Purpose: To investigate the efficacy and safety of a newly developed thermo-responsive sol-gel, ABT13107, for reducing the formation of intrauterine adhesions (IUAs) after hysteroscopic surgery. Materials and Methods: In this multicenter, prospective, randomized trial (Canadian Task Force classification I), 192 women scheduled to undergo a hysteroscopic surgery at one of the eight university hospitals in South Korea were randomized into the ABT13107 group or the comparator (Hyalobarrier ® ) group in a 1:1 ratio. During hysteroscopic surgery, ABT13107 or Hyalobarrier® was injected to sufficiently cover the entire intrauterine cavity. Results: The patients returned to their respective sites for safety assessments at postoperative weeks 1 and 4 and for efficacy assessments at postoperative week 4. The post-surgery incidence of IUAs was 23.4% in the ABT13107 group and 25.8% in the comparator group; this difference met the criteria for ABT13107 to be considered as not inferior to the comparator. No differences were found in the extent of adhesions, types of adhesions, or the cumulative American Fertility Society score between the two treatment groups. Most adverse events were mild in severity, and no serious adverse events occurred. Conclusion ABT13107, a new anti-adhesive barrier containing hyaluronic acid, was not inferior to the highly viscous hyaluronic acid anti-adhesive barrier, Hyalurobarrier® in IUA formation after hysteroscopic surgery (Clinical trial registration No. NCT 04007211).

Oral sulfate solution (OSS) is an emerging cleansing agent for bowel preparation. However, data comparing OSS to other conventional bowel preparations in Asian patients are limited. Therefore, the objective of this study was to compare the efficacy and tolerability of OSS to ascorbic acid plus polyethylene glycol (AA + PEG) in Asian patients. Methods: This was a prospective, randomized, parallel, investigator-blind study performed in two university hospitals in Korea. Bowel preparation efficacy was evaluated using both the Ottawa Bowel Preparation Scale (OBPS) and Boston Bowel Preparation Scale (BBPS). Results: Among 173 patients, 86 received OSS while 87 received AA + PEG for bowel preparation. Total OBPS score was 2.80 ± 2.48 in the OSS group and 4.49 ± 3.08 in the AA + PEG group, indicating significantly (p < 0.001) better efficacy with OSS. Total BBPS was higher in the OSS group (7.43 ± 1.49 vs. 6.51 ± 1.76, p < 0.001), indicating superior bowel preparation quality with OSS. Preparation-related adverse events were generally acceptable. Patients receiving OSS had more nausea (1.92 ± 0.94 vs. 1.54 ± 0.76, p = 0.004) and abdominal cramping (1.45 ± 0.78 vs. 1.17 ± 0.51, p = 0.006) than those receiving AA + PEG. However, overall satisfaction and taste were similar between the two groups. Conclusions: OSS had a non-inferior bowel cleansing efficacy than AA + PEG regardless of colon segment.

Acinetobacter baumannii is known for its multidrug antibiotic resistance. New approaches to treating drug-resistant bacterial infections are urgently required. Cathelicidin-related antimicrobial peptide (CRAMP) is a murine antimicrobial peptide that exerts diverse immune functions, including both direct bacterial cell killing and immunomodulatory effects. In this study, we sought to identify the role of CRAMP in the host immune response to multidrug-resistant Acinetobacter baumannii. Wild-type (WT) and CRAMP knockout mice were infected intranasally with the bacteria. CRAMP−/− mice exhibited increased bacterial colony-forming units (CFUs) in bronchoalveolar lavage (BAL) fluid after A. baumannii infection compared to WT mice. The loss of CRAMP expression resulted in a significant decrease in the recruitment of immune cells, primarily neutrophils. The levels of IL-6 and CXCL1 were lower, whereas the levels of IL-10 were significantly higher in the BAL fluid of CRAMP−/− mice compared to WT mice 1 day after infection. In an in vitro assay using thioglycollate-induced peritoneal neutrophils, the ability of bacterial phagocytosis and killing was impaired in CRAMP−/− neutrophils compared to the WT cells. CRAMP was also essential for the production of cytokines and chemokines in response to A. baumannii in neutrophils. In addition, the A. baumannii-induced inhibitor of κB-α degradation and phosphorylation of p38 MAPK were impaired in CRAMP−/− neutrophils, whereas ERK and JNK phosphorylation was upregulated. Our results indicate that CRAMP plays an important role in the host defense against pulmonary infection with A. baumannii by promoting the antibacterial activity of neutrophils and regulating the innate immune responses.

