BACKGROUND: Inflammatory bowel disease (IBD) is an incurable disease that negatively influences the quality of life of patients. Current and emerging therapies target proinflammatory cytokines and/or receptors to downregulate proinflammatory responses, but insufficient remission requires other therapeutic agents. Herein, we report that the synthetic antiinflammatory peptide 15 (SAP15) is capable of cell penetration and anti-inflammatory activity in human macrophages. METHODS: SAP15 was labeled with fluorescence and administered to human leukemia monocytic cells (THP-1) cells for cell penetration analysis. Using biolayer interferometry analysis, the binding affinity of SAP15 with histone deacetylase 5 (HDAC5) was measured. SAP15-treated THP-1 cells were analyzed by protein phosphorylation assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). In addition, in vivo analysis of the therapeutic effect on IBD was observed in a dextran sulfate sodium (DSS)-induced model. Samples from SAP15-treated mice were analyzed at both the macroscopic and microscopic levels using ELISA, myeloperoxidase (MPO) assays, and histological evaluations. RESULTS: SAP15 was internalized within the cytosol and nucleus of THP-1 cells and bound to the HDAC5 protein. SAP15-treated macrophages were assessed for protein phosphorylation and showed inhibited phosphorylation of HDAC5 and other immune-related proteins, which led to increased M2-like macrophage markers and decreased M1-like macrophage markers and tumor necrosis factor-a and interleukin-6 cytokine levels. The SAP15 treatment on IBD model showed significant recovery of colon length. Further histological analysis of colon demonstrated the therapeutic effect of SAP15 on mucosal layer. Moreover, proinflammatory cytokine levels and MPO activity from the plasma show that SAP15 is effective in reduced proinflammatory responses. CONCLUSION These findings suggest that SAP15 is a novel peptide with a novel cell-penetrating peptide with antiinflammatory property that can be used as a therapeutic agent for IBD and other inflammatory diseases.

Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1–30 days post-vaccination compared to baseline (median, −21.4 IU/ml from baseline), but the levels reverted to baseline by 91–180 days (median, −3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: −0.06, −0.39, and −0.04 log 10 IU/ml/year in pre-vaccination period, days 1–30, and days 31–90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, −13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A + NK cells was observed in the CD56dimCD16+ NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A + NK cells.

Subclinical hypothyroidism (SCH), characterized by elevated serum thyroid-stimulating hormone (TSH) levels and normal free thyroxine levels, usually presents without symptoms, and is often discovered incidentally during routine blood test. The Task Force of the Korean Thyroid Association Committee of Clinical Practice Guidelines has established a guideline to evaluate and manage SCH; the guideline emphasizes the implementation of diagnostic criteria based on the TSH reference range for Koreans and focuses on the proven health benefits of levothyroxine (LT4) treatment. Based on the Korea National Health and Nutrition Examination Survey (2013-2015), serum TSH level of 6.8 mIU/L is considered the reference value for SCH. SCH can be categorized as mild (TSH 6.8-10.0 mIU/L) or severe (TSH ＞10.0 mIU/L), and patients are classified as adults (age ＜70 years) or elderly patients (age ≥70years) depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, along with the thyroid peroxidase antibody test, preferably 2-3 months after the initial evaluation. Usually, LT4 treatment is not recommended for mild SCH in adults; however, treatment is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and can be considered for coexisting dyslipidemia. LT4 treatment is not recommended for mild or even severe SCH in elderly patients, in general. Patients with SCH who receive LT4 treatment, the LT4 dosage should be personalized, and serum TSH levels should be monitored to ensure optimal LT4 dosage (dosage that is neither excessive nor insufficient). Patients with SCH who do not receive LT4 treatment require periodic follow-up at appropriate testing intervals determined by disease severity. The guideline also provides several educational points applicable in clinical settings.

Purpose: To evaluate the expression of multiple chemokine receptors in peripheral blood T cells from patients with age-related macular degeneration (AMD). Materials and Methods: Peripheral blood mononuclear cells and/or aqueous humor were obtained from 24 AMD patients and 24 age- and sex-matched healthy controls. Chemokine receptor expression on T cells from peripheral blood was determined by multicolor flow cytometry. The levels of chemokines and cytokines in the aqueous humor from 12 AMD patients and six healthy controls were assessed. Results: AMD patients had increased expressions of CCR4 in CD4 + T cells (p=0.007) and CRTh2 in CD8 + T cells (p=0.002), and decreased expressions of CXCR3 in CD4+T cells (p=0.029) and CXCR3, CCR5, and CX 3CR1 in CD8+T cells (p=0.005, 0.019, and 0.007, respectively). Monocyte chemoattractant protein-1 levels were increased in the aqueous humor from AMD patients (p=0.018), while the levels of interleukin (IL)-4 and IL-22 were significantly decreased compared to controls (p=0.018 and 0.041, respectively). Conclusion The chemokine receptor profiles of T cells are altered in AMD patients compared to healthy controls without noticeable associations with chemokine levels in the aqueous humor. Further evaluation is needed to clarify the role of these alterations in AMD pathogenesis.

