A Review of Pathophysiology and Therapeutic Strategies Targeting TGF-ß in Graves' Ophthalmopathy.

TGF-ß plays a pivotal role in the pathogenesis of GO by promoting orbital tissue remodeling and fibrosis. This process involves the stimulation of orbital fibroblasts, leading to myofibroblast differentiation, increased production of inflammatory mediators, and hyaluronan accumulation. Studies have elucidated TGF-ß's role in driving fibrosis and scarring processes through both canonical and non-canonical pathways, particularly resulting in the activation of orbital myofibroblasts and the excessive accumulation of extracellular matrix. Additionally, recent in vitro and in vivo studies have been summarized, highlighting the therapeutic potential of targeting TGF-ß signaling pathways, which may offer promising treatment interventions for GO. This review aims to consolidate the current understanding of the multifaceted role of TGF-ß in the molecular and cellular pathophysiology in Graves' ophthalmopathy (GO) by exploring its contributions to fibrosis, inflammation, and immune dysregulation. Additionally, the review investigates the therapeutic potential of inhibiting TGF-ß signaling pathways as a strategy for treating GO.

The Dilemma for Early-Stage Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma: To Treat or Not to Treat?

BACKGROUND: Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (MALToma) is typically treated with radiotherapy. Some studies suggested a "wait and watch" approach due to the adverse effects of radiotherapy. However, the benefits of observation for localized conjunctival MALToma remain unclear. Therefore, we aimed to explore the clinical course of early-stage conjunctival MALToma, distinguish heterogeneity between T1 and T2 patients, and identify prognostic factors. METHODS: This retrospective study involved patients with stage T1-T2 conjunctival MALToma and lasted >6 months. Clinical characteristics were compared between T1 and T2 subjects. Prognostic factors were examined with Cox regression. RESULTS: The research comprised 32 subjects with early-stage conjunctival MALToma, of whom 25% underwent observation. No individuals expired regardless of choosing observation or radiotherapy. The T1 patients were younger (p = 0.002) and more inclined towards observation only (p = 0.035) than the T2 subjects. Despite more of the T1 patients undergoing watchful waiting than the T2 subjects, the T1 patients seemed to have longer systemic relapse-free survival than the T2 subjects (17 vs. 13 years, p = 0.343). CD43 may imply poor prognosis (p = 0.049). CONCLUSIONS: Careful observation may be suggested for early-stage conjunctival MALToma. While more of the T1 individuals were younger and chose observation than the T2 patients, survival seemed longer in the T1 subjects without significance. CD43 may indicate shorter survival in early-stage cases.

Evolution and emerging trends of named entity recognition: Bibliometric analysis from 2000 to 2023.

Identifying valuable information within the extensive texts documented in natural language presents a significant challenge in various disciplines. Named Entity Recognition (NER), as one of the critical technologies in text data processing and mining, has become a current research hotspot. To accurately and objectively review the progress in NER, this paper employs bibliometric methods. It analyzes 1300 documents related to NER obtained from the Web of Science database using CiteSpace software. Firstly, statistical analysis is performed on the literature and journals that were obtained to explore the distribution characteristics of the literature. Secondly, the core authors in the field of NER, the development of the technology in different countries, and the leading institutions are explored by analyzing the number of publications and the cooperation network graph. Finally, explore the research frontiers, development tracks, research hotspots, and other information in this field from a scientific point of view, and further discuss the five research frontiers and seven research hotspots in depth. This paper explores the progress of NER research from both macro and micro perspectives. It aims to assist researchers in quickly grasping relevant information and offers constructive ideas and suggestions to promote the development of NER.

Prognostic value of left ventricular and left atrial strain imaging in moderate to severe aortic stenosis: Insights from an Asian population.

