Connectome-based prediction of cognitive performance in patients with temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) patients often exhibit varying degrees of cognitive impairments. This study aims to predict cognitive performance in TLE patients by applying a connectome-based predictive model (CPM) to whole-brain resting-state functional connectivity (RSFC) data. METHODS: A CPM was established and leave-one-out cross-validation was employed to decode the cognitive performance of patients with TLE based on the whole-brain RSFC. RESULTS: Our findings indicate that cognitive performance in TLE can be predicted through the internal and network connections of the parietal lobe, limbic lobe, and cerebellum systems. These systems play crucial roles in cognitive control, emotion processing, and social perception and communication, respectively. In the subgroup analysis, CPM successfully predicted TLE patients with and without focal to bilateral tonic-clonic seizures (FBCTS). Additionally, significant differences were noted between the two TLE patient groups and the normal control group. CONCLUSION: This data-driven approach provides evidence for the potential of predicting brain features based on the inherent resting-state brain network organization. Our study offers an initial step towards an individualized prediction of cognitive performance in TLE patients, which may be beneficial for diagnosis, prognosis, and treatment planning.

Acute resistance exercise combined with whole body vibration and blood flow restriction: Molecular and neurocognitive effects in late-middle-aged and older adults.

Limited research exists regarding the effects of resistance exercise (RE) combined with whole body vibration (WBV), blood flow restriction (BFR), or both on the neuropsychological performance of working memory (WM) in late-middle-aged and older adults and regarding the physiological mechanisms underlying this effect. This study thus explored the acute molecular and neurophysiological mechanisms underlying WM performance following RE combined with WBV, BFR, or both. Sixty-six participants were randomly assigned into a WBV, BFR, or WBV + BFR group. Before and after the participants engaged in a single bout of isometric RE combined with WBV, BFR, or both, this study gathered data on several neurocognitive measures of WM performance, namely, accuracy rate (AR), reaction time (RT), and brain event-related potential (specifically P3 latency and amplitude), and data on biochemical indices, such as the levels of insulin-like growth factor-1 (IGF-1), norepinephrine (NE), and brain-derived neurotrophic factor (BDNF). Although none of the RE modalities significantly affected RTs and P3 latencies, ARs and P3 amplitudes significantly improved in the WBV and WBV + BFR groups. The WBV + BFR group exhibited greater improvements than the WBV group did. Following acute RE combined with WBV, BFR, or both, IGF-1 and NE levels significantly increased in all groups, whereas BDNF levels did not change. Crucially, only the changes in NE levels were significantly correlated with improvements in ARs in the WBV + BFR and WBV groups. The findings suggest that combining acute RE with WBV, BFR, or both could distinctively mitigate neurocognitive decline in late-middle-aged and older adults.

Attenuating mitochondrial dysfunction and morphological disruption with PT320 delays dopamine degeneration in MitoPark mice.

BACKGROUND: Mitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood. METHODS: In this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse. RESULTS: Our findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae. CONCLUSION: Our findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD.

Hypoxia-induced TREM1 promotes mesenchymal-like states of glioma stem cells via alternatively activating tumor-associated macrophages.

The mesenchymal subtype of glioblastoma (GBM) cells characterized by aggressive invasion and therapeutic resistance is thought to be dependent on cell-intrinsic alteration and extrinsic cellular crosstalk. Tumor-associated macrophages (TAMs) are pivotal in tumor progression, chemo-resistance, angiogenesis, and stemness maintenance. However, the impact of TAMs on the shifts in glioma stem cells (GSCs) states remains largely uncovered. Herein, we showed that the triggering receptor expressed on myeloid cells-1 (TREM1) preferentially expressed by M2-like TAMs and induced GSCs into mesenchymal-like states by modulating the secretion of TGFß2, which activated the TGFßR/SMAD2/3 signaling in GSCs. Furthermore, we demonstrated that TREM1 was transcriptionally regulated by HIF1a under the hypoxic environment and thus promoted an immunosuppressive type of TAMs via activating the TLR2/AKT/mTOR/c-MYC axis. Collectively, this study reveals that cellular communication between TAMs and GSCs through the TREM1-mediated TGFß2/TGFßR axis is involved in the mesenchymal-like transitions of GSCs. Our study provides valuable insights into the regulatory mechanisms between the tumor immune microenvironment and the malignant characteristics of GBM, which can lead to potential novel strategies targeting TAMs for tumor control.

Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation.

Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin-binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self-renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

Cost-effectiveness of pemigatinib as a second-line treatment for advanced intrahepatic cholangiocarcinoma with fibroblast growth factor receptor 2 fusions in Taiwan: from the evidence of the phase II trial and the perspective of Taiwan's National Health Insurance Administration.

BACKGROUND: In December 2022, the Taiwan National Health Insurance Administration (NHIA) announced the reimbursement of three dosages of pemigatinib 4.5 mg, 9 mg, and 13.5 mg for treating advanced intrahepatic cholangiocarcinoma (ICC) with fibroblast growth factor receptor 2 (FGFR2) fusions/rearrangements and set the reimbursement price for pemigatinib 4.5 mg at NT$6600. This study aims to analyze the cost-effectiveness of pemigatinib 13.5 mg as a second-line treatment compared to mFOLFOX and 5-FU chemotherapy for advanced ICC patients with FGFR2 fusions/rearrangements from the perspective of Taiwan's NHIA. METHODS: This study used a 3-state partitioned survival model to analyze the 5 year cost-effectiveness of pemigatinib as a second-line treatment for advanced ICC patients in whom first-line gemcitabine-based chemotherapy failed and to compare the results with those for the mFOLFOX and 5-FU chemotherapy regimens. Overall survival and progression-free survival were estimated from the FIGHT-202 trial (pemigatinib), ABC-06 trial (mFOLFOX), and NIFTY trial (5-FU). The price of pemigatinib 13.5 mg was set at the potentially highest listing price (NT$17,820). Other parameters of utility, disutility, and costs related to advanced ICC were obtained from the published literature. The willingness-to-pay threshold was three times the forecasted gross domestic product per capita in 2022 (NT$2,928,570). A 3% discount rate was applied to quality-adjusted life-years (QALYs) and costs. Several scenario analyses were performed, including a gradual price reduction for pemigatinib. Deterministic sensitivity analysis, probabilistic sensitivity analysis (PSA), and value of information were performed to assess uncertainty. RESULTS: Pemigatinib was not cost-effective compared to mFOLFOX or 5-FU in the base-case analysis. When the price of pemigatinib was reduced by 50% or more, pemigatinib gained a positive net monetary benefit (mFOLFOX: NT$55,374; 5-FU: NT$92,437) and a 72% (mFOLFOX) and 77.1% (5-FU) probability of being cost-effective. Most of the uncertainty came from the medication cost of pemigatinib, health state utility, and the overall survival associated with pemigatinib. CONCLUSIONS: According to the NCCN guidelines, the daily use of pemigatinib 13.5 mg at the hypothesized NHIA price of NT$17,820/13.5 mg was not cost-effective compared to mFOLFOX or 5-FU. The price reduction scenario suggested a 50% price reduction, NT$8910 per 13.5 mg, for advanced ICC patients with FGFR2 fusions/rearrangements.

