Side Chain Investigation of Imidazopyridazine as a Hinge Binder for Targeting Actionable Mutations of RET Kinase.

Actionable mutations of RET kinase have been identified as oncogenic drivers of solid tumors, including thyroid cancer, metastatic colorectal cancer, and nonsmall cell lung cancer. Although multikinase inhibitors and RET selective inhibitors are used to treat patients with RET alterations, there is insufficient research addressing certain issues: which actionable mutations arise from these therapies, how to improve the clinical response rate to RET inhibitors, and how to design new inhibitors to overcome drug resistance. Therefore, the development of sophisticated tool compounds is required to investigate the molecular mechanisms of actionable mutations and to develop breakthrough therapeutics for different RET alterations. Herein, we present our investigation into the side chains of imidazopyridazine hinge binders that are capable of inducing protein-ligand interaction patterns from the gatekeeper to the waterfront regions. Extending the substituents at the second and sixth positions enhanced the IC50 up to < 0.5 nM for diverse RET alterations.

Saikosaponin A Recovers Impaired Filaggrin Levels in Inflamed Skin by Downregulating the Expression of FRA1 and c-Jun.

Filaggrin (FLG) is an essential structural protein expressed in differentiated keratinocytes. Insufficient FLG expression contributes to the pathogenesis of chronic inflammatory skin diseases. Saikosaponin A (SSA), a bioactive oleanane-type triterpenoid, exerts anti-inflammatory activity. However, the effects of topically applied SSA on FLG expression in inflamed skin remain unclear. This study aimed to evaluate the biological activity of SSA in restoring reduced FLG expression. The effect of SSA on FLG expression in HaCaT cells was assessed through various biological methods, including reverse transcription PCR, quantitative real-time PCR, immunoblotting, and immunofluorescence staining. TNFα and IFNγ decreased FLG mRNA, cytoplasmic FLG protein levels, and FLG gene promoter-reporter activity compared to the control groups. However, the presence of SSA restored these effects. A series of FLG promoter-reporter constructs were generated to investigate the underlying mechanism of the effect of SSA on FLG expression. Mutation of the AP1-binding site (mtAP1) in the -343/+25 FLG promoter-reporter abrogated the decrease in reporter activities caused by TNFα + IFNγ, suggesting the importance of the AP1-binding site in reducing FLG expression. The SSA treatment restored FLG expression by inhibiting the expression and nuclear localization of FRA1 and c-Jun, components of AP1, triggered by TNFα + IFNγ stimulation. The ERK1/2 mitogen-activated protein kinase signaling pathway upregulates FRA1 and c-Jun expression, thereby reducing FLG levels. The SSA treatment inhibited ERK1/2 activation caused by TNFα + IFNγ stimulation and reduced the levels of FRA1 and c-Jun proteins in the nucleus, leading to a decrease in the binding of FRA1, c-Jun, p-STAT1, and HDAC1 to the AP1-binding site in the FLG promoter. The effect of SSA was evaluated in an animal study using a BALB/c mouse model, which induces human atopic-dermatitis-like skin lesions via the topical application of dinitrochlorobenzene. Topically applied SSA significantly reduced skin thickening, immune cell infiltration, and the expression of FRA1, c-Jun, and p-ERK1/2 compared to the vehicle-treated group. These results suggest that SSA can effectively recover impaired FLG levels in inflamed skin by preventing the formation of the repressor complex consisting of FRA1, c-Jun, HDAC1, and STAT1.

Gender-specific alteration of steroid metabolism and its impact on viral replication in a mouse model of hepatitis B virus infection.