BACKGROUND: Data regarding the prognostic value of left atrial (LA) strain in aortic stenosis (AS) is scarce, especially in Asian population and moderate AS. METHOD: Left ventricular global longitudinal strain (LVGLS), LA reservoir strain (LASr), conduit strain (LAScd), and contractile strain (LASct) were measured using automated speckle-tracking echocardiography in consecutive patients with moderate or severe AS. The primary endpoint was a composite of all-cause death (ACD) and major adverse cardiovascular events (MACE; myocardial infarction, syncope, and heart failure hospitalization). RESULTS: Of 712 patients (mean age, 78 ± 12 years; 370 [52%] moderate AS; 342 [48%] severe AS), average LV ejection fraction (LVEF) was 68 with SD of 12%. At a median follow-up of 18 months (interquartile range, 11-26 months), the primary endpoint occurred in 93 patients (60 deaths and 35 MACEs) and 221 patients underwent surgical or transcatheter aortic valve replacement (AVR). In the entire cohort, separate multivariable models adjusted for age, Charlson index, symptomatic status, time-dependent AVR, AS-severity, LA volume index and LVEF demonstrated that only LASr was associated with MACE+ACD (Hazard ratio, 0.97; P = 0.014). Subgroup analysis for MACE+ACD demonstrated consistent prognostication for LASr in moderate and severe AS; LVGLS was prognostic only in severe AS (all P ≤ 0.023). The optimal MACE+ACD cutoff for LASr from spline curves was 21.3%. Adjusted Kaplan-Meier curves demonstrated better event-free survival in patients with LASr >21.3% versus those with LASr ≤21.3% (P = 0.04). CONCLUSIONS: In both moderate and severe AS, only LASr robustly predicted outcomes; thus, including LASr in the AS staging algorithm should be considered.

The Role of Fibrogenesis and Extracellular Matrix Proteins in the Pathogenesis of Graves' Ophthalmopathy.

Graves' ophthalmopathy (GO), or thyroid eye disease (TED), is the most frequent extrathyroidal manifestation of Graves' disease (GD). Inflammation and subsequent aberrant tissue remodeling with fibrosis are important pathogenesis. There are many proposed mechanisms and molecular pathways contributing to tissue remodeling and fibrosis in GO, including adipogenesis, fibroblast proliferation and myofibroblasts differentiation, oxidative stress, endoplasmic reticulum (ER) stress, hyaluronan (HA) and glycosaminoglycans (GAGs) accumulation in the extracellular matrix (ECM) and new concepts of epigenetics modification, such as histone modification, DNA methylation, non-coding RNAs, and gut microbiome. This review summarizes the current understanding of ECM proteins and associated tissue remodeling in the pathogenesis and potential mediators for the treatment of GO.

Feasibility of in vitro calcification plaque disruption using ultrasound-induced microbubble inertial cavitation.

Percutaneous transluminal coronary angioplasty (PTCA) is a clinical method in which plaque-narrowed arteries are widened by inflating an intravascular balloon catheter. However, PTCA remains challenging to apply in calcified plaques since the high pressure required for achieving a therapeutic outcome can result in balloon rupture, vessel rupture, and intimal dissection. To address the problem with PTCA, we hypothesized that a calcified plaque can be disrupted by microbubbles (MBs) inertial cavitation induced by ultrasound (US). This study proposed a columnar US transducer with a novel design to generate inertial cavitation at the lesion site. Experiments were carried out using tubular calcification phantom to mimic calcified plaques. After different parameters of US + MBs treatment (four types of MBs concentration, five types of cycle number, and three types of insonication duration; n = 4 in each group), inflation experiments were performed to examine the efficacy of cavitation for a clinically used balloon catheter. Finally, micro-CT was used to investigate changes in the internal structure of the tubular plaster phantoms. The inflation threshold of the untreated tubular plaster phantoms was > 11 atm, and this was significantly reduced to 7.4 ± 0.7 atm (p = 5.2E-08) using US-induced MBs inertial cavitation at a treatment duration of 20 min with an acoustic pressure of 214 kPa, an MBs concentration of 4.0 × 108 MBs/mL, a cycle number of 100 cycles, and a pulse repetition frequency of 100 Hz. Moreover, micro-CT revealed internal damage in the tubular calcification phantom, demonstrating that US-induced MBs inertial cavitation can effectively disrupt calcified plaques and reduce the inflation threshold of PTCA. The ex vivo histopathology results showed that the endothelium of pig blood vessels remained intact after the treatment. In summary, the results show that US-induced MBs inertial cavitation can markedly reduce the inflation threshold in PTCA without damaging blood vessel endothelia, indicating the potential of the proposed treatment method.

