± 1.22 and 16.4%, 4.14 (3.53, 4.75), respectively, P < 0.05]. The diabetes incidence was also significantly greater in the PR group than in the N-PR group (45.2% vs 17.5%, P < 0.05). Furthermore, the PR group displayed elevated serum triglyceride and cholesterol levels compared to the N-PR group [1.64 (1.23, 2.33) and 4.54 (4.16, 5.93) vs 4.54 (4.16, 5.93) and 4.24 (3.53, 4.89), P < 0.05]. Logistic regression analysis revealed diabetes mellitus as an independent influencing factor in plaque-PR [odds ratio (95% confidence interval): 3.718 (1.207-11.454), P < 0.05]. CONCLUSION: HR-VWI can clearly show the morphology and signal characteristics of intracranial vascular walls and plaques. Intracranial atherosclerotic plaques in diabetic patients are more likely to show PR, suggesting poor plaque stability and a greater risk of stroke.

Serum prolactin levels were positively related to metabolic indexes and disorders in male obese patients.

PURPOSE: The role of prolactin (PRL) in glucolipid metabolism was inconsistent, and there were few studies on the metabolic role of PRL in obese patients. The study aims to explore association between PRL level and metabolic disorders in male obese patients. METHODS: A retrospective study was conducted. Eighty-nine male patients with obesity were included, and their clinical data were recorded. RESULTS: A total of 89 male obese patients were included in this study. Their average age was 24.5 ± 9.0 years and BMI was 42.8 ± 9.1 kg/m2. The average waist circumference and body fat percentage was 129.6 ± 19.6 cm and 42.9 ± 8.0%, respectively. The median prolactin levels were 10.0 ng/ml (range: 3.93-30.1 ng/ml). 79.0% (49/62) of these patients presented with NAFLD and 77.3% (68/88) of them was dyslipidemia. Further, serum prolactin level was positively correlated with BMI (r = 0.225, P = 0.034), body fat percentage (r = 0.326, P = 0.017), ALT (r = 0.273, P = 0.011) and AST (r = 0.245, P = 0.029). Compared with low PRL group (<10 ng/ml), the incidence of morbid obesity and NAFLD was higher in high PRL group (morbid obesity: 71.1% vs 45.5%, P = 0.018 and NAFLD: 91.2% vs 64.3%, P = 0.013). In addition, the risk of NAFLD and morbid obesity in high PRL group (>10 ng/ml) was higher than low PRL group (OR:5.187, 95%CI 1.194-22.544, P = 0.028 and OR: 4.375, 95% CI 1.595-11.994, P = 0.004). The increased risk of NAFLD and morbid obesity in the high PRL group still existed after adjusting for age and Testosterone. CONCLUSION: Serum prolactin levels were positively associated with deterioration of metabolic indexes in male obese patients, as well as NAFLD and morbid obesity.

Quantitative assessment of inflammation and evaluation of spatial heterogeneity for non-alcoholic fatty liver disease in mice based on iron-adjustive T1.

Background: A sensitive and non-invasive method is necessary to diagnose non-alcoholic fatty liver disease (NAFLD). We explored the iron-adjustive T1 (aT1) ability to quantify the degree of liver inflammation and evaluate the spatial heterogeneity. Methods: Male C57BL/6J mice were randomly categorized as the NAFLD model (n=40), NAFLD-related liver cirrhosis model (n=20), and normal mice (n=10). T1 and T2* maps were acquired using a 3.0T scanner of magnetic resonance imaging (MRI) and aT1 maps through post-processing corrected iron's effect on T1 using T2*. Pathological changes in the left and right liver lobes were assessed using the Non-alcoholic Steatohepatitis-Clinical Research Network scoring system, though hepatic ballooning lesion were rare in models. Spearman's and partial correlation analyses were used to evaluate correlations, and the receiver operating characteristic curve was used to analyze the diagnostic performance. Results: aT1 was highly correlated with NAFLD activity score (NAS) (r=0.747, P<0.001) but not with the fibrosis stage when adjusted by NAS (r=-0.135, P=0.147). The area under the curve (AUC) of the aT1 value distinguishing groups with 0< NAS <4 and NAS ≥4 was 0.802. On analyzing the histogram features of aT1, the entropy, interquartile range, range, and variance were significantly different between the groups with 0< NAS <4 and NAS ≥4 (P<0.05). The entropy was the risk factor of NAS ≥4. Conclusions: aT1 could help evaluate the inflammatory activity in NAFLD mice unaffected by mild fibrosis, and the higher the degree of inflammation, the higher the heterogeneity of the aT1 map.