Hepatitis B virus (HBV) is a sex-specific pathogen that is more severe in males than in females. Sex disparities in HBV infection have been attributed to hormonal differences between males and females. However, whether HBV infection affects the metabolic signatures of steroid hormones and how these influences viral replication remains unclear. In this study, we investigated whether HBV infection alters steroid metabolism and its effects on HBV replication. Serum samples from male and female mice obtained after the hydrodynamic injection of replication-competent HBV plasmids were subjected to quantitative steroid profiling. Serum steroid levels in mice were analyzed using an in vitro metabolism assay with the mouse liver S9 fraction. The alteration of steroids by HBV infection was observed only in male mice, particularly with significant changes in androgens, whereas no significant hormonal changes were observed in female mice. Among the altered steroids, dehydroepiandrosterone (DHEA) levels increased the most in male mice after HBV infection. An in vitro metabolism assay revealed that androgen levels were significantly reduced in HBV-infected male mice. Furthermore, the genes involved in DHEA biosynthesis were significantly upregulated in HBV-infected male mice. Interestingly, reduced dihydrotestosterone in male mice significantly inhibits viral replication by suppressing HBV promoter activity, suggesting a viral strategy to overcome the antiviral effects of steroid hormones in males. Our data demonstrated that HBV infection can cause sex-specific changes in steroid metabolism.

Erratum to "Bifunctional Tumor-Targeted Bioprobe for Phototheranosis".

[This corrects the article DOI: 10.34133/bmr.0002.].

User Sentiment Analysis Based on Securities Application Elements.

Designing securities applications for mobile devices is challenging due to their inherent complexity, necessitating improvement through the analysis of online reviews. However, research applying deep learning techniques to the sentiment analysis of Korean text remains limited. This study explores the use of Aspect-Based Sentiment Analysis (ABSA) as an effective alternative to traditional user research methods for securities application design. By analyzing large volumes of text-based user review data of Korean securities applications, the study identifies critical elements like "update", "screen", "chart", "login", "access", "authentication", "account", and "transaction", revealing nuanced user sentiments through techniques such as PMI, SVD, and Word2Vec. ABSA offers deeper insights compared to overall ratings, uncovering hidden areas of dissatisfaction despite positive biases in reviews. This research demonstrates the scalability and cost-effectiveness of ABSA in mobile-application design research.

Serum syndecan1 has the potential to reflect activity at diagnosis and predict death during follow-up in patients with ANCA-associated vasculitis.

OBJECTIVES: This study investigated whether serum syndecan1 at diagnosis reflects activity at diagnosis and predicts poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: The study included 79 patients with AAV from the cohort of Korean patients diagnosed with AAV. AAV-specific indices, including the Birmingham vasculitis activity score (BVAS), five-factor score (FFS), 36-item short-form survey (SF-36) physical and mental component summary (PCS and MCS), and vasculitis damage index (VDI), were assessed. Laboratory data including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also collected. The highest tertile and upper half of the BVAS were tentatively defined as having high AAV activity. Serum syndecan1 levels were measured in sera stored at diagnosis. RESULTS: Serum syndecan1 at diagnosis was significantly correlated with AAV activity and functional status, as assessed by BVAS, FFS, SF-36 PCS, MCS, and acute-phase reactants, including ESR and CRP. Patients with serum syndecan1 ≥ 76.1 ng/mL at diagnosis, and those with serum syndecan1 ≥ 60.0 ng/mL at diagnosis showed significantly higher risks for the highest tertile and the upper half of BVAS at diagnosis than those without, respectively. Patients with serum syndecan1 ≥ 120.1 ng/mL at diagnosis had a significantly higher risk for all-cause mortality during follow-up than those without, and further, exhibited a significantly lower cumulative patients' survival rate than those without. CONCLUSION: Serum syndecan1 at diagnosis may not only reflect AAV activity at diagnosis but may also be associated with all-cause mortality during follow-up.

Remnant cholesterol as a residual risk in atherosclerotic cardiovascular disease patients under statin-based lipid-lowering therapy: A post hoc analysis of the RACING trial.

