The efficacy of enoxolone in reducing erythema and pain after laser treatment: A randomized split-face pilot study.

BACKGROUND: Enoxolone, derived from licorice, possesses potent anti-inflammatory, and antioxidant properties. However, its effectiveness in alleviating post-laser reactions has not been extensively studied. AIMS: This randomized split-face pilot study aimed to evaluate the effects of enoxolone on skin following laser treatment. PATIENTS/METHODS: Ten healthy subjects underwent non-ablative 1550 nm Er:Glass fractional laser treatment and then randomly applied a moisturizer without enoxolone on one side of the face and a dermo-cosmetic formular containing 2% enoxolone mixed with the same moisturizer on the other side. The erythema index (EI), clinician's erythema assessment (CEA), and pain scores were recorded at 30 min, 60 min, and 24 h posttreatment. RESULTS: The group treated with enoxolone showed significantly lower EI and CEA compared to the control group at 24 h posttreatment. Additionally, pain scores were notably reduced in the enoxolone-treated group 30 min after treatment. CONCLUSIONS: This study suggests that dermo-cosmetic formular containing 2% enoxolone is effective in reducing erythema and pain following laser treatment.

Prediction of dysphagia aspiration through machine learning-based analysis of patients' postprandial voices.

BACKGROUND: Conventional diagnostic methods for dysphagia have limitations such as long wait times, radiation risks, and restricted evaluation. Therefore, voice-based diagnostic and monitoring technologies are required to overcome these limitations. Based on our hypothesis regarding the impact of weakened muscle strength and the presence of aspiration on vocal characteristics, this single-center, prospective study aimed to develop a machine-learning algorithm for predicting dysphagia status (normal, and aspiration) by analyzing postprandial voice limiting intake to 3 cc. METHODS: Conducted from September 2021 to February 2023 at Seoul National University Bundang Hospital, this single center, prospective cohort study included 198 participants aged 40 or older, with 128 without suspected dysphagia and 70 with dysphagia-aspiration. Voice data from participants were collected and used to develop dysphagia prediction models using the Multi-Layer Perceptron (MLP) with MobileNet V3. Male-only, female-only, and combined models were constructed using 10-fold cross-validation. Through the inference process, we established a model capable of probabilistically categorizing a new patient's voice as either normal or indicating the possibility of aspiration. RESULTS: The pre-trained models (mn40_as and mn30_as) exhibited superior performance compared to the non-pre-trained models (mn4.0 and mn3.0). Overall, the best-performing model, mn30_as, which is a pre-trained model, demonstrated an average AUC across 10 folds as follows: combined model 0.8361 (95% CI 0.7667-0.9056; max 0.9541), male model 0.8010 (95% CI 0.6589-0.9432; max 1.000), and female model 0.7572 (95% CI 0.6578-0.8567; max 0.9779). However, for the female model, a slightly higher result was observed with the mn4.0, which scored 0.7679 (95% CI 0.6426-0.8931; max 0.9722). Additionally, the other models (pre-trained; mn40_as, non-pre-trained; mn4.0 and mn3.0) also achieved performance above 0.7 in most cases, and the highest fold-level performance for most models was approximately around 0.9. The 'mn' in model names refers to MobileNet and the following number indicates the 'width_mult' parameter. CONCLUSIONS: In this study, we used mel-spectrogram analysis and a MobileNetV3 model for predicting dysphagia aspiration. Our research highlights voice analysis potential in dysphagia screening, diagnosis, and monitoring, aiming for non-invasive safer, and more effective interventions. TRIAL REGISTRATION: This study was approved by the IRB (No. B-2109-707-303) and registered on clinicaltrials.gov (ID: NCT05149976).

Efficacy and Safety of PrabotulinumtoxinA in Subjects With Benign Masseteric Hypertrophy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Phase 3 Trial and Open-Label Extension Study.

