The Impact of Sequential Therapies after First-Line Systemic Therapies in Unresectable Hepatocellular Carcinoma.

Background: The therapeutic options for hepatocellular carcinoma (HCC) have greatly expanded recently, and current first-line therapies include sorafenib, lenvatinib, and atezolizumab-bevacizumab. The aim of this study was to investigate the therapeutic efficacy of sequential systemic treatments after progressing to the first-line agent in patients with unresectable HCC. Methods: Data were collected from subjects with HCC, BCLC stage B or C, who received first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab from September 2020 to December 2022. The patients who progressed after first-line therapy were evaluated according to individual clinical status in order to decide whether or not to accept sequential therapy. The clinical baseline characteristics and overall survival (OS) of enrolled patients were collected and further analyzed. Results: Among the 127 enrolled patients, percentage of sequential therapy was 67.9%, 21.6%, and 37.5% in those with tumor progression after first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab, respectively. Acceptance of sequential therapy (HR 0.46, p = 0.041) and presentation of ALBI grade I (HR 0.36, p = 0.002) had a significantly positive impact on OS. Pre-treatment ALBI grade had a significant impact on the decision to accept sequential therapy in patients with progressed HCC. Conclusions: The patients who were able to undergo sequential therapy had a better survival outcome compared to those who received only one agent, and the pre-treatment ALBI level might be regarded as a cornerstone tool to assess survival outcomes in patients undergoing treatment for HCC.

The Different Shades of Thermogenic Adipose Tissue.

PURPOSE OF REVIEW: By providing a concise overview of adipose tissue types, elucidating the regulation of adipose thermogenic capacity in both physiological contexts and chronic wasting diseases (a protracted hypermetabolic state that precipitates sustained catabolism and consequent progressive corporeal atrophy), and most importantly, delving into the ongoing discourse regarding the role of adipose tissue thermogenic activation in chronic wasting diseases, this review aims to provide researchers with a comprehensive understanding of the field. RECENT FINDINGS: Adipose tissue, traditionally classified as white, brown, and beige (brite) based on its thermogenic activity and potential, is intricately regulated by complex mechanisms in response to exercise or cold exposure. This regulation is adipose depot-specific and dependent on the duration of exposure. Excessive thermogenic activation of adipose tissue has been observed in chronic wasting diseases and has been considered a pathological factor that accelerates disease progression. However, this conclusion may be confounded by the detrimental effects of excessive lipolysis. Recent research also suggests that such activation may play a beneficial role in the early stages of chronic wasting disease and provide potential therapeutic effects. A more comprehensive understanding of the changes in adipose tissue thermogenesis under physiological and pathological conditions, as well as the underlying regulatory mechanisms, is essential for the development of novel interventions to improve health and prevent disease.

Cellular and molecular characteristics of stromal Lkb1 deficiency-induced gastrointestinal polyposis based on single-cell RNA sequencing.

Liver kinase B1 (Lkb1), encoded by serine/threonine kinase (Stk11), is a serine/threonine kinase and tumor suppressor that is strongly implicated in Peutz-Jeghers syndrome (PJS). Numerous studies have shown that mesenchymal-specific Lkb1 is sufficient for the development of PJS-like polyps in mice. However, the cellular origin and components of these Lkb1-associated polyps and underlying mechanisms remain elusive. In this study, we generated tamoxifen-inducible Lkb1flox/flox;Myh11-Cre/ERT2 and Lkb1flox/flox;PDGFRα-Cre/ERT2 mice, performed single-cell RNA sequencing (scRNA-seq) and imaging-based lineage tracing, and aimed to investigate the cellular complexity of gastrointestinal polyps associated with PJS. We found that Lkb1flox/+;Myh11-Cre/ERT2 mice developed gastrointestinal polyps starting at 9 months after tamoxifen treatment. scRNA-seq revealed aberrant stem cell-like characteristics of epithelial cells from polyp tissues of Lkb1flox/+;Myh11-Cre/ERT2 mice. The Lkb1-associated polyps were further characterized by a branching smooth muscle core, abundant extracellular matrix deposition, and high immune cell infiltration. In addition, the Spp1-Cd44 or Spp1-Itga8/Itgb1 axes were identified as important interactions among epithelial, mesenchymal, and immune compartments in Lkb1-associated polyps. These characteristics of gastrointestinal polyps were also demonstrated in another mouse model, tamoxifen-inducible Lkb1flox/flox;PDGFRα-Cre/ERT2 mice, which developed obvious gastrointestinal polyps as early as 2-3 months after tamoxifen treatment. Our findings further confirm the critical role of mesenchymal Lkb1/Stk11 in gastrointestinal polyposis and provide novel insight into the cellular complexity of Lkb1-associated polyp biology. © 2024 The Pathological Society of Great Britain and Ireland.

