Easing the Burden of Tinnitus: A Narrative Review for Exploring Effective Pharmacological Strategies.

Many individuals seek medical attention for tinnitus, desiring relief from the distress caused by the condition; however, the treatment process is far from straightforward. The most effective treatments for chronic subjective tinnitus, such as tinnitus retraining therapy (TRT) and cognitive behavioral therapy (CBT), require considerable time and efforts. As a result, many of them express a desire for alleviation through medication. While it is true that medication is not generally recommended in treatment guidelines for chronic subjective tinnitus, in specific situations such as when accompanied by symptoms of depression or anxiety-drugs like antidepressants or anxiolytics may have a meaningful impact on symptom reduction. Additionally, medication can prove effective in certain specialized forms of tinnitus, such as typewriter tinnitus, as opposed to chronic subjective tinnitus. Although intratympanic dexamethasone injections for tinnitus have been reported to lack efficacy compared to a placebo, if patients perceive subjective satisfaction due to a placebo effect, it holds significance. From the perspective of patients suffering from tinnitus, even if the therapeutic mechanism is set aside, experiencing some degree of relief through certain medications can enhance compliance with evidence-based treatments like TRT and CBT.

Integration of National Health Insurance claims data and animal models reveals fexofenadine as a promising repurposed drug for Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common and costly progressive neurodegenerative disease of unclear etiology. A disease-modifying approach that can directly stop or slow its progression remains a major unmet need in the treatment of PD. A clinical pharmacology-based drug repositioning strategy is a useful approach for identifying new drugs for PD. METHODS: We analyzed claims data obtained from the National Health Insurance Service (NHIS), which covers a significant portion of the South Korean population, to investigate the association between antihistamines, a class of drugs commonly used to treat allergic symptoms by blocking H1 receptor, and PD in a real-world setting. Additionally, we validated this model using various animal models of PD such as the 6-hydroxydopmaine (6-OHDA), α-synuclein preformed fibrils (PFF) injection, and Caenorhabditis elegans (C. elegans) models. Finally, whole transcriptome data and Ingenuity Pathway Analysis (IPA) were used to elucidate drug mechanism pathways. RESULTS: We identified fexofenadine as the most promising candidate using National Health Insurance claims data in the real world. In several animal models, including the 6-OHDA, PFF injection, and C. elegans models, fexofenadine ameliorated PD-related pathologies. RNA-seq analysis and the subsequent experiments suggested that fexofenadine is effective in PD via inhibition of peripheral immune cell infiltration into the brain. CONCLUSION: Fexofenadine shows promise for the treatment of PD, identified through clinical data and validated in diverse animal models. This combined clinical and preclinical approach offers valuable insights for developing novel PD therapeutics.

Evaluation of Extra-Prostatic Extension on Deep Learning-Reconstructed High-Resolution Thin-Slice T2-Weighted Images in Patients with Prostate Cancer.

The aim of this study was to compare diagnostic performance for extra-prostatic extension (EPE) and image quality among three image datasets: conventional T2-weighted images (T2WIconv, slice thickness, 3 mm) and high-resolution thin-slice T2WI (T2WIHR, 2 mm), with and without deep learning reconstruction (DLR) in patients with prostatic cancer (PCa). A total of 88 consecutive patients (28 EPE-positive and 60 negative) diagnosed with PCa via radical prostatectomy who had undergone 3T-MRI were included. Two independent reviewers performed a crossover review in three sessions, in which each reviewer recorded five-point confidence scores for the presence of EPE and image quality using a five-point Likert scale. Pathologic topographic maps served as the reference standard. For both reviewers, T2WIconv showed better diagnostic performance than T2WIHR with and without DLR (AUCs, in order, for reviewer 1, 0.883, 0.806, and 0.772, p = 0.0006; for reviewer 2, 0.803, 0.762, and 0.745, p = 0.022). The image quality was also the best in T2WIconv, followed by T2WIHR with DLR and T2WIHR without DLR for both reviewers (median, in order, 3, 4, and 5, p < 0.0001). In conclusion, T2WIconv was optimal in regard to image quality and diagnostic performance for the evaluation of EPE in patients with PCa.