6-kDa early secretory antigenic target (ESAT6), a virulent factor of Mycobacterium tuberculosis, is involved in immune regulation. However, the underlying mechanism behind the activation and maturation of dendritic cells (DCs) by ESAT6 remains unclear. In this study, we investigated the effect on TLRs signaling on the regulation of ESAT6-induced activation and maturation of DCs. ESAT6 induced production of IL-6, TNF-α, and IL-12p40 in bone marrow-derived dendritic cells (BMDCs) from wild-type and TLR2-deficient mice, with this induction abolished in TLR4-deficient cells. NF-κB is essential for the ESAT6-induced production of the cytokines in BMDCs. TLR4 was also required for ESAT6-induced activation of NF-κB and MAPKs in BMDCs. ESAT6 additionally upregulated the expression of surface molecules CD80, CD86, and MHC-II, and also promoted the ability of CD4⁺ T cells to secrete IFN-γ via the TLR4-dependent pathway. Our findings suggest that TLR4 is critical in the activation and maturation of DCs in response to ESAT6.
Animals ; Cytokines ; Dendritic Cells ; Interleukin-12 Subunit p40 ; Interleukin-6 ; Mice ; Mycobacterium tuberculosis ; Mycobacterium ; T-Lymphocytes ; Toll-Like Receptor 4

BACKGROUND: The long-term data with direct acting antiviral agents were rare. This study investigated the durability of a sustained virologic response (SVR) and the improvement of fibrosis after daclatasvir and asunaprevir (DCV/ASV) treatment in genotype 1b (GT1b) hepatitis C virus (HCV)-infected patients. METHODS: A total of 288 HCV GT1b patients without baseline non-structural 5A (NS5A) resistance-associated substitution (RAS) treated with DCV/ASV were enrolled. Virologic response was measured at 12 weeks and 1 year after treatment completion. In cirrhotic patients, liver function, aspartate transaminase to platelet ratio index (APRI), FIB-4 index, fibrosis index (FI), and liver stiffness measurement (LSM) at baseline and 1 year after treatment completion were evaluated. RESULTS: SVR12 was obtained in 278 patients (96.5%). Six patients who checked NS5A RAS after treatment failure were RAS positive. Only one patient showed no durability of SVR. In cirrhotic patients who achieved SVR12 (n = 59), the changes of albumin (3.8 [2.2–4.7] to 4.3 [2.4–4.9] g/dL; P < 0.001), platelet count (99 [40–329] to 118 [40–399] × 103/mm3; P < 0.001), APRI (1.8 [0.1–14.8] to 0.6 [0.1–4.8]; P < 0.001), FIB-4 index (5.45 [0.6–32.8] to 3.3 [0.4–12.2]; P < 0.001), FI (5.5 [0.6–32.8] to 3.3 [0.4–12.2]; P < 0.001), and LSM (17.2 [5.3–48.0] to 11.2 [3.7–28.1] kPa; P = 0.001) between baseline and 1 year after treatment completion were observed. CONCLUSION: DCV/ASV treatment for HCV GT1b infected patients without RAS achieved high SVR rates and showed durable SVR. Cirrhotic patients who achieved SVR12 showed the improvement of liver function and fibrosis markers.
Antiviral Agents ; Aspartate Aminotransferases ; Blood Platelets ; Fibrosis ; Genotype ; Hepacivirus ; Hepatitis C ; Hepatitis ; Humans ; Liver ; Platelet Count ; Treatment Failure