Causal relationship between gut microbiota and glioblastoma: a two-sample Mendelian randomization study.

Background: Observational research and medical trials have suggested a connection between gut microbiota and glioblastoma, but it remains unclear if the relationship is causal. Method: A two-sample Mendelian randomization (MR) study was conducted by employing data from the MiBioGen consortium's largest genome-wide association study (n=18340) and the FinnGen consortium R8 release information (162 cases and 256,583 controls). Inverse variance weighted (IVW), weighted median estimator (WME), weighted model, MR-Egger, simple mode, and MR-PRESSO were used to determine the causal relationship between gut microbiota and glioblastoma. Reverse MR analysis was also performed on bacteria identified as causally related to glioblastoma. Results: Seven causal relationships were identified between genetic liability in the gut microbiota and glioblastoma, involving various bacterial families and genera. No significant causal effect was found on gut microbiota from glioblastoma, and no significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was observed. Conclusion: A two-sample MR analysis reveals a causal association between the gut microbiota and glioblastoma, highlighting the need for more investigation to comprehend the processes behind this association.

A new turn-on fluorescent probe for fast detection of diabetic biomarker beta-hydroxybutyrate in vitro.

Beta-hydroxybutyrate (ß-HB) serve as a valuable diagnostic biomarker for Diabetic Ketoacidosis (DKA). Here, a new Schiff base fluorescent probe T was designed and synthesized to detect ß-HB level in aqueous solution in vitro. The probe T can detect ß-HB sensitively and selectively in DMF solution (5.0 × 10-5 M) among other interfering species (cations, anions, amino acids, biomarkers). The detection limit of probe T for ß-HB was calculated to be 0.154 µM. These results demonstrate that the probe T may provide a convenient method for rapid detection of ß-HB to diagnose diabetic ketoacidosis.

Lipid metabolism-related gene expression in the immune microenvironment predicts prognostic outcomes in renal cell carcinoma.

Background: Rates of renal cell carcinoma (RCC) occurrence and mortality are steadily rising. In an effort to address this issue, the present bioinformatics study was developed with the goal of identifying major lipid metabolism biomarkers and immune infiltration characteristics associated with RCC cases. Methods: The Cancer Genome Atlas (TCGA) and E-MTAB-1980 were used to obtain matched clinical and RNA expression data from patients diagnosed with RCC. A LASSO algorithm and multivariate Cox regression analyses were employed to design a prognostic risk model for these patients. The tumor immune microenvironment (TIME) in RCC patients was further interrogated through ESTIMATE, TIMER, and single-cell gene set enrichment analysis (ssGSEA) analyses. Gene Ontology (GO), KEGG, and GSEA enrichment approaches were further employed to gauge the mechanistic basis for the observed results. Differences in gene expression and associated functional changes were then validated through appropriate molecular biology assays. Results: Through the approach detailed above, a risk model based on 8 genes associated with RCC patient overall survival and lipid metabolism was ultimately identified that was capable of aiding in the diagnosis of this cancer type. Poorer prognostic outcomes in the analyzed RCC patients were associated with higher immune scores, lower levels of tumor purity, greater immune cell infiltration, and higher relative immune status. In GO and KEGG enrichment analyses, genes that were differentially expressed between risk groups were primarily related to the immune response and substance metabolism. GSEA analyses additionally revealed that the most enriched factors in the high-risk group included the stable internal environment, peroxisomes, and fatty acid metabolism. Subsequent experimental validation in vitro and in vivo revealed that the most significantly differentially expressed gene identified herein, ALOX5, was capable of suppressing RCC tumor cell proliferation, invasivity, and migration. Conclusion: In summary, a risk model was successfully established that was significantly related to RCC patient prognosis and TIME composition, offering a robust foundation for the development of novel targeted therapeutic agents and individualized treatment regimens. In both immunoassays and functional analyses, dysregulated lipid metabolism was associated with aberrant immunological activity and the reprogramming of fatty acid metabolic activity, contributing to poorer outcomes.