BACKGROUND: Despite the widespread use of botulinum toxin (BTX) injection for the treatment of masseter muscle hypertrophy (MMH), there is no standard treatment option. OBJECTIVE: We report the efficacy and safety for BTX in MMH over a period of 48 weeks. METHODS: In double-blinded, placebo-controlled phase 3 trials, 180 patients (randomized 1:1) received treatment with placebo (normal saline) or prabotulinumtoxinA (48 units). Masseter muscle thickness (at maximal clenching and resting positions), 3D imaging analysis, and masseter muscle hypertrophy scale grades were analyzed at each time point. After the 24-week CORE study, all patients who met the same criteria of the CORE study at week 24 (n = 114) received only prabotulinumtoxinA, regardless of previous treatment, for an additional 24 weeks (48 weeks in total) for the open-label extension study. RESULTS: The largest differences in mean and percent changes from baseline in masseter muscle thickness were observed at 12 weeks, and there were significant differences between the 2 groups at all time points (all p < .001). The effect was independent of the number of injections. No serious adverse event was observed. CONCLUSION: PrabotulinumtoxinA could effectively ameliorate MMH without major complications.

RETRACTED: Choi et al. Validation of the CHA2DS2-VA Score (Excluding Female Sex) in Nonvalvular Atrial Fibrillation Patients: A Nationwide Population-Based Study. J. Clin. Med. 2022, 11, 1823.

The journal retracts the article "Validation of the CHA2DS2-VA Score (Excluding Female Sex) in Nonvalvular Atrial Fibrillation Patients: A Nationwide Population-Based Study" [...].

Application of 3D scanner to measure physical size and improvement of hip brace manufacturing technology in severe cerebral palsy patients.

This prospective pilot study aimed to develop a personalized hip brace for treating hip subluxation in children with cerebral palsy. Nineteen children, aged 1-15, with severe cerebral palsy participated in the study. Customized hip braces were created based on 3D scanner measurements and worn for 7 days. The primary outcome, Hip Migration Index (MI), and secondary outcomes, including range of motion (ROM) in the hip and knee joints, pain intensity, satisfaction, discomfort scores, CPCHILD, and wearability test, were assessed. The MI and ROM were assessed at screening and at Visit 1 (when the new hip brace was first worn), while other indicators were evaluated at screening, Visit 1, and Visit 2 (7 days after wearing the new hip brace). The study demonstrated significant improvements in the MI for the right hip, left hip, and both sides. However, there were no statistically significant differences in hip and knee joint ROM. Other indicators showed significant changes between screening, Visit 1, and Visit 2. The study suggests that customized hip braces effectively achieved immediate correction, positively impacting the quality of life and satisfaction in children with cerebral palsy. Furthermore, the hip braces have the potential to enhance compliance and prevent hip subluxation.Clinical Trial Registration number: NCT05388422.

Long-pulsed 1,064-nm gallium arsenide laser surgical device treatment for improving symptoms of onychomycosis: a comparative analysis.

BACKGROUND: Onychomycosis is the most common infective nail disease, and treatment includes topical and systemic antifungal medications. Recently, laser therapy has emerged as a therapeutic option for patients who are unable to take oral antifungal agents. We investigated the effectiveness and safety of a novel long-pulsed 1,064-nm gallium arsenide (GaAs) laser surgical device for onychomycosis. METHODS: This 24-week single-center, single-blind, active-controlled exploratory clinical study comparatively evaluated the long-pulsed 1,064-nm GaAs laser (Healer1064) with the short-pulsed Nd:YAG laser surgical device in 20 participants randomly assigned to receive either test or control treatment at 4-week intervals during the 12-week treatment period. The rate of clinical improvement was evaluated by two independent dermatologist evaluators using the Onychomycosis Severity Index-score (OSI-score) and Turbidity Scale with standard photographs. Overall improvement and patient satisfaction were evaluated. Safety evaluation included pain intensity and adverse events. RESULTS: In 44 (test: 25; control: 19) cases in 19 participants who completed treatment, the clinical improvement rate in the test and control groups was 52.00% (13/52 cases) and 44.44% (9/19 cases), respectively, with significantly lower pain scores in the test than the control group for every treatment visit (P < 0.05) and without severe adverse events. CONCLUSIONS: The novel long-pulsed 1,064-nm GaAs laser showed greater, albeit nonsignificant, clinical improvement and was associated with less pain during treatment. Thus, the Healer1064 can provide satisfactory treatment outcomes through painless and effective improvement in onychomycosis symptoms.