This study performed a cost-effectiveness analysis on the use of targeted therapy pemigatinib 13.5 mg daily in second-line treatment for Taiwanese patients with intrahepatic cholangiocarcinoma (ICC) harboring FGFR2 fusions/rearrangements. This regimen was approved by the U.S. Food and Drug Administration in 2020 and recommended by the National Comprehensive Cancer Network (NCCN). Taiwan's National Health Insurance Administration (NHIA) has announced the reimbursement of three pemigatinib dosages of 4.5 mg, 9 mg, and 13.5 mg to be listed in the NHI coverage in 2022. However, as of the middle of April 2023, only the listing price for pemigatinib 4.5 mg has been determined, while pricing for the other two dosages remains pending. Based on a hypothesized NHIA price of NT$17,820/13.5 mg, this study evaluated the cost-effectiveness of pemigatinib 13.5 mg as a second-line treatment for advanced ICC with FGFR2 fusions/rearrangements compared to mFOLFOX (a regimen recommended by NCCN) and 5-FU (a regimen fully covered by Taiwan NHIA) and recommended a listing price for NHIA as reference. Our study showed that the hypothesized price of NT$17,820/13.5 mg was not cost-effective compared to mFOLFOX or 5-FU. The price reduction scenario suggested a 50% reduction (NT$8910) in the hypothesized NHIA price for advanced ICC patients with FGFR2 fusions/rearrangements.

Treatment of Myopia with Atropine 0.125% Once Every Night Compared with Atropine 0.125% Every Other Night: A Pilot Study.

(1) Purpose: To investigate the efficacy of myopia treatment in children using atropine 0.125% once every two nights (QON) compared with atropine 0.125% once every night (HS). (2) Methods: This retrospective cohort study reviewed the medical records of two groups of children with myopia. Group 1 comprised children treated with atropine 0.125% QON, while group 2 included children treated with atropine 0.125% HS. The first 6 months of data of outcome measurements were subtracted as washout periods in those children undergoing both atropine QON and HS treatment. The independent t-test and Pearson's chi-square test were used to compare the baseline clinical characteristics between the two groups. A generalized estimating equations (GEE) model was used to determine the factors that influence treatment effects. (3) Results: The average baseline ages of group 1 (38 eyes from 19 patients) and group 2 (130 eyes from 65 patients) were 10.6 and 10.2 years, respectively. There were no significant differences in axial length (AL) or cycloplegic spherical equivalent (SEq) at baseline or changes of them after 16.9 months of follow-up. GEE showed that the frequency of atropine 0.125% use has no association with annual AL (QON vs. HS: 0.16 ± 0.10 vs. 0.18 ± 0.12) and SEq (QON vs. HS: -0.29 ± 0.44 vs. -0.34 ± 0.36) changes in all children with myopia. It also showed that older baseline age (B = -0.020, p < 0.001) was associated with lesser AL elongation. (4) Conclusion: The treatment effects of atropine 0.125% HS and QON were similar in this pilot study. The use of atropine 0.125% QON may be an alternative strategy for children who cannot tolerate the side effects of atropine 0.125% HS. This observation should be confirmed with further large-scale studies.

Molecular characterization of sub-frontal recurrent medulloblastomas reveals potential clinical relevance.

Background: Single recurrence in the sub-frontal region after cerebellar medulloblastoma (MB) resection is rare and the underlying molecular characteristics have not been specifically addressed. Methods: We summarized two such cases in our center. All five samples were molecularly profiled for their genome and transcriptome signatures. Results: The recurrent tumors displayed genomic and transcriptomic divergence. Pathway analysis of recurrent tumors showed functional convergence in metabolism, cancer, neuroactive ligand-receptor interaction, and PI3K-AKT signaling pathways. Notably, the sub-frontal recurrent tumors had a much higher proportion (50-86%) of acquired driver mutations than that reported in other recurrent locations. The acquired putative driver genes in the sub-frontal recurrent tumors functionally enriched for chromatin remodeler-associated genes, such as KDM6B, SPEN, CHD4, and CHD7. Furthermore, the germline mutations of our cases showed a significant functional convergence in focal adhesion, cell adhesion molecules, and ECM-receptor interaction. Evolutionary analysis showed that the recurrence could be derived from a single primary tumor lineage or had an intermediate phylogenetic similarity to the matched primary one. Conclusion: Rare single sub-frontal recurrent MBs presented specific mutation signatures that might be related to the under-dose radiation. Particular attention should be paid to optimally covering the sub-frontal cribriform plate during postoperative radiotherapy targeting.