Myeloid SENP3 deficiency protects mice from diet and age-induced obesity via regulation of YAP1 SUMOylation.

Obesity is characterized by chronic low-grade inflammation, which is driven by macrophage infiltration in adipose tissue and leads to elevated cytokines such as interleukin-1ß (IL-1ß) in the circulation and tissues. Previous studies demonstrate that SENP3, a redox-sensitive SUMO2/3-specific protease, is strongly implicated in the development and progression of cancer and cardiovascular diseases. However, the role of SENP3 in obesity-associated inflammation remains largely unknown. To better understand the effects of SENP3 on adipose tissue macrophage (ATM) activation and function within the context of obesity, we generated mice with myeloid-specific deletion of SENP3 (Senp3flox/flox;Lyz2-Cre mice). We found that the expression of SENP3 is dramatically increased in ATMs during high-fat diet (HFD)-induced obesity in mice. Senp3flox/flox;Lyz2-Cre mice show lower body weight gain and reduced adiposity and adipocyte size after challenged with HFD and during aging. Myeloid-specific SENP3 deletion attenuates macrophage infiltration in adipose tissue and reduces serum levels of inflammatory factors during diet and age-induced obesity. Furthermore, we found that SENP3 knockout markedly inhibits cytokine release from macrophage after lipopolysaccharide and palmitic acid treatment in vitro. Mechanistically, in cultured peritoneal macrophages, SENP3 protein level is enhanced by IL-1ß, in parallel with the upregulation of Yes-associated protein 1 (YAP1). Moreover, we demonstrated that SENP3 modulates de-SUMO modification of YAP1 and SENP3 deletion abolishes the upregulation of YAP1 induced by IL-1ß. Most importantly, SENP3 deficiency reduces YAP1 protein level in adipose tissue during obesity. Our results highlight the important role of SENP3 in ATM inflammation and diet and age-induced obesity.

Hepatitis Flares or Hepatic Decompensation after Discontinuation of Tenofovir Disoproxil Fumarate and Entecavir in Non-Cirrhotic Hepatitis B e Antigen-Negative Patients.

Hepatic events can occur after discontinuing antiviral therapy. We investigated factors associated with hepatitis flares and hepatic decompensation after discontinuing tenofovir disoproxil fumarate (TDF) and entecavir (ETV). Hepatitis flares within 6 months and hepatic decompensation were compared between non-cirrhotic hepatitis B e antigen-negative patients after discontinuing TDF or ETV by using the Cox proportional hazard model. The cumulative rates of hepatitis flare at 6 months after discontinuing ETV and TDF were 2% and 19%, respectively (p < 0.001). The respective rates of hepatic decompensation at 6 months were 0% and 7% (p = 0.009). Higher alanine aminotransferase (ALT) (AASLD criteria) at the end of treatment (EOT) (HR = 4.93; p = 0.001), an off-therapy dynamic change in HBV DNA (rapid rebound of HBV DNA from the nadir, ≥1 log10 IU/mL per month) (HR = 10.7; p < 0.001), and the discontinuation of TDF (HR = 6.44; p = 0.006) were independently associated with hepatitis flares within 6 months. Older age (HR = 1.06; p < 0.001) and an off-therapy dynamic change in HBV DNA (HR = 3.26; p = 0.028) were independently associated with hepatic decompensation after the discontinuation of antiviral therapy. In summary, we demonstrated several factors associated with hepatitis flares and hepatic decompensation after discontinuing antiviral therapy in non-cirrhotic hepatitis B e antigen-negative patients.

Identifying Minimal Hepatic Encephalopathy: A New Perspective from Magnetic Resonance Imaging.