Management strategies for vascular complications in hyaluronic acid filler injections: A case series analysis.

BACKGROUND: As hyaluronic acid (HA) filler injections have become increasingly popular in the esthetic field, so have their side effects. Vascular complications, which can lead to skin necrosis or permanent scarring, are a particularly dangerous complication and occur when the filler is injected directly into a blood vessel or when an adjacent blood vessel is compressed by the filler material. OBJECTIVE: To assess the clinical prognosis based on post-procedural management and clinical findings of HA filler vascular complications. METHODS: Herein, we present a case series of vascular complications due to HA filler and evaluate their clinical prognosis based on post-procedural management and clinical findings. Clinical assessments were performed using Doppler ultrasound, thermography, and laboratory tests. RESULTS: Factors including white blood cell count, the time of treatment initiation, and time of hyaluronidase injection influenced the clinical outcomes. Early recognition and prompt hyaluronidase injection proved crucial in preventing further damage and improving prognosis. CONCLUSION: This case series highlights the importance of early detection and appropriate management of HA filler complications. Physicians should be aware of the potential risks associated with fillers and promptly address any adverse effects to achieve optimal clinical outcomes. Further studies are warranted to confirm these findings and refine treatment strategies for the HA filler complications.

Usefulness of antegrade foam sclerotherapy for portal hypertensive variceal bleeding.

PURPOSE: This study investigates the usefulness of antegrade variceal embolization using sclerosant foam to evaluate technical success and clinical outcomes in cases of hypertensive variceal bleeding. METHODS: A total of 16 patients underwent percutaneous antegrade variceal embolization using foam sclerotherapy from August 2019 to January 2022. Among the patients, 12 cases were of gastroesophageal varices, two were rectal varices, and one case each was duodenal and jejunal varices, respectively. Sodium tetradecyl sulfate (STS) foam was used as a detergent for variceal bleeding sclerotherapy at various anatomical locations. The detergent was used in a foam form to promote clinical outcomes and enable the effective embolization of the entire blood vessel wall, including the ventral side, against gravity. Furthermore, STS foam could be used to help sufficiently deliver the drug to distal segments. A balloon catheter was also used to block the antegrade flow and prevent the dilution of the sclerosant. Technical success was defined as the completion of sclerotherapy for variceal bleeding as planned before the procedure to achieve the disappearance of variceal bleeding. Clinical success was defined as the complete obliteration of varices without recurrent bleeding during the follow-up period after the procedure. RESULTS: Technical success was 81.3%, and clinical success was 84.6%. Additionally, 15/16 of the procedures were emergencies, and there were no complications related to the procedure. CONCLUSION: Antegrade foam sclerotherapy using 3% STS for variceal bleeding is clinically safe and effective. Moreover, antegrade foam sclerotherapy can be a useful treatment option for patients with active variceal bleeding in emergency cases.

Kinematic mechanism of the rehabilitative effect of 4-channel NMES: post-hoc analysis of a prospective randomized controlled study.

The sequential 4-channel neuromuscular electrical stimulation (NMES), based on the normal contractile sequences of swallowing-related muscles, is a new rehabilitative treatment. The objective of this study was to explore the mechanism of the rehabilitative effect of the 4-channel NMES using kinematic analysis of videofluoroscopic swallowing study (VFSS) data. For this post-hoc analysis, we included a subset of participants from the prospective randomized controlled study on the clinical effectiveness of the sequential 4-channel NMES compared with that of the conventional 2-channel NMES. Seventeen subjects (11 and six in the 4- and 2-channel NMES groups, respectively) were eligible for the kinematic analysis of VFSS data. The hyoid bone movement was analyzed by evaluating the distance and time parameters with four peak points (A, B, C, D). The 4-channel NMES group showed significant improvement in vertical distances (A-C), horizontal distance (A-B, A-C), time interval (A-B-C) and total time, compared with their pretreatment data. The 2-channel NMES group showed significant improvements in time interval (A-B); however, the Euclidean distance (A-D) and mean velocity of the Euclidean distance (A-C) were significantly decreased. When the two groups were directly compared, the 4-channel group showed significantly greater improvement in horizontal distance (A-B), Euclidean distance (A-D), time interval (A-B-C), and mean velocity the Euclidean distance (A-D). The results in this study suggest that the sequential 4-channel NMES might lead to the physiologic circular movement of the hyoid bone during swallowing, and therefore be an effective treatment for dysphagia.Trial registration: Clinicaltrials.gov, registration number: NCT03670498.