Self-Retained, Sutureless Amniotic Membrane Transplantation for the Management of Ocular Surface Diseases.

Amniotic membrane (AM) has anti-inflammation, anti-fibrotic, and regenerative effects. Sutureless cryopreserved AM transplantation, ProKera® (Bio-Tissue, Inc., Miami, FL, USA), is easily applied by ophthalmologists in the treatment of ocular surface diseases. This retrospective study included patients with ocular surface diseases who received ProKera® between January 2022 and May 2023. Six patients (9 eyes) with a mean age of 56.8 ± 20.8 years old (range 25-74) and a mean follow-up period of 7.8 ± 4.1 months (range 1-12) were included, including 2 of recurrent conjunctival tumors with limbal and corneal involvement (cases 1-2), 1 of pterygium with marked astigmatism (case 3) and 3 of Stevens-Johnson syndrome (SJS, cases 4-6). ProKera® was inserted after the lesion excision and deep keratectomy in cases 1-3, and no recurrence or corneal complication was noted. Cases 4-5 were discharged from the intensive care unit and presented with severe chronic SJS. Most ocular manifestations improved significantly after symblepharon release and ProKera® insertion, except for corneal conjunctivalization in 1 eye (case 5). Case 6 involved early ProKera® use at the bedside during acute SJS, resulting in complete resolution. We concluded that the adjunctive application of ProKera® can be effective for ocular surface reconstruction and provides options to intervene earlier for outpatients or patients unstable for invasive surgical intervention.

Correction: Effect of Telehealth Services on Mitral and Tricuspid Regurgitation Progression: Retrospective Study.

[This corrects the article DOI: 10.2196/47947.].

Stereotactic radiosurgery for orbital cavernous hemangiomas.

OBJECTIVE: The goal of this study was to assess the safety and efficacy of single-session Gamma Knife radiosurgery (GKRS) for orbital cavernous hemangiomas (OCHs). METHODS: Patients who presented with an OCH between September 1999 and May 2022 and were treated with single-session GKRS were included in this single-center cohort study. RESULTS: There were 23 patients (7 males and 16 females) in this study. The median margin dose was 12 Gy (range 11-13 Gy). The median clinical and radiological follow-ups were 45 months (range 5-190 months) and 45 months (range 6-190 months), respectively. Nine (69.2%) of 13 patients with visual acuity impairment had improvement in best corrected visual acuity. Of the 8 patients with visual field defects, 5 patients (62.5%) had complete resolution. Tumor regression was observed in 22 patients (95.7%). The mean relative reduction in tumor volume was 82.6% ± 23.7%. The relative reductions in tumor volume were 33%, 49%, 72%, 84%, and 89% at 6, 12, 24, 36, and 48 months, respectively. Adverse effects of radiation were not observed. CONCLUSIONS: GKRS appears to be safe and efficacious for treating OCHs over long-term follow-up. The treatment is associated with a high rate of regression in OCHs and remarkable improvement in both visual acuity and visual field deficits.

Effect of Telehealth Services on Mitral and Tricuspid Regurgitation Progression: Retrospective Study.

