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Objective: The labyrinthitis poses inferior quality of life with prolonged vestibular symptoms in patients with sudden sensorineural hearing loss with vertigo (SSNHLV). This study utilized a novel coherence analysis in video head impulse test (vHIT) to investigate vertigo outcomes in SSNHLV patients., Methods: A retrospective review included 48 SSNHLV patients completing high-dose steroid treatment between December 2016 and April 2023, and 38 healthy volunteers were prospectively enrolled between November 2022 and April 2023 in our academic tertiary referral center. Magnitude-squared wavelet coherence was measured between eye and head velocities in vHIT to represent the degree of correlation across different frequency bands. Vertigo recovery, assessed by visual analog scale equal to zero at 2 weeks and 2 months, was analyzed using a multivariable Cox regression model., Results: The VAS among patients with SSNHLV was 5.73 ± 2.45 (mean ± standard deviation). Higher coherent frequencies in the horizontal semicircular canal (SCC), posterior SCC, mean, and minimal coherent frequencies of all three SCCs combined were significantly associated with early complete vertigo remission at two weeks post-treatment. In the multivariate analysis, the minimal coherent frequency among the three SCCs emerged as an independent factor (hazard ratio [HR] 2.040, 95% confidence interval [CI] 1.776-2.304). At two months post-treatment, in addition to the previously significant parameters, vestibulo-ocular reflex (VOR) abnormality in the posterior SCC, gains in the horizontal and posterior SCCs, total and overt saccades in the horizontal SCC, coherent frequency in the anterior SCC, and mean VOR gain of all three SCCs combined were also statistically significantly related to total vertigo relief., Conclusion: The greater minimal coherent frequency among the three SCCs was a strong factor contributing to earlier relief of vertigo in patients with SSNHLV. Coherence analysis in vHIT may be more sensitive than time series analysis for evaluating vertigo prognosis prediction.

Backgrounds: High-intensity statin is recommended for patients undergoing percutaneous coronary intervention (PCI), and ezetimibe is recommended to be added in patients not achieving low-density lipoprotein cholesterol (LDL-C) targets. Moderate-intensity statin plus ezetimibe can reduce LDL-C levels similar to high-intensity statin. The aim of this study is to examine the long-term efficacy and safety of moderate-intensity statin plus ezetimibe as the first-line strategy compared to high-intensity statin in patients undergoing PCI., Method: Data was obtained from the Health Insurance Review and Assessment Service database of South Korea. Patients who underwent PCI from 2012 to 2017 were included. The primary efficacy endpoint was major adverse cardiac cerebrovascular events (MACCEs), a composite of all-cause death, revascularization, or ischemic stroke. The safety endpoint was new-onset diabetes mellitus (DM)., Results: A total of 45,501 patients received high-intensity statin (n = 38,340) or moderate-intensity statin plus ezetimibe (n = 7,161). Among propensity-score-matched 7,161 pairs, MACCEs occurred in 1,460 patients with high-intensity statin and 1,406 patients with moderate-intensity statin plus ezetimibe (33.8% vs. 31.9%, hazard ratio 0.96, 95% confidence interval 0.89-1.03, P = 0.27) at a median follow-up of 2.7 years. DM was newly diagnosed in 398 patients with high-intensity statin and 342 patients with moderate-intensity statin plus ezetimibe (12.5% vs. 10.7%; hazard ratio 0.84, 95% confidence interval 0.73-0.97, P = 0.02)., Conclusion: In patients undergoing PCI, moderate-intensity statin plus ezetimibe demonstrated a similar risk of MACCEs but a lower risk of new-onset DM than high-intensity statin. Early combination treatment of moderate-intensity statin and ezetimibe may be a useful and safe lipid-lowering strategy after PCI., (© 2024. The Author(s).)

Objectives: This study investigated the optimal timing for percutaneous coronary intervention (PCI) in patients with NSTEMI complicated by heart failure (HF)., Methods: In total, 762 patients with NSTEMI and HF in a multicenter, prospective registry in South Korea were classified according to the Killip classification (Killip class 2, n = 414 and Killip class 3, n = 348) and underwent early (within 24 h) and delayed (after 24 h) PCI. The primary outcome was all-cause mortality which was further analyzed with landmark analysis with two months as a cut-off. Secondary outcomes were cardiovascular death, in-hospital cardiogenic shock (CS), readmission due to HF, and acute myocardial infarction during follow-up., Results: Delayed PCI was associated with lower rates of 2-month mortality (6.1 % vs. 15.8 %, p = 0.007) and in-hospital CS (4.3 % vs. 14.1 %, p = 0.003), along with lower risks of 2-month mortality (hazard ratio [HR] = 0.38, 95 % confidence interval [CI] = 0.18-0.83, p = 0.014), in-hospital CS (HR = 0.29, 95 % CI = 0.12-0.71, p = 0.006) in multivariate Cox models of Killip class 3 patients. There was no statistical difference of incidence and risk of all predefined outcomes according to varying timing of PCI in Killip 2 patients., Conclusions: Based on these results, the timing of PCI in patients with NSTEMI complicated by HF should be determined based on HF severity. Delayed PCI should be considered in patients with NSTEMI and more severe HF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pleomorphic adenoma is a benign tumor and the most common salivary gland neoplasm. Metastasizing pleomorphic adenoma shares histological characteristics with pleomorphic adenoma but exhibits malignant behavior, including local lymph node involvement and/or distant metastasis. Several potential risk factors for metastasizing pleomorphic adenoma have been identified, some of which are associated with incomplete tumor clearance due to inadequate surgical techniques used in the treatment of primary pleomorphic adenoma. Here, we present a rare case of metastasizing pleomorphic adenoma originating from the parotid gland and describe its clinical features. The patient was a 75-year-old female with a surgical history of enucleation of a pleomorphic adenoma in the left parotid gland. Total parotidectomy and left neck dissection were performed for the left parotid tumor this time, and the patient attended one postoperative outpatient visit but subsequently was lost to follow-up., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: The prognostic implication of mildly reduced ejection fraction (mrEF) after acute myocardial infarction has not been clearly demonstrated. We investigated the long-term risk of cardiovascular death and its predictors in patients with mrEF following acute myocardial infarction., Methods and Results: A total of 18 668 patients who presented with acute myocardial infarction were included in 2 prospective, multicenter registries. The incidence of adverse cardiovascular events according to the left ventricular ejection fraction (EF) strata at index admission were evaluated. A score system consisting of clinical variables were developed to predict long-term cardiovascular death in the mrEF group. There were 2548 patients with reduced EF (EF ≤40%), 4266 patients with mrEF (EF 41%-49%), and 11 854 patients with preserved EF (EF ≥50%). During a median follow-up period of 37.9 months, the cardiovascular death rate was 22.3% in the reduced EF group, 10.3% in the mrEF group, and 7.3% in the preserved EF group ( P <0.001). In the mrEF group, age>65 years, hypertension, stroke, severe renal insufficiency, and Killip class ≥3 were independent predictors for cardiovascular death. Presence of >2 predictors best discriminated the high-risk patients for cardiovascular death with an area under the curve of 0.746. Incidence of cardiovascular death in the high-risk mrEF group was comparable with the rEF group, while it was lower in the low-risk mrEF group than in the pEF group., Conclusions: Patients with mrEF after acute myocardial infarction had a modest risk of cardiovascular death. Clinical predictors could help discriminate a high-risk subpopulation with cardiovascular death risks comparable with those in the reduced EF group.