BACKGROUND: Remnant cholesterol (remnant-C) levels during lipid-lowering therapy (LLT) may indicate residual risk. OBJECTIVE: We aimed to investigate the clinical outcomes based on on-treatment remnant-C distribution in patients with atherosclerotic cardiovascular disease (ASCVD) under statin-based LLT. METHODS: In this post hoc analysis of the RACING trial, 3,348 ASCVD patients with lipid profiles 1 year after randomization were investigated. Remnant-C was calculated as total cholesterol minus low-density lipoprotein cholesterol (LDL-C) minus high-density lipoprotein cholesterol. The primary endpoint was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. RESULTS: The study population was grouped into tertiles according to on-treatment remnant-C: high (> 20.5 mg/dL; n = 1,116), intermediate (14‒20.5 mg/dL; n = 1,031), and low (≤14.0 mg/dL; n = 1,201) remnant-C groups. The high remnant-C group showed the highest incidence of the primary endpoint at 3 years (11.0 %, 10.3 %, and 7.5 % in the high, intermediate, and low remnant-C groups, respectively; p = 0.009). The high remnant-C levels at 1 year were independently associated with an increased risk of the primary outcome, whereas achieving LDL-C <55 or 70 mg/dL was not associated with the incidence of the primary endpoint. The on-treatment remnant-C cut-off of 17 mg/dL (median) demonstrated the ability to discriminate between patients at higher and lower risks for the primary endpoints (hazard ratio: 1.42; 95 % confidence interval: 1.14‒1.78; p = 0.002). CONCLUSIONS: In patients with ASCVD undergoing statin-based LLT, high on-treatment remnant-C values were associated with unfavorable clinical outcomes. On-treatment remnant-C levels may serve as an additional means of assessing residual cardiovascular risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials. gov ID: NCT03044665.

Patient-reported outcomes between whole-breast plus regional irradiation and whole-breast irradiation only in pN1 breast cancer after breast conserving surgery and taxane-based chemotherapy: A randomized phase 3 clinical trial (KROG 17-01).

BACKGROUND: The role of regional node irradiation (RNI) with whole-breast irradiation (WBI) in patients with pN1 breast cancer receiving taxane-based adjuvant chemotherapy is not well defined. The KROG 1701 trial, a phase III, multicenter, non-inferiority study, aimed to compare the disease-free survival between WBI+RNI and WBI alone in this patient cohort. Comprehensive patient-reported outcomes (PROs) collected at multiple time points are reported. METHODS: The trial (NCT03269981) enrolled patients with pN1 breast cancer after breast-conserving surgery and taxane-based adjuvant chemotherapy, allocating them to receive either WBI +RNI or WBI only. PROs were assessed using EORTC QLQ-C30 and QLQ-BR23 modules at baseline, during RT, and at subsequent follow-up intervals of 3-6 months, and annually up to 4years. RESULTS: From April 2017 to December 2021, 840 patients were enrolled; 777 received intervention as assigned, and 750 completed baseline PRO questionnaires (387 in WBI+RNI, 363 in WBI only). All PRO domains showed improvements over time (p<0.001). During RT, the WBI+RNI group reported greater fatigue and nausea. Higher arm symptom scores were observed in the WBI+RNI group 3 months post-treatment (p=0.030). No other significant PRO domain differences, including arm/breast symptoms, were observed between the two groups. CONCLUSION: In patients with pN1 breast cancer treated with taxane-based chemotherapy, adding RNI to WBI resulted in minor, temporary declines in specific PRO domains, but these differences were not clinically significant. This indicates that overall patient experience between WBI+RNI and WBI is comparable, supporting the safety and patient tolerability of both treatments.

Failed Thrombus Aspiration and Reduced Myocardial Perfusion in Patients With STEMI and Large Thrombus Burden.