BACKGROUND: Mitral regurgitation (MR) and tricuspid regurgitation (TR) are common cardiac conditions with high mortality risks, which can be improved through early intervention. Telehealth services, which allow for remote monitoring of patient conditions, have been proven to improve the health management of chronic diseases, but the effects on MR and TR progression are unknown. OBJECTIVE: This study aimed to explore whether patients receiving telehealth services have less MR and TR progression compared with a control group. We also aimed to identify the determinants of MR and TR progression. METHODS: This single-center retrospective study conducted at the National Taiwan University Hospital compared MR and TR progression (defined as either progression to moderate or greater MR and TR or MR and TR progression by ≥2 grades during the study period) between the telehealth and control groups. Patients had a minimum of 2 transthoracic echocardiograms at least 6 months apart; baseline mild-moderate MR and TR or lower; and no prior surgeries on the mitral or tricuspid valve. Telehealth patients were defined as those who received telehealth services for at least 28 days within 3 months of baseline. Basic demographics, baseline blood pressure measurements, prescribed medication, and Charlson Comorbidity Index components were obtained for all patients. RESULTS: A total of 1081 patients (n=226 in the telehealth group and n=855 in the control group) were included in the study analyses. The telehealth group showed significantly lower baseline systolic blood pressure (P<.001), higher Charlson Comorbidity Index (P=.02), higher prevalence of prior myocardial infarction (P=.01) and heart failure (P<.001), higher beta-blocker (P=.03) and diuretic (P=.04) use, and lower nitrate use (P=.04). Both groups showed similar cardiac remodeling conditions at baseline. Telehealth was found to be neutral for both MR (hazard ratio 1.10, 95% CI 0.80-1.52; P=.52) and TR (hazard ratio 1.27, 95% CI 0.92-1.74; P=.14) progression. Determinants for moderate or greater MR progression included older age, female sex, diuretic use, larger left atrial dimension, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, and lower left ventricular ejection fraction. Determinants of moderate or greater TR progression included older age, female sex, diuretic use, presence of atrial fibrillation, LA dimension, left ventricular end-systolic dimension, and lower left ventricular ejection fraction; statin use was found to be protective. CONCLUSIONS: This is the first study to assess the association between telehealth services and the progression of MR and TR. Telehealth patients, who had more comorbidities, displayed similar MR and TR progression versus control patients, indicating that telehealth may slow MR and TR progression. Determinants of MR and TR progression included easy-to-measure traditional echo parameters of cardiac function, older age, female sex, and atrial fibrillation, which can be incorporated into a telehealth platform and advanced alert system, improving patient outcomes through personalized care.

The Challenges and Therapeutic Prospects in Eye Disease.

A number of key insights into eye disease have been revealed in the past decade, which has resulted in the development of novel, effective, targeted therapies such as teprotumumab for the treatment of thyroid eye disease (also known as Graves' orbitopathy) [...].

Role of antidiabetic agents in type 2 diabetes patients with chronic kidney disease.

Insulin resistance is a condition in which the target tissues have a decreased response to insulin signaling, resulting in glucose uptake defect, and an increased blood sugar level. Pancreatic beta cells thus enhance insulin production to compensate. This situation may cause further beta cell dysfunction and failure, which can lead diabetes mellitus (DM). Insulin resistance is thus an important cause of the development of type 2 DM. Insulin resistance has also been found to have a strong relationship with cardiovascular disease and is common in chronic kidney disease (CKD) patients. The mechanisms of insulin resistance in CKD are complex and multifactorial. They include physical inactivity, inflammation and oxidative stress, metabolic acidosis, vitamin D deficiency, adipose tissue dysfunction, uremic toxins, and renin-angiotensin-aldosterone system activation. Currently, available anti-diabetic agents, such as biguanides, sulfonylureas, thiazolidinediones, alfa-glucosidase inhibitors, glucagon-like peptide-1-based agents, and sodium-glucose co-transporter-2 inhibitors, have different effects on insulin resistance. In this short review, we describe the potential mechanisms of insulin resistance in CKD patients. We also review the interaction of currently available anti-diabetic medications with insulin resistance.

Analysis of Left Ventricular Indexes and Mortality Among Asian Adults With Hemodynamically Significant Chronic Aortic Regurgitation.