Blood Loss in Operation Is Independently Predictive of Postoperative Ventriculoperitoneal Shunt in Pediatric Patients With Posterior Fossa Tumors.

BACKGROUND: To identify the risk factors for postoperative hydrocephalus and the need for ventriculoperitoneal (VP) shunt after posterior fossa tumor (PFT) resection in pediatric patients and establish a predictive model. METHODS: A total of 217 pediatric patients (≤14 years old) with PFTs who underwent tumor resection from November 2010 to December 2020 were divided into a VP shunt group (n = 29) and non-VP shunt group (n = 188). Univariate and multivariate logistic regression were performed. A predictive model was established based on the independent predictors. Receiver operating characteristic curves were generated to determine the cutoff values and areas under the curve (AUCs). The Delong test was performed to compare the AUCs. RESULTS: Age less than three years (P = 0.015, odds ratio [OR] = 3.760), blood loss (BL) (P = 0.002, OR = 1.601), and locations at fourth ventricle (P < 0.001, OR = 7.697) were the independent predictors. The predictive model was as follows: total score = age (<3; yes = 2, no = 0) + BL + tumor locations (fourth ventricle; yes = 5, no = 0). The AUC of our model was higher than those of age less than three years, BL, locations at the fourth ventricle, and compound factors (age <3 + locations) (0.842 vs 0.609, 0.734, 0.732, and 0.788, respectively). The cutoff values of the model and BL were 7.5 points and 2.75 U, respectively. CONCLUSIONS: BL, age less than three years, and tumors at the fourth ventricle were independent predictors. Model scores over 7.5 points predict a high risk.

FAM129A promotes self-renewal and maintains invasive status via stabilizing the Notch intracellular domain in glioma stem cells.

BACKGROUND: Glioma stem cells (GSCs) are a subpopulation of tumor cells with self-renewal and tumorigenic capabilities in glioblastomas (GBMs). Diffuse infiltration of GSCs facilitates tumor progression and frustrates efforts at effective treatment. Further compounding this situation is the currently limited understanding of what drives GSC invasion. Here we comprehensively evaluated the significance of a novel invasion-related protein, Family with Sequence Similarity 129 Member A (FAM129A), in infiltrative GSCs. METHODS: Western blotting, immunohistochemistry, and gene expression analysis were used to quantify FAM129A in glioma specimens and cancer datasets. Overexpression and knockdown of FAM129A in GSCs were used to investigate its effects on tumor growth and invasion. RNA-seq, qRT-PCR, western blotting, and co-precipitation assays were used to investigate FAM129A signaling mechanisms. RESULTS: FAM129A is preferentially expressed in invasive frontiers. Targeting FAM129A impairs GSC invasion and self-renewal. Mechanistically, FAM129A acted as a positive regulator of Notch signaling by binding with the Notch1 intracellular domain (NICD1) and preventing its degradation. CONCLUSIONS: FAM129A and NICD1 provide a precise indicator for identifying tumor margins and aiding prognosis. Targeting them may provide a significantly therapeutic strategy for GSCs.

Construction and Verification of an RNA-Binding Protein-Associated Prognostic Model for Gliomas.

OBJECTIVE: To construct and verificate an RNA-binding protein (RBP)-associated prognostic model for gliomas using integrated bioinformatics analysis. METHODS: RNA-sequencing and clinic pathological data of glioma patients from The Cancer Genome Atlas (TCGA) database and the Chinese Glioma Genome Atlas database (CGGA) were downloaded. The aberrantly expressed RBPs were investigated between gliomas and normal samples in TCGA database. We then identified prognosis related hub genes and constructed a prognostic model. This model was further validated in the CGGA-693 and CGGA-325 cohorts. RESULTS: Totally 174 differently expressed genes-encoded RBPs were identified, containing 85 down-regulated and 89 up-regulated genes. We identified five genes-encoded RBPs (ERI1, RPS2, BRCA1, NXT1, and TRIM21) as prognosis related key genes and constructed a prognostic model. Overall survival (OS) analysis revealed that the patients in the high-risk subgroup based on the model were worse than those in the low-risk subgroup. The area under the receiver operator characteristic curve (AUC) of the prognostic model was 0.836 in the TCGA dataset and 0.708 in the CGGA-693 dataset, demonstrating a favorable prognostic model. Survival analyses of the five RBPs in the CGGA-325 cohort validated the findings. A nomogram was constructed based on the five genes and validated in the TCGA cohort, confirming a promising discriminating ability for gliomas. CONCLUSION: The prognostic model of the five RBPs might serve as an independent prognostic algorithm for gliomas.