Nucleotide-binding domain 1 (Nod1) is a cytosolic receptor that is responsible for the recognition of a bacterial peptidoglycan motif containing meso-diaminophimelic acid. In this study, we sought to identify the role of Nod1 in host defense in vivo against pulmonary infection by multidrug resistant Acinetobacter baumannii. Wildtype (WT) and Nod1-deficient mice were intranasally infected with 3×107 CFU of A. baumannii and sacrificed at 1 and 3 days post-infection (dpi). Bacterial CFUs, cytokines production, histopathology, and mouse β-defensins (mBD) in the lungs of infected mice were evaluated. The production of cytokines in response to A. baumannii was also measured in WT and Nod1-deficient macrophages. The bacterial clearance in the lungs was not affected by Nod1 deficiency. Levels of IL-6, TNF-α, and IL-1β in the lung homogenates were comparable at days 1 and 3 between WT and Nod1-deficient mice, except the TNF-α level at day 3, which was higher in Nod1-deficient mice. There was no significant difference in lung pathology and expression of mBDs (mBD1, 2, 3, and 4) between WT and Nod1-deficient mice infected with A. baumannii. The production of IL-6, TNF-α, and NO by macrophages in response to A. baumannii was also comparable in WT and Nod1-deficient mice. Our results indicated that Nod1 does not play an important role in host immune responses against A. baumannii infection.
Acinetobacter baumannii* ; Acinetobacter* ; Animals ; Cytokines ; Cytosol ; Interleukin-6 ; Lung ; Macrophages ; Mice* ; Pathology ; Peptidoglycan

Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.
ACTH Syndrome, Ectopic ; Adrenalectomy ; Adrenocorticotropic Hormone* ; Carcinoid Tumor ; Cushing Syndrome ; Humans ; Hypertension ; Korea ; Lymph Node Excision ; Lymph Nodes ; Male ; Metastasectomy ; Middle Aged ; Obesity, Abdominal ; Small Cell Lung Carcinoma ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

BACKGROUND/AIMS: To evaluate the long-term efficacy and safety of endoscopic injection of N-butyl-2-cyanoacrylate (NBC; Histoacryl) for treatment of bleeding gastric varices. METHODS: We retrospectively analyzed the records of 455 patients with gastric variceal hemorrhage (GVH) who were consecutively treated with NBC from January 2004 to July 2013, with a mean follow-up period of 582 days. The patients' endoscopic findings, initial hemostasis, complications, rebleeding rates, and bleeding-related death rates were reviewed. RESULTS: Hemostasis was achieved initially in 96.9% (441/455) of patients; rebleeding occurred in 35.2% (160/455), and the bleeding-related death rate was 6.8% (31/455) during follow-up. Complications included fever (6.8%), abdominal pain (3.7%), diarrhea (1.3%), spontaneous bacterial peritonitis (0.7%), bacteremia (0.4%), and embolism (0.2%). A red-color sign on concomitant esophageal varices (EVs) (p = 0.002) and previous history of variceal bleeding (p < 0.001) were significant risk factors for rebleeding within 1 year. The Child-Pugh score (p < 0.001), presence of hepatocellular carcinoma (p = 0.001), and failure of initial hemostasis (p < 0.001) were the risk factors most closely associated with bleeding-related death. CONCLUSIONS: This study provides a comprehensive overview of the outcomes and prognostic factors of patients with GVH. The results may help in the selection of effective treatment strategies for patients with GVH.
Adult ; Aged ; Aged, 80 and over ; Enbucrilate/adverse effects/*therapeutic use ; Endoscopy, Gastrointestinal ; Esophageal and Gastric Varices/complications/diagnosis/mortality/*therapy ; Female ; Gastrointestinal Hemorrhage/diagnosis/etiology/mortality/*therapy ; *Hemostatic Techniques/adverse effects/mortality ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Young Adult

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.
Abdominal Pain/*chemically induced/diagnosis ; Acute Disease ; Diagnosis, Differential ; Fever of Unknown Origin/*chemically induced/diagnosis ; Graves Disease/*drug therapy ; Humans ; Male ; Methimazole/*adverse effects/*therapeutic use ; Middle Aged ; Pancreatitis/*chemically induced/diagnosis ; Treatment Outcome

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.
Abdominal Pain/*chemically induced/diagnosis ; Acute Disease ; Diagnosis, Differential ; Fever of Unknown Origin/*chemically induced/diagnosis ; Graves Disease/*drug therapy ; Humans ; Male ; Methimazole/*adverse effects/*therapeutic use ; Middle Aged ; Pancreatitis/*chemically induced/diagnosis ; Treatment Outcome