Clinicopathological characteristics of unicentric Castleman disease: A single-center experience of 12 patients.

BACKGROUND: Castleman disease (CD) is an uncommon lymphoproliferative disorder with distinct pathological characteristics. Unicentric Castleman disease (UCD) presents as a single lymph node enlargement, often without significant symptoms. Complete surgical resection is the standard treatment for UCD. This study aimed to explore the clinicopathological features of UCD in a Taiwanese population. METHODS: We retrospectively identified 12 patients with UCD who had undergone surgical treatment between January 1, 2006 and June 30, 2022 at the National Taiwan University Hospital. Clinical and radiological findings were retrieved from medical records. All available pathological slides were reviewed. RESULTS: The patients' mean age was 38.1 years (range, 17 to 69); five (41.7%) were male, and seven (58.3%) were female. Nearly all cases of UCD were in the mediastinum, except for one case in the neck. Most patients were asymptomatic and without abnormal laboratory test results. Computed tomography revealed well-defined tumor borders, contrast enhancement, and occasional calcification. Ten patients underwent en bloc tumor resection, while the remaining two underwent partial resection. Among them, seven (58.3%) underwent video-assisted thoracoscopic surgery (VATS), and four (33.3%) underwent thoracotomy. The mean follow-up duration was 92 months. The patients who underwent total resection had no recurrence. CONCLUSION: Detailed clinicopathological information on UCD in the Taiwanese population is present in our article. Both complete and partial surgery are effective for treatment. VATS may be preferred over thoracotomy due to less operative time and bleeding.

Continuous Positive Airway Pressure Treatment and Hypertensive Adverse Outcomes in Pregnancy: A Systematic Review and Meta-Analysis.

Importance: Pregnancy may contribute to the development or exacerbation of obstructive sleep apnea (OSA) and increase the risk of gestational complications. Continuous positive airway pressure (CPAP) is the first-line and criterion standard treatment for OSA and is regarded as the most feasible choice during pregnancy. However, the association between CPAP therapy in pregnant women with OSA and reduced gestational complications remains inconclusive. Objective: To investigate the association between CPAP therapy in pregnant women with OSA and the reduction of adverse hypertensive outcomes during gestation. Data Sources: Keyword searches of PubMed, Embase, and the Cochrane Database of Systematic Reviews and Clinical Trials were conducted from inception to November 5, 2023. Study Selection: Original studies reporting the treatment effect of CPAP use on lowering hypertension and preeclampsia risks in pregnant women with OSA were selected. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed in the reporting of reviews. Data were independently extracted by 2 authors. Random-effects model meta-analyses were performed and risk ratios (RRs) reported. Subgroup analysis, meta-regression based on age and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and publication bias assessment were also conducted. Main Outcome and Measures: The primary outcome was the RR of gestational hypertension and preeclampsia between pregnant women with OSA receiving CPAP treatment and those who did not receive CPAP treatment. Results: Six original studies in 809 participants (mean age, 31.4 years; mean BMI, 34.0) were identified and systematically reviewed for meta-analysis. The pooled results showed significant differences between the intervention (CPAP use) and the control (non-CPAP use) groups in reducing the risk of gestational hypertension (RR, 0.65; 95% CI, 0.47-0.89; P = .008) and preeclampsia (RR, 0.70; 95% CI, 0.50-0.98; P = .04). Meta-regression revealed that patients' age (coefficient, -0.0190; P = .83) and BMI (coefficient, -0.0042; P = .87) were not correlated with reduction of risk of hypertension and preeclampsia. Conclusions and Relevance: These findings suggest that implementing CPAP treatment in pregnant women with OSA may reduce the risk of gestational hypertension and preeclampsia.

Importance of age at 2nd implantation and interimplant interval to the outcome of bilateral prelingually deafened pediatric cochlear implantation.