Quantitative assessment of hyperperfusion using arterial spin labeling to predict hemorrhagic transformation in acute ischemic stroke patients with mechanical endovascular therapy.

OBJECTIVES: This study was aimed to quantitatively assess hyperperfusion using arterial spin labeling (ASL) to predict hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients. METHODS: This study enrolled 98 AIS patients with anterior circulation large vessel occlusion within 24 h of symptom onset. ASL was performed before mechanical endovascular therapy. On pre-treatment ASL maps, a region with relative cerebral blood flow (CBF) ≥ 1.4 was defined as an area of hyperperfusion. The maximum CBF (CBFmax) of hyperperfusion was calculated for each patient. A non-contrast CT scan was performed during the subacute phase for the evaluation of HT. Good clinical outcome was defined as a 90-day modified Rankin scale score of 0-2. RESULTS: The CBFmax of hyperperfusion (odds ratio, 1.023; 95% confidence interval [CI], 1.005-1.042; p = 0.012) was an independent risk factor for the status of HT. The CBFmax of hyperperfusion for HT showed an area under the curve of 0.735 (95% CI, 0.588-0.882) with optimal cutoff value, sensitivity, and specificity being 146.5 mL/100 g/min, 76.9%, and 69.6%, respectively. There was a statistically significant relationship between HT grades (from no HT to PH2) and CBFmax of hyperperfusion with a Spearman rank correlation of 0.446 (p = 0.001). In addition, low CBFmax of hyperperfusion were associated with good functional outcome (95% CI, 17.130-73.910; p = 0.002). CONCLUSIONS: High CBFmax of hyperperfusion was independently associated with subsequent HT and low CBFmax of hyperperfusion linked to good functional outcome. There was a positive correlation between HT grade and CBFmax. CLINICAL RELEVANCE STATEMENT: Arterial spin labeling is a noninvasive and contrast agent-independent technique, which is sensitive in detecting hyperperfusion. This study shows that the cerebral blood flow of hyperperfusion is associated with clinical prognosis, which will benefit more patients. KEY POINTS: • Quantitative assessment of hyperperfusion using pre-treatment arterial spin labeling to predict hemorrhagic transformation and prognosis in acute ischemic stroke patients. • The maximum cerebral blood flow of hyperperfusion was associated with hemorrhagic transformation and clinical prognosis and higher maximum cerebral blood flow of hyperperfusion was associated with higher grade hemorrhagic transformation. • The maximum cerebral blood flow of hyperperfusion can predict hemorrhagic transformation which enables timely intervention to prevent parenchymal hematoma.

Pediatric pituitary neuroendocrine tumors-a 13-year experience in a tertiary center.

Introduction: Pediatric pituitary neuroendocrine tumor is a rare condition, and despite previous research focusing on this specific group, the main factors influencing the surgical cure rate have not been identified. Methods: We conducted a single-center retrospective study on pediatric pituitary neuroendocrine tumor patients who visited Peking Union Medical College Hospital between 2010 and 2023. We collected data on their clinical characteristics, imaging features, surgical outcomes, and follow-up information. Additionally, we used multiple-factor logistic regression to investigate the factors affecting the surgical cure rate of pediatric pituitary neuroendocrine tumor. Results: 232 patients were diagnosed with pediatric pituitary neuroendocrine tumors, with a higher incidence in females. The most common type was ACTH-secreting adenoma (90/232), followed by prolactin-secreting adenoma (63/232), and growth hormone-secreting adenoma (41/232). The majority of pediatric adenomas were macroadenomas (139/232), and some tumors were associated with cystic changes or hemorrhage (58/232), while a few exhibited invasion of the cavernous sinus (33/232). The results of the multivariate analysis indicated that the different hormone secretion types, macroadenoma or the presence of cystic changes or hemorrhage were not significant risk factors for the cure rate after the first surgery. However, the invasion of the cavernous sinus was found to be an important factor influencing the postoperative cure rate. Most pediatric pituitary neuroendocrine tumors with cavernous sinus invasion were macroadenomas, and some displayed characteristics of refractory pituitary neuroendocrine tumors, with some patients experiencing irreversible complications after surgery. Conclusion: Pediatric pituitary neuroendocrine tumors are complex, and the postoperative cure rate is particularly poor for tumors with cavernous sinus invasion. Although macroadenoma itself does not significantly impact the postoperative cure rate, it is still recommended to diagnose and treat early to avoid unnecessary surgery or surgical complications.