Background: Little is known about the characteristics and long-term clinical outcomes of patients with heart failure with improved ejection fraction (HFimpEF) after acute myocardial infarction., Methods and Results: From a multicenter, consecutive cohort of patients with acute myocardial infarction undergoing percutaneous coronary intervention, patients with an initial echocardiogram with left ventricular ejection fraction ≤40% and at least 1 follow-up echocardiogram after 14 days and within 2 years of the initial event were considered for analyses. HFimpEF was defined as an initial left ventricular ejection fraction ≤40% and serial left ventricular ejection fraction >40% with an increase of ≥10% from baseline at follow-up. Independent factors predicting HFimpEF were identified, and clinical outcomes of patients with HFimpEF were compared with those without improvement. From an initial cohort of 10 719 patients with acute myocardial infarction, 191 patients with HFimpEF and 256 patients with non-HFimpEF who had initial and follow-up echocardiographic data were analyzed. The median follow-up duration was 4.5 (interquartile range, 2.9-5.0) years. The factors predicting HFimpEF were lower peak creatine kinase myocardial band, smaller left ventricular dimensions, lower ratio between early mitral inflow velocity and mitral annular early diastolic velocity ', and the use of β blockers or renin-angiotensin system blockers at discharge. HFimpEF was associated with a significantly decreased risk of all-cause death compared with non-HFimpEF (hazard ratio, 0.377 [95% CI, 0.234-0.609]; P <0.001). In 2-year landmark analysis, these findings were consistent not only before but also after the landmark point. Similar findings were true for cardiovascular death and admission for heart failure., Conclusions: Patients with HFimpEF after acute myocardial infarction showed distinct clinical and echocardiographic characteristics and were associated with better long-term clinical outcomes., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02806102.

Background:  Dyspnea is frequent during ticagrelor-based dual antiplatelet therapy (DAPT) for acute myocardial infarction (AMI). However, its clinical characteristics or management strategy remains uncertain., Methods:  The study assessed 2,617 AMI patients from the Ticagrelor versus Clopidogrel in Stabilized Patients with AMI (TALOS-AMI) trial. Dyspnea during 1-month ticagrelor-based DAPT and following DAPT strategies with continued ticagrelor or de-escalation to clopidogrel from 1 to 12 months were evaluated for drug adherence, subsequent dyspnea, major adverse cardiovascular events (MACE), and bleeding events., Results:  Dyspnea was reported by 538 patients (20.6%) during 1 month of ticagrelor-based DAPT. Adherence to allocated DAPT over the study period was lower in the continued ticagrelor arm than the de-escalation to clopidogrel, particularly among the dyspneic population (81.1% vs. 91.5%, p  < 0.001). Among ticagrelor-treated patients with dyspnea, those switched to clopidogrel at 1 month had a lower frequency of dyspnea at 3 months (34.3% vs. 51.7%, p  < 0.001) and 6 months (25.5% vs. 38.4%, p  = 0.002) than those continued with ticagrelor. In patients with dyspnea in their 1-month ticagrelor-based DAPT, de-escalation was not associated with increased MACE (1.3% vs. 3.9%, hazard ratio [HR]: 0.31, 95% confidence interval [CI]: 0.08-1.11, p  = 0.07) or clinically relevant bleeding (3.2% vs. 6.2%, HR: 0.51, 95% CI: 0.22-1.19, p  = 0.12) at 1 year., Conclusion:  Dyspnea is a common side effect among ticagrelor-based DAPTs in AMI patients. Switching from ticagrelor to clopidogrel after 1 month in AMI patients may provide a reasonable option to alleviate subsequent dyspnea in ticagrelor-relevant dyspneic patients, without increasing the risk of ischemic events (NCT02018055)., Competing Interests: K.C. received research grants from Medtronic, Abbott, ChongKunDang Pharm, and Boston Scientific. All other authors declare no competing interests., (Thieme. All rights reserved.)

In this study, we synthesized levan shell hydrophobic silica nanoclusters encapsulating doxorubicin (L-HSi-Dox) and evaluated their potential as ultrasound-responsive drug delivery systems for cancer treatment. L-HSi-Dox nanoclusters were successfully fabricated by integrating a hydrophobic silica nanoparticle-doxorubicin complex as the core and an amphiphilic levan carbohydrate polymer as the shell by using an electrospray technique. Characterization analyses confirmed the stability, size, and composition of the nanoclusters. In particular, the nanoclusters exhibited a controlled release of Dox under aqueous conditions, demonstrating their potential as efficient drug carriers. The levanic groups of the nanoclusters enhanced the targeted delivery of Dox to specific cancer cells. Furthermore, the synergism between the nanoclusters and ultrasound effectively reduced cell viability and induced cell death, particularly in the GLUT5-overexpressing MDA-MB-231 cells. In a tumor xenograft mouse model, treatment with the nanoclusters and ultrasound significantly reduced the tumor volume and weight without affecting the body weight. Collectively, these results highlight the potential of the L-HSi-Dox nanoclusters and ultrasound as promising drug delivery systems with an enhanced therapeutic efficacy for biomedical applications.

A 73-year-old woman having a throat lump sensation and dysphagia for the past several months presented at our otorhinolaryngology outpatient clinic. A physical examination disclosed a protruding subepithelial mass over the right tonsil fossa. The mass was not tender and had no mucosal lesions or signs of active infection. Therefore, we arranged face and neck computed tomography scans, which reported a solitary osseous lesion over the anterior-right aspect of the C1-2 joint. Considering the rarity and unfamiliar anatomy of this disease, we built a 3D-printed model to assist with the surgical rehearsal of the procedure as well as with a preoperation discussion with the patient and her family. We arranged a combined Otolaryngology-Neurosurgery department approach after discussion with the neurosurgeon and successfully removed the lesion without sacrificing the overlying longus capitis muscle. The pathology examination revealed no evidence of malignancy. The final diagnosis was cervical spine solitary osteochondroma. The patient had a complete recovery of both oral cavity and normal swallowing function. No tumor recurred during the 3-year follow-up. On the basis of this case, in-house 3D-printing technology can offer a rapid, reliable model for an interdisciplinary team to use to enhance personalized presurgical planning, thus providing better patient engagement during hospitalization., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and publication of this article.

Background: The TALOS-AMI study highlighted the effectiveness of a de-escalation strategy shifting from ticagrelor to clopidogrel 1 month after percutaneous coronary intervention (PCI), resulting in significant reduction in clinical events, primarily attributed to a substantial decrease in bleeding events. Nevertheless, the impact of this strategy on outcomes based on sex remains unclear., Methods: This was a post-hoc analysis of the TALOS-AMI study. At 1 month after PCI, patients who remained adherent to aspirin and ticagrelor without experiencing major adverse events were randomized into either the de-escalation group (clopidogrel plus aspirin) or the active control group (ticagrelor plus aspirin) for an additional 12 months. The primary endpoint encompassed a composite of cardiovascular death, myocardial infarction, stroke, and Bleeding Academic Research Consortium bleeding type 2 or greater at 12 months after randomization., Results: Among the 2,697 patients included in this study, 454 (16.8%) were women. Women, characterized by older age and a higher prevalence of hypertension, diabetes, impaired renal function, and non-ST-segment myocardial infarction, exhibited a lower primary endpoint at 12 months compared to men [adjusted hazards ratio (HR), 0.60; 95% confidence interval (CI), 0.37-0.95; P  = 0.03]. Compare to the active control group, the de-escalation group demonstrated a reduced risk of the primary endpoint in both women (adjusted HR, 0.38; 95% CI, 0.15-0.95; P  = 0.039) and men (adjusted HR, 0.56; 95% CI, 0.40-0.79; P  = 0.001) (interaction P  = 0.46)., Conclusions: In stabilized patients post-PCI with drug-eluting stents for acute myocardial infarction, the primary endpoint was lower among women compared to men. In this cohort, the benefits of an unguided de-escalation strategy from ticagrelor to clopidogrel were comparable in women and men., Competing Interests: KC has received research grants from ChongKunDang Pharm, Medtronic, Abbott, and Boston Scientific. CK has received research grants and speaker's fees from ChongKunDang Pharm. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Shin, Jun, Kim, Kim, Park, Choo, Hwang, Lee, Oh, Kim, Yim, Ahn and Chang.)