A Large Pleomorphic Adenoma in Nasal Cavity Misdiagnosed as Inverted Papilloma.

Pleomorphic adenoma (PA) is a benign tumor characterized by slow-growing mixed tumors in the craniofacial area. It is relatively common in salivary glands; however, PA of the nasal cavity, which arises in the minor salivary glands, is rare. We present the case of a large PA in the nasal cavity of an adult immunocompetent woman with nasal obstruction and intermittent epistaxis. Based on preoperative radiologic examinations, she was misdiagnosed with an inverted papilloma. Endoscopic resection was performed under general anesthesia. Pathologically, the patient was confirmed to have PA, which has great cellularity and few stromal components. No complications or recurrences during the 1-year follow-up period were observed.

Aromadendrin inhibits PMA-induced cytokine formation/NF-κB activation in A549 cells and ovalbumin-induced bronchial inflammation in mice.

Hyperproduction of immune cell-derived inflammatory molecules and recruitment of immune cells promote the development of allergic asthma (AA). Aromadendrin (ARO) has various biological properties including anti-inflammatory effects. In this study, we evaluated the ameliorative effects of ARO on the development of AA in vitro and in vivo. Phorbol 12-myristate 13-acetate (PMA, 100 nM) was used to induce inflammation in A549 airway epithelial cells. The cohesion of A549 and eosinophil EOL-1 cells was studied. Ovalbumin (30 or 60 µg)/Alum (3 mg) mixture was adapted for AA induction in mice. ARO (5 or 10 mg/kg, p. o.) was administered to mice to investigate its ameliorative effect on AA development. Enzyme-linked immunosorbent assay, western blotting, and hematoxylin and eosin/periodic acid Schiff staining were performed to study the ameliorative effect of ARO on bronchial inflammation. In PMA-stimulated A549 cells, the upregulation of cytokines (interleukin [IL]-1ß/IL-6/tumor necrosis factor alpha [TNF-α]/monocyte chemoattractant protein [MCP]-1]) and nuclear factor kappa B (NF-κB) activation was effectively reduced by ARO pretreatment. ARO suppressed the adhesion of A549 cells and eosinophils. In ovalbumin-induced AA mice, the levels of cells, such as eosinophils, Th2 cytokines, MCP-1 in bronchoalveolar lavage fluid, IgE in serum, and inducible nitric oxide synthase/cyclooxygenase-2 expression in the lung tissue were upregulated, which were all suppressed by ARO. In addition, the increase in cell inflow and mucus formation in the lungs of AA mice was reversed by ARO as per histological analysis. ARO also modulated NF-κB activation in the lungs of AA mice. Overall, the anti-inflammatory properties of ARO in vitro/in vivo studies of AA were notable. Thus, ARO has a modulatory effect on bronchial inflammation and may be a potential adjuvant for AA treatment.

Return to Sports Activity After Reverse Total Shoulder Arthroplasty.