Advances in genetic abnormalities, epigenetic reprogramming, and immune landscape of intracranial germ cell tumors.

Intracranial germ cell tumors (IGCTs) are a rare subtype of central nervous system neoplasms that predominantly affect young individuals and exhibit a higher incidence in East Asia. IGCTs can be pathologically divided into two main categories: germinomas and non-germinomatous germ cell tumors (NGGCTs). Despite the scarcity of this disease, recent advancements in molecular biology techniques have facilitated the discovery of the inherent genetic and molecular characteristics of IGCTs. Somatic mutations that result in the activation of the KIT/RAS/MAPK and PI3K/AKT/mTOR pathways, chromosomal instability leading to characteristic changes in chromosomal fragments (notably 12p gain), and potentially diagnostic miRNAs (such as miR-371a-3p) may provide valuable insights for the efficient diagnosis, targeted therapy, and prognosis evaluation of IGCTs. Additionally, transcriptomic and methylomic analyses have provided new perspectives on the intrinsic development of IGCTs, further elucidating their equivalence with GCTs at other sites. The evaluation of the tumor immune landscape may guide prognosis prediction and immunotherapy for IGCT patients. Nevertheless, current research still faces challenges such as the absence of basic laboratory research systems, a single source of large sample research data, and a limited overall volume of research. The incorporation of larger sample sizes, the implementation of more innovative evaluation systems, and the employment of novel experimental methods are urgently required to become the focus of future research.

Case report: Identification of potential prognosis-related LAG3 overexpression and DICER1 mutation in pituitary carcinoma: two cases.

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.

Preoperative and postoperative blood testosterone levels in patients with acromegaly: a prospective study.

Purpose: To investigate the prevalence of low blood testosterone level (LTL) and its determinant factors among active male acromegaly patients, as well as the effect of surgery on LTL in male acromegaly patients. Methods: A retrospective, single-center study focused on 252 male acromegaly patients aged 18 years-60 years diagnosed in the Peking Union Medical College Hospital from January 2015 to December 2018 was carried out. The measurements of preoperative and postoperative testosterone levels, serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and other clinical data were analyzed. Results: Forty per cent of subjects included were diagnosed with LTL pre surgery. Patients were divided into normal testosterone level (NTL) and LTL groups based on their testosterone level. There were significant differences (p < 0.01) between groups in the presence of macroadenomas, invasion of the cavernous sinus, compression of the optic chiasm, and serum GH and prolactin levels pre surgery. Invasion of the cavernous sinus [odds ratio (OR) = 4.299; p = 0.000] and serum prolactin level (OR = 1.023, p = 0.001) were independent predictors of LTLs in male patients before surgical intervention. A total of 67.9% of LTL patients recovered during the follow-up, with a new-onset rate of 3.4%. Body mass index, invasion of the cavernous sinus, GH, IGF-1, and prolactin levels, the presence of a prolactin-secreting tumor, and recovery from acromegaly were significantly different (p < 0.05) in the NTL group and in the LTL group during the follow-up. The presence of a prolactin-secreting tumor (OR = 0.224; p = 0.001) and recovery from acromegaly (OR = 0.168; p = 0.006) were independent predictors of LTLs in male acromegaly patients during the follow-up. Conclusion: The invasiveness of tumor and levels of blood prolactin are independent factors for LTLs before surgery, whereas GH and IGF-1 levels are not. Most male patients can recover from LTL after tumor restriction surgery: those who recover from acromegaly have a better chance of recovering from LTL.

Amide proton transfer could be a surrogate imaging marker for predicting vascular cognitive impairment.

BACKGROUD: Emerging evidence suggests an overlap in the underlying pathways contributing to both cerebral small vessel disease (CSVD) and the neurodegenerative disease. Studies investigating the progression of CSVD should incorporate markers that reflect neurodegenerative lesions. OBJECTIVE: We aim to investigate whether Amide proton transfer (APT) can serve as a potential marker for reflecting vascular cognitive impairment (VCI). METHOD: Participants were categorized into one of three groups based on their Montreal Cognitive Assessment (MoCA) scores: normal control group (age,54.9 ± 7.9; male, 52.9%), mild cognitive impairment (MCI) group (age,55.7 ± 6.9; male, 42.6%), or vascular dementia (VaD) group (age,57.6 ± 5.5, male, 58.5%). One way analysis of variance was performed to compare the demographic and APT variables between groups. Multiple logistic regression analysis wwas constructed to examine the relationship between APT values and VCI grouping. A hierarchical linear regression model was employed to examine the associations between patients' demographic factors, imaging markers, APT values, and MoCA. RESULTS: The APT values of frontal white matter, hippocampus, amygdala, and thalamus were significantly different among different groups (p < 0.05). The APT values of frontal white matter, amygdala, and thalamus indicate a significant positive effect on MCI grouping. the APT values of frontal white matter, amygdala, and thalamus indicate a significant positive effect on VaD grouping. The demographic data, CSVD imaging markers and APT values can account for 5.1%, 20.1% and 27.7% of the variation in MoCA, respectively. CONCLUSION: APT imaging can partially identifying and predicting the occurrence of VCI.