BACKGROUND: In Taiwan, the number of cases of sequential bilateral pediatric cochlear implantation (CI) is increasing but data regarding its effectiveness and impact of the reimbursement policy are lacking. We examined the speech perception and quality of life (QOL) of bilateral prelingually deaf children who underwent sequential CI, considering the effects of age at the time of second implantation and interimplant interval. METHODS: We enrolled 124 Mandarin-speaking participants who underwent initial cochlear implant (CI1) in 2001-2019 and a second CI (CI2) in 2015-2020. Patients were followed up for ≥2 years and were categorized into groups based on age at the time of CI2 implantation (<3.5, 3.6-7, 7.1-10, 10.1-13, and 13.1-18 years) and interimplant interval (0.5-3, 3.1-5, 5.1-7, 7.1-10, and >10 years). We evaluated speech perception, device usage rates, and QOL using subjective questionnaires (Speech, Spatial, and Qualities of Hearing and Comprehension Cochlear Implant Questionnaire). RESULTS: Speech perception scores of CI2 were negatively correlated with ages at the time of CI1 and CI2 implantation and interimplant interval. Older age and a longer interimplant interval were associated with higher nonuse rates for CI2 and worse auditory performance and QOL. Among individuals aged >13 years with interimplant intervals >10 years, up to 44% did not use their second ear. Patients aged 7.1 to 10 years had better speech perception and higher questionnaire scores than those aged 10.1 to 13 and 13.1 to 18 years. Furthermore, patients aged 10.1 to 13 years had a lower rate of continuous CI2 usage compared to those aged 7.1 to 10 years. CONCLUSION: Timely implantation of CI2 is essential to achieve optimal outcomes, particularly among sequentially implanted patients with long-term deafness in the second ear and no improvement with hearing aids following CI1 implantation. For CI2 implantation, an upper limit of age of 10 years and interimplant interval of 7 years are essential to prevent suboptimal outcomes. These data can provide useful information to implant recipients, their families, and medical and audiological professionals, enabling a comprehensive understanding of the benefits and potential impacts of the timing of CI2 implantation.

Systematic review and meta-analysis of AI-based conversational agents for promoting mental health and well-being.

Conversational artificial intelligence (AI), particularly AI-based conversational agents (CAs), is gaining traction in mental health care. Despite their growing usage, there is a scarcity of comprehensive evaluations of their impact on mental health and well-being. This systematic review and meta-analysis aims to fill this gap by synthesizing evidence on the effectiveness of AI-based CAs in improving mental health and factors influencing their effectiveness and user experience. Twelve databases were searched for experimental studies of AI-based CAs' effects on mental illnesses and psychological well-being published before May 26, 2023. Out of 7834 records, 35 eligible studies were identified for systematic review, out of which 15 randomized controlled trials were included for meta-analysis. The meta-analysis revealed that AI-based CAs significantly reduce symptoms of depression (Hedge's g 0.64 [95% CI 0.17-1.12]) and distress (Hedge's g 0.7 [95% CI 0.18-1.22]). These effects were more pronounced in CAs that are multimodal, generative AI-based, integrated with mobile/instant messaging apps, and targeting clinical/subclinical and elderly populations. However, CA-based interventions showed no significant improvement in overall psychological well-being (Hedge's g 0.32 [95% CI -0.13 to 0.78]). User experience with AI-based CAs was largely shaped by the quality of human-AI therapeutic relationships, content engagement, and effective communication. These findings underscore the potential of AI-based CAs in addressing mental health issues. Future research should investigate the underlying mechanisms of their effectiveness, assess long-term effects across various mental health outcomes, and evaluate the safe integration of large language models (LLMs) in mental health care.

Pharmacotherapy for obstructive sleep apnea - A systematic review and meta-analysis of randomized controlled trials.