Type C hepatic encephalopathy (HE) is a condition characterized by brain dysfunction caused by liver insufficiency and/or portal-systemic blood shunting, which manifests as a broad spectrum of neurological or psychiatric abnormalities, ranging from minimal HE (MHE), detectable only by neuropsychological or neurophysiological assessment, to coma. Though MHE is the subclinical phase of HE, it is highly prevalent in cirrhotic patients and strongly associated with poor quality of life, high risk of overt HE, and mortality. It is, therefore, critical to identify MHE at the earliest and timely intervene, thereby minimizing the subsequent complications and costs. However, proper and sensitive diagnosis of MHE is hampered by its unnoticeable symptoms and the absence of standard diagnostic criteria. A variety of neuropsychological or neurophysiological tests have been performed to diagnose MHE. However, these tests are nonspecific and susceptible to multiple factors (eg, aging, education), thereby limiting their application in clinical practice. Thus, developing an objective, effective, and noninvasive method is imperative to help detect MHE. Magnetic resonance imaging (MRI), a noninvasive technique which can produce many objective biomarkers by different imaging sequences (eg, Magnetic resonance spectroscopy, DWI, rs-MRI, and arterial spin labeling), has recently shown the ability to screen MHE from NHE (non-HE) patients accurately. As advanced MRI techniques continue to emerge, more minor changes in the brain could be captured, providing new means for early diagnosis and quantitative assessment of MHE. In addition, the advancement of artificial intelligence in medical imaging also presents the potential to mine more effective diagnostic biomarkers and further improves the predictive efficiency of MHE. Taken together, advanced MRI techniques may provide a new perspective for us to identify MHE in the future. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Multilayer network analysis of dynamic network reconfiguration in patients with moderate-to-severe obstructive sleep apnea and its association with neurocognitive function.

BACKGROUND: Brain functional network disruption and neurocognitive dysfunction have been reported in obstructive sleep apnea (OSA) patients. Nevertheless, most research studies static networks, while brain evolution continues dynamically. PURPOSE: To investigate the characteristics of dynamical networks in moderate-to-severe OSA patients using multilayer network analysis of dynamic networks and compare their association with neurocognitive function. METHODS: Twenty-seven moderate-to-severe OSA patients and twenty-five matched healthy controls (HCs) who completed the examination of the Epworth sleepiness scale (ESS), neurocognitive function, polysomnography, and functional magnetic resonance imaging (fMRI) were prospectively included. The dynamic variations of resting-state functional networks in both groups were described via network switching rate. Switching rates and their correlation with clinical parameters were analyzed. RESULTS: At the global level, network switching rates were notably lower in the OSA group than in the HCs group (p = 0.002). More specifically, the differences include the default mode network (DMN), auditory network, and ventral attention network at the subnetwork level, and the right rolandic operculum, left middle temporal gyrus, and right precentral gyrus at the nodal level. Furthermore, these altered switching rates have a close correlation with ESS, sleep parameters, and neurocognitive function. CONCLUSION: Patients with moderate-to-severe OSA showed lower network switching rates, especially in the DMN, auditory network, and ventral attention network. The disruption of dynamic functional networks may be a potentially crucial mechanism of neurocognitive dysfunction in moderate-to-severe OSA patients.

Gray Matter Thickness and Subcortical Nuclear Volume in Men After SARS-CoV-2 Omicron Infection.