Background: The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using second-generation drug-eluting stents (DESs)., Methods: Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group)., Results: Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639)., Conclusion: The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES., Trial Registration: ClinicalTrials.gov Identifier: NCT03068494., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

A few studies have reported comparative analysis of clinical outcomes between balloon-expandable valve (BEV) and self-expandable valve (SEV) after transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis using newer-generation devices. However, those reports were mostly limited to short-term outcomes and Western populations. In the present study, data of patients with severe aortic stenosis who underwent TAVR between March 2016 and December 2018 were obtained from the National Health Insurance Service in Korea. The primary end point, defined as all-cause mortality, was compared in BEV (SAPIEN 3, Edwards Lifesciences, Irvine, California) and SEV (Evolut R, Medtronic, Minneapolis, MN) groups using a propensity-score matching analysis. Cumulative event rates of ischemic stroke, repeat procedures, and permanent pacemaker insertion (PPI) were evaluated as secondary outcomes. All events were followed up to a maximum of 3 years. A total of 1,172 patients underwent transfemoral TAVR, of whom 707 (60.3%) were treated with BEV and 452 (38.6%) with SEV. After 1:1 propensity-score matching, the BEV group showed lower all-cause mortality after a median follow-up of 12.0 months (mean: 13.1 ± 9.3 months) based on Cox proportional hazard model analysis (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.45 to 0.99, p = 0.04). Cumulative incidence of ischemic stroke was not statistically different between the 2 groups (HR 0.68, 95% CI 0.29 to 1.59, p = 0.37). PPI occurred less frequently in the BEV group (HR 0.4, 95% CI 0.25 to 0.64, p < 0.01). Repeat procedures were rare (1 patient in BEV and 2 patients in SEV group). In conclusion, Korean nation-wide data analysis showed that BEV was associated with less all-cause death and incidence of PPI after TAVR than was SEV using a newer-generation device., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: In patients with acute myocardial infarction (AMI) who have high ischemic risk, data on the efficacy and safety of the de-escalation strategy of switching from ticagrelor to clopidogrel are lacking., Objective: To evaluate the outcomes of the de-escalation strategy compared with dual antiplatelet therapy (DAPT) with ticagrelor in stabilized patients with AMI and high ischemic risk following percutaneous coronary intervention (PCI)., Design, Setting, and Participants: This was a post hoc analysis of the Ticagrelor vs Clopidogrel in Stabilized Patients With Acute Myocardial Infarction (TALOS-AMI) trial, an open-label, assessor-blinded, multicenter, randomized clinical trial. Patients with AMI who had no event during 1 month of ticagrelor-based DAPT after PCI were included. High ischemic risk was defined as having a history of diabetes or chronic kidney disease, multivessel PCI, at least 3 lesions treated, total stent length greater than 60 mm, at least 3 stents implanted, left main PCI, or bifurcation PCI with at least 2 stents. Data were collected from February 14, 2014, to January 21, 2021, and analyzed from December 1, 2021, to June 30, 2022., Intervention: Patients were randomly assigned to either de-escalation from ticagrelor to clopidogrel or ticagrelor-based DAPT., Main Outcomes and Measures: Ischemic outcomes (composite of cardiovascular death, myocardial infarction, ischemic stroke, ischemia-driven revascularization, or stent thrombosis) and bleeding outcomes (Bleeding Academic Research Consortium type 2, 3, or 5 bleeding) were evaluated., Results: Of 2697 patients with AMI (mean [SD] age, 60.0 [11.4] years; 454 [16.8%] female), 1371 (50.8%; 684 assigned to de-escalation and 687 assigned to ticagrelor-based DAPT) had high ischemic risk features and a significantly higher risk of ischemic outcomes than those without high ischemic risk (1326 patients [49.2%], including 665 assigned to de-escalation and 661 assigned to ticagrelor-based DAPT) (hazard ratio [HR], 1.74; 95% CI, 1.15-2.63; P = .01). De-escalation to clopidogrel, compared with ticagrelor-based DAPT, showed no significant difference in ischemic risk across the high ischemic risk group (HR, 0.88; 95% CI, 0.54-1.45; P = .62) and the non-high ischemic risk group (HR, 0.65; 95% CI, 0.33-1.28; P = .21), without heterogeneity (P for interaction = .47). The bleeding risk of the de-escalation group was consistent in both the high ischemic risk group (HR, 0.64; 95% CI, 0.37-1.11; P = .11) and the non-high ischemic risk group (HR, 0.42; 95% CI, 0.24-0.75; P = .003), without heterogeneity (P for interaction = .32)., Conclusions and Relevance: In stabilized patients with AMI, the ischemic and bleeding outcomes of an unguided de-escalation strategy with clopidogrel compared with a ticagrelor-based DAPT strategy were consistent without significant interaction, regardless of the presence of high ischemic risk.

Schwannomas are rare slow-growing benign tumors arising from Schwann cells lining the nerve sheaths. Head and neck schwannomas account for about one-third of all cases, and only 4% of them arise from the sinonasal tract. Its diagnosis is based on histology and immunohistochemistry. Complete surgical excision is the most recommended treatment option, and endoscopic surgery has been widely performed in recent years. In this study, we presented a case of a 55-year-old female with schwannoma arising from the lateral wall of the nasal cavity, causing epistaxis and rhinorrhea. The patient underwent endoscopic excision with prompt resolution of symptoms. The reported cases of nasal cavity schwannoma were reviewed and summarized for educational purposes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Normal alignment of the foot is important because the feet support the body's weight. The intrinsic muscles of the foot mainly maintain the alignment and movement of the foot, whereas the abductor hallucis (AbdH) aligns the first metatarsophalangeal joint and maintains the medial longitudinal arch., Objective: This study was conducted to investigate the muscle activity of the AbdH and hallux valgus (HV) angle during three different foot exercises., Methods: Participants included 15 subjects aged 20-24 years with mild HV. All subjects performed three different foot exercises in random order: short foot exercise (SF), toe spread out exercise (TSO), and TSO with a pressure bio-feedback unit (TSOP). The muscle activity of the AbdH and the HV angle were measured during each foot exercise using surface electromyography and X-ray and then compared using one-way repeated-measures analysis of variance, followed by Bonferroni adjustment., Results: AbdH muscle activity differed significantly among SF, TSO, and TSOP. AbdH muscle activity was greater in TSOP (89.60%) than in SF (19.99%) and TSO (60.96%) (p= 0.006). The HV angle was significantly smaller in TSOP (15.72∘) than in SF (18.85∘) and TSO (16.81∘) (p= 0.001)., Conclusions: TSOP can be recommended as an effective AbdH strengthening exercise in subjects with mild HV.