Continuous positive airway pressure is the first-line and gold-standard treatment for obstructive sleep apnea (OSA). Pharmacotherapy is not commonly used in treating OSA until recently. Combined noradrenergic and antimuscarinic agents have been clinically applied for OSA patients with variable results. This meta-analysis study aimed to investigate the efficacy of the combined regimen on OSA. A systematic literature search was performed up to November 2022 for the effects of the combined regimen on OSA. Eight randomized controlled trials were identified and systematically reviewed for meta-analysis. There were significant mean differences between OSA patients taking a combined regimen and placebo in apnea-hypopnea index (AHI) [mean difference (MD) -9.03 events/h, 95%CI (-16.22, -1.83 events/h; P = 0.01] and lowest oxygen saturation [MD 5.61%, 95% CI % (3.43, 7.80); P < 0.01]. Meta-regression showed that a higher proportion of male participants was associated with a greater reduction of AHI (p = 0.04). This study showed a positive but modest effect of pharmacotherapy in the reduction of OSA severity. The combination drugs are most applicable to male OSA patients based on their efficacy and pharmacological susceptibility. Pharmacotherapy may be applied as an alternative, adjunctive or synergistic treatment under careful consideration of its side effects.

Dietary oxidized frying oil activates hepatic stellate cells and accelerates the severity of carbon tetrachloride- and thioacetamide-induced liver fibrosis in mice.

Deep-frying is a common cooking practice worldwide, and after repeated heating's, the oil undergoes various chemical reactions, including hydrolysis, polymerization, lipid oxidation, and the Maillard reaction. Studies have pointed out that oxidized dietary frying oil may cause teratogenesis in mice and increase cancer and cardiovascular risks. The liver is the main organ involved in dietary nutrient catabolism, detoxification, bile production, and lipid metabolism. Nevertheless, the effects of oxidized frying oil exposure on the activation of hepatic stellate cells (HSCs) and liver fibrosis are still unclear. In this study, we showed that exposure to oxidized frying oil enhanced the sensitivity of HSCs to transforming growth factor (TGF)-ß1-induced α-smooth muscle actin (α-SMA), collagen 1a2, collagen 1a1, metalloproteinase-2, and phosphorylated smad2/3 activation. In both carbon tetrachloride (CCl4)- and thioacetamide (TAA)-induced liver fibrosis mouse models, we showed that long-term administration of a 10% fried oil-containing diet significantly upregulated fibrogenesis genes expression and deposition of hepatic collagen. Furthermore, long-term fried oil exposure not only promoted macrophage infiltration and increased inflammatory-related gene expression, but also accumulated excess cholesterol and lipid peroxidation in the liver tissues. In conclusion, our study demonstrated that feeding a fried oil-containing diet may trigger TGF-ß1-induced HSCs activation and thereby promote liver damage and fibrosis progression through enhancing the inflammatory response and lipid peroxidation.

Isolated Epiglottic Manifestations of HIV Infection: Two Cases Reports.

Diagnosis of the Human Immunodeficiency Virus (HIV) remains challenging due to non-specific clinical presentations and mostly flu-like symptoms, e.g., fever, headache, sore throat, and general weakness. Oral lesions, such as oral candidiasis and Kaposi sarcoma, are also frequently associated with HIV infection, whereas laryngeal manifestations are rare. We report two cases of newly diagnosed HIV patients with clinical presentations of sore throat, and endoscopy revealed an epiglottic ulcerative tumor-like lesion. A laryngomicrosurgical biopsy of the lesions was performed for persistent symptoms and suspicion of malignancy. The result revealed acute and chronic inflammation without a conclusive pathology diagnosis. Further laboratory analysis was arranged in consideration of autoimmune diseases, Epstein-Barr virus (EBV), and HIV infection due to their persistent and atypical symptoms. The results were positive for HIV infection. These patients were treated successfully with antiviral treatment and the laryngeal symptoms improved within weeks. In patients with idiopathic and persistent epiglottitis or an epiglottic ulcer after medical treatment, HIV infection needs to be considered as a potential etiology in order to institute proper treatment.

Automated 3D segmentation of the aorta and pulmonary artery for predicting outcomes after thoracoscopic lobectomy in lung cancer patients.