Statin therapy reduces dementia risk in atrial fibrillation patients receiving oral anticoagulants.

AIMS: Atrial fibrillation (AF) is linked to an increased risk of dementia, even in stroke-free patients. The impact of statin therapy on dementia risk is unclear in AF patients receiving oral anticoagulant (OAC) (vitamin K antagonist and direct-acting OAC). We sought to investigate the impact of statin therapy on dementia risk in AF patients receiving OAC. METHODS AND RESULTS: Using the Korean National Health Insurance Service database, 91 018 non-valvular AF (NVAF) patients from January 2013 to December 2017 were included in the analysis. Of the total, 17 700 patients (19.4%) were in the statin therapy group, and 73 318 patients (80.6%) were in the non-statin therapy group. The primary endpoint was the occurrence of dementia. The median duration of follow-up was 2.1 years. Statin therapy was associated with a significantly lower dementia risk than non-statin therapy for CHA2DS2-VASc scores ≥2 (hazard ratio = 0.77, 95% confidence interval 0.64-0.90, P = 0.026) in NVAF patients receiving OAC. The statin therapy group had a significantly lower dementia risk in a dose-dependent relationship compared with the non-statin therapy group (P for trend <0.001). CONCLUSION: In NVAF patients who received OAC, statin therapy lowered the dementia risk compared with no statin therapy. Furthermore, statin therapy is associated with a dose-dependent reduction in dementia risk.

Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis.

Contrary to many reports that antiplatelet agents inhibit cancer growth and metastasis, new solid tumors have been reported in patients receiving long-term antiplatelet therapy. We investigated the effects of these agents directly on cancer cells in the absence of platelets to mimic the effects of long-term therapy. When four antiplatelet agents (aspirin, clopidogrel, prasugrel, and ticagrelor) were administered to colon cancer cells, cancer cell proliferation was inhibited similarly to a previous study. However, surprisingly, when cells were treated with a purinergic P2Y12 inhibitor (purinergic antiplatelet agent), the motility of the cancer cells was significantly increased. Therefore, gene expression profiles were identified to investigate the effect of P2Y12 inhibitors on cell mobility, and Serpin family 1 (SERPINE1) was identified as a common gene associated with cell migration and cell death in three groups. Antiplatelet treatment increased the level of SERPINE1 in cancer cells and also promoted the secretion of SERPINE1 into the medium. Increased SERPINE1 was found to induce MMP1 and, thus, increase cell motility. In addition, an increase in SERPINE1 was confirmed using the serum of patients who received these antiplatelet drugs. With these results, we propose that SERPINE1 could be used as a new target gene to prevent the onset and metastasis of cancer in patients with long-term antiplatelet therapy.

Directing ricin-based immunotoxins with targeting affibodies and KDEL signal peptide to cancer cells effectively induces apoptosis and tumor suppression.

The plant toxin ricin, especially its cytotoxic A chain (RTA), can be genetically engineered with targeting ligands to develop specific anti-cancer recombinant immunotoxins (RITs). Here, we used affibody molecules targeting two cancer biomarkers, the receptors HER2 and EGFR, along with the KDEL signal peptide to construct two cancer-specific ricin-based RITs, HER2Afb-RTA-KDEL and EGFRAfb-RTA-KDEL. The affibodies successfully provided target-specificity and subsequent receptor-mediated endocytosis and the KDEL signal peptide routed the RITs through the retrograde transport pathway, effectively delivering RTA to the cytosol as well as avoiding the alternate recycling pathway that typical cancer cells frequently have. The in vivo efficacy of RITs was enhanced by introducing the albumin binding domain (AlBD) to construct AlBD/HER2Afb/RTA-KDEL. Systemic administration of AlBD-containing RITs to tumor-bearing mice significantly suppressed tumor growth without any noticeable side-effects. Collectively, combining target-selective affibody molecules, a cytotoxic RTA, and an intracellularly designating peptide, we successfully developed cancer-specific and efficacious ricin-based RITs. This approach can be applied to develop novel protein-based "magic bullets" to effectively suppress tumors that are resistant to conventional anti-cancer drugs.