Three-Dimensional Fast Spin Echo Pituitary MRI in Treatment-Naïve Cushing's Disease: Reduced Impact of Reader Experience and Increased Diagnostic Accuracy.

BACKGROUND: In patients with Cushing's disease, the preoperative identification of pituitary adenomas is crucial to treatment. However, increasing diagnostic accuracy remains an unresolved issue. PURPOSE: To evaluate the diagnostic accuracy and the impact of readers' experience regarding high-resolution contrast-enhanced magnetic resonance imaging (hrMRI) for identifying pituitary adenomas in comparison with conventional contrast-enhanced MRI (cMRI) and dynamic contrast-enhanced MRI (dMRI). STUDY TYPE: Retrospective. POPULATION: Sixty-five patients (median age, 39 years; interquartile range [IQR], 28-53 years; 60% females) with treatment-naïve Cushing's disease. FIELD STRENGTH/SEQUENCE: 3-T, seven fast spin echo sequences. ASSESSMENT: The diagnostic accuracies of identifying pituitary adenomas on cMRI, dMRI, combined cMRI and dMRI (cdMRI), and hrMRI were independently evaluated by six readers with three experience levels (high: >20 years, modest: 10-20 years, low: <10 years; two readers for each experience level). Readers were asked to localize the lesion, and measure its diameter on the sequence where identified. The reference standard was postoperative histopathology. The impact of readers' experience and interobserver agreement were assessed. Image quality was assessed using a 5-point Likert scale, including overall image quality, sharpness, and structural conspicuity. STATISTICAL TESTS: McNemar's test, Cochran's test, Wilcoxon signed-rank test, Mann-Whitney U test, and κ statistics for interobserver agreement. A P-value <0.05 was considered statistically significant. RESULTS: For identifying pituitary adenomas (median diameter, 5 mm; IQR, 4-5 mm), hrMRI had significantly higher sensitivity (87.7%-93.8%) than cMRI, dMRI, and cdMRI (52.3%-75.4%) for readers with different experience levels. The interobserver agreement was moderate (κ = 0.461-0.523). The sensitivity for hrMRI was comparable between readers with different experience levels (P = 0.371). All image quality scores on hrMRI were significantly higher than cMRI and dMRI (5.0 vs. 4.0). DATA CONCLUSION: For identifying pituitary adenomas in patients with treatment-naïve Cushing's disease, hrMRI may show high diagnostic accuracy and seems not to be affected by readers' experience. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Classification of temporal lobe epilepsy based on neuropsychological tests and exploration of its underlying neurobiology.

Objective: To assist improving long-term postoperative seizure-free rate, we aimed to use machine learning algorithms based on neuropsychological data to differentiate temporal lobe epilepsy (TLE) from extratemporal lobe epilepsy (extraTLE), as well as explore the relationship between magnetic resonance imaging (MRI) and neuropsychological tests. Methods: Twenty-three patients with TLE and 23 patients with extraTLE underwent neuropsychological tests and MRI scans before surgery. The least absolute shrinkage and selection operator were firstly employed for feature selection, and a machine learning approach with neuropsychological tests was employed to classify TLE using leave-one-out cross-validation. A generalized linear model was used to analyze the relationship between brain alterations and neuropsychological tests. Results: We found that logistic regression with the selected neuropsychological tests generated classification accuracies of 87.0%, with an area under the receiver operating characteristic curve (AUC) of 0.89. Three neuropsychological tests were acquired as significant neuropsychological signatures for the diagnosis of TLE. We also found that the Right-Left Orientation Test difference was related to the superior temporal and the banks of the superior temporal sulcus (bankssts). The Conditional Association Learning Test (CALT) was associated with the cortical thickness difference in the lateral orbitofrontal area between the two groups, and the Component Verbal Fluency Test was associated with the cortical thickness difference in the lateral occipital cortex between the two groups. Conclusion: These results showed that machine learning-based classification with the selected neuropsychological data can successfully classify TLE with high accuracy compared to previous studies, which could provide kind of warning sign for surgery candidate of TLE patients. In addition, understanding the mechanism of cognitive behavior by neuroimaging information could assist doctors in the presurgical evaluation of TLE.