Importance: The clinical manifestations and effects on the brain of the SARS-CoV-2 Omicron variant in the acute postinfection phase remain unclear. Objective: To investigate the pathophysiological mechanisms underlying clinical symptoms and changes to gray matter and subcortical nuclei among male patients after Omicron infection and to provide an imaging basis for early detection and intervention. Design, Setting, and Participants: In this cohort study, a total of 207 men underwent health screening magnetic resonance imaging scans between August 28 and September 18, 2022; among them, 98 provided complete imaging and neuropsychiatric data. Sixty-one participants with Omicron infection were reevaluated after infection (January 6 to 14, 2023). Neuropsychiatric data, clinical symptoms, and magnetic resonance imaging data were collected in the acute post-Omicron period, and their clinical symptoms were followed up after 3 months. Gray matter indexes and subcortical nuclear volumes were analyzed. Associations between changes in gray matter and neuropsychiatric data were evaluated with correlation analyses. Exposures: Gray matter thickness and subcortical nuclear volume change data were compared before and after Omicron infection. Main Outcomes and Measures: The gray matter indexes and subcutaneous nuclear volume were generated from the 3-dimensional magnetization-prepared rapid acquisition gradient echo and were calculated with imaging software. Results: Ninety-eight men underwent complete baseline data collection; of these, 61 (mean [SD] age, 43.1 [9.9] years) voluntarily enrolled in post-Omicron follow-up and 17 (mean [SD] age, 43.5 [10.0] years) voluntarily enrolled in 3-month follow-up. Compared with pre-Omicron measures, Beck Anxiety Inventory scores were significantly increased (median, 4.50 [IQR, 1.00-7.00] to 4.00 [IQR, 2.00-9.75]; P = .006) and depressive distress scores were significantly decreased (median, 18.00 [IQR, 16.00-20.22] to 16.00 [IQR, 15.00-19.00]; P = .003) at the acute post-Omicron follow-up. Fever, headache, fatigue, myalgia, cough, and dyspnea were the main symptoms during the post-Omicron follow-up; among the participants in the 3-month follow-up, fever (11 [64.7%] vs 2 [11.8%]; P = .01), myalgia (10 [58.8%] vs 3 (17.6%]; P = .04), and cough (12 [70.6%] vs 4 [23.5%]; P = .02) were significantly improved. The gray matter thickness in the left precuneus (mean [SD], 2.7 [0.3] to 2.6 [0.2] mm; P < .001) and right lateral occipital region (mean [SD], 2.8 [0.2] to 2.7 [0.2] and 2.5 [0.2] to 2.5 [0.2] mm; P < .001 for both) and the ratio of the right hippocampus volume to the total intracranial volume (mean [SD]. 0.003 [0.0003] to 0.003 [0.0002]; P = .04) were significantly reduced in the post-Omicron follow-up. The febrile group had reduced sulcus depth of the right inferior parietal region compared with the nonfebrile group (mean [SD], 3.9 [2.3] to 4.8 [1.1]; P = .048. In the post-Omicron period, the thickness of the left precuneus was negatively correlated with the Beck Anxiety Inventory scores (r = -0.39; P = .002; false discovery rate P = .02), and the ratio of the right hippocampus to the total intracranial volume was positively correlated with the Word Fluency Test scores (r = 0.34; P = .007). Conclusions and Relevance: In this cohort study of male patients infected with the Omicron variant, the duration of symptoms in multiple systems after infection was short. Changes in gray matter thickness and subcortical nuclear volume injury were observed in the post-Omicron period. These findings provide new insights into the emotional and cognitive mechanisms of an Omicron infection, demonstrate its association with alterations to the nervous system, and verify an imaging basis for early detection and intervention of neurological sequelae.

Construction of a novel circRNA-miRNA-ferroptosis related mRNA network in ischemic stroke.

Molecule alterations are important to explore the pathological mechanism of ischemic stroke (IS). Ferroptosis, a newly recognized type of regulated cell death, is related to IS. Identification of the interactions between circular RNA (circRNA), microRNA (miRNA) and ferroptosis related mRNA may be useful to understand the molecular mechanism of IS. The circRNA, miRNA and mRNA transcriptome data in IS, downloaded from the Gene Expression Omnibus (GEO) database, was used for differential expression analysis. Ferroptosis related mRNAs were identified from the FerrDb database, followed by construction of circRNA-miRNA-ferroptosis related mRNA network. Enrichment and protein-protein interaction analysis of mRNAs in circRNA-miRNA-mRNA network was performed, followed by expression validation by reverse transcriptase polymerase chain reaction and online dataset. A total of 694, 41 and 104 differentially expressed circRNAs, miRNAs and mRNAs were respectively identified in IS. Among which, dual specificity phosphatase 1 (DUSP1), nuclear receptor coactivator 4 (NCOA4) and solute carrier family 2 member 3 (SLC2A3) were the only three up-regulated ferroptosis related mRNAs. Moreover, DUSP1, NCOA4 and SLC2A3 were significantly up-regulated in IS after 3, 5 and 24 h of the attack. Based on these three ferroptosis related mRNAs, 4 circRNA-miRNA-ferroptosis related mRNA regulatory relationship pairs were identified in IS, including hsa_circ_0071036/hsa_circ_0039365/hsa_circ_0079347/hsa_circ_0008857-hsa-miR-122-5p-DUSP1, hsa_circ_0067717/hsa_circ_0003956/hsa_circ_0013729-hsa-miR-4446-3p-SLC2A3, hsa_circ_0059347/hsa_circ_0001414/hsa_circ_0049637-hsa-miR-885-3p-SLC2A3, and hsa_circ_0005633/hsa_circ_0004479-hsa-miR-4435-NCOA4. In addition, DUSP1 is involved in the signaling pathway of fluid shear stress and atherosclerosis. Relationship of regulatory action between circRNAs, miRNAs and ferroptosis related mRNAs may be associated with the development of IS.