Important Cells and Factors from Tumor Microenvironment Participated in Perineural Invasion.

Perineural invasion (PNI) as the fourth way for solid tumors metastasis and invasion has attracted a lot of attention, recent research reported a new point that PNI starts to include axon growth and possible nerve "invasion" to tumors as the component. More and more tumor-nerve crosstalk has been explored to explain the internal mechanism for tumor microenvironment (TME) of some types of tumors tends to observe nerve infiltration. As is well known, the interaction of tumor cells, peripheral blood vessels, extracellular matrix, other non-malignant cells, and signal molecules in TME plays a key role in the occurrence, development, and metastasis of cancer, as to the occurrence and development of PNI. We aim to summarize the current theories on the molecular mediators and pathogenesis of PNI, add the latest scientific research progress, and explore the use of single-cell spatial transcriptomics in this invasion way. A better understanding of PNI may help to understand tumor metastasis and recurrence and will be beneficial for improving staging strategies, new treatment methods, and even paradigm shifts in our treatment of patients.

Clinical features and outcomes of pediatric intracranial gliomas: results from single center's 226 cases and corroborated with SEER database.

BACKGROUND: Pediatric gliomas are the most common central nervous system (CNS) tumors in children and adolescents and show different clinical and histopathological characteristics from the adult. The prognostic factors were poorly defined in pediatric intracranial gliomas. METHODS: We collected pediatric intracranial glioma cases in our institution between February 2011 and June 2022. The patient clinical data, tumor growth characteristics, treatments, and follow-up data were analyzed by Cox regression analysis to identify impact factors on the prognosis of pediatric intracranial glioma patients. To corroborate our data, an independent cohort of pediatric intracranial glioma from the Surveillance, Epidemiology, and End Results Program (SEER) database was analyzed. RESULTS: A total of 181 cases of pediatric low-grade glioma (PLGG) and 45 cases of pediatric high-grade glioma (PHGG) were included. In multivariate Cox regression analysis, tumor size > 59.5 mm (p = 0.006) and non-gross total resection (non-GTR; subtotal resection, STR, p = 0.042; biopsy, p = 0.012) were associated with decreased overall survival (OS) in PLGG patients. In PHGG patients, only chemotherapy (p = 0.023) was associated with OS while tumor size was marginally prognostic for OS (p = 0.051). Additional independent analysis of 2734 PLGG and 741 PHGG from the SEER database corroborated that larger tumor size was associated with decreased OS in LGG (p = 0.001) and HGG (p < 0.001) patients, separately. CONCLUSION: In this study, we found that tumor size was a significant prognostic factor for the OS of PLGG patients in our series. Besides the tumor size, the extent of resection also independently impacted the prognosis of PLGG patients. While in PHGG patients, only chemotherapy was associated with improved OS and tumor size was marginally prognostic.

Understanding the failure process of sulfide-based all-solid-state lithium batteries via operando nuclear magnetic resonance spectroscopy.