Background: Preoperative two-dimensional manual measurement of pulmonary artery diameter in a single-cut axial view computed tomography (CT) image is a commonly used non-invasive prediction method for pulmonary hypertension. However, the accuracy may be unreliable. Thus, this study aimed to evaluate the correlation of short-term surgical outcomes and pulmonary artery/aorta (PA/Ao) diameter ratio measured by automated three-dimensional (3D) segmentation in lung cancer patients who underwent thoracoscopic lobectomy. Materials and methods: We included 383 consecutive lung cancer patients with thin-slice CT images who underwent lobectomy at a single institute between January 1, 2011 and December 31, 2019. Automated 3D segmentation models were used for 3D vascular reconstruction and measurement of the average diameters of Ao and PA. Propensity-score matching incorporating age, Charlson comorbidity index, and lobectomy performed by uniportal VATS was used to compare clinical outcomes in patients with PA/Ao ratio ≥1 and those <1. Results: Our segmentation method measured 29 (7.57%) patients with a PA/Ao ratio ≥1. After propensity-score matching, a higher overall postoperative complication classified by the Clavien-Dindo classification (p = 0.016) were noted in patients with 3D PA/Ao diameter ratio ≥1 than those of <1. By multivariate logistic regression, patients with a 3D PA/Ao ratio ≥ 1 (p = 0.013) and tumor diameter > 3 cm (p = 0.002) both significantly predict the incidence of postoperative complications. Conclusions: Pulmonary artery/aorta diameter ratio ≥ 1 measured by automated 3D segmentation may predict postoperative complications in lung cancer patients who underwent lobectomy.

Anti-Epstein-Barr Viral Agents from the Medicinal Herb-Derived Fungus Alternaria alstroemeriae Km2286.

Chromatographic separation on the liquid-state fermented products produced by the fungal strain Alternaria alstroemeriae Km2286 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1-9. Structures were determined by spectroscopic analysis as four undescribed perylenequinones, altertromins A-D (1-4), along with altertoxin IV (5), altertoxin VIII (6), stemphyperylenol (7), tenuazonic acid (8), and allo-tenuazonic acid (9). Compounds 1-6 exhibited antiviral activities against Epstein-Barr virus (EBV) with EC50 values ranging from 0.17 ± 0.07 to 3.13 ± 0.31 µM and selectivity indices higher than 10. In an anti-neuroinflammatory assay, compounds 1-4, 6, and 7 showed inhibitory activity of nitric oxide production in lipopolysaccharide-induced microglial BV-2 cells, with IC50 values ranging from 0.33 ± 0.04 to 4.08 ± 0.53 µM without significant cytotoxicity. This is the first report to describe perylenequinone-type compounds with potent anti-EBV and anti-neuroinflammatory activities.

Design and Evaluation Challenges of Conversational Agents in Health Care and Well-being: Selective Review Study.

BACKGROUND: Health care and well-being are 2 main interconnected application areas of conversational agents (CAs). There is a significant increase in research, development, and commercial implementations in this area. In parallel to the increasing interest, new challenges in designing and evaluating CAs have emerged. OBJECTIVE: This study aims to identify key design, development, and evaluation challenges of CAs in health care and well-being research. The focus is on the very recent projects with their emerging challenges. METHODS: A review study was conducted with 17 invited studies, most of which were presented at the ACM (Association for Computing Machinery) CHI 2020 conference workshop on CAs for health and well-being. Eligibility criteria required the studies to involve a CA applied to a health or well-being project (ongoing or recently finished). The participating studies were asked to report on their projects' design and evaluation challenges. We used thematic analysis to review the studies. RESULTS: The findings include a range of topics from primary care to caring for older adults to health coaching. We identified 4 major themes: (1) Domain Information and Integration, (2) User-System Interaction and Partnership, (3) Evaluation, and (4) Conversational Competence. CONCLUSIONS: CAs proved their worth during the pandemic as health screening tools, and are expected to stay to further support various health care domains, especially personal health care. Growth in investment in CAs also shows the value as a personal assistant. Our study shows that while some challenges are shared with other CA application areas, safety and privacy remain the major challenges in the health care and well-being domains. An increased level of collaboration across different institutions and entities may be a promising direction to address some of the major challenges that otherwise would be too complex to be addressed by the projects with their limited scope and budget.

