In adults, mild traumatic brain injury (MTBI) frequently results in impairments of cognitive functions which would lead to psychological consequences in the future. Cerebrolysin is a nootropic drug, and can significantly improve cognitive function in patients with Alzheimer's disease and stroke. The purpose of this study was to investigate how Cerebrolysin therapy enhances cognitive recovery for mild traumatic brain injury patients using a double-blinded, placebo-controlled, randomized phase II pilot study. Patients having head injury within 24 h sent to our hospital were screened and recruited if patients were alert and conscious, and had intracranial contusion haemorrhage. From July 2009 to June 2010, totally, thirty-two patients were recruited in the double-blinded, placebo-controlled, and randomized study. Patients were randomized to receive Cerebrolysin (Group A, once daily intravenous infusion of 30 mL Cerebrolysin over a 60-min period for 5 days) or placebo (Group B, same dosage and administration of normal saline as Group A). The primary outcome measures were differences of cognitive function including Mini-Mental Status Examination (MMSE), and Cognitive Abilities Screening Instrument (CASI) scores between baseline and week 1, between baseline and week 4, and between baseline and week 12. Thirty-two patients completed the trial. For Group A, the CASI score difference between baseline and week 12 was 21.0 ± 20.4, a significantly greater change than that of Group B (7.6 ± 12.1) (p = 0.0461). Besides, drawing function (one of the domains of CASI; p = 0.0066) on week 4 and both drawing function (p = 0.0472) and long-term memory (one of the domains of CASI; p = 0.0256) on week 12were also found to be significantly improved in the patients receiving Cerebrolysin treatment. Our results suggest that Cerebrolysin improves the cognitive function of the MTBI in patients at 3rd month after injury, especially for long-term memory and drawing function.
Malignant brain tumors consist of malignancies originated primarily within the brain and the metastatic lesions disseminated from other organs. In spite of intensive studies, malignant brain tumors remain to be a medical challenge. Patient-derived organoid (PDO) can recapitulate the biological features of the primary tumor it was derived from and has emerged as a promising drug-screening model for precision therapy. Here we show a proof-of-concept based on early clinical study entailing the organoids derived from the surgically resected tumors of 26 patients with advanced malignant brain tumors enrolled during December 2020 to October 2021. The tumors included nine glioma patients, one malignant meningioma, one primary lymphoma patient, and 15 brain metastases. The primary tumor sites of the metastases included five from the lungs, three from the breasts, two from the ovaries, two from the colon, one from the testis, one of melanoma origin, and one of chondrosarcoma. Out of the 26 tissues, 13 (50%) organoids were successfully generated with a culture time of about 2 weeks. Among these patients, three were further pursued to have the organoids derived from their tumor tissues tested for the sensitivity to different therapeutic drugs in parallel to their clinical care. Our results showed that the therapeutic effects observed by the organoid models were consistent to the responses of these patients to their treatments. Our study suggests that PDO can recapitulate patient responses in the clinic with high potential of implementation in personalized medicine of malignant brain tumors.
OBJECTIVE: Although no benefits of extracranial-intracranial (EC-IC) bypass surgery in preventing secondary stroke have been identified previously, the outcomes of initial symptomatic ischemic stroke and stenosis and/or occlusion among the Asian population in patients with or without bypass intervention have yet to be discussed. The authors aimed to evaluate the subsequent risk of secondary vascular disease and cardiac events in patients with and without a history of this intervention.METHODS: This retrospective nationwide population-based Taiwanese registry study included 205,991 patients with initial symptomatic ischemic stroke and stenosis and/or occlusion, with imaging data obtained between 2001 and 2010. Patients who underwent EC-IC bypass (bypass group) were compared with those who had not undergone EC-IC bypass, carotid artery stenting, or carotid artery endarterectomy (nonbypass group). Patients with any previous diagnosis of ischemic or hemorrhagic stroke, moyamoya disease, cancer, or trauma were all excluded.RESULTS: The risk of subsequent ischemic stroke events decreased by 41% in the bypass group (adjusted hazard ratio [HR] 0.59, 95% CI 0.46–0.76, p < 0.001) compared with the nonbypass group. The risk of subsequent hemorrhagic stroke events increased in the bypass group (adjusted HR 2.47, 95% CI 1.67–3.64, p < 0.001) compared with the nonbypass group.CONCLUSIONS: Bypass surgery does play an important role in revascularization of the ischemic brain, while also increasing the risk of hemorrhage in the early postoperative period. This study highlights the fact that the high risk of bypass surgery obscures the true benefit of revascularization of the ischemic brain and also emphasizes the importance of developing improved surgical technique to treat these high-risk patients.
