Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis.Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.

Objective: In this study, changes in treatment methods and patient prognosis were analyzed using a Korean nationwide medical insurance information database. Methods: Patients with subarachnoid hemorrhage who received surgical treatment for cerebral aneurysm from 2005 to 2020 were included. The specific surgery type was classified using the surgical code and according to whether stents were used. Yearly trends in mortality rates and poor prognosis, using tracheostomy as proxy, were analyzed by a simple regression analysis. A multistep logistic regression analysis was performed to evaluate the risk factors of mortality and poor prognosis. Results: Overall, 83,587 patients were included. Females were predominant (64.5%). Microsurgical clip usage rate decreased by approximately two-thirds from 78.8% in 2005 to 24.4% in 2020. Contrarily, endovascular treatment proportion gradually increased, and stent-assisted coil embolization rate surpassed microsurgical clip usage rate in 2020 (24.6% vs. 24.4%). In the multivariate analysis, endovascular treatment correlated positively with 3-month mortality (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 1.07–1.19, P<0.0001), although correlated negatively with poor prognosis (tracheostomy) (HR: 0.93, 95% CI: 0.89–0.98, P=0.0050). Conclusions According to the treatment trend analysis, during the 16 years studied, for patients with subarachnoid hemorrhage due to ruptured cerebral aneurysm, the endovascular treatment rate increased rapidly and stent-assisted coil embolization rate surpassed that of microsurgical clip ligation. Diversification of treatment methods has led to a decrease in mortality and improved prognosis.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background/Aims: The kidneys and retina are highly vascularized organs that frequently exhibit shared pathologies, with nephropathy often associated with retinopathy. Previous studies have successfully predicted estimated glomerular filtration rates (eGFRs) using fundus photographs. We evaluated the performance of the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas in eGFR prediction. Methods: We enrolled patients with fundus photographs and corresponding creatinine measurements taken on the same date. One photograph per eye was randomly selected, resulting in a final dataset of 45,108 patients (88,260 photographs). Data including sex, age, and blood creatinine levels were collected for eGFR calculation using the MDRD and CKD-EPI formulas. EfficientNet B3 models were used to predict each parameter. Results: Deep neural network models accurately predicted age and sex using fundus photographs. Sex was identified as a confounding variable in creatinine prediction. The MDRD formula was more susceptible to this confounding effect than the CKD-EPI formula. Notably, the CKD-EPI formula demonstrated superior performance compared to the MDRD formula (area under the curve 0.864 vs. 0.802). Conclusions Fundus photographs are a valuable tool for screening renal function using deep neural network models, demonstrating the role of noninvasive imaging in medical diagnostics. However, these models are susceptible to the influence of sex, a potential confounding factor. The CKD-EPI formula, less susceptible to sex bias, is recommended to obtain more reliable results.

Background/Aims: Portal vein thrombosis (PVT) frequently occurs in patients with inflammatory bowel disease (IBD), particularly when influenced by factors such as abdominal infections, IBD flare-ups, or surgical procedures. The implications of PVT range from immediate issues such as intestinal ischemia to long-term concerns including portal hypertension and its complications. However, there is a notable gap in comprehensive studies on PVT in IBD, especially with the increasing incidence of IBD in Asia. This research aimed to evaluate the clinical features and outcomes of PVT in patients with IBD at a leading hospital in South Korea. Methods: This retrospective analysis reviewed adult patients diagnosed with both IBD and PVT from 1989 to 2021 at a renowned South Korean medical center. The study focused on patient characteristics, specifics of PVT, administered treatments, and outcomes, all confirmed through enhanced CT scans. Results: A total of 78 patients met the study’s criteria. Notably, only 20.5% (16/78) were treated with oral anticoagulants; however, a vast majority (96.2%; 75/78) achieved complete radiographic resolution (CRR). When comparing patients receiving anticoagulants to those who did not, a significant preference for anticoagulant use was observed in cases where the main portal vein was affected, as opposed to just the left or right veins (p = 0.006). However, multivariable analysis indicated that neither anticoagulant use nor previous surgeries significantly impacted CRR. Conclusions Patients with IBD and PVT generally had favorable outcomes, regardless of anticoagulant use.

Background/Aims: Proprotein-converting enzyme subtilisin-kexin type 9 (PCSK9) inhibitors act more promptly and efficiently than statins and reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS). This study aimed to assess the short-term effects of perioperative administration of a single-dose PCSK9 inhibitor in patients with ACS. Methods: This study included 789 consecutive patients undergoing percutaneous coronary intervention (PCI) for ACS. The primary clinical endpoint was the occurrence of major adverse cardiovascular events (MACEs) within one month, including cardiac death, non-fatal myocardial infarction, unanticipated revascularization, stroke, stent thrombosis, and rehospitalization for ischemic causes or heart failure. Results: PCSK9 inhibitors were administered to 201 of 789 patients. MACEs occurred in eight patients (4.0%) in the treated group and 60 patients (10.2%) in the non-treated group for one month (hazard ratio 0.38, 95% confidence interval 0.18 to 0.80, p = 0.010). The benefit of PCSK9 inhibitors in terms of MACEs was greater in the subgroup of patients treated more than 1 hour before PCI than in the subgroup treated less than 1 hour before PCI or treated after PCI and in the non-treated group. Conclusions In patients undergoing PCI for ACS, the risk of MACEs was lower in those treated with perioperative single-dose PCSK9 inhibitors than in those in the untreated group. This benefit was especially noticeable in the subgroups treated > 1 hour before PCI than in those treated less than 1 hour before PCI or after PCI, regardless of the clinical presentation of ACS.