BACKGROUND: Thrombus aspiration (TA) is used to decrease large thrombus burden (LTB), but it can cause distal embolization. OBJECTIVES: The aim of this study was to investigate the impact of TA failure on defective myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) and LTB. METHODS: In total, 812 consecutive patients with STEMI and LTB (thrombus grade ≥3) were enrolled, who underwent manual TA during the primary percutaneous coronary intervention. TA failure was defined as the absence of thrombus retrieval, presence of prestenting thrombus residue, or distal embolization. The final TIMI (Thrombolysis In Myocardial Infarction) flow grades and other myocardial perfusion parameters of the failed TA group were matched with those of the successful TA group. RESULTS: The proportion of final TIMI flow grade 3 was lower (74.6% vs 82.2%; P = 0.011) in the failed TA group (n = 279 [34.4%]) than in the successful TA group (n = 533 [65.6%]). The failed TA group also had lower myocardial blush grade, lower ST-segment resolution, and a higher incidence of microvascular obstruction than the successful TA group. TA failure was independently associated with low final TIMI flow grade (risk ratio: 1.525; 95% CI: 1.048-2.218; P = 0.027). Old age, Killip class ≥III, vessel tortuosity, calcification, and a culprit vessel other than the left anterior descending coronary artery were associated with TA failure. CONCLUSIONS: TA failure is associated with reduced myocardial perfusion in patients with STEMI and LTB. Advanced age, hemodynamic instability, hostile coronary anatomy such as tortuosity or calcification, and non-left anterior descending coronary artery status might attenuate TA performance. (Gangwon PCI Prospective Registry [GWPCI]; NCT02038127).

Aspirin Monotherapy vs No Antiplatelet Therapy in Stable Patients With Coronary Stents Undergoing Low-to-Intermediate Risk Noncardiac Surgery.

BACKGROUND: Current guidelines recommend the perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery. However, supporting evidence is limited. OBJECTIVES: This study aimed to compare continuing aspirin monotherapy vs temporarily holding all antiplatelet therapy before noncardiac surgery in patients with previous DES implantation. METHODS: We randomly assigned patients who had received a DES >1 year previously and were undergoing elective noncardiac surgery either to continue aspirin or to discontinue all antiplatelet agents 5 days before noncardiac surgery. Antiplatelet therapy was recommended to be resumed no later than 48 hours after surgery, unless contraindicated. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, or stroke between 5 days before and 30 days after noncardiac surgery. RESULTS: A total of 1,010 patients underwent randomization. Among 926 patients in the modified intention-to-treat population (462 patients in aspirin monotherapy group and 464 patients in the no-antiplatelet therapy group), the primary composite outcome occurred in 3 patients (0.6%) in the aspirin monotherapy group and 4 patients (0.9%) in the no antiplatelet group (difference, -0.2 percentage points; 95% CI: -1.3 to 0.9; P > 0.99). There was no stent thrombosis in either group. The incidence of major bleeding did not differ significantly between groups (6.5% vs 5.2%; P = 0.39), whereas minor bleeding was significantly more frequent in the aspirin group (14.9% vs 10.1%; P = 0.027). CONCLUSIONS: Among patients undergoing low-to-intermediate risk noncardiac surgery >1 year after stent implantation primarily with a DES, in the setting of lower-than-expected event rates, we failed to identify a significant difference between perioperative aspirin monotherapy and no antiplatelet therapy with respect to ischemic outcomes or major bleeding. (Perioperative Antiplatelet Therapy in Patients With Drug-eluting Stent Undergoing Noncardiac Surgery [ASSURE-DES]; NCT02797548).

Comparative analysis of molecular and histological glioblastomas: insights into prognostic variance.