Background: There are little published data on return to sports (RTS) after reverse total shoulder arthroplasty (RTSA). Purpose: To (1) determine the rate and timing of RTS after RTSA in an Asian population, (2) analyze predictive factors for RTS, and (3) determine the relationship between RTS after RTSA and clinical/radiological outcomes. Study Design: Case-control study; Level of evidence, 3. Methods: A retrospective review was performed on consecutive patients with diagnosis of irreparable rotator cuff tear (RCT), cuff tear arthropathy (CTA), or degenerative osteoarthritis who underwent RTSA between May 2017 and May 2020. Included were patients who played sports preoperatively in ≤3 years and had ≥2-year follow-up. Patients were divided into 2 groups based on responses to a telephone survey about RTS after RTSA: those who returned to sports (group A) and those who did not (group B). Patient characteristics, pre- and postoperative clinical features and functional scores, and radiologic outcomes (acromial fracture, scapular notching, heterotopic ossification, and loosening of humeral and glenoid component) were compared between the groups. Results: Of 59 eligible patients, 44 patients (28 in group A, 16 in group B) were included. The RTS rate after RTSA was 63.6%, and the mean RTS time was 9.1 months (range, 3-36 months). There was a significant group difference in body mass index (BMI) (group A, 24.3 ± 2.1; group B, 27.1 ± 4.4; P = .01) and preoperative diagnosis (CTA/irreparable RCT/degenerative osteoarthritis diagnoses: group A, 13/12/3; group B, 3/6/7; P = .03). Patients in group A showed significantly higher forward flexion (P = .03) and higher Simple Shoulder Test score (P = .02) than group B at final clinical follow-up. No significant difference in radiological outcomes was found between the groups. Conclusion: Patients with a low BMI and those diagnosed with CTA or irreparable RCT were found to have better RTS rates after undergoing RTSA, and forward flexion and Simple Shoulder Test scores at final follow-up were significantly higher in the RTS group, with no significant differences in complications.

Chronic rhinosinusitis is not associated with increased incidence of acute myocardial infarction: A national population-based study.

BACKGROUND & AIMS: Chronic rhinosinusitis (CRS) is one of the most prevalent upper respiratory tract diseases. However, little is known the effect of CRS on the cardiovascular aspects of patients. This study aimed to investigate the incidence of acute myocardial infarction (AMI) in patients with CRS compared with that in the general population. METHODS: This retrospective cohort study was performed using the Korean National Health Insurance Service (NHIS) database. To minimize confounding, age, sex, and cardiovascular risk profiles were adjusted. The primary endpoint was newly diagnosed AMI in patients between January 2005 and December 2018. The relative risk of AMI in patients with CRS was compared with that in controls. Kaplan-Meier survival curves and Cox proportional regression tests were used for statistical analyses. RESULTS: Among 5,179,981 patients from the NHIS database, 996,679 patients with CRS were selected. The control group was 10 times (n = 9,966,790) the number of individuals in the CRS group. The CRS group had better cardiovascular profiles than those of the control group and had an adjusted hazard ratio of 0.99 (95% confidence interval, 0.97-1.02) for AMI. CONCLUSION: There was no significant association between the two groups regardless of the presence of nasal polyps. This is the first study adjusting cardiovascular risk profiles and analyzing the relationship between CRS and AMI. CRS was not associated with a high incidence of AMI after adjusting for cardiovascular risk factors.

Comparison of the Efficacy of Diluted Polyethylene Glycol and Low-Density (0.1% w/v) Barium Sulfate Suspension for CT Enterography.

Purpose: To compare small bowel distension and side effects between a diluted polyethylene glycol (PEG) solution and a low-density (0.1% w/v) barium sulfate suspension (LDBSS) for CT enterography (CTE) preparation. Materials and Methods: Total 173 consecutive patients who underwent CTE were enrolled in this study. The LDBSS (1 L) was used in 50 patients, and the diluted iso-osmotic PEG solution (1 L) was used in 123 patients. Two blinded radiologists independently scored jejunal and ileal distensions on a 5-point scale. To compare side effects between the two groups, the patients reported whether they had immediate complications after the administration of the oral contrast media. Results: For ileal and jejunal distension, the diluted PEG solution showed no difference from the LDBSS for either reader (ileum: reader 1, median, 4; 4, interquartile range, 3-4; 3-4, p = 0.997; reader 2, median, 4; 4, interquartile range, 3.3-4.0; 3-4, p = 0.064; jejunum: reader 1, median, 2; 2, interquartile range, 2-3; 2-3, p = 0.560; reader 2, median, 3; 2, interquartile range, 2-3; 2-3, p = 0.192). None of the patients complained of immediate complications following administration of either of the oral contrast media. Conclusion: The diluted PEG solution showed comparable bowel distension compared to LDBSS and no immediate side effects; thus, it can be a useful alternative.

