This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control.Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 1011 colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5–6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

Background and Objectives: Voice change after thyroidectomy is a common complication that affects a patient’s quality of life. In this study, we aimed to compare voice outcomes between minimally invasive open hemithyroidectomy (MIOT) and conventional hemithyroidectomy.Materials and Method We enrolled 215 patients who underwent hemithyroidectomy performed by an experienced surgeon at our institute between June 2017 and December 2021. All patients underwent voice evaluations, including subjective and objective assessments, preoperatively and 2 weeks and 2 months postoperatively. Results: Sixty-one patients underwent MIOT (M group) and 154 patients underwent conventional hemithyroidectomy (C group). There were 50 female (82.0%) and 11 male (18.0%) in the M group, and 129 female (83.8%) and 25 male (16.2%) in the C group. In both groups, the thyroidectomy-related voice questionnaire score increased at 2 weeks and 2 months postoperatively. However, no statistically significant differences were observed between the two groups. Voice parameters were analyzed according to sex. There were some changes in the parameters in both groups. However, no statistically significant differences were observed between the two groups. Conclusion Our study showed no differences in the acoustic results between MIOT and conventional hemithyroidectomy.

Background/Aims: While most cancer patients with end-of-life (EOL) care receive antibiotic treatments, antibiotic use should be decided appropriately considering the benefits, side effects, resistance, and cost effects. Antimicrobial stewardship programs (ASP) are important for patients with EOL care, but there is limited study analyzing actual antibiotic use in EOL care and the perceptions of Korean medical staff. Methods: Electronic medical records of 149 deceased cancer patients hospitalized in the medical hospitalist units at Asan Medical Center in Seoul from May 2019 to September 2021 were reviewed. Basic information, antibiotic use, duration, and changes were investigated. We surveyed medical staff’s perceptions of antibiotics in cancer patients with EOL. Results: Of the 149 cancer patients with EOL care, 146 (98.0%) agreed with physician orders for life-sustaining treatment (POLST). In total, 143 (95.9%) received antibiotics, 110 (76.9%) received combination antibiotic treatment, and 116 (81.1%) were given antibiotics until the day of death. In a survey of 60 medical staff, 42 (70.0%) did not know about ASP, and 24 (40.0%) thought ASP was important in EOL care. Nineteen doctors (31.7%) discussed the use or discontinuation of antibiotics with patients or caregivers when writing POLST, but only 8 patients (5.6%) stopped antibiotics after POLST. Conclusions Most cancer patients with EOL care continue to receive antibiotics until just before their death. A careful approach is needed, considering the benefits and side effects of antibiotic use, and the patient’s right to self-decision. It is necessary to actively improve awareness of ASP and its importance for medical staff.

Background: Psoriasis is a T cell-mediated disorder. Appropriate treatment of psoriasis can result in a plethora of dynamic changes in the T cells and their cytokine production. Studies on the expression of Th1 and Th17 inflammatory cytokines after various treatments have reported inconsistent results. Objective: This study aimed to investigate the changes in inflammatory cytokine expression in psoriasis skin lesions before and after psoriasis treatment. Methods: Five patients with plaque psoriasis were enrolled in the study. The tissue mRNA and protein levels of interleukin (IL)-12, IL-2, interferon (IFN)-γ, IL-23, IL-17A, and IL-22 in psoriatic skin lesions before and after psoriasis treatment were detected using real-time polymerase chain reaction and immunohistochemical staining, respectively. Results: The decrease in the psoriasis area and severity index was accompanied by a reduction in IL-12 and IL-23 mRNA levels and a concomitant reduction of IL-2 and IL-17A protein levels in psoriasis skin lesions. Both mRNA and protein levels of IFN-γ in psoriatic skin lesions increased after treatment. Conclusion The mRNA levels of tissue inflammatory cytokines (IL-12 and IL-23) and the protein levels of tissue inflammatory cytokines (IL-2 and IL-17A) significantly decreased after psoriasis treatment. The mRNA and protein levels of IFN-γ increased, even after psoriasis treatment.