Although various studies on predictive markers in the use of PD-1/PD-L1 inhibitors are in progress, only PD-L1 expression levels in tumor tissues are currently used. In the present study, we investigated whether baseline serum levels of IL-6 can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. In our cohort of 125 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) were significantly higher in those with low IL-6 (<13.1 pg/ml) than those with high IL-6 (ORR 33.9% vs. 11.1%, p=0.003; DCR 80.6% vs. 34.9%, p<0.001). The median progression-free survival was 6.3 months (95% confidence interval [CI], 3.9–8.7) in the low IL-6 group, significantly longer than in the high IL-6 group (1.9 months, 95% CI, 1.6–2.2, p<0.001). The median overall survival in the low IL-6 group was significantly longer than in the high IL-6 group (not reached vs. 7.4 months, 95% CI, 4.8–10.0). Thus, baseline serum IL-6 levels could be a potential biomarker for predicting the efficacy and survival benefit of PD-1/PD-L1 inhibitors in NSCLC.

Esthesioneuroblastoma as a source of ectopic Cushing's syndrome is rare, and to the best of our knowledge, only 20 cases have been reported worldwide. A 46-year-old healthy man visited a local clinic for general weakness and hyposmia, and underwent examination with serial endocrinological workup and brain imaging. ⁶⁸Gallium-DOTA-TOC positron emission tomography scan was helpful where diagnosis of sellar MRI and inferior petrosal sinus sampling were discordant. Combined transcranial and endoscopic endonasal approach surgery was performed, and a diagnosis of esthesioneuroblastoma was given.
Cushing Syndrome ; Diagnosis ; Esthesioneuroblastoma, Olfactory ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Neuroimaging ; Petrosal Sinus Sampling ; Positron-Emission Tomography

PURPOSE: A cross-sectional survey was conducted to explore the current awareness and use of complementary and alternative medicine (CAM), as well as attitudes toward CAM, in patients with cancer and their family members in South Korea. MATERIALS AND METHODS: Between September 21 and October 31, 2017, a 25-item questionnaire regarding CAM experiences among cancer patients and their family members was conducted in 10 oncology clinics in South Korea after institutional review board approval at each institution. RESULTS: In total, 283/310 patients were analyzed. The median age was 60 years, and 60% were male. Most of the patients were actively receiving anticancer treatment at the time of the survey. A total of 106 patients (37%) had experienced a median of two types (interquartile range, 1 to 3) of CAM. Belief in CAM (odds ratio [OR], 3.015; 95% confidence interval [CI], 1.611 to 5.640) and duration of disease (OR, 1.012; 95% CI, 1.004 to 1.020) were independent factors for using CAM in multivariable analysis. Belief in CAM was significantly associated with current use of CAM (OR, 3.633; 95% CI, 1.567 to 8.424). Lay referral was the most common reason for deciding to use CAM, and only 25% of patients (72/283) discussed CAM with their physicians. CONCLUSION: Patient attitudes toward and confidence in CAM modalities were strongly associated with their CAM experiences, and only a small number of patients had an open discussion about CAM with their physicians. A patient education program for CAM is needed.
Complementary Therapies ; Cross-Sectional Studies ; Ethics Committees, Research ; Humans ; Korea ; Male ; Patient Education as Topic ; Referral and Consultation

OBJECTIVES: Mèniére's disease is one of the most common causes of episodic vestibular syndrome that shows symptom complexes of recurrent vertigo, hearing loss, tinnitus and ear fullness. Isosorbide (Isobide) is a osmotic diuretics which has been used for Meniere's disease to reduce the endolymphatic pressure. The purpose of this study was to evaluate the efficacy of isosorbide in the treatment of Mèniére's disease by comparing the combined therapy of isosorbide and betahistine (Meniace) to betahistine only. METHODS: Among 220 patients enrolled with Mèniére's disease from 9 centers, 187 patients completed this clinical study. Patients were randomly subjected either to betahistine alone therapy at dose of 6 mg three times a day (n=97) or to combined therapy with isosorbide (dose of 30 mL three times a day) and betahistine (n=90) for 12 weeks. Two groups were compared at 4 and 12 weeks after treatment on frequency of vertigo, hearing level (pure tone audiometry, speech audiometry), electocochleography (ECoG), tinnitus (Tinnitus Handicap Inventory, THI) and quality of life (Korean functional level scale, Korean dizziness handicap inventory). RESULTS: During first 4 weeks after treatment, the frequency of vertigo was not reduced in either betahistine alone therapy group or combined therapy group. However, between 8 and 12 weeks, the frequency of vertigo was significantly reduced in either group, and in the combined group frequency of vertigo was more significantly reduced than in the betahistine alone therapy group (p=0.041). The hearing level, ECoG, tinnitus and quality of life was not significantly different between two groups. CONCLUSION: Isosorbide and betahistine combined therapy were more effective for vertigo control than betahistine alone therapy. Isosorbide is an effective diuretic in vertigo control in definite Mèniére's disease.
Audiometry, Speech ; Betahistine ; Clinical Study ; Diuretics, Osmotic ; Dizziness ; Ear ; Hearing ; Hearing Loss ; Humans ; Isosorbide ; Meniere Disease ; Quality of Life ; Tinnitus ; Vertigo

No abstract available.
Diagnosis* ; Postpartum Period* ; Pregnancy* ; Thyroid Diseases*