Deep Learning Algorithm for Tumor Segmentation and Discrimination of Clinically Significant Cancer in Patients with Prostate Cancer.

BACKGROUND: We investigated the feasibility of a deep learning algorithm (DLA) based on apparent diffusion coefficient (ADC) maps for the segmentation and discrimination of clinically significant cancer (CSC, Gleason score ≥ 7) from non-CSC in patients with prostate cancer (PCa). METHODS: Data from a total of 149 consecutive patients who had undergone 3T-MRI and been pathologically diagnosed with PCa were initially collected. The labelled data (148 images for GS6, 580 images for GS7) were applied for tumor segmentation using a convolutional neural network (CNN). For classification, 93 images for GS6 and 372 images for GS7 were used. For external validation, 22 consecutive patients from five different institutions (25 images for GS6, 70 images for GS7) representing different MR machines were recruited. RESULTS: Regarding segmentation and classification, U-Net and DenseNet were used, respectively. The tumor Dice scores for internal and external validation were 0.822 and 0.7776, respectively. As for classification, the accuracies of internal and external validation were 73 and 75%, respectively. For external validation, diagnostic predictive values for CSC (sensitivity, specificity, positive predictive value and negative predictive value) were 84, 48, 82 and 52%, respectively. CONCLUSIONS: Tumor segmentation and discrimination of CSC from non-CSC is feasible using a DLA developed based on ADC maps (b2000) alone.

Correlation Between Computed Tomography Findings and the Laboratory Test-Derived Severity Score in Patients With Severe Acute Alcoholic Hepatitis.

OBJECTIVE: This study aimed to compare computed tomography (CT) findings between patients with severe and nonsevere acute alcoholic hepatitis (AAH). METHODS: We included 96 patients diagnosed with AAH between January 2011 and October 2021 who underwent 4-phase liver CT and laboratory blood tests. Two radiologists reviewed the initial CT images with respect to distribution and grade of hepatic steatosis; transient parenchymal arterial enhancement (TPAE); and presence of cirrhosis, ascites, and hepatosplenomegaly. A Maddrey discriminant function score (4.6 × [patient's prothrombin time - control] + total bilirubin [mg/mL]) was used as cutoff indicator for severity, with a score of 32 or higher indicating severe disease. The image findings were compared between the severe (n = 24) and nonsevere (n = 72) groups using the χ 2 test or Fisher exact test. After univariate analysis, the most significant factor was identified using a logistic regression analysis. RESULTS: In the univariate analysis, there were significant between-group differences in the TPAE, liver cirrhosis, splenomegaly, and ascites ( P < 0.0001, P < 0.0001, P = 0.0002, and P = 0.0163, respectively). Among them, TPAE was the only significant factor for severe AAH ( P < 0.0001; odds ratio, 48.1; 95% confidence interval, 8.3-280.6). Using this single indicator, the estimated accuracy, positive predictive, and negative predictive values were 86%, 67%, and 97%, respectively. CONCLUSIONS: Transient parenchymal arterial enhancement was the only significant CT finding in severe AAH.

Association between Dynamic Contrast-Enhanced MRI Parameters and Prognostic Factors in Patients with Primary Rectal Cancer.

BACKGROUND: To evaluate the association between perfusion parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with prognostic factors in primary rectal cancer patients. METHODS: A sample of 51 patients with pathologically proven rectal adenocarcinoma through surgery were retrospectively enrolled. All the patients underwent preoperative DCE-MRI including 3D-spoiled gradient echo. Two radiologists determined the tumor border after radiologic-pathologic correlation and drew regions of interest. The perfusion parameters, including the volume transfer constant (Ktrans), were calculated under the extended Toft model. The prognostic factors included TN stage, circumferential resection margin, extramural venous invasion, Kirsten-ras mutation, tumor size, carcinoembryonic antigen, and tumor differentiation. The association was assessed via correlation or t-test. For significant prognostic factors, receiver operating characteristic (ROC) curve analyses were performed to estimate the diagnostic predictive values. RESULTS: Ktrans only showed a significant difference according to tumor differentiation, between the well-differentiated (n = 6) and moderately differentiated (n = 45) groups (0.127 ± 0.032, 0.084 ± 0.036, p = 0.036). The AUC was 0.838 (95% CI, 0.702-0.929), and the estimated accuracy, sensitivity, and specificity were 87%, 90%, and 60%, respectively. CONCLUSIONS: Ktrans showed a significant difference based on tumor differentiation, which may be conducive to prediction of prognosis in primary rectal cancer.