Computed Tomography-derived intratumoral and peritumoral radiomics in predicting EGFR mutation in lung adenocarcinoma.

OBJECTIVE: To investigate the value of Computed Tomography (CT) radiomics derived from different peritumoral volumes of interest (VOIs) in predicting epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma patients. MATERIALS AND METHODS: A retrospective cohort of 779 patients who had pathologically confirmed lung adenocarcinoma were enrolled. 640 patients were randomly divided into a training set, a validation set, and an internal testing set (3:1:1), and the remaining 139 patients were defined as an external testing set. The intratumoral VOI (VOI_I) was manually delineated on the thin-slice CT images, and seven peritumoral VOIs (VOI_P) were automatically generated with 1, 2, 3, 4, 5, 10, and 15 mm expansion along the VOI_I. 1454 radiomic features were extracted from each VOI. The t-test, the least absolute shrinkage and selection operator (LASSO), and the minimum redundancy maximum relevance (mRMR) algorithm were used for feature selection, followed by the construction of radiomics models (VOI_I model, VOI_P model and combined model). The performance of the models were evaluated by the area under the curve (AUC). RESULTS: 399 patients were classified as EGFR mutant (EGFR+), while 380 were wild-type (EGFR-). In the training and validation sets, internal and external testing sets, VOI4 (intratumoral and peritumoral 4 mm) model achieved the best predictive performance, with AUCs of 0.877, 0.727, and 0.701, respectively, outperforming the VOI_I model (AUCs of 0.728, 0.698, and 0.653, respectively). CONCLUSIONS: Radiomics extracted from peritumoral region can add extra value in predicting EGFR mutation status of lung adenocarcinoma patients, with the optimal peritumoral range of 4 mm.

Isolation, Culture, and Adipogenic Induction of Stromal Vascular Fraction-derived Preadipocytes from Mouse Periaortic Adipose Tissue.

Perivascular adipose tissue (PVAT) is an adipose tissue depot that surrounds blood vessels and exhibits the phenotypes of white, beige, and brown adipocytes. Recent discoveries have shed light on the central role of PVAT in regulating vascular homeostasis and participating in the pathogenesis of cardiovascular diseases. A comprehensive understanding of PVAT properties and regulation is of great importance for the development of future therapies. Primary cultures of periaortic adipocytes are valuable for studying PVAT function and the crosstalk between periaortic adipocytes and vascular cells. This paper presents an economical and feasible protocol for the isolation, culture, and adipogenic induction of stromal vascular fraction-derived preadipocytes from mouse periaortic adipose tissue, which can be useful for modeling adipogenesis or lipogenesis in vitro. The protocol outlines tissue processing and cell differentiation for culturing periaortic adipocytes from young mice. This protocol will provide the technological cornerstone at the bench side for the investigation of PVAT function.

The evaluation and treatment of acute anterior circulation occlusion stroke with high clot burden: Progressive stratified aspiration thrombectomy vs. stent retriever thrombectomy.