Background: Sufficient shoulder flexor strength is necessary for accurate movement of the shoulder joint because several factors can cause compensatory movements of the scapula., Objective: We investigated the influence of external fixation on the isometric shoulder flexors strength (ISFS) in individuals with and without scapular elevation (SE) during shoulder flexion., Methods: The healthy and SE groups included 29 individuals. The ISFS was measured using a tensiometer (kg) under conditions of with and without external fixation, in a random order. The change in the ISFS (the strength difference with and without external fixation) was compared between the healthy and SE groups using an independent t-test., Results: The change in the ISFS differed significantly between the healthy and SE groups (3.5% and 32.3%, respectively; p= 0.001)., Conclusion: These findings suggest that external fixation should be considered during shoulder flexion to determine the ISFS accurately in individuals with compensated SE.

Targeted delivery of therapeutic agents to cancer cells is crucial for effective cancer treatment without adverse effects. In this study, we developed a novel delivery carrier, Aptamer-modified tetrahedral DNA nanostructure (TDN) immobilized Liposome (ApTL), for specific delivery to nucleolin-overexpressing cancer cells. We demonstrated that targeted ApTL was highly effective in delivering plasmid and mRNA to nucleolin-overexpressing cancer cells compared to non-targeted ApTL with a non-specific aptamer. ApTL, which is highly negative and nano-sized, specifically delivered nucleic acids to MDA-MB-231 and HeLa cancer cells, primarily via lipid-raft-mediated endocytosis. Furthermore, the co-delivery of mRNA and doxorubicin resulted in increased apoptosis and reduced cancer cell viability. Interestingly, co-delivery of mRNA and Dox did not show a significant difference in EGFP expression at 24 h but dramatically increased EGFP expression at 48 h, making ApTL/mEGFP/Dox a promising candidate for detecting live cancer cells after targeted cancer drug treatment. Our results suggest that ApTL can be a promising tool for the targeted delivery of therapeutic agents to nucleolin-overexpressing cancer cells, providing a new strategy for cancer theragnostic., (© 2023 Wiley-VCH GmbH.)

Certain cancers, such as triple-negative breast cancer (TNBC), pose a challenging prognosis due to the absence of identifiable hormone-related receptors and effective targeted therapies. Consequently, novel therapeutics are required for these cancers, offering minimal side effects and reduced drug resistance. Unexpectedly, siRNA-7, initially employed as a control, exhibited significant efficacy in inhibiting cell viability in MDA-MB-231 cells. Through a genome-wide search of seed sequences, the targets of siRNA-7 were identified as cancer-related genes, namely PRKCE, RBPJ, ZNF737, and CDC7 in MDA-MB-231 cells. The mRNA repression analysis confirmed the simultaneous suppression by siRNA-7. Combinatorial administration of single-targeting siRNAs demonstrated a comparable reduction in viability to that achieved by siRNA-7. Importantly, siRNA-7 selectively inhibited cell viability in MDA-MB-231 cells, while normal HDF-n cells remained unaffected. Furthermore, in a xenograft mouse model, siRNA-7 exhibited a remarkable 76% reduction in tumor volume without any loss in body weight. These findings position siRNA-7 as a promising candidate for a novel, safe, specific, and potent TNBC cancer therapeutic. Moreover, the strategy of multiple suppressing small interfering RNA holds potential for the treatment of various diseases associated with gene overexpression., (© 2023 Wiley-VCH GmbH.)

A rapid hemostatic sealant can save a patient's life from shock and death due to severe trauma or excessive bleeding from the wound site during surgery. However, an ideal hemostatic sealant needs to meet the standards of safety, efficacy, usability, cost, and approvability and overcome new challenges. Here, we devised a combinatorial hemostatic sealant of PEG succinimidyl glutarate-based cross-linking branched polymers (CBPs) and the active hemostatic peptide (AHP). After ex vivo optimization, the best hemostatic combination was called an active cross-linking hemostatic sealant (ACHS). Interestingly, ACHS formed cross-links with serum proteins, blood cells, and tissue and interconnected coating on blood cells, which might induce hemostasis and tissue adhesion based on SEM images. Moreover, ACHS showed the highest coagulation efficacy, formation, and agglomeration of thrombi within 12 s, and in vitro biocompatibility. Mouse model experiments represented rapid hemostasis within 1 min, wound closure of the liver incision, and less bleeding than the commercialized sealant with tissue biocompatibility. ACHS has the advantages of rapid hemostasis, mild sealant, and easy supply by chemical synthesis without inhibition by anticoagulants, which might minimize bacterial infection by immediate wound closure. Therefore, ACHS could become a new-type hemostatic sealant to match surgical needs for internal bleeding., (© 2023 Wiley-VCH GmbH.)

Background: The use of a cardioverter defibrillator for the primary prevention of sudden cardiac death is not recommended within 40 days after acute myocardial infarction (AMI). We investigated the predictors for early cardiac death among patients who were admitted for AMI and successfully discharged., Methods: Consecutive patients with AMI were enrolled in a multicenter prospective registry. Among 10,719 patients with AMI, 554 patients with in-hospital death and 62 patients with early non-cardiac death were excluded. Early cardiac death was defined as a cardiac death within 90 days after index AMI., Results: Early cardiac death after discharge occurred in 168/10,103 (1.7%) patients. A defibrillator was not implanted in all patients with early cardiac death. Killip class ≥3, chronic kidney disease stage ≥4, severe anemia, cardiopulmonary support usage, no dual antiplatelet therapy at discharge, and left ventricular ejection fraction (LVEF) ≤35% were independent predictors for early cardiac death. The incidence of early cardiac death according to the number of factors added to LVEF criteria in each patient was 3.03% for 0 factor, 8.11% for 1 factor, and 9.16% for ≥2 factors. Each model that sequentially added the factors in the presence of LVEF criteria showed a significant gradual increase in predictive accuracy and an improvement in reclassification capability. A model with all factors showed C-index 0.742 [95% CI 0.702-0.781], p < 0.001; IDI 0.024 [95% CI 0.015-0.033], p < 0.001; and NRI 0.644 [95% CI 0.492-0.795], p < 0.001., Conclusion: We identified six predictors for early cardiac death after discharge from AMI. These predictors would help to discriminate high-risk patients over current LVEF criteria and to provide an individualized therapeutic approach in the subacute stage of AMI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Choi, Lee, Kim, Kim, Hwang, Choo, Lim, Kim, Kim, Byeon, Oh, Jeon, Yoo, Park, Kim, Ahn, Ho Jeong, Hwang and Chang.)

An elevated heart rate at admission or discharge is known to be associated with poor cardiovascular outcomes in patients with acute myocardial infarction (AMI). The association between post-discharge average office-visit heart rate and cardiovascular outcomes in patients with AMI has rarely been studied. We analyzed data for 7840 patients from the COREA-AMI registry who had their heart rates measured at least three times after hospital discharge. The office-visit heart rates were averaged and categorized into four groups by quartiles (<68, 68-74, 74-80, and >80 beats per minute). The primary end point was a composite of cardiovascular death, myocardial infarction, and ischemic stroke. During a median of 5.7 years of follow-up, major adverse cardiovascular events (MACE) affected 1357 (17.3%) patients. An average heart rate higher than 80 bpm was associated with an increased incidence of MACE compared to the reference average heart rate of 68-74 bpm. When dichotomized into <74 or ≥74 bpm, a lower average heart rate was not associated with MACE in patients with LV systolic dysfunction, in contrast to those without LV systolic dysfunction. An elevated average heart rate at office visits after AMI was associated with an increased risk of cardiovascular outcomes. Heart rate monitoring at office visits after discharge provides an important predictor related to cardiovascular events.