Quercetin Attenuates the Production of Pro-Inflammatory Cytokines in H292 Human Lung Epithelial Cells Infected with Pseudomonas aeruginosa by Modulating ExoS Production.

The type three secretion system (T3SS) is a major virulence system of Pseudomonas aeruginosa (P. aeruginosa). The effector protein Exotoxin S (ExoS) produced by P. aeruginosa is secreted into the host cells via the T3SS. For the purpose of an experiment on inhibitors with regard to ExoS secretion, we developed a sandwich-type enzyme-linked immunosorbent assay (ELISA) system. Quercetin was selected because it has a prominent ExoS inhibition effect and also is known to have anti-inflammatory and antioxidant effects on mammalian cells. In this study, we investigated the effects of quercetin on the expression and secretion of ExoS using ELISA and Western blot analysis methods. The results showed that the secretion of ExoS was significantly decreased by 10 and 20 µM of quercetin. Also, popB, popD, pscF, and pcrV which are composed of the T3SS needle, are reduced by quercetin at the mRNA level. We also confirmed the inhibitory effect of quercetin on cytokines (IL-6, IL-1ß, and IL-18) in P. aeruginosa-infected H292 cells by real-time polymerase chain reaction (PCR) and ELISA. Collectively, quercetin inhibits the secretion of ExoS by reducing both ExoS production and the expression of the needle protein of T3SS. Furthermore, these results suggest that quercetin has the potential to be used as an anti-toxic treatment for the inflammatory disease caused by P. aeruginosa infection.

Closed loop obstruction of small bowel: CT signs predicting successful non-surgical treatment.

PURPOSE: To clarify the computed tomography (CT) findings related to successful conservative treatments in patients with closed-loop small bowel obstruction (CL-SBO) without evidence of bowel strangulation. METHODS: Sixty-four patients (71 CT scans) diagnosed with CL-SBO by CT and received initial conservative treatments from May 2010 to August 2020 were retrospectively included. Two blinded radiologists reviewed the CT findings, including the transition zone (number, distance, and location), maximum bowel diameter, mesenteric haziness, mesenteric fluid, increased unenhanced bowel wall attenuation, decreased bowel wall enhancement, small bowel feces sign, whirl sign, bowel wall thickening, ascites, and degree of obstruction. The findings of the success and failure groups of conservative treatment were compared. Interobserver agreement was assessed for all findings. RESULTS: Among the 71 cases, conservative treatments were successful in 42 cases (59 %) but failed in 29 cases (41 %). In multivariable analyses, the distance between the transition zones (>1 cm) and low-degree obstruction were independently associated with successful conservative treatments, with odds ratios of 6.23 and 3.52, respectively. The combination of these two CT findings exhibited a specificity of 89.7 % with a positive likelihood ratio of 3.01. Interobserver agreement of the degree of obstruction and the distance between the transition zones was almost perfect (ĸ = 0.814 and 0.914, respectively). CONCLUSIONS: The distance between the transition zones (>1 cm) and low-grade obstruction are independent CT predictors of successful conservative treatments in CL-SBO patients. Initial conservative treatments are recommended for patients with both CT findings.

Comparison of Computed Diffusion-Weighted Imaging b2000 and Acquired Diffusion-Weighted Imaging b2000 for Detection of Prostate Cancer.

