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Letter to the Editor Open Access
Epigenetics, Epigenomics, and Personalized Medicine
Sanjoy Majumder, Rutupurna Das, Annapurna Sahoo, Kunja Bihari Satapathy, Gagan Kumar Panigrahi
Published online November 11, 2024
Gene Expression. doi:10.14218/GE.2024.00058
Original Article Open Access
The Role of Gamma Knife Radiosurgery in the Management of Grade 2 Meningioma
Enmeng Bao, Kuanyu Wang, Dezhi Gao, Bin Luo, Ali Liu, Shibin Sun
Published online December 17, 2024
Neurosurgical Subspecialties. doi:10.14218/NSSS.2024.00002
Abstract
The role of radiosurgery in the treatment of grade 2 meningioma remains unclear. This study aimed to evaluate the long-term outcomes of gamma knife radiosurgery (GKRS) in patients [...] Read more.

The role of radiosurgery in the treatment of grade 2 meningioma remains unclear. This study aimed to evaluate the long-term outcomes of gamma knife radiosurgery (GKRS) in patients with grade 2 meningiomas and to identify factors influencing tumor control and survival.

In this retrospective study, seventy patients underwent GKRS for grade 2 meningioma between 2007 and 2016. Tumor recurrence was categorized as local, marginal, or distant. Survival curves were estimated using the Kaplan-Meier method, while the log-rank test and Cox proportional hazards model were employed to analyze potential risk factors.

The median follow-up period was 48 months (range: 8 to 132 months). The one-year, three-year, and five-year local control rates were 92%, 73%, and 65%, respectively. The one-, three-, and three-year progression-free survival rates were 87%, 51%, and 44%, respectively. Multiple lesions and multiple prior recurrences were identified as negative predictors of marginal control and progression-free survival. Similarly, multiple lesions and marginal doses ≤13 Gy were associated with poor local control. Serious complications related to gamma knife use occurred in 4% of patients.

Our results support that GKRS is a reasonable treatment option in the management of grade 2 meningiomas. However, outfield progression remains a significant challenge, particularly in patients with multiple prior relapses and/or multiple lesions. More aggressive treatment strategies should be explored for these high-risk patients.

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Original Article Open Access
Microvascular Decompression Combined with Nerve Combing for Atypical Trigeminal Neuralgia
Jiayu Liu, Guangyong Wu, Bo Liu, Jingru Zhou, Cungang Fan, Donliang Wang, Bo Hei, Fang Li, Jia Ouyang, Zhi Liu, Qingpei Hao, Ruen Liu
Published online December 4, 2024
Neurosurgical Subspecialties. doi:10.14218/NSSS.2024.00003
Abstract
Atypical trigeminal neuralgia (ATN) is a chronic pain condition characterized by persistent facial pain that does not respond well to conventional medical treatments, often leading [...] Read more.

Atypical trigeminal neuralgia (ATN) is a chronic pain condition characterized by persistent facial pain that does not respond well to conventional medical treatments, often leading to significant impairment in quality of life. This study examined the clinical characteristics and surgical outcomes of microvascular decompression combined with nerve combing in patients with ATN.

We conducted a retrospective analysis of surgical techniques, clinical data, and treatment outcomes in 40 patients from January 2009 to January 2018. Pain levels and patient prognoses were assessed using the Visual Analog Scale and the Barrow Neurological Institute (BNI) pain score. Dynamic monitoring of arterial blood pressure was performed, and levels of total adrenaline, norepinephrine, and dopamine were measured before and during the nerve combing procedure.

During surgery, veins combined with arachnoid adhesions and arachnoid adhesions alone were observed compressing the trigeminal nerve in seven patients (17.50%) and 33 patients (82.50%), respectively. Immediate postoperative BNI scores indicated excellent outcomes (P = 2) in 30 patients (75.00%) and good outcomes (P = 3) in four patients (10.00%). Long-term postoperative BNI scores showed excellent outcomes (P = 2) in 25 patients (62.50%) and good outcomes (P = 3) in seven patients (17.50%). All patients experienced an increase in arterial blood pressure during nerve combing, and the mean levels of adrenaline and norepinephrine before combing showed significant improvement (P < 0.05).

Microvascular decompression combined with nerve combing achieves favorable results in treating ATN. Long-term trigeminal nerve compression and central sensitization may contribute to the etiology in these patients.