OBJECTIVE: To evaluate the safety and effectiveness of the progressive stratified aspiration thrombectomy (PSAT) in treatment of patients with acute ischemic stroke and large vessel occlusion (AIS-LVO). METHODS: 117 AIS-LVO patients with high clot burden who underwent emergency endovascular treatment were included. All patients were divided into two groups according to surgical technique: PSAT group, stent retriever thrombectomy (SRT) group. The primary outcome was the 90-day mRS, the secondary outcomes included recanalization rate, the 24-h and 7-day NIHSS, the 7-day symptomatic intracranial hemorrhage (SICH) rate and 90-days mortality. RESULTS: 65 patients underwent PSAT, and 52 patients underwent SRT. The PSAT group performed better than SRT group regarding the successful recanalization rate (86.3 % vs. 71.2 %, P < 0.05) and time from puncture to recanalization (70 min [IQR, 58-87 min] vs. 87 min [IQR, 68-103 min], P < 0.05). The 7-day NIHSS score of the PSAT group was lower than that of the SRT group (12 [10-18] vs. 12 [8-25], P < 0.05). It was worth noting that at the 90-day follow-up, the favorable functional outcome (mRS 0-2) rate of PSAT group was higher (P < 0.05). There was no significant difference in terms of the 24-h NIHSS score after surgery (15 [10-18] vs. 15 [10-22], P > 0.05), SICH (23.1 % vs. 26.9 %, P > 0.05) and mortality rate between the two groups (13.4 % vs. 19.2 %, P > 0.05). CONCLUSIONS: It is safe and effective to treat high clot burden AIS-LVO patients with PSAT, which has a better reperfusion rate and prognostic outcome than SRT.

Effects of repetitive transcranial magnetic stimulation on motor function and language ability in cerebral palsy: A systematic review and meta-analysis.

Objective: This review was conducted to assess the quality of the evidence of effectiveness of repetitive transcranial magnetic stimulation (rTMS) in treating motor and language ability of cerebral palsy (CP). Method: Medline, Cochrane library, Web of Science, Embase, PubMed, and CNKI databases were searched up to July 2021 by two independent reviewers. Randomized controlled trials (RCTs) that were published in English and Chinese and met the following criteria were included. The population comprised patients who met the diagnostic criteria for CP. Intervention included the following: comparison about rTMS and sham rTMS or comparison about rTMS combine with other physical therapy and other physical therapy. Outcomes included motor function, as follows: gross motor function measure (GMFM), Gesell Development Diagnosis Scale, fine motor function measure (FMFM), Peabody developmental motor scale, and Modified Ashworth scale. For language ability, sign-significant relation (S-S) was included. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. Results: Finally, 29 studies were included in the meta-analysis. Results of evaluation using the Cochrane Collaborative Network Bias Risk Assessment Scale showed that 19 studies specifically explained randomization, among which two studies described allocation concealment, four studies blinded participants and persons and had low risk of bias, and six studies explained that the assessment of outcome measures was blinded. Significant improvements in motor function were observed. The GMFM of total score was determined by using the random-effect model [I2 = 88%; MD = -1.03; 95% CI (-1.35, -0.71); P < 0.0001] and FMFM was determined by using the fixed-effect model [P = 0.40 and I2 = 3%; SMDs = -0.48, 95% CI (-0.65, -0.30); P < 0.01]. For language ability, the language improvement rate was determined using a fixed-effect model [P = 0.88 and I2 = 0%; MD = 0.37, 95% CI (0.23, 0.57); P < 0.01]. According to the PEDro scale, 10 studies had low-quality, four studies had excellent quality, and the other studies had good quality. Using the GRADEpro GDT online tool, we included a total of 31 outcome indicators, as follows: 22 for low quality, seven for moderate quality, and two for very low quality. Conclusion: The rTMS could improve the motor function and language ability of patients with CP. However, rTMS prescriptions varied, and the studies had low sample sizes. Studies using rigorous and standard research designs about prescriptions and large samples are needed to collect sufficient evidence about the effectiveness of using rTMS to treat patients with CP.

Treatment of coronary pseudoaneurysm detected after percutaneous coronary intervention for chronic total occlusion: A case report.

BACKGROUND: Coronary pseudoaneurysm (CPA) are associated with iatrogenic coronary artery dissection or perforation, which rarely reported formation early after percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). This study reported a case of CPA that developed 4 weeks after PCI for CTO. CASE REPORT: A 40-year-old man was admitted with unstable angina and diagnosed with CTO of the left anterior descending artery (LAD) and right coronary artery. The CTO of the LAD was successfully treated by PCI. However, reexamination by coronary arteriography and optical coherence tomography after 4 weeks confirmed a CPA at the stented middle segment of the LAD. The CPA was treated surgically by the implantation of a Polytetrafluoroethylene-coated stent. reexamination at the 5-month follow-up revealed a patent stent in the LAD and no CPA-like manifestations. Intravascular ultrasound showed no intimal hyperplasia or in-stent thrombogenesis. CONCLUSION: CPA might develop within weeks after PCI for CTO. While it could be successfully treated by the implantation of a Polytetrafluoroethylene-coated stent.