Background/Aims: This study examined the long-term outcomes of undifferentiated-type early gastric cancer (UD EGC) with positive horizontal margins (HMs) after endoscopic resection (ER) and compared them between additional surgery and nonsurgical management. Methods: From 2005 to 2015, a total of 1,124 patients with UD EGC underwent ER at 18 tertiary hospitals in Korea. Of them, 92 patients with positive HMs as the only noncurative factor (n=25) or with both positive HMs and tumor size >2 cm (n=67) were included. These patients underwent additional surgery (n=40), underwent additional endoscopic treatment (n=6), or were followed up without further treatment (n=46). Results: No lymph node (LN) metastasis was found in patients who underwent additional surgery. During a median follow-up of 57.7 months (interquartile range, 27.6 to 68.8 months), no LN or distant metastases or gastric cancer-related deaths occurred in the overall cohort. At baseline, the residual cancer rate was 57.8% (26/45) after additional surgery or ER. The 5-year local recurrence rate was 33.6% among patients who were followed up without additional treatment. The 5-year overall survival rates were 95.0% and 87.8% after additional surgery and nonsurgical management (endoscopic treatment or close follow-up), respectively (log-rank p=0.224). In the multivariate Cox regression analysis, nonsurgical management was not associated with an increased risk of mortality. Conclusions UD EGC with positive HMs after ER may have favorable long-term outcomes and a very low risk of LN metastasis. Nonsurgical management may be suggested as an alternative, particularly for patients with old age or chronic illness.

Background/Aims: This study examined the long-term outcomes of undifferentiated-type early gastric cancer (UD EGC) with positive horizontal margins (HMs) after endoscopic resection (ER) and compared them between additional surgery and nonsurgical management. Methods: From 2005 to 2015, a total of 1,124 patients with UD EGC underwent ER at 18 tertiary hospitals in Korea. Of them, 92 patients with positive HMs as the only noncurative factor (n=25) or with both positive HMs and tumor size >2 cm (n=67) were included. These patients underwent additional surgery (n=40), underwent additional endoscopic treatment (n=6), or were followed up without further treatment (n=46). Results: No lymph node (LN) metastasis was found in patients who underwent additional surgery. During a median follow-up of 57.7 months (interquartile range, 27.6 to 68.8 months), no LN or distant metastases or gastric cancer-related deaths occurred in the overall cohort. At baseline, the residual cancer rate was 57.8% (26/45) after additional surgery or ER. The 5-year local recurrence rate was 33.6% among patients who were followed up without additional treatment. The 5-year overall survival rates were 95.0% and 87.8% after additional surgery and nonsurgical management (endoscopic treatment or close follow-up), respectively (log-rank p=0.224). In the multivariate Cox regression analysis, nonsurgical management was not associated with an increased risk of mortality. Conclusions UD EGC with positive HMs after ER may have favorable long-term outcomes and a very low risk of LN metastasis. Nonsurgical management may be suggested as an alternative, particularly for patients with old age or chronic illness.

Background: We purposed to evaluate the seasonality and associated factors of the incidence of gout attacks in Korea. Methods: We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected. Results: Two hundred-five patients (men, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The median age, body mass index, attack duration, and serum uric acid level at enrollment were 50.0 years, 25.4, 5.0 days, and 7.4 mg/dL, respectively. Gout attacks were most common during spring (43.4%, P < 0.001) and in March (23.4%, P < 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The median diurnal temperature change on the day of the attack was highest in the spring (9.8°C), followed by winter (9.3°C), fall (8.6°C), and summer (7.1°C) (P = 0.027). The median change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.0%, spring; 0.3%, summer; −0.9%, fall; −1.2%, winter; P = 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 64 gout flares developed (21 in the initial attack group). No significant seasonal variation in the follow-up flares was found. Conclusion In this prospective study, the most common season and month of gout attacks in Korea are spring and March, respectively. Alcohol is the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack are associated with gout attack in our cohort.

BACKGROUND/AIM: The aim of this study was to evaluate the stability and simplicity of papillary balloon dilatation by retrospectively analyzing the results of performing concurrent papillary balloon dilatation in conjunction with percutaneous transhepatic biliary drainage (PTBD) in the patients with biliary obstruction due to common bile duct stones or a tumor who were difficult to treat with an endoscopic approach. METHODS: We retrospectively analyzed a total of 21 patients who were treated through a percutaneous transhepatic biliary approach after they were diagnosed with biliary obstruction due to a tumor and biliary stones in a single medical institution for four years from 2012 to 2015. RESULTS: Sixteen out of 21 patients (76.2%) underwent percutaneous transhepatic biliary drainage and papillary balloon dilatation. For 5 patients (23.8%) in whom it was difficult to perform the procedure simultaneously due to the patient's poor overall condition such as pancreatitis and septic shock, papillary balloon dilatation was performed 5-8 days after biliary drainage. Nineteen of 21 patients (90.5%) were successfully treated by a single procedure without residual stones or restenosis, but in two patients, stones were removed two times and three times. CONCLUSIONS: The use of a percutaneous transhepatic biliary approach to patients in whom endoscopy cannot be performed is considered safe and effective. In addition, unless the procedure is specifically contraindicated, the use of papillary balloon dilatation performed simultaneously with PTBD can reduce patient inconvenience and procedure frequency.
Common Bile Duct ; Dilatation* ; Drainage* ; Endoscopy ; Gallstones ; Humans ; Pancreatitis ; Retrospective Studies ; Shock, Septic