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Original Article Open Access
Impact of Intermediate-term Oral Contraceptive Use on Oxidative Stress, Lipid Profile, and Liver Function in Iraqi Women: A Comprehensive Biochemical Assessment
Hayder Hatem Sultan, Amir Teimourpour, Ziba Majidi, Fariba Nabatchian
Published online January 25, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00035
Abstract
Oral contraceptive pills (OCPs) are commonly used for contraception, but their long-term effects on oxidative stress, lipid profiles, and liver function remain unclear. This study [...] Read more.

Oral contraceptive pills (OCPs) are commonly used for contraception, but their long-term effects on oxidative stress, lipid profiles, and liver function remain unclear. This study aimed to evaluate the impact of intermediate-term OCP use (Yasmin) on oxidative stress, lipid profile, and liver function, with particular emphasis on antioxidant markers, lipid metabolism, and hepatic enzyme activity, to better understand the potential metabolic and hepatic effects.

A case-control study was conducted in Maysan Governorate, Iraq, involving 150 women (100 OCP users and 50 non-users). Blood samples were collected from Al-Sadr Teaching Hospital and a specialized clinic between February and April 2023. Serum levels of antioxidants, lipids, and liver enzymes were measured using biochemical assays.

OCP users had significantly lower levels of glutathione peroxidase vitamin E and uric acid (p < 0.001) compared to non-users. Lipid profiles showed that OCP users had higher levels of triglyceride and low-density lipoprotein (p < 0.05), whereas total cholesterol was significantly higher in non-users (p < 0.05). Liver enzyme activity, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total serum bilirubin, did not show statistically significant differences (p > 0.05). Longer duration of OCP use was significantly negatively correlated with vitamin E levels (r = −0.67), glutathione peroxidase activity (r = −0.56), uric acid levels (r = −0.45) and high-density lipoprotein (r = −0.54). Positive correlations were found between the duration of OCP use and total cholesterol (r = 0.62), triglyceride (r = 0.58), low-density lipoprotein (r = 0.60), and liver enzymes alanine aminotransferase (r = 0.66) and aspartate aminotransferase (r = 0.64).

Intermediate-term OCP use was associated with changes in oxidative stress and lipid metabolism, potentially increasing cardiovascular and metabolic risks. Regular monitoring of these parameters is recommended for OCP users.

Full article
Original Article Open Access
The Aquaporin-4 Inhibitor, N-(1,3,4-thiadiazol-2-yl)-3-pyridinecarboxamide, Inhibits the Glymphatic System: A Laboratory Study
Chuang Lian, Te Zhang, Peng Cheng, Longyun Li, Guoqing Zhao, Xuli Ren
Published online November 15, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00029
Abstract
Aquaporin-4 (AQP4) plays a crucial role in the glymphatic system and is vital for maintaining homeostasis in the central nervous system. This study aimed to investigate the effects [...] Read more.

Aquaporin-4 (AQP4) plays a crucial role in the glymphatic system and is vital for maintaining homeostasis in the central nervous system. This study aimed to investigate the effects of N-(1,3,4-thiadiazol-2-yl)-3-pyridinecarboxamide (TGN-020), a selective AQP4 inhibitor, on glymphatic function and to assess its impact on short-term behavior in mice.

In this laboratory study, mice were randomly assigned to TGN-020-treated and control groups. We evaluated glymphatic function by measuring the distribution of Evans blue dye in the brain following injection into the cisterna magna. Behavioral assessment of cognitive function was performed using open field and Morris water maze tests. AQP4 protein expression levels were analyzed via immunohistochemistry. Statistical comparisons were conducted using the one-way analysis of variance to evaluate the results among groups.

Our findings revealed that the areas of Evans blue dye in the dorsal (p < 0.001) and ventral (p < 0.001) surfaces of the brain were significantly reduced in the TGN-020 group compared to the control group, indicating impaired glymphatic function. However, behavioral tests demonstrated no significant short-term changes; the mean distance traveled in the open field was 4,345 cm in the control group and 4,049 cm in the TGN-020 group (p = 0.5625), while the mean speed was 2.649 cm/s for controls and 2.868 cm/s for the TGN-020 group (p = 0.6762). In the Morris water maze, latency was comparable (36.33 s for TGN-020 vs. 34.89 s for controls, p = 0.758). Additionally, no significant differences in AQP4 expression intensity were observed between the two groups.

Our study demonstrates that acute inhibition of AQP4 through a single dose of TGN-020 significantly impairs glymphatic function without inducing short-term behavioral abnormalities in mice. These findings contribute to understanding AQP4’s role in the glymphatic system and its potential implications for neurological function.