Objective: To quantitatively analyze and compare the forces and moments generated by thermoformed polyethylene terephthalate glycol (PETG) and direct-printed TC-85 clear aligners (CAs), with various margin designs, during premolar rotation. Methods: In total, 132 CAs were fabricated and divided into four groups (n = 33 per group). Group C consisted of thermoformed PETG aligners with a 2 mm gingival margin. Group E comprised direct-printed TC-85 aligners with equi-gingival margin, whereas Group G utilized direct-printed TC-85 aligners with 2 mm gingival margins.Finally, Group T featured direct-printed TC-85 aligners with an additional 1 mm thickness at the mesial embrasure. The forces and moments were measured using a 6-axis force/moment transducer at 2°, 3°, and 4° of rotation. All measurements were conducted at 37°C to simulate intraoral conditions. Forces were measured in the buccolingual, anteroposterior, and vertical directions, while moments were measured in the mesiodistal, buccolingual, and rotational planes. Results: The PETG aligners (Group C) showed significantly increased buccal and posterior force across the rotation angles (P < 0.05), whereas the intrusive force remained consistent. In contrast, the TC-85 aligners maintained consistent forces across all rotation angles.Direct-printed aligners demonstrated significantly lower intrusive forces than PETG aligners (P < 0.001). Group T exhibited reduced unwanted forces while maintaining effective rotational moments. Furthermore, all direct-printed aligners showed more predictable force delivery patterns than thermoformed aligners. Conclusions Direct-printed TC-85 aligners demonstrated superior force consistency and reduced unwanted side effects compared with traditional PETG aligners. Although marginal design modifications did not significantly improve rotational efficiency, they effectively reduced unwanted intrusive forces.

Purpose: The immunological response and adverse effects of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients receiving coronavirus disease-2019 (COVID-19) vaccines remain unclear. We aimed to evaluate the effects of these vaccines on AAV disease activity. Materials and Methods: We reviewed the medical records of 52 patients with AAV who had received at least second doses of the COVID-19 vaccine and evaluated their immunogenicity by measuring the anti-spike (S) antibody (Ab) titer levels using the Roche Elecsys® immunoassay. Responses to the Birmingham Vasculitis Activity Score (BVAS) tool and 36-Item Short Form Survey before and after vaccination were obtained to assess AAV disease activity. Vaccine reactivity was measured using a standardized questionnaire. Results: We enrolled 52 patients with AAV. No differences were found between those who received second and third doses of vaccination in terms of AAV type, disease activity, vaccine type, or the use of immunosuppressive agents, including steroids. The median anti-S Ab titer was 3967.0 after third doses compared to 419.0 after second doses (p=0.001). Except for mycophenolate mofetil (MMF), when immunosuppressants were administered in conjunction with steroids, the Ab titer was higher after the third vaccination than that after the second dose. The BVAS remained unchanged before and after second and third doses. No life-threatening adverse events were reported. Conclusion Although COVID-19 vaccine may not produce sufficient antibodies in patients taking MMF, the vaccine did not exacerbate disease activity or cause severe side effects. Therefore, COVID-19 vaccines should be considered in patients with AAV.

Background and Objectives: Among various emerging catheter-based treatments for severe tricuspid regurgitation (TR), the spacer device can reduce the regurgitation orifice without manipulating the valve leaflet. However, its clinical application has been hampered by traumatic anchoring to the myocardium and the coaxial alignment of the balloon resulting in insufficient TR reduction. This study aimed to evaluate the early-stage safety, technical feasibility, and preliminary efficacy of the novel atraumatic vertical spacer in patients with isolated severe TR. Methods: All procedures were guided by fluoroscopy and transthoracic echocardiography.The maximum device placement time with an inflated balloon was 24 hours. Changes in the amount of TR, right ventricular function, and patient hemodynamics were measured during balloon deployment. Results: A total of 7 patients (median age 74), underwent successful device implantation without procedure-related complications. During balloon inflation (median 25 minutes), there were no symptoms or signs indicative of TR intolerance. TR was reduced by 1 grade or greater in all patients, with 2 patients exhibiting a reduction of 3 grades, from torrential TR to a moderate degree. Mild TR after balloon inflation was achieved in 3 patients with baseline severe TR. The TR reduction observed during initial balloon deployment was sustained during the subsequent balloon maintenance period. Conclusions The Pivot-balloon procedure was safe, technically feasible, and effective in reducing TR in patients with severe TR. No periprocedural complications or adverse cardiovascular events were reported during device placement with TR reduction observed in all patients. However, longer-term follow-up is needed to confirm safety and treatment effect.

Background and Objectives: The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men. Methods: COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups. Conclusions In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.