Dynamic white matter changes in recovered COVID-19 patients: a two-year follow-up study.

Background and purpose: Long COVID with regard to the neurological system deserves more attention, as a surge of treated patients are being discharged from the hospital. As the dynamic changes in white matter after two years remain unknown, this characteristic was the focus of this study. Methods: We investigated 17 recovered COVID-19 patients at two years after discharge. Diffusion tensor imaging, neurite orientation dispersion and density imaging were performed to identify white matter integrity and changes from one to two years after discharge. Data for 13 revisited healthy controls were collected as a reference. Subscales of the Wechsler Intelligence scale were used to assess cognitive function. Repeated-measures ANOVA was used to detect longitudinal changes in 17 recovered COVID-19 patients and 13 healthy controls after one-year follow-up. Correlations between diffusion metrics, cognitive function, and other clinical characteristics (i.e., inflammatory factors) were also analyzed. Results: Longitudinal analysis showed the recovery trends of large-scale brain regions, with small-scale brain region deterioration from one year to two years after SARS-CoV-2 infection. However, persistent white matter abnormalities were noted at two years after discharge. Longitudinal changes of cognitive function showed no group difference. But cross-sectional cognitive difference between recovered COVID-19 patients and revisited HCs was detected. Inflammation levels in the acute stage correlated positively with white matter abnormalities and negatively with cognitive function. Moreover, the more abnormal the white matter was at two years, the greater was the cognitive deficit present. Conclusion: Recovered COVID-19 patients showed longitudinal recovery trends of white matter. But also had persistent white matter abnormalities at two years after discharge. Inflammation levels in the acute stage may be considered predictors of cognition and white matter integrity, and the white matter microstructure acts as a biomarker of cognitive function in recovered COVID-19 patients. These findings provide an objective basis for early clinical intervention.

Sofosbuvir/velpatasvir/voxilaprevir for patients with chronic hepatitis C virus infection previously treated with NS5A direct-acting antivirals: a real-world multicenter cohort in Taiwan.

BACKGROUND: Real-world data are scarce about the effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for retreating East Asian patients with hepatitis C virus (HCV) infection who previously received NS5A direct-acting antivirals (DAAs). We conducted a multicenter study to assess the performance of SOF/VEL/VOX in patients who were not responsive to prior NS5A inhibitors in Taiwan. METHODS: Between September 2021 and May 2022, 107 patients who failed NS5A inhibitor-containing DAAs with SOF/VEL/VOX salvage therapy for 12 weeks were included at 16 academic centers. The sustained virologic response at off-treatment week 12 (SVR12) was assessed in the evaluable (EP) and per-protocol (PP) populations. The safety profiles were also reported. RESULTS: All patients completed 12 weeks of treatment and achieved an end-of-treatment virologic response. The SVR12 rates were 97.2% (95% confidence interval (CI) 92.1-99.0%) and 100% (95% CI 96.4-100%) in EP and PP populations. Three (2.8%) patients were lost to off-treatment follow-up and did not meet SVR12 in the EP population. No baseline factors predicted SVR12. Two (1.9%) not-fatal serious adverse events (AE) occurred but were unrelated to SOF/VEL/VOX. Sixteen (15.0%) had grade 2 total bilirubin elevation, and three (2.8%) had grade 2 alanine transaminase (ALT) elevation. Thirteen (81.3%) of the 16 patients with grade 2 total bilirubin elevation had unconjugated hyperbilirubinemia. The estimated glomerular filtration rates (eGFR) were comparable between baseline and SVR12, regardless of baseline renal reserve. CONCLUSIONS: SOF/VEL/VOX is highly efficacious and well-tolerated for East Asian HCV patients previously treated with NS5A inhibitor-containing DAAs. CLINICAL TRIALS REGISTRATION: The study was not a drug trial. There was no need for clinical trial registration.