Importance: Chronic hemodynamically significant aortic regurgitation (AR) is associated with excess risk of death, yet data for Asian patients are lacking, and whether Asian patients can abide by Western guidelines as to when aortic valve surgery should be performed is unknown. Objective: To assess AR presentation and cutoffs of left ventricular ejection fraction (LVEF), LV end-systolic dimension index (LVESDi), and LV end-systolic volume index (LVESVi) that are associated with risk of death in Asian patients with AR. Design, Setting, and Participants: This retrospective cohort study included consecutive patients with chronic, moderately severe to severe AR from 3 tertiary referral centers (2 in Japan and 1 in Taiwan) from June 11, 2008, through November 19, 2020, with follow-up through November 11, 2021. Exposures: Aortic regurgitation severity, graded by a comprehensive integrated approach. Main Outcomes and Measures: The primary outcome was the association between volume-derived LVEF, LVESDi, and LVESVi and all-cause death (ACD). The secondary outcome was the association of these LV indexes with cardiovascular death (CVD). Clinical and echocardiographic data were analyzed retrospectively. A de novo disk-summation method was used to derive LV volumes and volume-derived LVEF. Results: Of 1259 patients (mean [SD] age, 64 [17] years; 934 [74%] male), 515 (41%) were Japanese and 744 (59%) were Taiwanese. The median follow-up was 4.1 years (IQR, 1.56-7.24 years). The mean (SD) body surface area was 1.67 (0.21) m2; LVEF, 55% (11%); LVESDi, 24.7 (5.7) mm/m2; LVESVi, 50.1 (28.0) mL/m2; and indexed mid-ascending aorta size, 24.7 (5.5) mm/m2. Aortic valve surgery occurred in 483 patients (38%); 240 patients (19%) died during follow-up. Overall mean (SD) 8-year survival was 74% (2%). Separate multivariate models adjusted for covariates demonstrated independent associations of LVEF, LVESDi, and LVESVi with ACD (LVEF: hazard ratio [HR] per 10%, 0.80; 95% CI, 0.70-0.92; P = .002; LVESDi: HR, 1.04; 95% CI, 1.01-1.06; P = .002; LVESVi: HR per 10 mL/m2, 1.11; 95% CI, 1.05-1.17; P < .001) and CVD (LVEF: HR per 10%, 0.69; 95% CI, 0.56-0.85; P < .001; LVESDi: HR, 1.05; 95% CI, 1.01-1.09; P = .01; LVESVi per 10 mL/m2: HR, 1.15; 95% CI, 1.06-1.24; P < .001). In the total cohort, spline curves showed that mortality started to increase for an LVEF of 53% or less, LVESDi of 22 mm/m2 or greater, and LVESVi of 46 mL/m2 or greater for both ACD and CVD. Early surgery was beneficial in 3 strata of LVESDi (<20, 20 to <25, and ≥25 mm/m2) and 2 strata of LVESVi (<46 and ≥46 mL/m2). Conclusions and Relevance: This multicenter cohort study of Asian patients with hemodynamically significant AR found cutoff values of LVEF, LVESDi, and LVESVi that were associated with increased risk of death. These findings suggest that Western guidelines seem applicable in Asian patients and, most importantly, that indexed LV parameters with a lower cutoff could be used in discriminating patients with excess mortality risk.

Trajectory of Humoral Responses to Two Doses of ChAdOx1 nCoV-19 Vaccination in Patients Receiving Maintenance Hemodialysis.