The role of statins after endovascular abdominal aortic aneurysm repair (EVAR) has not been well established in an Asian context. In this study, the use of statins and their association with long-term health outcomes were evaluated in patients undergoing EVAR using the Korean National Health Insurance Service database. Among the 8893 patients who underwent EVAR from 2008 to 2018, 3386 (38.1%) were on statins prior to the procedure. Patients using statins had a higher prevalence of comorbidities, such as hypertension (88.4% vs. 71.5%), diabetes mellitus (24.5% vs. 14.1%), and heart failure (21.6% vs. 13.1%), compared with non-users (all p < 0.001). After propensity score matching, statin use prior to EVAR was associated with a lower risk of all-cause mortality (HR 0.85, 95% CI 0.78-0.92, p < 0.001) and cardiovascular mortality (HR 0.66, 95% CI 0.51-0.86, p = 0.002). Statin use following EVAR was associated with a lower risk of adverse events, but not significantly so. Patients on statins both preceding and following EVAR had a lower risk of all-cause mortality (HR 0.82, 95% CI 0.73-0.91, p < 0.001) and cardiovascular mortality (HR 0.62, 95% CI 0.44-0.87, p = 0.007), compared with statin non-users. Among Korean patients undergoing EVAR, the persistent use of statins prior to and after the procedure was associated with a lower risk of mortality, compared with non-statin users.

This study aimed to determine the impact on hearing prognosis of the coherent frequency with high magnitude-squared wavelet coherence (MSWC) in video head impulse test (vHIT) among patients with sudden sensorineural hearing loss with vertigo (SSNHLV) undergoing high-dose steroid treatment. This study was a retrospective cohort study. SSNHLV patients treated at our referral center from December 2016 to December 2020 were examined. The cohort comprised 64 patients with SSNHLV undergoing high-dose steroid treatment. MSWC was measured by calculating the wavelet coherence analysis (WCA) at various frequencies from a vHIT. The hearing prognosis were analyzed using a multivariable Cox regression model and convolution neural network (CNN) of WCA. There were 64 patients with a male-to-female ratio of 1:1.67. The greater highest coherent frequency of the posterior semicircular canal (SCC) was associated with the complete recovery (CR) of hearing. After adjustment for other factors, the result remained robust (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.86-2.35). In the feature extraction with Resnet-50 and proceeding SVM in the horizontal image cropping style, the classification accuracy [STD] for (CR vs. partial + no recovery [PR + NR]), (over-sampling of CR vs. PR + NR), (extensive data extraction of CR vs. PR + NR), and (interpolation of time series of CR vs. PR + NR) were 83.6% [7.4], 92.1% [6.8], 88.9% [7.5], and 91.6% [6.4], respectively. The high coherent frequency of the posterior SCC was a significantly independent factor that was associated with good hearing prognosis in the patients who have SSNHLV. WCA may be provided with comprehensive ability in vestibulo-ocular reflex (VOR) evaluation. CNN could be utilized to classify WCA, predict treatment outcomes, and facilitate vHIT interpretation. Feature extraction in CNN with proceeding SVM and horizontal cropping style of wavelet coherence plot performed better accuracy and offered more stable model for hearing outcomes in patients with SSNHLV than pure CNN classification. Clinical and Translational Impact Statement-High coherent frequency in vHIT results in good hearing outcomes in SSNHLV and facilitates AI classification.

Few studies have reported comparisons of out-of-hospital clinical outcomes after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) in the era of current-generation valves that reflect the real-world situation. Data on patients with severe AS aged 65 years or older who underwent TAVR or SAVR between 2015 and 2018 were obtained from the National Health Insurance Service in Korea and clinical event rate was analyzed. The primary endpoint was all-cause death at 1 year. The cohort included a total of 4623 patients over 65 years of age, of whom 1269 (27.4%) were treated with TAVR. After 1:1 propensity score matching, 2120 patients were included in the study. TAVR was associated with reduced 1-year mortality (hazard ratio (HR): 0.55; 95% confidence interval (CI): 0.42−0.70; p < 0.001). There was no difference between the groups in the incidence of ischemic stroke (HR: 0.72, 95% CI: 0.43−1.20; p = 0.21) and intracranial hemorrhage (HR: 1.10; p = 0.74). Permanent pacemaker insertion was observed more frequently in the TAVR cohort (9.4% vs. 2.5%, HR: 3.95, 95% CI: 2.57−6.09; p < 0.001), whereas repeat procedures were rare in both treatments (0.5% vs. 0.3%, p = 0.499). In the nation-wide real-world data analysis, TAVR with current-generation devices showed significantly lower 1-year mortality compared to SAVR in severe AS patients.

Background & Aims: Data regarding the relationship between malnutrition and clinical outcomes of acute myocardial infarction (AMI) is limited. The study aims to evaluate the clinical impact of malnutrition in AMI patients after percutaneous coronary intervention (PCI)., Methods and Results: The COREA-AMI registries identified 10,161 AMI patients who underwent PCI from January 2004 to August 2014. Patients with geriatric nutritional risk index (GNRI) scores of <82, 82 to <92, 92 to <98, and ≥98 were categorized as having severe, moderate, mild malnutrition risk, and absence of risk, respectively. Associations of GNRI with Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding, all-cause death, and major cardiovascular events (MACEs; a composite of cardiovascular death, myocardial infarction, or ischemic stroke) were evaluated. Over 50% of AMI patients were malnourished, with 25.0%, 22.7%, and 4.9% having mild, moderate, and severe malnutrition risks, respectively. Over a median 4.9-year follow-up, patients with malnutrition risk had higher risks of BARC 3 or 5 bleeding (adjusted hazard ratios [aHRs], 1.27, 1.55, and 2.02 for mild, moderate, and severe, respectively; p < 0.001), all-cause death (aHRs, 1.26, 1.46, and 1.85 for mild, moderate, and severe, respectively; p < 0.001), and MACEs (aHRs, 1.14, 1.32, and 1.67 for mild, moderate, and severe, respectively; p < 0.001) than patients without risk., Conclusion: Elevated malnutrition risk was common among AMI patients undergoing PCI and was strongly associated with a higher risk of major bleeding, all-cause death, and major ischemic events., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Diabetes mellitus (DM) is a critical risk factor for the pathogenesis and progression of coronary artery disease, with a higher prevalence of complex coronary artery disease, including bifurcation lesions. This study aimed to elucidate the optimal stenting strategy for coronary bifurcation lesions in patients with DM., Methods: A total of 905 patients with DM and bifurcation lesions treated with second-generation drug-eluting stents (DES) from a multicenter retrospective patient cohort were analyzed. The primary outcome was the 5-year incidence of target lesion failure (TLF), which was defined as a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization., Results: Among all patients with DM with significant bifurcation lesions, 729 (80.6%) and 176 (19.4%) were treated with one- and two-stent strategies, respectively. TLF incidence differed according to the stenting strategy during the mean follow-up of 42 ± 20 months. Among the stent strategies, T- and V-stents were associated with a higher TLF incidence than one-stent strategy (24.0 vs. 7.3%, p < 0.001), whereas no difference was observed in TLF between the one-stent strategy and crush or culotte technique (7.3 vs. 5.9%, p = 0.645). The T- or V-stent technique was an independent predictor of TLF in multivariate analysis (hazard ratio, 3.592; 95% confidence interval, 2.117-6.095; p < 0.001). Chronic kidney disease, reduced left ventricular ejection fraction, and left main bifurcation were independent predictors of TLF in patients with DM., Conclusion: T- or V-stenting in patients with DM resulted in increased cardiovascular events after second-generation DES implantation., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03068494?term=03068494&draw=2&rank=1, identifier: NCT03068494., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cha, Hong, Kim, Lim, Joo, Park, Yu, Kang, Kim, Gwon, Chun, Hur, Han, Rha, Chae, Jeong, Heo, Yoon, Park, Hong, Doh, Cha, Kim, Lee, Chang, Hwang, Choi, Jeong, Song, Choi, Nam, Koo and Lim.)