The performance of all-solid-state lithium metal batteries (SSLMBs) is affected by the presence of electrochemically inactive (i.e., electronically and/or ionically disconnected) lithium metal and solid electrolyte interphase (SEI), which are jointly termed inactive lithium. However, the differentiation and quantification of inactive lithium during cycling are challenging, and their lack limits the fundamental understanding of SSLMBs failure mechanisms. To shed some light on these crucial aspects, here, we propose operando nuclear magnetic resonance (NMR) spectroscopy measurements for real-time quantification and evolution-tracking of inactive lithium formed in SSLMBs. In particular, we examine four different sulfide-based solid electrolytes, namely, Li10GeP2S12, Li9.54Si1.74P1.44S11.7Cl0.3, Li6PS5Cl and Li7P3S11. We found that the chemistry of the solid electrolyte influences the activity of lithium. Furthermore, we demonstrate that electronically disconnected lithium metal is mainly found in the interior of solid electrolytes, and ionically disconnected lithium metal is found at the negative electrode surface. Moreover, by monitoring the Li NMR signal during cell calendar ageing, we prove the faster corrosion rate of mossy/dendritic lithium than flat/homogeneous lithium in SSLMBs.

Growing and symptomatic intracranial arachnoid cyst in an elderly patient: a case report and literature review.

We report an elderly patient with a symptomatic and growing arachnoid cyst. Physician should be cautious in counseling asymptomatic arachnoid cyst patients, regardless of their age, and inform them of the possibility, although rare, of growth and symptom development even in their late life.

Deep Learning Segmentation and Reconstruction for CT of Chronic Total Coronary Occlusion.

Background CT imaging of chronic total occlusion (CTO) is useful in guiding revascularization, but manual reconstruction and quantification are time consuming. Purpose To develop and validate a deep learning (DL) model for automated CTO reconstruction. Materials and Methods In this retrospective study, a DL model for automated CTO segmentation and reconstruction was developed using coronary CT angiography images from a training set of 6066 patients (582 with CTO, 5484 without CTO) and a validation set of 1962 patients (208 with CTO, 1754 without CTO). The algorithm was validated using an external test set of 211 patients with CTO. The consistency and measurement agreement of CTO quantification were compared between the DL model and the conventional manual protocol using the intraclass correlation coefficient, Cohen κ coefficient, and Bland-Altman plot. The predictive values of CT-derived Multicenter CTO Registry of Japan (J-CTO) score for revascularization success were evaluated. Results In the external test set, 211 patients (mean age, 66 years ± 11 [SD]; 164 men) with 240 CTO lesions were evaluated. Automated segmentation and reconstruction of CTOs by DL was successful in 95% of lesions (228 of 240) without manual editing and in 48% of lesions (116 of 240) with the conventional manual protocol (P < .001). The total postprocessing and measurement time was shorter for DL than for manual reconstruction (mean, 121 seconds ± 20 vs 456 seconds ± 68; P < .001). The quantitative and qualitative CTO parameters evaluated with the two methods showed excellent correlation (all correlation coefficients > 0.85, all P < .001) and minimal measurement difference. The predictive values of J-CTO score derived from DL and conventional manual quantification for procedure success showed no difference (area under the receiver operating characteristic curve, 0.76 [95% CI: 0.69, 0.82] and 0.76 [95% CI: 0.69, 0.82], respectively; P = .55). Conclusion When compared with manual reconstruction, the deep learning model considerably reduced postprocessing time for chronic total occlusion quantification and had excellent correlation and agreement in the anatomic assessment of occlusion features. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Loewe in this issue.

Cost-Effectiveness Analysis of a New Second-Line Treatment Regimen for Advanced Intrahepatic Cholangiocarcinoma: Biomarker-Driven Targeted Therapy of Pemigatinib Versus 5-FU Chemotherapy.