PURPOSE: Whether molecular glioblastomas (GBMs) identify with a similar dismal prognosis as a "classical" histological GBM is controversial. This study aimed to compare the clinical, molecular, imaging, surgical factors, and prognosis between molecular GBMs and histological GBMs. METHODS: Retrospective chart and imaging review was performed in 983 IDH-wildtype GBM patients (52 molecular GBMs and 931 histological GBMs) from a single institution between 2005 and 2023. Propensity score-matched analysis was additionally performed to adjust for differences in baseline variables between molecular GBMs and histological GBMs. RESULTS: Molecular GBM patients were substantially younger (58.1 vs. 62.4, P = 0.014) with higher rate of TERTp mutation (84.6% vs. 50.3%, P < 0.001) compared with histological GBM patients. Imaging showed higher incidence of gliomatosis cerebri pattern (32.7% vs. 9.2%, P < 0.001) in molecular GBM compared with histological GBM, which resulted in lesser extent of resection (P < 0.001) in these patients. The survival was significantly better in molecular GBM compared to histological GBM (median OS 30.2 vs. 18.4 months, P = 0.001). The superior outcome was confirmed in propensity score analyses by matching histological GBM to molecular GBM (P < 0.001). CONCLUSION: There are distinct clinical, molecular, and imaging differences between molecular GBMs and histological GBMs. Our results suggest that molecular GBMs have a more favorable prognosis than histological GBMs.

Recovery of 240 metagenome-assembled genomes from coastal mariculture environments in South Korea.

The mariculture industry has seen a rapid expansion in recent years due to the increasing global demand for seafood. However, the industry faces challenges from climate change and increased pathogen pressure. Additionally, the chemicals used to enhance mariculture productivity are changing ocean ecosystems. This study analyzed 36 surface-water metagenomes from South Korean mussel, oyster, scallop, and shrimp farms to expand our understanding of aquaculture microbial genetic resources and the potential impacts of these anthropogenic inputs. We recovered 240 non-redundant species-level metagenome-assembled genomes (MAGs), comprising 224 bacteria, 13 archaea, and three eukaryotes. Most MAGs were assigned to Proteobacteria, Bacteroidota, and Actinobacteriota, with 40.7% remaining unclassified at the species level. Among the three eukaryotic MAGs, one was identified as a novel lineage of green algae, highlighting the uncharacterized genetic diversity in mariculture environments. Additionally, 22 prokaryotic MAGs harbored 26 antibiotic and metal resistance genes, with MAGs carrying beta-lactamases being particularly prevalent in most farms. The obtained microbiome data from mariculture environments can be utilized in future studies to foster healthy, sustainable mariculture practices.

The Clinical Utility of Serum Alpha-1-Acid Glycoprotein in Reflecting the Cross-Sectional Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single-Centre Retrospective Study.

Background and Objectives: This study investigated whether serum alpha-1-acid glycoprotein (AGP) at diagnosis could reflect the cross-sectional activity represented by the Birmingham vasculitis activity score (BVAS) and further predict poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 70 patients with AAV. Clinical data at diagnosis, including AAV-specific indices and acute-phase reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were reviewed. All-cause mortality, relapse, end-stage kidney disease (ESKD), cerebrovascular accident, and acute coronary syndrome were evaluated as poor outcomes of AAV. Serum AGP was measured using the sera obtained and stored at diagnosis. Results: The median age of the patients was 63.0 years, with 29 male and 41 female patients. The median serum AGP was 150.9 µg/mL. At diagnosis, serum AGP was significantly correlated with BVAS and ESR but not CRP or serum albumin. Additionally, serum AGP showed significant correlations with the sum scores of ear-nose-throat and pulmonary manifestations; however, no significant differences in serum AGP according to each poor outcome were observed. Although serum AGP at diagnosis tended to be associated with ESKD occurrence during follow-up, serum AGP at AAV diagnosis was not significantly useful in predicting the future occurrence of poor outcomes of AAV during follow-up. Conclusions: In this study, we demonstrated the clinical utility of serum AGP at AAV diagnosis in assessing the cross-sectional activity represented by BVAS in patients with AAV for the first time.

Revisiting gliomatosis cerebri in adult-type diffuse gliomas: a comprehensive imaging, genomic and clinical analysis.