Background: Data regarding prognosis and management after nuisance bleeding (NB) is limited. The purpose was to examine the prognostic significance of NB in patients receiving potent dual antiplatelet treatment (DAPT) after acute myocardial infarction and the impact of de-escalation of DAPT on clinical outcomes thereafter., Methods: From the TALOS-AMI trial (Ticagrelor Versus Clopidogrel in Stabilized Patients With Acute Myocardial Infarction)' 2583 patients were used to investigate the clinical impact of NB (defined as Bleeding Academic Research Consortium [BARC] 1 bleeding) during 1-month treatment with ticagrelor-based DAPT after acute myocardial infarction. We assessed the associations between NB within 1 month and BARC 2, 3, or 5 bleeding and major adverse cardiovascular event (a composite of cardiovascular death, myocardial infarction, stroke) from 1 to 12 months. We also evaluated the effect of de-escalation to clopidogrel in patients with or without NB., Results: NB occurred in 416 patients (16.7%) after 1 month of ticagrelor-based DAPT. At 1 year, NB was not associated with increase in BARC 2, 3, or 5 bleeding (hazard ratio [HR]' 1.29 [95% CI' 0.7-2.14]) and major adverse cardiovascular event (HR' 1.72 [95% CI' 0.87-3.39]). However, patients with NB had an increased risk of BARC 2, 3, or 5 bleeding at 6 months (HR, 1.94 [95% CI, 1.08-3.48]; P =0.026), which diminished over the next 6 months. De-escalation from ticagrelor to clopidogrel reduced the incidence of BARC 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in NB (HR' 0.31 [95% CI' 0.10-0.92]) and non-NB patients (HR' 0.58 [95% CI' 0.37-0.90]) without heterogeneity ( P interaction=0.291). There was no increase in major adverse cardiovascular event after DAPT de-escalation, irrespective of NB., Conclusions: NB was frequent in patients with acute myocardial infarction on 1-month ticagrelor-based DAPT and was associated with an early increase of bleeding. DAPT de-escalation after NB may reduce bleeding without increasing ischemic events., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02018055.

Background: We evaluated the effectiveness of extended dual antiplatelet therapy (DAPT) usage after 2nd-generation drug elution stent implantation in acute myocardial infarction (AMI) survivors with high ischemic risk characteristics who had no major bleeding for 24 months under at least 1 year of DAPT maintenance., Materials and Methods: The primary ischemic and bleeding endpoints were the risk of mortality and the risk of BARC 3 or 5 (major) bleeding. We investigated the event rates for 2-5 years after the index procedure., Results: Of 3382 post-AMI survivors who met the PEGASUS-TIMI 54 (PEGASUS) criteria and without major bleeding until 2 years, 2281 (67.4%) maintained DAPT over 24 months, and 1101 (32.5%) switched DAPT to a single antiplatelet agent. The >24 M DAPT group showed a lower risk of mortality than the 12-24 M DAPT group (7.2 vs. 9.2%; adjusted hazard ratio: 0.648; 95% confidence interval: 0.595-0.976; p < 0.001). The mortality risk was significantly greater as the number of PEGASUS criteria increased ( p < 0.001). DAPT > 24 months was not significantly associated with a decreased risk for major bleeding in the population meeting the PEGASUS criteria (2.0 vs. 1.1%; p = 0.093). The results were consistent after propensity-score matching and inverse probability weighting to adjust for baseline differences., Conclusion: Extended DAPT over 24 months was associated with a lower risk of mortality without increasing the risk of major bleeding among 2 years survivors after AMI who met the PEGASUS criteria and had no major bleeding events before 24 months., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee, Hwang, Choo, Lim, Kim, Kim, Byeon, Choi, Oh, Choi, Yoo, Chung, Ahn, Jeong and Chang.)

Background Antithrombotic agents to treat patients with acute myocardial infarction can cause bleeding, which may reveal undiagnosed cancer. However, the relationship between bleeding and new cancer diagnosis and the prognostic impact is still unclear. Methods and Results We analyzed the new cancer diagnosis, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and all-cause death of 10 364 patients with acute myocardial infarction without a history of previous cancer in a multicenter acute myocardial infarction registry. During a median of 4.9 years, 1109 patients (10.7%) experienced Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and 338 patients (3.3%) were newly diagnosed with cancer. Bleeding Academic Research Consortium 2, 3, or 5 bleeding was associated with an increased risk of new cancer diagnosis (subdistribution hazard ratio [sHR] 3.29 [95% CI, 2.50-4.32]). In particular, there were robust associations between gastrointestinal bleeding and new gastrointestinal cancer diagnosis (sHR, 19.96 [95% CI, 11.30-29.94]) and between genitourinary bleeding and new genitourinary cancer diagnosis (sHR, 28.95 [95% CI, 14.69-57.07]). The risk of all-cause death was not lower in patients diagnosed with new gastrointestinal cancer after gastrointestinal bleeding (hazard ratio [HR], 4.05 [95% CI, 2.04-8.02]) and diagnosed with new genitourinary cancer after genitourinary bleeding (HR, 2.79 [95% CI, 0.81-9.56]) than in patients newly diagnosed with cancer without previous bleeding. Conclusions Clinically significant bleeding, especially gastrointestinal and genitourinary bleeding, in patients with AMI was associated with an increased risk of new cancer diagnoses. However, the bleeding preceding new cancer detection was not associated with better survival. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02385682 and NCT02806102.