BACKGROUND AND OBJECTIVES: The National Comprehensive Cancer Network recommends a second-line treatment of pemigatinib for patients with intrahepatic cholangiocarcinoma with fibroblast growth factor receptor 2 (FGFR2) fusions/rearrangements and modified FOLFOX (mFOLFOX) for those without FGFR2 alterations. However, these regimens are not yet covered by Taiwa's National Health Insurance. This cost-effectiveness analysis evaluated the cost-effectiveness of the pemigatinib/mFOLFOX regimen as the second-line treatment for advanced intrahepatic cholangiocarcinoma based on FGFR2 status in comparison with the regimen of fluorouracil chemotherapy and provided a cost-effectiveness analysis-based reference price for pemigatinib. METHODS: A three-state partitioned survival model with a 5-year time horizon was constructed for patients with advanced intrahepatic cholangiocarcinoma who did not respond to first-line therapy. Overall and progression-free survival functions of pemigatinib, mFOLFOX, and fluorouracil were estimated from the FIGHT-202, ABC-06, and NIFTY trials, respectively. The utility of health states and disutility of adverse events were obtained from the literature. The genetic testing fee and price of pemigatinib were set as the market price. Other costs related to advanced intrahepatic cholangiocarcinoma were calculated using National Health Insurance claims data. The willingness-to-pay threshold was three times the gross domestic product per capita in 2021 (NT$2,889,684). A 3% discount rate was applied to quality-adjusted life-years and costs. Scenario analyses included a gradual price reduction of pemigatinib, alternative survival models, application of a National Health Insurance payment conversion factor to non-medication costs, and consideration of life-years as effectiveness. A deterministic sensitivity analysis, probabilistic sensitivity analysis, and a value of information analysis were performed. RESULTS: The new regimen provided an incremental 0.13 quality-adjusted life-years, with incremental costs of NT$459,697, yielding an incremental cost-effectiveness ratio of NT$3,411,098 per quality-adjusted life-year and an incremental net monetary benefit of - NT$70,268. The new regimen was found to be 53.2% cost effective in the probabilistic sensitivity analysis. The expected value of uncertainty measured by the expected value of perfect information was NT$80,695/person. In scenario analyses, the incremental net monetary benefit was positive when the price of pemigatinib was reduced by 40% or more. When applying a conversion factor to non-medical costs, the probability of the new regimen being cost effective was slightly increased from 53.2 to 56.5% compared with the base-case analysis. The utility and the cost of the new regimen were the main drivers of uncertainty. CONCLUSIONS: Although the new second-line genetic-based and biomarker-driven regimen of pemigatinib/mFOLFOX appears not cost effective for patients with advanced intrahepatic cholangiocarcinoma in the base-case analysis, our analysis suggests it is highly likely to be cost effective in the case of a 40% price reduction on pemigatinib.

Assessment of automatic rib fracture detection on chest CT using a deep learning algorithm.

OBJECTIVES: To evaluate deep neural networks for automatic rib fracture detection on thoracic CT scans and to compare its performance with that of attending-level radiologists using a large amount of datasets from multiple medical institutions. METHODS: In this retrospective study, an internal dataset of 12,208 emergency room (ER) trauma patients and an external dataset of 1613 ER trauma patients taking chest CT scans were recruited. Two cascaded deep neural networks based on an extended U-Net architecture were developed to segment ribs and detect rib fractures respectively. Model performance was evaluated with a 95% confidence interval (CI) on both the internal and external dataset, and compared with attending-level radiologist readings using t test. RESULTS: On the internal dataset, the AUC of the model for detecting fractures at per-rib level was 0.970 (95% CI: 0.968, 0.972) with sensitivity of 93.3% (95% CI: 92.0%, 94.4%) at a specificity of 98.4% (95% CI: 98.3%, 98.5%). On the external dataset, the model obtained an AUC of 0.943 (95% CI: 0.941, 0.945) with sensitivity of 86.2% (95% CI: 85.0%, 87.3%) at a specificity of 98.8% (95% CI: 98.7%, 98.9%), compared to the sensitivity of 70.5% (95% CI: 69.3%, 71.8%) (p < .0001) and specificity of 98.8% (95% CI: 98.7%, 98.9%) (p = 0.175) by attending radiologists. CONCLUSIONS: The proposed DL model is a feasible approach to identify rib fractures on chest CT scans, at the very least, reaching a level on par with attending-level radiologists. KEY POINTS: • Deep learning-based algorithms automatically detected rib fractures with high sensitivity and reasonable specificity on chest CT scans. • The performance of deep learning-based algorithms reached comparable diagnostic measures with attending level radiologists for rib fracture detection on chest CT scans. • The deep learning models, similar to human readers, were susceptible to the inconspicuity and ambiguity of target lesions. More training data was required for subtle lesions to achieve comparable detection performance.