Although gliomatosis cerebri (GC) has been removed as an independent tumor type from the WHO classification, its extensive infiltrative pattern may harbor a unique biological behavior. However, the clinical implication of GC in the context of the 2021 WHO classification is yet to be unveiled. This study investigated the incidence, clinicopathologic and imaging correlations, and prognostic implications of GC in adult-type diffuse glioma patients. Retrospective chart and imaging review of 1,211 adult-type diffuse glioma patients from a single institution between 2005 and 2021 was performed. Among 1,211 adult-type diffuse glioma patients, there were 99 (8.2%) patients with GC. The proportion of molecular types significantly differed between patients with and without GC (P = 0.017); IDH-wildtype glioblastoma was more common (77.8% vs. 66.5%), while IDH-mutant astrocytoma (16.2% vs. 16.9%) and oligodendroglioma (6.1% vs. 16.5%) were less common in patients with GC than in those without GC. The presence of contrast enhancement, necrosis, cystic change, hemorrhage, and GC type 2 were independent risk factors for predicting IDH mutation status in GC patients. GC remained as an independent prognostic factor (HR = 1.25, P = 0.031) in IDH-wildtype glioblastoma patients on multivariable analysis, along with clinical, molecular, and surgical factors. Overall, our data suggests that although no longer included as a distinct pathological entity in the WHO classification, recognition of GC may be crucial considering its clinical significance. There is a relatively high incidence of GC in adult-type diffuse gliomas, with different proportion according to molecular types between patients with and without GC. Imaging may preoperatively predict the molecular type in GC patients and may assist clinical decision-making. The prognostic role of GC promotes its recognition in clinical settings.

Mucin-Rich Brain Metastasis May Show the T2-FLAIR Mismatch Sign: A Case Report and Literature Review.

This study describes a unique case of single mucin-rich brain metastasis in a patient with breast cancer, mimicking the T2-fluid attenuation inversion recovery (FLAIR) mismatch sign and masquerading as an isocitrate dehydrogenase-mutant astrocytoma. This case highlights the importance of considering mucin-rich lesions in the differential diagnosis of intracranial tumors exhibiting T2-FLAIR mismatch. Clinicians must recognize the potential convergence in imaging characteristics between these metastases and gliomas to guarantee prompt and accurate patient care.

Impact of proton pump inhibitor use on clinical outcomes in East Asian patients receiving clopidogrel following drug-eluting stent implantation.

BACKGROUND: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. METHODS: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3-5) and gastrointestinal (GI) bleeding (BARC types 3-5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. RESULTS: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18-8.78). The incidence of major bleeding and GI bleeding (BARC types 3-5) was comparable between PPI users and non-users in the PS-matched cohort. CONCLUSIONS: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

Drug-Coated Balloon Angioplasty in Patients Undergoing Complex Percutaneous Coronary Intervention.

Background: There are limited clinical data on drug-coated balloon (DCB)-based percutaneous coronary intervention (PCI) compared with drug-eluting stent (DES)-only PCI in patients with complex coronary artery lesions. Objectives: The goal of the current study was to investigate the efficacy of DCB in patients undergoing PCI for complex coronary artery lesions. Methods: From an institutional registry of patients with de novo complex coronary artery lesions, 126 patients treated with DCB-based PCI were compared with 234 propensity score-matched patients treated with DES-only PCI. Complex coronary artery lesions were defined as the presence of at least 1 of the following: bifurcation, chronic total occlusion, unprotected left main disease, long lesion ≥38 mm, multivessel disease, lesion requiring ≥3 devices, or severe calcification. The primary endpoint was target vessel failure (TVF) at 2 years, a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization. Results: Baseline characteristics were comparable between the 2 groups. DCB-based PCI showed a comparable risk of TVF vs DES-based PCI (7.6% vs 8.1%; HR: 0.81; 95% CI: 0.33-1.99; P = 0.638). The risks of cardiac death (5.0% vs 5.7%; HR: 0.78; 95% CI: 0.24-2.49), target vessel-related myocardial infarction (0.9% vs 1.3%; HR: 2.65; 95% CI: 0.26-27.06), and target vessel revascularization (3.5% vs 2.0%; HR: 1.30; 95% CI: 0.30-5.67) were also comparable between the 2 groups. Conclusions: DCB-based PCI showed comparable risks of TVF vs those of DES-only PCI in patients with complex coronary artery lesions. DCB might be considered as a suitable alternative device to DES in patients undergoing complex PCI. (Long-term Outcomes and Prognostic Factors in Patient Undergoing CABG or PCI; NCT03870815).