The ChAdOx1 nCoV-19 (AZD1222) vaccine is one of the most commonly delivered SARS-CoV-2 vaccines worldwide; however, few clinical studies have investigated its immunogenicity in dialysis patients. We prospectively enrolled 123 patients on maintenance hemodialysis at a medical center in Taiwan. All patients were infection-naive, had received two doses of the AZD1222 vaccine, and were monitored for 7 months. The primary outcomes were anti-SARS-CoV-2 receptor-binding domain (RBD) antibody concentrations before and after each dose and 5 months after the second dose and neutralization capacity against ancestral SARS-CoV-2, delta, and omicron variants. The anti-SARS-CoV-2 RBD antibody titers significantly increased with time following vaccination, with a peak at 1 month after the second dose (median titer, 498.8 U/mL; interquartile range, 162.5 to 1,050 U/mL), and a 4.7-fold decrease at 5 months. At 1 month after the second dose, 84.6, 83.7, and 1.6% of the participants had neutralizing antibodies against the ancestral virus, delta variant, and omicron variant, respectively, measured by a commercial surrogate neutralization assay. The geometric mean 50% pseudovirus neutralization titers for the ancestral virus, delta variant, and omicron variant were 639.1, 264.2, and 24.7, respectively. The anti-RBD antibody titers correlated well with neutralization capacity against the ancestral virus and delta variant. Transferrin saturation and C-reactive protein were associated with neutralization against the ancestral virus and delta variant. Although two doses of the AZD1222 vaccine initially elicited high anti-RBD antibody titers and neutralization against the ancestral virus and delta variant in hemodialysis patients, neutralizing antibodies against omicron variant were rarely detected, and the anti-RBD and neutralization antibodies waned over time. Additional/booster vaccinations are warranted in this population. IMPORTANCE Patients with kidney failure have worse immune response following vaccination compared to general population, but few clinical studies have investigated immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccination in hemodialysis patients. Here, we showed two doses of AZD1222 vaccines lead to high seroconversion rate of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies, and more than 80% patients acquired neutralizing antibodies against ancestral virus and delta variant. However, seldom did they obtain neutralizing antibodies against the omicron variant. The geometric mean 50% pseudovirus neutralization titer against the ancestral virus was 25.9-fold higher than that against the omicron variant. Also, there was a substantial decay in anti-RBD titers with time. Our findings provided evidence supporting that more protective measures, including additional/booster vaccinations, is warranted in these patients during the current COVID-19 pandemic.

Effect of dialysis modalities on risk of hospitalization for gastrointestinal bleeding.

Dialysis patients are at risk of both thromboembolic and bleeding events, while thromboembolism prevention and treatment may confer a risk of major bleeding. Gastrointestinal (GI) bleeding is a great concern which can result in high subsequent mortality rates. Our object was to clarify whether hemodialysis (HD) and peritoneal dialysis (PD) confer different incidence of GI bleeding, and further assist individualized decision-making on dialysis modalities. We conducted a population-based retrospective cohort study which included all incident dialysis patients above 18 years old derived from the National Health Insurance database from 1998 to 2013 in Taiwan. 6296 matched pairs of HD and PD patients were identified. A propensity score matching method was used to minimize the selection bias. The adjusted hazard ratio for GI bleeding was 1.13 times higher in the HD group than in the PD group, and data from the unmatched cohort and the stratified analysis led to similar results. Among subgroup analysis, we found that the use of anticoagulants will induce a much higher incidence of GI bleeding in HD patients as compared to in PD patients. We concluded that PD is associated with a lower GI bleeding risk than HD, and is especially preferred when anticoagulation is needed.

Sympathetic ophthalmia following radiation-induced scleral necrosis in choroidal melanoma.

Sympathetic ophthalmia (SO) is a bilateral granulomatous panuveitis. We report a rare case of SO presenting after scleral necrosis as a late complication of Gamma Knife radiotherapy for choroidal melanoma. A 55-year-old woman presented with primary choroidal melanoma in the right eye and has been treated with Gamma Knife radiotherapy with stable tumor size. Five years after radiotherapy, a pigmented protrusive uveal mass was visibly noted over the superior sclera of the same eye, corresponding to periocular soft tissue enhancement on computed tomography. Biopsies of the pigmented mass showed the absence of malignancy. One month later, acute blurred vision with signs of sympathetic ophthalmia developed in the left eye. The patient received high-dose systemic corticosteroids and immunomodulatory therapy. The intraocular inflammation in the left eye subsided with improving vision, and the uveal mass in the right eye flattened after the anti-inflammatory therapy. Scleral necrosis is a rare complication following radiotherapy for choroidal melanoma and may incite sympathetic ophthalmia, for which prompt and aggressive treatment is important to save vision, especially for the fellow eye.