The Impact of Mouth-Taping in Mouth-Breathers with Mild Obstructive Sleep Apnea: A Preliminary Study.

BACKGROUND: Many patients with obstructive sleep apnea (OSA) are mouth-breathers. Mouth-breathing not only narrows the upper airway, consequently worsening the severity of OSA, but also it affects compliance with nasal continuous positive airway pressure (CPAP) treatment. This study aimed to investigate changes in OSA by the use of mouth tape in mouth-breathers with mild OSA. METHOD: Mouth-breathers with mild OSA who met inclusion criteria and tolerated the sealing of the mouth were enrolled in the study. We used 3M silicone hypoallergenic tape was used to seal the mouths of the participants during sleep. The home sleep test (HST) used in this study was ApneaLink®. Subjects received both a baseline HST and an outcome HST to be used 1 week later while their mouths were taped. The changes between the baseline and the outcome HSTs were compared, and the factors that influenced the differences in the sleep-test parameters after the shift of the breathing route were analyzed. A "responder" was defined as a patient who experienced a reduction from the baseline snoring index of at least 50% under mouth-taping in the HST; otherwise, patients were considered as having a poor response. RESULTS: A total of 20 patients with mild OSA were included. Following the taping of the mouth, a good response was found in 13 patients (65%). The median apnea/hypopnea index (AHI) decreased significantly, from 8.3 to 4.7 event/h (by 47%, p = 0.0002), especially in supine AHI (9.4 vs. 5.5 event/h, p = 0.0001). The median snoring index (SI) was also improved (by 47%, 303.8 vs. 121.1 event/h, p = 0.0002). Despite no significant difference in the mean saturation, improvements in the oxygen desaturation index (8.7 vs. 5.8, p = 0.0003) and the lowest saturation (82.5% vs. 87%, p = 0.049) were noted. The change in AHI was associated with baseline AHI (r = -0.52, p = 0.02), oxygen desaturation index (ODI) (r = -0.54, p = 0.01), and SI (r = -0.47, p = 0.04). The change in SI was strongly associated with baseline SI (r = -0.77, p = 0.001). CONCLUSIONS: Mouth-taping during sleep improved snoring and the severity of sleep apnea in mouth-breathers with mild OSA, with AHI and SI being reduced by about half. The higher the level of baseline AHI and SI, the greater the improvement was shown after mouth-taping. Mouth-taping could be an alternative treatment in patients with mild OSA before turning to CPAP therapy or surgical intervention.

Correction: Wang et al. Automated 3D Segmentation of the Aorta and Pulmonary Artery on Non-Contrast-Enhanced Chest Computed Tomography Images in Lung Cancer Patients. Diagnostics 2022, 12, 967.

Errors occurred in the standard deviation of the Dice similarity coefficient (DSC) described in the original publication [...].

A Novel Methodology for Detecting Variations in Cell Surface Antigens Using Cell-Tearing by Optical Tweezers.

The quantitative analysis of cell surface antigens has attracted increasing attention due to the antigenic variation recognition that can facilitate early diagnoses. This paper presents a novel methodology based on the optical "cell-tearing" and the especially proposed "dilution regulations" to detect variations in cell surface antigens. The cell attaches to the corresponding antibody-coated slide surface. Then, the cell-binding firmness between a single cell and the functionalized surface is assayed by optically tearing using gradually reduced laser powers incorporated with serial antibody dilutions. Groups B and B3 of red blood cells (RBCs) were selected as the experiment subject. The results indicate that a higher dilution called for lower power to tear off the cell binding. According to the proposed relative-quantitative analysis theory, antigenic variation can be intuitively estimated by comparing the maximum allowable dilution folds. The estimation result shows good consistency with the finding in the literature. This study suggests a novel methodology for examining the variation in cell surface antigens, expected to be widely capable with potential sensor applications not only in biochemistry and biophysics, but also in the micro-/nano- engineering field.

Automated 3D Segmentation of the Aorta and Pulmonary Artery on Non-Contrast-Enhanced Chest Computed Tomography Images in Lung Cancer Patients.