The elusive nature of brain tumor progression, hidden behind the blood-brain barrier, presents significant challenges for treatment monitoring in high-grade gliomas. In this feasibility study, we evaluate a novel approach to tracking glioblastoma through liquid biopsy, assessing whether tumor cells leave detectable molecular footprints in both blood and cerebrospinal fluid (CSF). Using the MiSelect R II System with specialized microfluidic technology, we analyzed paired blood and CSF samples from six glioblastoma patients, revealing a striking presence of circulating tumor cells (CTCs)– with higher abundance in CSF, where detection rates reached 100% compared to 83.3% in blood. Our technical validation demonstrates the system’s capability to identify CTCs through multi-marker analysis (EGFR+/GFAP+/CD45-). Preliminary observations revealed higher CTC counts in CSF (median 15.5 cells/mL) compared to blood (median 3.0 cells/mL), with notable differences between compartments suggesting they may reflect distinct aspects of disease biology. In a patient who developed progressive disease, we observed a substantial increase in CSF CTCs from 14 to 116 cells/mL, warranting further investigation in larger cohorts. Additionally, we detected CTC clusters in both compartments, an intriguing finding with potential biological significance. While our interim analysis provides technical proof-of-concept for CTC detection in glioblastoma patients, the limited sample size precludes definitive conclusions regarding clinical utility. These findings establish a methodological foundation for future comprehensive studies exploring the relationship between CTC dynamics and clinical outcomes in high-grade gliomas.
Background: Liver cancer and notably hepatocellular carcinoma (HCC), results in significantly high mortality rates worldwide. Chronic hepatitis and fatty liver, recognized precursors, underscore the imperative need for effective preventive strategies. This study explores colchicine, traditionally acknowledged for its anti-inflammatory properties and investigates its potential in liver cancer prevention. Methods: Utilizing the iHi Data Platform of China Medical University Hospital, Taiwan, this study analyzed two decades of medical data, incorporating 10,353 patients each in the Colchicine and Non-Colchicine cohorts, to investigate the association between colchicine use and liver cancer risk. Results: The study identified that colchicine users exhibited a 19% reduction in liver cancer risk, with a multivariable-adjusted odds ratio of 0.81 after accounting for confounding variables. Additionally, the influence of gender and comorbidities like diabetes mellitus on liver cancer risk was identified, corroborating the existing literature. A notable finding was that the prolonged use of colchicine was associated with improved outcomes, indicating a potential dose–response relationship. Conclusions: This study proposes a potential new role for colchicine in liver cancer prevention, extending beyond its established anti-inflammatory applications. While the findings are promising, further research is essential to validate these results. This research may serve as a foundation for future studies, aiming to further explore colchicine’s role via clinical trials and in-depth investigations, potentially impacting preventive strategies for liver cancer.
Treating metastatic brain tumors remains a significant challenge. This study introduces and applies the Patient-Derived Tumor Spheroid (PDTS) system, an ex vivo model for precision drug testing on metastatic brain tumor. The PDTS system utilizes a decellularized extracellular matrix (dECM) derived from adipose tissue, combined with the tumor cells, to form tumor spheroids. These spheroids were subsequently used to test anticancer drugs, with results compared to the clinical outcomes observed after administering these treatments to patients. To assess the validity of the data, the correlation between the drug responses observed in the PDTS model and actual patient outcomes was analyzed. Chi-square tests evaluated the significance of associations between lab predictions and clinical outcomes, using a significance threshold of p < 0.05. In preliminary data, 17 patients met the criteria for final analysis, which showed an overall 57% accuracy (p-value = 0.463), with improvements to 73% accuracy (p-value = 0.072) when patients receiving certain treatments were excluded. This PDTS offers real-time results within three weeks, simultaneous testing of multiple drugs, and the ability to culture and store tumor cells for reproducibility. Despite some limitations, further development of this model could enhance its clinical application and improve patient outcomes.