Long-Term Follow-Up in IgG4-Related Ophthalmic Disease: Serum IgG4 Levels and Their Clinical Relevance.

(1) Background: To analyze the association between long-term changes in serum IgG4 levels and the clinical course of patients with IgG4-related ophthalmic disease (IgG4-ROD). (2) Methods: Retrospective analysis of 25 patients with IgG4-ROD. (3) Results: Mean age at diagnosis was 60.68 years. Fifty-six percent of patients had bilateral ocular involvement and 32% had systemic associations. The ocular structures involved were the lacrimal gland (76%), orbital soft tissue (36%), extraocular muscle (20%) and infraorbital nerve (20%). According to last follow-up, 9 (36%) patients had normalized IgG4 levels, and 16 (64%) patients had elevated IgG4 levels. Patients with normalized IgG4 levels had better response to initial steroid treatment and attained a significantly lower IgG4 level after treatment (p = 0.002). The highest IgG4 levels were at baseline and disease recurrence, and lowest after initial treatment. At final follow-up, IgG4 levels differed in patients with remission (mean 326.25 mg/dL) and stable disease (mean 699.55 mg/dL). Subgroup analysis was performed in patients with remission, categorized according to whether IgG4 levels were normalized (9 patients) or elevated (10 patients) on last follow up. The elevated group had a higher percentage of bilateral disease, lacrimal gland involvement and recurrence. (4) Conclusions: IgG4-ROD patients with a greater response to initial steroid therapy were more inclined to have normalized IgG4 levels in the long term. Some patients remained in remission despite persistently elevated IgG4 levels, and had regular follow-up without treatment.

Comparison Between Bicuspid and Tricuspid Aortic Regurgitation: Presentation, Survival, and Aorta Complications.

Background: Although the Asian population is growing globally, data in Asian subjects regarding differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in aortic regurgitation (AR) remain unexplored. Objectives: The aim of this study was to examine differences between Asian BAV-AR and TAV-AR in significant AR, including aorta complications. Methods: The study included 711 consecutive patients with chronic moderate to severe and severe AR from 2008 to 2020. Outcomes included all-cause death, aortic valve surgery (AVS), and incidence of aortic dissection (AD). Results: There were 149 BAV-AR (mean age: 48 ± 16 years) and 562 TAV-AR (mean age: 68 ± 15 years; P < 0.0001) patients; baseline indexed left ventricle and indexed aorta size were larger in TAV-AR. Total follow-up was 4.8 years (IQR: 2.0-8.4 years), 252 underwent AVS, and 185 died during follow-up; 18 cases (only 1 BAV) of AD occurred, with a mean maximal aorta size of 60 ± 9 mm. The 10-year AVS incidence was higher in TAV-AR (51% ± 4%) vs BAV-AR (40% ± 5%) even after adjustment for covariates (P < 0.0001). The 10-year survival was higher in BAV-AR (86% ± 4%) vs TAV-AR (57% ± 3%; P < 0.0001) and became insignificant after age adjustment (P = 0.33). Post-AVS 10-year survival was 93% ± 5% in BAV-AR and 78% ± 5% in TAV-AR, respectively (P = 0.08). The 10-year incidence of AD was higher in TAV-AR (4.8% ± 1.5%) than in BAV-AR (0.9% ± 0.9%) and was determined by aorta size ≥45 mm (P ≤ 0.015). Compared with an age- and sex-matched population in Taiwan, TAV-AR (HR: 3.1) had reduced survival (P < 0.0001). Conclusions: Our findings suggest that TAV-AR patients were at a later stage of AR course and had a high AD rate as opposed to BAV-AR patients in Taiwan, emphasizing the importance of early referral for timely management. Surgery on the aorta with a lower threshold in TAV-AR should be considered.