Pulmonary hypertension should be preoperatively evaluated for optimal surgical planning to reduce surgical risk in lung cancer patients. Preoperative measurement of vascular diameter in computed tomography (CT) images is a noninvasive prediction method for pulmonary hypertension. However, the current estimation method, 2D manual arterial diameter measurement, may yield inaccurate results owing to low tissue contrast in non-contrast-enhanced CT (NECT). Furthermore, it provides an incomplete evaluation by measuring only the diameter of the arteries rather than the volume. To provide a more complete and accurate estimation, this study proposed a novel two-stage deep learning (DL) model for 3D aortic and pulmonary artery segmentation in NECT. In the first stage, a DL model was constructed to enhance the contrast of NECT; in the second stage, two DL models then applied the enhanced images for aorta and pulmonary artery segmentation. Overall, 179 patients were divided into contrast enhancement model (n = 59), segmentation model (n = 120), and testing (n = 20) groups. The performance of the proposed model was evaluated using Dice similarity coefficient (DSC). The proposed model could achieve 0.97 ± 0.66 and 0.93 ± 0.16 DSC for aortic and pulmonary artery segmentation, respectively. The proposed model may provide 3D diameter information of the arteries before surgery, facilitating the estimation of pulmonary hypertension and supporting preoperative surgical method selection based on the predicted surgical risks.

Non-opioid recreational drug use and a prolonged HIV outbreak among men who have sex with men in Taiwan: An incident case-control study, 2006-2015.

BACKGROUND/PURPOSE: Limited data are available on the role of illicit non-injecting drug use in a prolonged HIV outbreak that predominantly affected men who have sex with men (MSM) in Taiwan since 2006. We aimed to assess associations between specific types of drug use and incident HIV infections in this outbreak. METHODS: We conducted a retrospective case-control study among MSM clients at voluntary counselling and testing (VCT) service at National Taiwan University Hospital (Taipei, Taiwan). We used BED IgG-capture enzyme immunoassay to identify incident HIV infection (cases), individually matched to HIV-negative MSM clients (controls) by HIV testing date. We used a structured questionnaire to obtain the information on illicit drug use and sexual risk behaviors. RESULTS: From a total of 15,305 MSM client visits during 2006-2015, 387 cases were matched to 1012 controls. Use of inhaled nitrites (adjusted odds ratio [aOR] 2.1), MDMA (aOR 2.9), amphetamines (aOR 1.6), and ketamine (aOR 1.5) were independently associated with incident HIV infection. Polydrug (≥2 drugs) use was associated with the highest risk (aOR 4.3; 95% CI 2.6-7.2). While the proportion of MSM VCT clients who reported use of any recreational drug remained stable during 2006-2015 (average: 9.7%, P: 0.38), there was a shift in specific types of drug use, from MDMA/ketamine to inhaled nitrites/amphetamine, after 2011 (all Ps < 0.05). CONCLUSION: Non-opioid recreational drugs use is associated with incident HIV infection in this prolonged HIV outbreak. There is an urgent need to formulate an effective public health response to mitigate the risk.

Characteristics and outcome differences in male and female oral cavity cancer patients in Taiwan.

ABSTRACT: Oral cavity squamous cell carcinoma (OSCC) is a leading cause of death in Taiwan. Most of the patients in the literature are male. The risk factors, cancer characteristics, and treatment outcomes were investigated in female patients and compared with male patients in this study.This retrospective study recruited 2046 OSCC patients between 1995 and 2019. The age, tumor subsites, and survival were reviewed and recorded. Overall survival and disease-free survival were the main outcomes.Female patients represented 6.7% of the entire study cohort. Females were diagnosed at an older age and an earlier local stage than male patients (P < .001). Female patients were less exposed to cigarettes, alcohol, and betel-quid (all P < .001). The tongue (55.1%) was the most frequent subsite in females, while the buccal cavity (38.4%) and the tongue (35.3%) were more likely (P < .001) to be associated with the male gender. Female patients in the tongue cancer subgroup presented less frequently with extra-nodal extension compared with male patients (P = .040). No significant differences in recurrence or overall deaths were observed between the genders during the follow-up period.The OSCC male to female ratio in Taiwan was 14:1. Female OSCC occurred more frequently on the tongue, and was diagnosed at an older age and at an earlier tumor stage than in male patients. No survival difference was found between female and male OSCC patients.