The relationship between visit-to-visit blood pressure variability (BPV) and cardiovascular outcomes remains unclear. Our study assessed the prognostic implications of visit-to-visit BPV in patients after acute myocardial infarction (AMI). The present study enrolled 7,375 patients who underwent percutaneous coronary intervention for AMI and at least five measurements of blood pressure after hospital discharge. Visit-to-visit BPV was estimated as variability independent of mean. The primary endpoint was all-cause mortality. The secondary endpoints were major cardiovascular events (the composite of cardiovascular death, myocardial infarction, and ischemic stroke) and hospitalization for heart failure. During a median follow-up of 5.8 years, adjusted risks of all-cause mortality, major cardiovascular events, and hospitalization for heart failure continuously increased as systolic BPV and diastolic BPV increased. Patients in the highest quartile of systolic BPV (versus lowest) had increased risk of all-cause mortality (adjusted hazard ratio (aHR) 1.51 [95% confidence interval (CI) 1.23-1.85]), major cardiovascular events (aHR 1.31 [95% CI 1.1-1.55]), and hospitalization for heart failure (aHR 2.15 [95% CI 1.49-3.1]). Patients in the highest quartile of diastolic BPV was also associated with all-cause mortality (aHR 1.39 [95% CI 1.14-1.7]), major cardiovascular events (aHR 1.29 [95% CI 1.08-1.53]), and hospitalization for heart failure (aHR 2.01[95% CI 1.4-2.87]). Both systolic and diastolic BPV improved the predictive ability of the GRACE (Global Registry of Acute Coronary Events) risk score for both all-cause mortality and major cardiovascular events. Higher visit-to-visit BPV was associated with increased risks of mortality and cardiovascular events in patients after AMI., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: This study aimed to determine whether drug doses per kilogram of lean body mass (LBM) were associated with dose-limiting toxicity (DLT) events in head and neck cancer (HNC) patients., Methods: This retrospective cohort study included 179 HNC patients who underwent induction chemotherapy (IC) at a medical center from May 1, 2014, to May 31, 2021. HNC patients' characteristics, tumor factors, IC regimen and dose, laboratory data, and body composition factors, including lean body mass (LBM) and skeletal muscle index (SMI), derived from CT, MRI, or PET scan images and drug dose per kilogram LBM were recorded. Dose-limiting toxicity (DLT) events were regarded as the primary outcome. Multivariate logistic regression was used to establish a novel risk score for DLT events by the abovementioned variables. The above-mentioned risk score was validated in another cohort., Results: The overall DLT events during the first cycle of IC for 179 HNC patients was 24%. After stratifying by gender, docetaxel per kilogram LBM > 2.52 mg/kg (adjusted odds ratio [aOR]: 3.18; 95% confidence interval [CI], 1.25-8.09), pre-treatment glutamic pyruvic transaminase (GPT) > 40 U/L (aOR, 2.61; 95% CI, 1.03-6.64), and history of chronic liver diseases (aOR, 3.98; 95% CI, 1.03-15.46) were significant variables in male HNC patients. The DLT events risk was categorized by summation of the above-mentioned risk factors for male HNC patients. Three risk groups were stratified by overall event of 17.6%, 25.8%, and 75%. The above-mentioned risk score had an acceptable discriminatory ability in another validation cohort., Conclusions: Among male HNC patients treated with IC, docetaxel per kilogram LBM more than 2.52 mg/kg, pre-treatment GPT > 40 U/L, and history of chronic liver disease were significant risk factors for DLT events. Identifying high-risk patients could help physicians prevent severe/fatal complications among HNC patients undergoing IC, especially for the male individuals., (© 2022. The Author(s).)

The current study aimed to investigate the association between serum UA levels and the mortality rate of AMI patients. We analyzed 5888 patients with successfully revascularized AMI (mean age: 64.0 ± 12.7 years). The subjects were divided into the high UA group (uric acid >6.5 mg/dL for males, >5.8 mg/dL for females) or the normal UA group based on initial serum UA level measured at admission. The primary outcome was all-cause mortality. A total of 4141 (70.3%) and 1747 (29.7%) patients were classified into the normal UA group and high UA groups, respectively. Over a median follow-up of 5.02 (3.07, 7.55) years, 929 (21.5%) and 532 (34.1%) patients died in each group. Cox regression analysis identified high UA levels as an independent predictor of all-cause mortality (unadjusted hazard ratio (HR) 1.69 [95% CI 1.52−1.88]; p < 0.001, adjusted HR 1.18 [95% CI: 1.05−1.32]; p = 0.005). The results were consistent after propensity-score matching and inverse probability weighting to adjust for baseline differences. The predictive accuracies of conventional clinical factor discrimination and reclassification were significantly improved upon the addition of hyperuricemia (C-index 0.788 [95% CI 0.775−0.801]; p = 0.005, IDI 0.004 [95% CI 0.002−0.006]; p < 0.001, NRI 0.263 [95% CI 0.208−0.318]; p < 0.001)., Competing Interests: The authors declare no conflict of interest.

Background: Differences in the impact of the 1- or 2-stent strategy in similar coronary bifurcation lesion conditions are not well understood. This study investigated the clinical outcomes and its predictors between 1 or 2 stents in propensity score-matched (PSM) complex bifurcation lesions., Methods and results: We analyzed the data of patients with bifurcation lesions, obtained from a multicenter registry of 2,648 patients (median follow up, 53 months). The patients were treated by second generation drug-eluting stents (DESs). The primary outcome was target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TVMI), and ischemia-driven target lesion revascularization (TLR). PSM was performed to balance baseline clinical and angiographic discrepancies between 1 and 2 stents. After PSM (N=333 from each group), the 2-stent group had more TLRs (hazard ratio [HR] 3.14, 95% confidence interval [CI] 1.42-6.97, P=0.005) and fewer hard endpoints (composite of cardiac death and TVMI; HR 0.44, 95% CI 0.19-1.01, P=0.054), which resulted in a similar TLF rate (HR 1.40, 95% CI 0.83-2.37, P=0.209) compared to the 1-stent group. Compared with 1-stent, the 2-stent technique was more frequently associated with less TLF in the presence of main vessel (p interaction =0.008) and side branch calcification (p interaction =0.010)., Conclusions: The 2-stent strategy should be considered to reduce hard clinical endpoints in complex bifurcation lesions, particularly those with calcifications.

This study aimed to investigate the relationship between a complex percutaneous coronary intervention (C-PCI) and long-term clinical outcomes in the AMI cohort. A total of 10,329 patients were categorized into the C-PCI and non-C-PCI groups. The primary ischemic endpoint was a composite of major adverse cardiac events (MACEs, cardiac death, myocardial infarction, stent thrombosis and revascularization). The primary bleeding endpoint was the risk of overt bleeding (BARC 2, 3 or 5). The median follow-up duration was 4.9 (2.97, 7.16) years. The risks of MACEs and bleeding were significantly higher in the C-PCI group (hazard ratio (HR): 1.72; 95% confidence interval (CI): 1.60 to 1.85; p < 0.001; and HR: 1.32; 95% CI: 1.17 to 1.50; p < 0.001, respectively). After propensity score matching, compared to the non-C-PCI group, the adjusted MACE rate in C-PCI remained significantly higher (p < 0.001), but no significant interaction (p = 0.273) was observed for bleeding. Significant differences in overt bleeding were observed only within the first three months (p = 0.024). The MACEs were consistently higher in the C-PCI group with or without severe comorbid conditions (p < 0.001 for both). Patients with AMI who undergo C-PCI experience worse long-term ischemic outcomes after successful PCI, regardless of the presence of severe comorbidities.

Heart failure (HF) is a frequent consequence of myocardial infarction (MI). Identification of the precise, time-dependent composition of inflammatory cells may provide clues for the establishment of new biomarkers and therapeutic approaches targeting post-MI HF. Here, we investigate the spatiotemporal dynamics of MI-associated immune cells in a mouse model of MI using spatial transcriptomics and single-cell RNA-sequencing (scRNA-seq). We identify twelve major immune cell populations; their proportions dynamically change after MI. Macrophages are the most abundant population at all-time points (>60%), except for day 1 post-MI. Trajectory inference analysis shows upregulation of Trem2 expression in macrophages during the late phase post-MI. In vivo injection of soluble Trem2 leads to significant functional and structural improvements in infarcted hearts. Our data contribute to a better understanding of MI-driven immune responses and further investigation to determine the regulatory factors of the Trem2 signaling pathway will aid the development of novel therapeutic strategies for post-MI HF., (© 2022. The Author(s).)