Two separate studies were conducted to establish bioequivalence (BE) for two doses of atorvastatin/metformin sustained-release (SR) fixed dose combination (FDC) versus the same dosage of the individual component (IC) tablets in healthy male subjects under fed conditions (study 1, BE of atorvastatin/metformin SR 20/500 mg FDC; study 2, BE of atorvastatin/metformin SR 20/750 mg FDC). Each study was a randomized, open-label, single oral dose, two-way crossover design. Serial blood samples were collected pre-dose and up to 36 hours post-dose for atorvastatin and 24 hours for metformin. Plasma concentrations of atorvastatin, 2-OH atorvastatin and metformin were analyzed using a validated liquid chromatography tandem mass-spectrometry. A non-compartmental analysis was used to calculate pharmacokinetic (PK) variables and analysis of variance was performed on the lognormal-transformed PK variables. A total of 75 subjects completed the study 1 (36 subjects) and study 2 (39 subjects). The 90% confidence intervals for the adjusted geometric mean ratio of Cmax and the AUC0-t were within the predefined 0.80 to 1.25 range. The number of subjects reporting at least one adverse event following FDC treatments was comparable to that following IC treatments. The two treatments were well tolerated. Therefore, atorvastatin/metformin SR 20/500 mg and 20/750 mg FDC tablets are expected to be used as alternatives to IC tablets to decrease the pill burden and increase patient compliance.
Atorvastatin Calcium* ; Chromatography, Liquid ; Cross-Over Studies* ; Humans ; Male* ; Metformin* ; Patient Compliance ; Pharmacokinetics* ; Plasma ; Tablets* ; Therapeutic Equivalency

PURPOSE: To evaluate the effect of anti-interleukin-33 (anti-IL-33) on a mouse model of ovalbumin (OVA)-induced acute kidney injury (AKI). METHODS: Twenty-four female BALB/c mice were assigned to 4 groups: group A (control, n=6) was administered sterile saline intraperitoneally (i.p.) and intranasally (i.n.); group B (allergic, n=6) was administered i.p./i.n. OVA challenge; group C (null treatment, n=6) was administered control IgG i.p. before OVA challenge; and group D (anti-IL-33, n=6) was pretreated with 3.6 µg of anti-IL-33 i.p. before every OVA challenge. The following were evaluated after sacrifice: serum blood urea nitrogen and creatinine levels, Kidney injury molecule-1 gene (Kim-1) and protein (KIM-1) expression in renal parenchyma, and expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phosphorylated endothelial NOS (p-eNOS), and phosphorylated AMP kinase (p-AMPK) proteins in renal parenchyma. RESULTS: After OVA injection and intranasal challenge, mice in groups B and C showed significant increases in the expression of Kim-1 at both the mRNA and protein levels. After anti-IL-33 treatment, mice in group D showed significant Kim-1 down-regulation at the mRNA and protein levels. Group D also showed significantly lower COX-2 protein expression, marginally lesser iNOS expression than groups B and C, and p-eNOS and p-AMPK expression at baseline levels. CONCLUSIONS: Kim-1 could be a useful marker for detecting early-stage renal injury in mouse models of OVA-induced AKI. Further, anti-IL-33 might have beneficial effects on these mouse models.
Acute Kidney Injury ; Adenylate Kinase ; Animals ; Blood Urea Nitrogen ; Creatinine ; Cyclooxygenase 2 ; Down-Regulation ; Female ; Humans ; Immunoglobulin G ; Interleukin-33 ; Kidney* ; Mice ; Nitric Oxide Synthase Type II ; Ovalbumin ; Ovum ; RNA, Messenger