Purpose: To compare the sensitivity of tumor detection and inter-observer agreement between acquired diffusion-weighted imaging (aDWI) b2000 and computed DWI (cDWI) b2000 in patients with prostate cancer (PCa). Materials and Methods: Eighty-eight patients diagnosed with PCa by radical prostatectomy and having undergone pre-operative 3 Tesla-MRI, including DWI (b, 0, 100, 1000, 2000 s/mm2), were included in the study. cDWI b2000 was obtained from aDWI b0, b100, and b1000. Two independent reviewers performed a review of the aDWI b2000 and cDWI b2000 images in random order at 4-week intervals. A region of interest was drawn for the largest tumor on each dataset, and a Prostate Imaging-Reporting and Data System (PI-RADS) score based on PI-RADS v2.1 was recorded. Histologic topographic maps served as the reference standard. Results: The study population's Gleason scores were 6 (n = 16), 7 (n = 53), 8 (n = 9), and 9 (n = 10). According to the reviewers, the sensitivities of cDWI b2000 and aDWI b2000 showed no significant differences (for reviewer 1, both 94% [83/88]; for reviewer 2, both 90% [79/88]; p = 1.000, respectively). The kappa values of cDWI b2000 and aDWI b2000 for the PI-RADS score were 0.422 (95% confidence interval [CI], 0.240-0.603) and 0.495 (95% CI, 0.308-0.683), respectively. Conclusion: cDWI b2000 showed comparable sensitivity with aDWI b2000, in addition to sustained moderate inter-observer agreement, in the detection of PCa.

Relationship between Chronic Rhinosinusitis and the Incidence of Head and Neck Cancer: A National Population-Based Study.

We analyzed the relationship between chronic rhinosinusitis (CRS) and the incidence of head and neck cancers (HNCs) in a Korean adult population. This retrospective cohort study included data from the Korean National Health Insurance Service database. Adjustments were made to minimize risk variables for sex, age, diabetes, hypertension, dyslipidemia, and rhinitis between the two groups. The primary endpoint was newly diagnosed HNC between January 2009 and December 2018. Among 1,337,120 subjects in the Korean National Health Insurance Service database, data from 324,774 diagnosed with CRS (CRS group) and 649,548 control subjects (control group) were selected. Patients with CRS exhibited a statistically significant greater risk for nasal cavity/paranasal sinus cancer, hypopharynx/larynx cancer, and thyroid cancer compared with the control group. In the CRS group, the adjusted hazard ratios for nasal cavity/paranasal sinus cancer were 1.809 (95% confidence interval (CI) 1.085-3.016), 1.343 (95% CI 1.031-1.748) for hypopharynx and larynx cancer, and 1.116 (95% CI 1.063-1.173) for thyroid cancer. CRS was associated with a higher incidence of HNCs. Therefore, physicians should carefully consider the possibility of HNC progression and implement therapeutic strategies to minimize the impact of these diseases.

Does Metabolic Syndrome Affect the Incidence and Prognosis of Sudden Sensorineural Hearing Loss?

Earlier studies reported that the occurrence of sudden sensorineural hearing loss (SSNHL) is associated with chronic metabolic disorders such as hypertension, diabetes, and hyperlipidemia. Instead of focusing on the relationship between SSNHL and each metabolic disorder, this study aimed to identify the association with metabolic syndrome as a whole, including either prehypertension or prediabetes. As a case-control study, we reviewed 239 patients who experienced SSNHL, and compared them with the same number of healthy subjects (N = 478). Metabolic syndrome-related variables of SSNHL patients were compared to those of healthy control subjects. In addition, patients with SSNHL were classified into two subgroups: the first subgroup showed improvement in hearing ('response group'), and the second did not present significant improvement ('non-response group'). Metabolic syndrome was diagnosed according to the US National Heart, Lung, and Blood Institute's National Cholesterol Education Program Adult Treatment Panel III criteria. The risk for SSNHL was 4.3 times higher in patients with metabolic syndrome compared with patients without the syndrome (95% confidence interval, 1.98 to 9.33), even after adjusting for variables that showed significant between-group differences. The likelihood of being unresponsive to treatment was higher in those with metabolic syndrome (1.21 to 3.93; adjusted odds ratio = 2.18), and when the initial hearing loss pattern on a pure-tone audiometry was high tone or flat. Metabolic syndrome appears to be an independent risk factor for SSNHL and, simultaneously, a predictor of poor prognosis.