Application of the 2022 ACR/EULAR criteria for Takayasu arteritis to previously diagnosed patients based on the 1990 ACR criteria.

OBJECTIVES: Recently, a joint group of the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) proposed new criteria for Takayasu arteritis (TAK) (the 2022 ACR/EULAR criteria). This study applied the 2022 ACR/EULAR criteria to patients with previously diagnosed TAK based on the 1990 ACR criteria and investigated the concordance rate between the two criteria according to the four imaging modalities. METHODS: This study reviewed the medical records of 179 patients who met the 1990 ACR criteria for TAK. The imaging modalities included conventional angiography, computed tomography angiography, fluorodeoxyglucose-positron emission tomography, and magnetic resonance angiography. RESULTS: Regardless of the imaging modalities, the concordance rate between the two criteria was 85.5% when including all patients, whereas it increased to 98.1% when only patients aged ≤60 years were included. Among the four imaging modalities, computed tomography angiography exhibited the highest concordance rate between the two criteria (85.6%). The concordance rate among patients aged >60 years was 95.7%. Only one patient aged 50-60 years was reclassified as having both TAK and giant cell arteritis. CONCLUSIONS: The concordance rate was 85.5% regardless of the imaging modalities and increased to 86.9% on simultaneous computed tomography angiography and fluorodeoxyglucose-positron emission tomography imaging.

Identification of prognostic imaging biomarkers in H3 K27-altered diffuse midline gliomas in adults: impact of tumor oxygenation imaging biomarkers on survival.

PURPOSE: To investigate prognostic markers for H3 K27-altered diffuse midline gliomas (DMGs) in adults with clinical, qualitative and quantitative imaging phenotypes, including tumor oxygenation characteristics. METHODS: Retrospective chart and imaging reviews were conducted on 32 adults with H3 K27-altered DMGs between 2017 and 2023. Clinical and qualitative imaging characteristics were analyzed. Quantitative imaging assessment was performed from the tumor mask via automatic segmentation to calculate normalized cerebral blood volume (nCBV), capillary transit time heterogeneity (CTH), oxygen extraction fraction (OEF), relative cerebral metabolic rate of oxygen (rCMRO2), and mean ADC values. Leptomeningeal metastases (LM) was diagnosed with imaging. Cox analyses were conducted to determine predictors of overall survival (OS) in entire patients and a subgroup of patients with contrast-enhancing (CE) tumor. RESULTS: The median patient age was 40.5 years (range 19.9-75.7), with an OS of 30.3 months (interquartile range 11.3-32.3). In entire patients, the presence of LM was the only independent predictor of OS (hazard ratio [HR] = 6.01, P = 0.009). In the subgroup of 23 (71.9%) patients with CE tumors, rCMRO2 of CE tumor (HR = 1.08, P = 0.019) and the presence of LM (HR = 5.92, P = 0.043) were independent predictors of OS. CONCLUSION: The presence of LM was independently associated with poor prognosis in adult patients with H3 K27-altered DMG. In patients with CE tumors, higher rCMRO2 of CE tumor, which may reflect higher metabolic activity in the tumor oxygenation microenvironment, may be a useful imaging biomarker to predict poor prognosis.