Full article
Review Article Open Access
Mimickers and Associated Neoplasms of Castleman Disease
Xiaohui Zhang, Sara Niyazi, Huazhang Guo, Ling Zhang
Published online March 24, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00047
Abstract
Castleman disease (CD) is a lymphoproliferative condition with a broad range of morphological and clinical presentations. It is categorized into distinct pathological and clinical [...] Read more.

Castleman disease (CD) is a lymphoproliferative condition with a broad range of morphological and clinical presentations. It is categorized into distinct pathological and clinical subtypes, including localized unicentric CD, idiopathic multicentric CD, and human herpesvirus 8-associated or human herpesvirus 8-negative variants. Diagnosing CD requires adherence to internationally recognized guidelines that integrate clinical, laboratory, and histological findings. However, distinguishing CD from other diseases can be complex, as numerous benign and malignant conditions can mimic its features. Additionally, individuals diagnosed with CD are at an elevated risk of developing various malignancies. In this article, we reviewed benign and malignant conditions that can mimic CD.

Literature search is conducted and reviewed.

Mimickers of CD include follicular hyperplasia, indolent B-cell lymphoproliferative disorders, peripheral T-cell malignancies, classic Hodgkin lymphoma, follicular dendritic cell tumors, plasma cell disorders, immunoglobulin G4 -related lymphadenopathy, autoimmune-associated lymphadenopathy, infectious causes of lymphadenopathy, and systemic syndromes like POEMS and TAFRO. Various malignancies are associated with CD, including plasma cell proliferations, lymphomas, follicular dendritic cell neoplasms, and Kaposi sarcoma.

This review explores the differential diagnoses and neoplasms linked to CD, emphasizing their role in accurate classification, treatment decisions, and patient management. A comprehensive understanding of CD and its mimickers is crucial for ensuring accurate diagnosis and appropriate patient management in clinical practice.

Full article
Original Article Open Access
Evaluation of Plasma Neurodegenerative Biomarkers for Diagnosing Minimal Hepatic Encephalopathy and Predicting Overt Hepatic Encephalopathy in Chinese Patients with Hepatic Cirrhosis
Qiuyu Cheng, Yunhui Liu, Zhongyuan Yang, Meng Zhang, Tingting Liu, Yuxin Niu, Wei Liu, Lanyue Huang, Yuzhao Feng, Xiaoyun Zhang, Xiaoping Luo, Qin Ning, Tao Chen
Published online December 12, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00413
Abstract
The performance of neurodegenerative biomarkers—neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1)—in [...] Read more.

The performance of neurodegenerative biomarkers—neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1)—in diagnosing minimal hepatic encephalopathy (MHE) has not been systematically evaluated, simultaneously, nor have their associations with the development of overt hepatic encephalopathy (OHE). This study aimed to evaluate the performance of plasma NfL, GFAP, tau, and UCHL1 in diagnosing MHE and predicting the development of OHE in Chinese patients with hepatic cirrhosis.

In this prospective study, 124 patients with hepatic cirrhosis were recruited. The Psychometric Hepatic Encephalopathy Score was used to diagnose MHE, and OHE development was observed during a 30-day follow-up period. Plasma levels of NfL, GFAP, tau, and UCHL1 were measured using the highly sensitive single-molecule array when MHE was diagnosed. Additionally, serum interleukin-6 (IL-6) levels and the model for end-stage liver disease (MELD) and MELD-Na scores were also measured.

MHE was diagnosed in 57 (46.0%) patients. Patients with MHE had significantly higher plasma levels of NfL and GFAP (34.2 vs. 22.4 pg/mL and 173 vs. 97.6 pg/mL, respectively; both p < 0.001) and lower tau levels (8.4 vs. 11.6 pg/mL, p = 0.048) compared to those without MHE. Plasma NfL (odds ratios = 1.027, 95% confidence interval [CI]: 1.006–1.048; p = 0.013) and serum ammonia levels (odds ratios = 1.021, 95% CI: 1.006–1.036; p = 0.007) were independently associated with MHE occurrence. A combination of NfL, GFAP, tau, and UCHL1 was effective in diagnosing MHE in all cirrhotic patients (area under the receiver operating characteristic curve [hereinafter referred to as AUROC]: 0.748, 95% CI: 0.662–0.821), with an accuracy, sensitivity, and specificity of 71.0%, 71.9%, and 71.6%, respectively. In patients without previous OHE, the combination had an AUROC of 0.764 (95% CI: 0.673–0.840), with an accuracy, sensitivity, and specificity of 72.5%, 71.7%, and 73.0%, respectively. Furthermore, GFAP (hazard ratio (HR) = 1.003, 95% CI: 1.000–1.005; p = 0.044), IL-6 (HR = 1.003, 95% CI: 1.001–1.004; p < 0.001), and MELD score (HR = 1.139, 95% CI: 1.072–1.210; p < 0.001)—but not NfL, tau, and UCHL1—were identified as risk factors for 30-day OHE development.