Purpurin suppresses atopic dermatitis via TNF-α/IFN-γ-induced inflammation in HaCaT cells.

OBJECTIVE: We investigated whether purpurin inhibits various pathways of inflammation leading to atopic dermatitis. INTRODUCTION: 1,2,4-Trihydroxyanthraquinone, commonly called purpurin, is an anthraquinone that is a naturally occurring red/yellow dye. Purpurin is a highly antioxidative anthraquinone and previous studies have reported antibacterial, anti-tumor, and anti-oxidation activities in cells and animals. However, the skin inflammatory inhibition activity mechanism study of purpurin has not been elucidated in vitro. METHODS: In this study, we investigated the anti-inflammatory activity of purpurin in HaCaT (human keratinocyte) cell lines stimulated with a mixture of tumor necrosis factor-alpha (TNF-α)/Interferon-gamma (IFN-γ). The inhibitory effect of Purpurin on cytokines (IL-6, IL-8, and IL-1ß) and chemokine (TARC, MDC, and RANTES) was confirmed by ELISA and RT-qPCR. We investigated each signaling pathway and the action of inhibitors through western blots. RESULTS: The expression levels of cytokines and chemokines were dose-dependently suppressed by purpurin treatment in TNF-α/IFN-γ-induced HaCaT cells from ELISA and real-time PCR. Purpurin also inhibited protein kinase B (AKT), mitogen-activated protein kinase (MAPKs), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) activation in TNF-α/IFN-γ-stimulated HaCaT cells. Additionally, there was a synergistic effect when purpurin and inhibitor were applied together, and inflammation was dramatically reduced. CONCLUSION: Therefore, these results demonstrate that purpurin exhibits anti-inflammatory and anti-atopic dermatitis activity in HaCaT cells.

Impact of bevacizumab and secondary cytoreductive surgery on survival outcomes in platinum-sensitive relapsed ovarian clear cell carcinoma: A multicenter study in Korea.

OBJECTIVE: This study investigated survival outcomes for platinum-sensitive relapsed ovarian clear cell carcinoma (OCCC) by treatment method. METHODS: OCCC patients with platinum-sensitive recurrence that received secondary treatment at five institutions between July 2007 and June 2021 were included. Patient characteristics and survival outcomes were compared according to the use of bevacizumab (BEV) during second-line chemotherapy and secondary cytoreductive surgery (CRS). RESULTS: 138 patients were included. The BEV (n = 36) and non-BEV (n = 102) groups had similar initial FIGO stages and proportions of secondary CRS. The BEV group showed improved progression-free survival (PFS; median, 15.4 vs. 7.5 months; P = 0.042) and overall survival (OS; P = 0.043) compared to the non-BEV group. In multivariate analyses, BEV was identified as an independent prognostic factor for PFS (adjusted hazard ratio [aHR], 0.571; 95% confidence interval [CI], 0.354-0.921; P = 0.022) and OS (aHR, 0.435; 95%CI, 0.195-0.970; P = 0.042). The secondary CRS group (n = 42) had early-stage disease at diagnosis more frequently (P = 0.009) and multi-site metastasis (P < 0.001) at recurrence less frequently than the no surgery group (n = 96). The secondary CRS group showed significantly better PFS (median, 33.7 vs. 7.2 months; P < 0.001) and OS (P < 0.001). Secondary CRS was associated with a significantly improved PFS (aHR, 0.297; 95% CI, 0.183-0.481; P < 0.001) and OS (aHR, 0.276; 95% CI, 0.133-0.576; P = 0.001). The BEV and non-BEV groups showed similar PFS and OS among the patients who underwent secondary CRS. In contrast, the BEV group showed improved PFS and OS among patients who did not undergo surgery. CONCLUSIONS: The use of BEV during second-line chemotherapy and secondary CRS may improve PFS and OS in patients with platinum-sensitive relapsed OCCC. Further prospective studies are warranted.