Fracture Resistance of Monolithic Zirconia Crowns Depending on Different Marginal Thicknesses.

Under some clinical conditions, the preparation of crowns of limited marginal thickness is inevitable. In such situations, it is questionable whether the same ideal preparation criteria can be applied equally. Since there are only a small number of studies focusing on the fracture resistance with respect to the marginal thickness, there is a need for a study evaluating whether zirconia crowns of limited marginal thickness are clinically acceptable. The purpose of this study is to evaluate the fracture resistance of monolithic zirconia crowns of limited marginal thickness in the posterior area. Methods: Abutments and CAD/CAM zirconia crowns with a marginal thickness of 1.0 mm were set as the control group, while experimental groups A, B, and C possessed reduced marginal thicknesses of 0.8 mm, 0.6 mm, and 0.4 mm, respectively (n = 10 per group). Resin-based abutment dies and monolithic zirconia crowns were fabricated using the CAD/CAM technique, and a universal testing machine was used to measure the fracture load value. Fractured specimens were examined with a scanning electron microscope. The data were analyzed using a one-way ANOVA and Bonferroni post hoc test (p < 0.05). Results: The means and standard deviations of the fracture load values of the control group and the three experimental groups were as follows: control group (1.0 mm): 3090.91 ± 527.77 N; group A (0.8 mm): 2645.39 ± 329.21 N; group B (0.6 mm): 2256.85 ± 454.15 N; group C (0.4 mm): 1957.8 ± 522.14 N. Conclusions: The crowns fabricated with a CAD/CAM zirconia block with limited marginal thicknesses of 0.6 mm and 0.4 mm showed significantly lower fracture resistance values compared to those with the recommended margin thickness of 1.0 mm.

Cryolipolysis for abdominal subcutaneous fat reduction: A prospective, multicenter, single arm, clinical study.

Various treatment methods are used for noninvasive body contouring. To evaluate the efficacy and safety of a newly designed cryolipolysis device using a three-dimensional cooling method for abdominal fat reduction. Twenty-five participants with clinically apparent abdominal fat tissue participated in the study. The thickness of fat tissue below the umbilicus level was measured using a caliper at baseline and 12 weeks after the first treatment. The height of abdominal subcutaneous fat tissue on ultrasonography and participant satisfaction were assessed at every visit for 16 weeks. All adverse events (AEs) during the study period were recorded. p values <0.05 were considered statistically significant. Twenty-four participants completed this study; the mean BMI of participants was 29.34 ± 2.36 kg/m2 . The mean thickness of abdominal subcutaneous fat was significantly lower at 12 weeks (40.4 ± 6.8 mm, p < 0.001) than at baseline (49.3 ± 8.5 mm). Differences in the height of abdominal subcutaneous fat compared to that at baseline were 1.02 ± 0.41 cm (12 weeks, p < 0.001) and 1.13 ± 0.44 cm (16 weeks, p < 0.001). Rates of abdominal subcutaneous fat reduction at 12 and 16 weeks compared to that at baseline were 28.45% and 31.13%, respectively. The ratio of abdominal circumference to hip circumference at 12 and 16 weeks was significantly decreased compared to that at baseline. Most participants (95.8%) reported improvement in satisfaction scores at 16 weeks. There were no serious AEs during the entire study period. The study demonstrated the efficacy of a noninvasive cryolipolysis device using a three-dimensional cooling method for reducing abdominal subcutaneous fat.

Validation of the CHA2DS2-VA Score (Excluding Female Sex) in Nonvalvular Atrial Fibrillation Patients: A Nationwide Population-Based Study.