Long-Lasting Effect after Single Hyaluronate Injection for Unilateral Vocal Fold Paralysis: Does Concentration Matter?

BACKGROUND: Early injection laryngoplasty (EIL) using hyaluronic acid (HA) is an effective treatment for glottic insufficiency in patients with acute unilateral vocal fold paralysis (UVFP). Most patients benefit by showing improvement in voice and quality of life and implied reduced need for permanent laryngoplasty. However, injected HA might resolve within a short period, so its long-term outcomes and the need for secondary procedures need to be clarified. METHODS: Patients who underwent EIL with HA for acute UVFP from January 2015 to December 2018 were included. The factors that may associate with the prognosis including voice performance and laryngeal configuration at presentation, the cause of UVFP, and the type of HA for EIL were analyzed. RESULTS: Ninety-four patients were included for analysis, with a mean follow-up period of 25.1 months (95% CI: 22.8-27.4 months). After primary HA injection, 22 patients (23.4%) underwent secondary procedures (rate: 13.1% per person-year), and most (63.6%) of the events occurred after one year from the first injection. The rate of secondary procedures within the first 12 months was 9.0% (14.1% and 4.3% for low-concentrated HA (LHA) and high-concentrated HA (HHA), respectively). The incidence of the secondary procedures was higher in the LHA group (18.2%) (p = 0.026) than in the HHA group (7.5%). CONCLUSIONS: The rate of secondary procedures was lower than the prediction based on the resorption time of HA, a finding that could be partly accounted for by both natural nerve recovery and a long-lasting effect of EIL. EIL with HHA had a lower rate of re-treatment than that with LHA, suggesting a better clinical utility for acute UVFP.

Ketogenic Diet Enhances the Cholesterol Accumulation in Liver and Augments the Severity of CCl4 and TAA-Induced Liver Fibrosis in Mice.

Persistent chronic liver diseases increase the scar formation and extracellular matrix accumulation that further progress to liver fibrosis and cirrhosis. Nevertheless, there is no antifibrotic therapy to date. The ketogenic diet is composed of high fat, moderate to low-protein, and very low carbohydrate content. It is mainly used in epilepsy and Alzheimer's disease. However, the effects of the ketogenic diet on liver fibrosis remains unknown. Through ketogenic diet consumption, ß-hydroxybutyrate (bHB) and acetoacetate (AcAc) are two ketone bodies that are mainly produced in the liver. It is reported that bHB and AcAc treatment decreases cancer cell proliferation and promotes apoptosis. However, the influence of bHB and AcAc in hepatic stellate cell (HSC) activation and liver fibrosis are still unclear. Therefore, this study aimed to investigate the effect of the ketogenic diet and ketone bodies in affecting liver fibrosis progression. Our study revealed that feeding a high-fat ketogenic diet increased cholesterol accumulation in the liver, which further enhanced the carbon tetrachloride (CCl4)- and thioacetamide (TAA)-induced liver fibrosis. In addition, more severe liver inflammation and the loss of hepatic antioxidant and detoxification ability were also found in ketogenic diet-fed fibrotic mouse groups. However, the treatment with ketone bodies (bHB and AcAc) did not suppress transforming growth factor-ß (TGF-ß)-induced HSC activation, platelet-derived growth factor (PDGF)-BB-triggered proliferation, and the severity of CCl4-induced liver fibrosis in mice. In conclusion, our study demonstrated that feeding a high-fat ketogenic diet may trigger severe steatohepatitis and thereby promote liver fibrosis progression. Since a different ketogenic diet composition may exert different metabolic effects, more evidence is necessary to clarify the effects of a ketogenic diet on disease treatment.