Dynamic contrast-enhanced magnetic resonance imaging for risk stratification in patients with prostate cancer.

BACKGROUND: To investigate the usefulness of perfusion parameters derived from dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) of patients diagnosed as prostate cancer (PCa) in differentiating clinically significant cancer [CSC, Gleason score (GS) ≥7] from non-CSC (GS 6). METHODS: A total of 94 patients diagnosed between August 2018 and September 2020 as PCa by radical prostatectomy were included in this retrospective study (mean age: 68.7 years, range, 47-83 years). All of the patients had undergone DCE-MRI on a single 3T-MR scanner. Whole-tumor volume was measured by reviewing a pathologic topographic map as a reference standard. The quantitative DCE perfusion parameters, including volume transfer constant (Ktrans), rate constant (kep), extracellular extravascular space (EES) volume fraction (ve), plasma volume fraction (vp) and area of region of interest (ROI) were calculated under an extended Tofts model. A receiver operating characteristic (ROC) curve analysis by pair-wise comparison was performed to compare the diagnostic performances of the perfusion parameters. RESULTS: The study population comprised GS 6 (n=17), GS 7 (n=57), GS 8 (n=9) and GS 9 (n=11) cases. Among the perfusion parameters, ve differed significantly between CSC (0.238±0.095) and non-CSC (0.300±0.126) (P=0.0308). Area under the curve (AUC) was 0.643 (95% CI, 0.538-0.739), and a maximum accuracy of 64%, a sensitivity of 66%, and a specificity of 53% were estimated. Area of ROI also differed significantly between CSC (201.89±163.87 mm2) and non-CSC (84.99±85.82 mm2) (P=0.0054). AUC was 0.807 (95% CI, 0.713-0.881), and maximum accuracy, sensitivity, and specificity were 81%, 82%, and 76%, respectively. CONCLUSIONS: Size of the tumor and interstitial space volume fraction are significant parameters in differentiating aggressiveness in PCa.

Methyl p­hydroxycinnamate exerts anti­inflammatory effects in mouse models of lipopolysaccharide­induced ARDS.

Methyl p­hydroxycinnamate (MH), an esterified derivative of p­Coumaric acid exerts anti­inflammatory effects on lipopolysaccharide (LPS)­stimulated RAW264.7 macrophages. Based on these effects, the present study investigated the protective role of MH in a mouse model of LPS­induced acute respiratory distress syndrome (ARDS). The results demonstrated that administration of LPS (5 mg/kg intranasally) markedly increased the neutrophil/macrophage numbers and levels of inflammatory molecules (TNF­α, IL­6, IL­1ß and reactive oxygen species) in the bronchoalveolar lavage fluid (BALF) of mice. On histological examination, the presence of inflammatory cells was observed in the lungs of mice administered LPS. LPS also notably upregulated the secretion of monocyte chemoattractant protein­1 and protein content in BALF as well as expression of inducible nitric oxide synthase in the lungs of mice; it also caused activation of p38 mitogen­activated protein kinase (MAPK) and NF­κB signaling. However, MH treatment significantly suppressed LPS­induced upregulation of inflammatory cell recruitment, inflammatory molecule levels and p38MAPK/NF­κB activation, and also led to upregulation of heme oxygenase­1 (HO­1) expression in the lungs of mice. In addition, the ability of MH to induce HO­1 expression was confirmed in RAW264.7 macrophages. Taken together, the findings of the present study indicated that MH may exert protective effects against airway inflammation in ARDS mice by inhibiting inflammatory cell recruitment and the production of inflammatory molecules.