Incidence and risk factors of cancers in acromegaly: a Chinese single-center retrospective study.

PURPOSE: To evaluate the incidence of malignancies in acromegaly and to identify risk factors for newly-diagnostic cancers, especially the excessive growth hormone (GH) and insulin-like growth factor-1 (IGF-1). METHODS: A retrospective cohort including 1738 consecutive hospitalized patients with acromegaly in a single referral center between 2012 and 2020 (mean follow-up 4.3 years). A gender- and age-matched case-control study (280 patients from the cohort) was performed for risk factor analysis. RESULTS: One hundred thirteen malignancies (67 diagnosed after acromegaly) were observed. The overall newly-diagnostic cancer risk of acromegaly was higher than the general population (standardized incidence ratio (SIR) 2.81; 95% CI 2.18-3.57). The risk of thyroid cancer (n = 33, SIR 21.42; 95% CI 13.74-30.08) and colorectal cancer (n = 8, SIR 3.17; 95% CI 1.37-6.25) was elevated. In the overall cohort, IGF-1 (ULN: 1.27 vs. 0.94, p = 0.057), GH (1.30 vs. 1.00 ng/ml, p = 0.12), and disease-controlled rate (34.9% vs. 45.9%, p = 0.203) at the last visit did not reach significance between patients with and without post-diagnostic cancer. In the case-control study, GH (1.80 vs. 0.90 ng/ml, p = 0.018) and IGF-1 (ULN: 1.27 vs. 0.91, p = 0.003) at the last visit were higher in patients with post-diagnostic cancers, with a lower disease-controlled rate. Elder age was a risk factor for cancer. Other metabolic comorbidities and the size of pituitary tumors were similar. CONCLUSION: The risk of malignancies, especially thyroid cancer, was increased in patients with acromegaly in our center. More cancer screening should be considered when managing acromegaly, especially in patients with higher posttreatment GH and IGF-1.

OCT3/4 is a potential immunohistochemical biomarker for diagnosis and prognosis of primary intracranial germ cell tumors: a systematic review and meta-analysis.

Introduction: Intracranial 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. Methods: Meta-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. Results: Nine 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. Discussion: This 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.

Prediction of intracranial hemorrhage after internal carotid artery stenting in patients with symptomatic severe carotid stenosis by computed tomography perfusion.

Background: To explore the risk of intracranial hemorrhage (ICH) after internal carotid artery stenting (CAS) in patients with symptomatic severe carotid stenosis by computed tomography perfusion (CTP). Methods: The clinical and imaging data of 87 patients with symptomatic severe carotid stenosis who underwent CTP before CAS were retrospectively analyzed. The absolute values of the cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) were calculated. The relative values (i.e., the rCBF, rCBV, rMTT, and rTTP), defined as the comparison between ipsilateral and contralateral hemispheres, were also derived. The degree of carotid artery stenosis was divided into 3 grades, and the Willis' circle was classified into 4 types. The relationship between the occurrence of the ICH and CTP parameters, the Willis' circle type, and the clinical baseline data were evaluated. A receiver operating characteristic (ROC) curve analysis was performed to determine the most effective CTP parameter for the prediction of ICH. Results: In total, 8 patients (9.2%) developed ICH after CAS. The results showed that the CBF (P=0.025), MTT (P=0.029), rCBF (P=0.006), rMTT (P=0.004), rTTP (P=0.006), and the degree of carotid artery stenosis (P=0.021) differed significantly between the ICH group and non-ICH group. The ROC curve analysis showed that the CTP parameter with the maximal area under the curve (AUC) for ICH was rMTT (AUC =0.808), which indicated that patients with an rMTT >1.88 were more likely to develop ICH (sensitivity: 62.5%, specificity: 96.2%). The occurrence of ICH after CAS was not related to the type of Willis' circle (P=0.713). Conclusions: CTP can be used to predict ICH after CAS in patients with symptomatic severe carotid stenosis, and patients with a preoperative rMTT >1.88 should be closely monitored for evidence of ICH after CAS.