Relationship between the Blood Urea Nitrogen to Creatinine Ratio and In-Hospital Mortality in Non-Traumatic Subarachnoid Hemorrhage Patients: Based on Propensity Score Matching Method.

(1) Background: To explore the correlation between the blood urea nitrogen to creatinine ratio (UCR) and in-hospital mortality in non-traumatic subarachnoid hemorrhage patients. (2) Methods: Specific clinical information was collected from the Medical Information Mart for Intensive Ⅳ (MIMIC-Ⅳ) database. The optimal cut-off value of the UCR was calculated with ROC curve analysis conducted using the maximum Youden index for the prediction of survival status. Univariable and multivariable logistic regression analyses were also carried out to assess the prognostic significance of UCR, and the Kaplan−Meier (K−M) analysis was conducted to draw the survival curves. Then, the 1:1 propensity score matching (PSM) method was applied to improve the reliability of the research results while balancing the unintended influence of underlying confounders. (3) Results: This retrospective cohort study included 961 patients. The optimal cut-off value of the UCR for in-hospital mortality was 27.208. The PSM was performed to identify 92 pairs of score-matched patients, with balanced differences exhibited for nearly all variables. According to the K−M analysis, those patients with a UCR of more than 27.208 showed a significantly higher level of in-hospital mortality compared to the patients with a UCR of less than 27.208 (p < 0.05). After the adjustment for possible confounders, those patients whose UCR was more than 27.208 still had a significantly higher level of in-hospital mortality than the patients whose UCR was less than 27.208, as revealed by the multivariable logistic regression analysis (OR = 3.783, 95% CI: 1.959~7.305, p < 0.001). Similarly, the in-hospital mortality remained substantially higher for those patients in the higher UCR group than for the patients in the lower UCR group after PSM. (4) Conclusion: A higher level of the UCR was evidently associated with an increased risk of in-hospital mortality, which made the ratio useful as a prognostic predictor of clinical outcomes for those patients with non-traumatic subarachnoid hemorrhage.

The effect of COVID-19 vaccination on epileptic seizures in patients with epilepsy: A clinical observation in China.

This observational retrospective study was conducted on patients with epilepsy (PWE) in China who had at least one dose of COVID-19 vaccine and it investigated the safety of vaccination by analyzing changes in epileptic seizures and their influencing factors. Consecutive PWE who were followed up in the epilepsy clinic between June 2021 and May 2022 were enrolled. Data on vaccine type, demographic information, clinical characteristics of epilepsy, and treatment were collected through a questionnaire survey and retrospectively analyzed. PWE were divided into a stable seizure group and a worsening seizure group based on seizure episodes at least 90 days after the first vaccine dose. A total of 79 PWE were included. After vaccination, 14 patients (17.7%) had worsening seizures, 92.9% of whom had an increased seizure frequency. Compared with patients in the stable seizure group, patients in the worsening seizure group had significant differences in baseline monthly seizure frequency (P = .012), improper antiseizure medication (ASM) administration (P = .003) and a disrupted sleep routine (P = .016). Multivariate logistic regression analysis showed that improper ASM administration (OR 6.186, 95% confidence interval [CI] 1.312-29.170; p = .021) and a disrupted sleep routine (OR 6.326, 95% CI 1.326-30.174; p = .021) were significantly associated with seizure worsening. In short, COVID-19 vaccination is safe for PWE, and only those with poor seizure control have the possibility of seizure exacerbation after COVID-19 vaccination. The vaccination per se does not represent a major influencing factor, but the improper use of ASMs and a disrupted sleep routine may be correlated with seizure aggravation after vaccination.