This study aimed to investigate the efficacy of the HFA-PEFF score in predicting the long-term risks in patients with acute myocardial infarction (AMI) and an HFA-PEFF score ≥ 2. The subjects were divided according to their HFA-PEFF score into intermediate (2−3 points) and high (4−6 points) score groups. The primary outcome was all-cause mortality. Of 1018 patients with AMI and an HFA-PEFF score of ≥2, 712 (69.9%) and 306 (30.1%) were classified into the intermediate and high score groups, respectively. Over a median follow-up of 4.8 (3.2, 6.5) years, 114 (16.0%) and 87 (28.4%) patients died in each group. Multivariate Cox regression identified a high HFA-PEFF score as an independent predictor of all-cause mortality [hazard ratio (HR): 1.53, 95% CI: 1.15−2.04, p = 0.004]. The predictive accuracies for the discrimination and reclassification were significantly improved (C-index 0.750 [95% CI 0.712−0.789]; p = 0.049 and NRI 0.330 [95% CI 0.180−0.479]; p < 0.001) upon the addition of a high HFA-PEFF score to clinical risk factors. The model was better at predicting combined events of all-cause mortality and heart failure readmission (C-index 0.754 [95% CI 0.716−0.791]; p = 0.033, NRI 0.372 [95% CI 0.227−0.518]; p < 0.001). In the AMI cohort, the HFA-PEFF score can effectively predict the prognosis of patients with an HFA-PEFF score of ≥2.

Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy in Taiwan. Therefore, refining the diagnostic sensitivity of biomarkers for early-stage tumours and identifying therapeutic targets are critical for improving the survival rate of HNSCC patients. Metabolic reprogramming contributes to cancer development and progression. Metabolic pathways, specifically, play a crucial role in these diverse biological and pathological processes, which include cell proliferation, differentiation, apoptosis and carcinogenesis. Here, we investigated the role and potential prognostic value of the ubiquitin-conjugating enzyme E2 (UBE2) family in HNSCC. Gene expression database analysis followed by tumour comparison with non-tumour tissue showed that UBE2C was upregulated in tumours and was associated with lymph node metastasis in HNSCC patients. Knockdown of UBE2C significantly reduced the invasion/migration abilities of SAS and CAL27 cells. UBE2C modulates glycolysis pathway activation and HIF-1α expression in SAS and CAL27 cells. CoCl 2 (HIF-1α inducer) treatment restored the expression of glycolytic enzymes and the migration/invasion abilities of UBE2C knockdown cells. Based on our findings, UBE2C expression mediates HIF-1α activation, increasing glycolysis pathway activation and the invasion/migration abilities of cancer cells. UBE2C may be an independent prognostic factor and a therapeutic target in HNSCC., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: In-laboratory, polysomnography (PSG) is the gold standard for diagnosing obstructive sleep apnea syndrome (OSAS). However, the long waiting list and sleeping at a hospital make patients hesitate to undergo the examination, thereby delaying diagnosis. During coronavirus disease 2019 (COVID-19) pandemic, sleep labs are almost closed, and the delay is worsening. The home sleep test (HST) enables subjects to be tested at home, a familiar and comfortable environment, without a long waiting list. This study assessed the accuracy of a type III HST in diagnosing OSAS in the Taiwanese population and identified factors affecting the diagnostic accuracy., Methods: This retrospective study included 67 patients with clinically suspected OSAS. All patients were allocated to receive both PSG and the HST. The apnea-hypopnea index (AHI) measured through PSG was used as the standard. The sensitivity, specificity, and accuracy of the HST in diagnosing and evaluating the severity of OSAS were analyzed., Results: Among the 67 patients, no significant difference was noted in the average AHI values obtained using PSG and the HST ( p = 0.103). The AHI obtained from HST was significantly correlated with that obtained from PSG, with the correlation coefficient being 0.779 ( p < 0.001). The sensitivity, specificity, and accuracy of the HST in diagnosing OSAS were 94.9%, 62.5%, and 91.0%, respectively, and 80.0%, 74.1%, and 77.6% in diagnosing moderate to severe OSAS. Furthermore, the difference in AHIs measured using the two tests were positively correlated with the severity of sleep apnea., Conclusion: The HST used in preliminary screening of patients with suspected OSAS achieved an accuracy of >90%. For patients with moderate to severe OSAS, the accuracy was below 80%. Therefore, for patients who receive an OSAS diagnosis through the HST, arrangement of PSG is recommended for determining the severity of the OSAS and giving proper treatment., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Warthin tumor with ulceration of the surrounding skin is extremely rare, making it difficult to differentiate from parotid cancer in the clinical setting. We report a 65-year-old man with a Warthin tumor in the right parotid gland that had ulceration of the overlying skin. The patient presented with right upper neck mass 2 years ago. Ultrasound and fine needle aspiration were done, and Warthin tumor was suspected. One year later, the mass was enlarged with ulceration of the skin. Superficial parotidectomy with fusiform excision of the skin was performed, and histopathological diagnosis revealed a Warthin tumor with inflammatory change. We proposed that this unique manifestation may have been induced by fine needle aspiration, enlargement of the tumor, and ischemic changes secondary to pulmonary arteriovenous malformations.

Purpose: The study aimed to evaluate 1) the correlation of doses of swallowing-related organs at risk (OAR) with severe swallowing-related late adverse effects (AE) in nasopharyngeal carcinoma (NPC) patients and 2) the effect of high mean doses of OARs on overall survival (OS)., Patients and Methods: This retrospective cohort study enrolled non-metastatic Stage I-IV NPC patients from January 2012 to June 2017. OAR mean doses and severe (≥G3) swallowing-related late AE (xerostomia, dysphagia, and lung infection) were evaluated by t -test and validated using receiver operating characteristic curves. The risk factors of OS were calculated by Cox regression methods., Results: This study enrolled 185 (43 female, 142 male) NPC patients, mean age 52.4 years, primarily with Stage III (93, 50.3%) or Stage IV (67, 36.2%) disease. The mean doses of pharyngeal constrictor muscle (PCM), superior-middle PCM (SMPCM), and superior PCM (SPCM) were significantly higher in those with severe (≥G3) lung infection than in those without (65.7 vs 62.2 Gy, p = 0.036; 68.1 vs 64.2 Gy, p = 0.015; and 70.0 vs 65.9 Gy, p = 0.012, respectively). Patients with severe (≥G3) dysphagia had significant higher mean doses of base of tongue (56.2 vs 50.2 Gy, p = 0.008), laryngeal box (50.6 vs 46.4 Gy, p = 0.036), PCM (65.4 vs 62.1 Gy, p = 0.008), SMPCM (67.1 vs 64.2 Gy, p = 0.014), and SPCM (69.3 vs 65.8 Gy, p = 0.004). Mean SMPCM dose >64.9 Gy (adjusted hazard ratio [aHR] = 3.2, 95% confidence interval [CI] 1.2-8.8, p = 0.021), age >62 years (aHR = 2.7, 95% CI 1.1-6.9, p = 0.032), N3 status (aHR = 4.0, 95% CI 1.8-9.0, p = 001), and severe late AE of lung infection (aHR = 4.6, 95% CI 1.5-14.0, p = 0.007) significantly affected OS., Conclusion: Severe lung infection and dysphagia were associated with significantly higher mean doses of PCM, SMPCM, and SPCM. Among these OARs, only a high SMPCM mean dose was a risk factor for OS in NPC patients., Competing Interests: All authors report no conflicts of interest in this work., (© 2022 Liu et al.)