Sex (i.e., female sex) confers one point for the CHA2DS2-VASc score. For this reason, females with atrial fibrillation (AF) always have a CHA2DS2-VASc score of at least 1. To compare the CHA2DS2-VA (excluding female sex) and CHA2DS2-VASc scores in Korean AF patients using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke in nonvalvular AF patients between 2013 and 2017. The predictive values of the CHA2DS2-VA and CHA2DS2-VASc scores for ischemic stroke were evaluated using the C-statistic and net reclassification improvement (NRI). The primary outcome was the occurrence of ischemic stroke. A total of 185,637 patients with AF (49.7% women) were included in this study. The mean ages were 66.5 years for females and 64.9 years for males. The incidence of ischemic stroke in male patients was similar to females (3.63%/year vs. 3.72%/year, p = 0.273, respectively). In addition, no sex difference was apparent for stroke risk in AF patients stratified by risk factor component and age group. In the C-statistic analysis, the predictive ability of the CHA2DS2-VA score for ischemic stroke was similar to the CHA2DS2-VASc score. Additionally, CHA2DS2-VA performed better for predicting ischemic stroke in AF patients with risk scores of ≥2 (AUC 0.701 vs. 0.689, z = 4.596, p < 0.001) or those aged ≥75 years (AUC 0.715 vs. 0.701, z = 4.957, p < 0.001). In Korean AF patients, female sex is not a specific risk factor that contributes to the development of ischemic stroke. The CHA2DS2-VA score, which excludes female sex, may be a more suitable risk score for guiding anticoagulation decisions in Korean AF patients.

A randomized, participant- and evaluator-blinded, matched-pair prospective study to compare the safety and efficacy between polycaprolactone-based fillers in the correction of nasolabial folds.

Polycaprolactone (PCL)-based fillers are widely used for skin rejuvenation and wrinkle reduction. The objective of this study is to compare the efficacy and safety of newly developed PCL-based fillers (SYB filler®; SF-01) and widely used existing PCL-based fillers (Ellansé-M®) for correction of moderate-to-severe nasolabial folds. In a randomized, participant-and evaluator-blinded, matched-pair, prospective study, participants were randomized for injections of SF-01 or Ellansé-M® in both nasolabial folds. Efficacy was evaluated using the Wrinkle Severity Rating Scale (WSRS), Global Esthetic Improvement Scale (GAIS), and a three-dimensional (3D) scanner. All adverse events (AEs) were examined and reported. At month 12, both SF-01-and Ellansé-M®-treated groups showed statistically significant improvements in the WSRS, GAIS, and 3D scanner scores compared to baseline. The difference in changes in WSRS scores at month 12 between the two groups was 0.08 ± 0.34 compared to baseline. The upper limit of the 95.0% confidence interval was 0.0031, which was lower than the predefined margin for non-inferiority (0.35). All AEs were injection site-related (swelling, pain, and erythema) and disappeared within 30 min after the procedure. SF-01 was non-inferior to Ellansé-M® and demonstrated favorable efficacy and safety at 12 months after correcting moderate-to-severe nasolabial folds.

Safety and efficacy of high-intensity focused ultrasound for treatment of periorbital, perioral, and neck wrinkles: Prospective open single-center single-arm confirmatory clinical trial.

Periorbital, perioral, and neck wrinkles are one of the most common concerns of aging skin. We evaluated the efficacy and safety of high-intensity focused ultrasound (HIFU) device with a 5.5-MHz transducer and a 2.0-mm focal depth for improving periorbital, perioral, and neck wrinkles. A total of 102 participants were enrolled, and 34 each were assigned to the periorbital, perioral, and neck groups. All subjects were treated with HIFU three times at 2-week intervals at the corresponding treatment site. Objective measurements and clinical evaluations were performed at 10 and 16 weeks after treatment. Based on the primary efficacy evaluation, the mean Cutometer R7 value was significantly increased at 10 weeks post-treatment compared to baseline in all treated groups. In addition, all other Cutometer values, PRIMOS and Antera 3D camera evaluation results, classification of wrinkle assessment results, and Subject Global Aesthetic Improvement Scale also showed that the periorbital, perioral, and neck wrinkles were significantly improved at 10 and 16 weeks post-treatment. No permanent adverse effects were observed during the follow-up period. HIFU treatment using 5.5-MHz transducers (2.0-mm focal depth) could be an effective and safe treatment modality for the treatment of periorbital, perioral, and neck wrinkles.