The combination of plasma levels of NfL, GFAP, tau, and UCHL1 performs well in diagnosing MHE. Additionally, MELD score, IL-6, and GFAP appear to be significant predictors of OHE development in patients with hepatic cirrhosis.

Full article
Review Article Open Access
Beyond the Cure: Navigating Hepatocellular Risk and Surveillance after Hepatitis C Eradication in the Direct-acting Antiviral Era
Chencheng Xie, Ashwani K. Singal
Published online February 8, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00499
Abstract
Direct-acting antivirals (DAAs) have dramatically changed the landscape of chronic hepatitis C virus (HCV) treatment and significantly reduced the risk of HCV-related hepatocellular [...] Read more.

Direct-acting antivirals (DAAs) have dramatically changed the landscape of chronic hepatitis C virus (HCV) treatment and significantly reduced the risk of HCV-related hepatocellular carcinoma (HCC) after achieving sustained virologic response. However, the risk of HCC persists, particularly in patients with pre-treatment cirrhosis or fibrosis stage 3 (F3), even after DAA-induced viral eradication. While professional guidelines agree on the need for surveillance in cirrhotic patients, there is no consensus regarding surveillance for the pre-treatment F3 population following HCV eradication. The risk of HCC in the F3 population falls below the threshold for cost-effective surveillance. However, co-existing risk factors—such as diabetes, hepatic steatosis, alcohol use, advanced age, and elevated alpha-fetoprotein levels—may warrant reconsideration of HCC surveillance in this group. This underscores the need for an individualized, risk-based approach to HCC surveillance. This review provided a simplified algorithm to assist clinicians in managing patients with HCV after DAA-induced sustained virologic response.

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Illuminating and Instructive Clinical Case Open Access
A Case of Severe Cholestatic Hepatitis Induced by a Novel Dual Agonist of Glucagon-like Peptide-1 and Glucose-dependent Insulinotropic Polypeptide Receptors
Junmin Jiang, Meifeng Shi, Shuduo Wu, Minling Cao
Published online October 30, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00287
Abstract
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are increasingly used in the management of type 2 diabetes mellitus and [...] Read more.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are increasingly used in the management of type 2 diabetes mellitus and obesity due to their ability to stimulate insulin secretion, delay gastric emptying, and suppress appetite. The combination of GLP-1 and GIP agonists improves glycemic control and promotes weight loss. However, the introduction of these novel therapies has raised safety concerns, including the risk of cholestatic hepatitis. We report a case of a patient with obesity who was prescribed a GLP-1/GIP dual-receptor agonist as part of his treatment regimen. Importantly, both before the initiation of this therapy and during the course of treatment, the patient was not taking any other medications. Shortly after receiving four doses of the therapy, the patient developed symptoms of severe cholestatic hepatitis, including jaundice and elevated liver enzyme levels. During hospitalization, no alternative causes for the condition were identified, and a liver biopsy confirmed the diagnosis of drug-induced cholestatic hepatitis. This is the first recorded case of cholestatic hepatitis induced by a GLP-1/GIP dual agonist, and it aimed to raise global awareness of this potential side effect.

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Review Article Open Access
Repeated Esophagogastroduodenoscopy and Colonoscopy in the Diagnosis of Gastrointestinal Bleeding
Tao Liu, Liu Han, Deliang Liu, Yuyong Tan
Published online December 30, 2024
Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00024
Abstract
Esophagogastroduodenoscopy and colonoscopy play important roles in diagnosing gastrointestinal bleeding; however, they may sometimes fail to identify the source of the bleeding [...] Read more.

Esophagogastroduodenoscopy and colonoscopy play important roles in diagnosing gastrointestinal bleeding; however, they may sometimes fail to identify the source of the bleeding during the initial examination. In such cases, repeated endoscopic examination may be beneficial. Currently, no consensus exists on which patients would benefit from repeated examination. In this review, we discuss the role of repeated endoscopy and conclude that repeated esophagogastroduodenoscopy and colonoscopy can help improve detection rates. It is particularly valuable to repeat the procedure when the quality of the initial endoscopy is poor, the patient’s condition deteriorates, or other examinations suggest that lesions are within the scope of endoscopy.

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