Background: This study investigated the real-world efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in Korean adults with type 2 diabetes mellitus (T2DM), whose insulin treatment was switched to IDegAsp. Methods: This was a multicenter, retrospective, observational study comprising two 26-week treatment periods, before and after switching to IDegAsp, respectively. Korean adults with uncontrolled T2DM treated with basal or premix insulin (±oral antidiabetic drugs) were enrolled. The primary objective was to compare the degree of glycosylated hemoglobin (HbA1c) change in each 26-week observation period. The analyses included changes in HbA1c, fasting plasma glucose (FPG), body weight, proportion of participants achieving HbA1c <7.0%, hypoglycemic events, and total daily insulin dose (ClinicalTrials.gov, number NCT04656106). Results: In total, 196 adults (mean age, 65.95 years; mean T2DM duration, 18.99 years) were analyzed. The change in both HbA1c and FPG were significantly different between the pre-switching and the post-switching period (0.28% vs. –0.51%, P<0.001; 5.21 mg/dL vs. –23.10 mg/dL, P=0.005), respectively. After switching, the rate of achieving HbA1c <7.0% was significantly improved (5.10% at baseline vs. 11.22% with IDegAsp, P=0.012). No significant differences (before vs. after switching) were observed in body weight change, and total daily insulin dose. The rates of overall and severe hypoglycemia were similar in the two periods. Conclusion In real-world clinical practice in Korea, the change of insulin regimen to IDegAsp was associated with an improvement in glycemic control without increase of hypoglycemia, supporting the use of IDegAsp for patients with T2DM uncontrolled with basal or premix insulin.

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical’s MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue diseaseILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone.Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited antiapoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

The commensal microbiota contributes to the maintenance of immune homeostasis in the human body. Autoimmunity can be aggravated or alleviated by the microbiota, which affects both innate and adaptive immune cells. Many studies have demonstrated the role of gut dysbiosis, the alteration of the gut microbiome, in the development and progression of numerous autoimmune diseases. Systemic sclerosis (SSc) is an autoimmune disease of the connective tissue and is characterized by skin and lung fibrosis, as well as injuries in small arteries. Recent studies have shown variable degrees of dysbiosis in SSc patients and the effect of probiotics on these patients, providing evidence for the potential link between microbiota and SSc. However, further research is needed to elucidate the key microorganisms and the mechanisms through which they affect the pathoimmunological process of SSc. This review summarizes the current knowledge regarding the association between microbiota and SSc, and discusses the changing perspectives and potential therapy strategies based on the microbiota and its products.
Arteries ; Autoimmune Diseases ; Autoimmunity ; Connective Tissue ; Dysbiosis ; Fibrosis ; Gastrointestinal Microbiome ; Homeostasis ; Human Body ; Humans ; Lung ; Microbiota ; Probiotics ; Scleroderma, Systemic ; Skin

Although the causes of hypertension are usually unknown, about 10% of the cases occur secondary to specific etiologies, which are often treatable. Common categories of secondary hypertension include renal parenchymal disease, renovascular stenosis, vascular and endocrinologic disorders. For diseases involving the renal parenchyma and adrenal glands, ultrasonography (US), computed tomography (CT) or magnetic resonance (MR) imaging is recommended. For renovascular stenosis and vascular disorders, Doppler US, conventional or noninvasive (CT or MR) angiography is an appropriate modality. Nuclear imaging can be useful in the differential diagnosis of endocrine causes. Radiologists should understand the role of each imaging modality and its typical findings in various causes of secondary hypertension. This article focuses on appropriate imaging approaches in accordance with the categorized etiologies leading to hypertension.
Adrenal Glands ; Angiography ; Constriction, Pathologic ; Diagnosis, Differential ; Diagnostic Imaging ; Humans ; Hypertension* ; Magnetic Resonance Imaging ; Ultrasonography

Vulvar squamous cell carcinoma (SCC) consists of two different etiologic categories: human papilloma virus (HPV)-associated (HPV (+)) and HPV-non-associated (HPV (−)). There have been no genome-wide studies on the genetic alterations of vulvar SCCs or on the differences between HPV (+) and HPV (−) vulvar SCCs. In this study, we performed whole-exome sequencing and copy number profiling of 6 HPV (+) and 9 HPV (−) vulvar SCCs and found known mutations (TP53, CDKN2A and HRAS) and copy number alterations (CNAs) (7p and 8q gains and 2q loss) in HPV (−) SCCs. In HPV (+), we found novel mutations in PIK3CA, BRCA2 and FBXW7 that had not been reported in vulvar SCCs. HPV (−) SCCs exhibited more mutational loads (numbers of nonsilent mutations and driver mutations) than HPV (+) SCCs, but the CNA loads and mutation signatures between HPV (+) and HPV (−) SCCs did not differ. Of note, 40% and 40% of the 15 vulvar SCCs harbored PIK3CA and FAT1 alterations, respectively. In addition, we found that the SCCs harbored kataegis (a localized hypermutation) in 2 HPV (+) SCCs and copy-neutral losses of heterozygosity in 4 (one HPV (+) and 3 HPV (−)) SCCs. Our data indicate that HPV (+) and HPV (−) vulvar SCCs may have different mutation and CNA profiles but that there are genomic features common to SCCs. Our data provide useful information for both HPV (+) and HPV (−) vulvar SCCs and may aid in the development of clinical treatment strategies.

The occurrence of hepatocellular carcinoma (HCC) is closely associated with viral hepatitis or alcoholic hepatitis. Although active surveillance is ongoing in Korea, advanced or metastatic HCC is found at initial presentation in many patients. Metastatic HCC presents with a hypervascular intrahepatic tumor and extrahepatic lesions such as lung or lymph node metastases. Cases of HCC presenting as carcinoma of unknown primary have been rarely reported. The authors experienced a case of metastatic HCC in a patient who presented with a metastatic bone lesion but no primary intrahepatic tumor. This case suggests that HCC should be considered as a differential diagnosis when evaluating the primary origin of metastatic carcinoma.
Antineoplastic Agents/therapeutic use ; Bone Neoplasms/*diagnosis/diagnostic imaging/secondary ; Carcinoma, Hepatocellular/*diagnosis/drug therapy ; Cervical Cord/pathology ; Chemoembolization, Therapeutic ; Gamma Rays ; Humans ; Liver Neoplasms/*diagnosis/drug therapy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasms, Unknown Primary/pathology ; Niacinamide/analogs & derivatives/therapeutic use ; Pelvic Bones/pathology ; Phenylurea Compounds/therapeutic use ; Tomography, X-Ray Computed

Calcaneus is largest tarsal bone and the fracture of calcaneus is most common tarsal fractures. Calcaneal fractures are divided into extra-articular and intra-articular fractures. Intra-articular calcaneal fractures could be classified as tongue type and joint depression type using simple lateral radiograph (Essex-Lopresti classification), but Sanders suggested new classification according to involving the posterior facet of calcaneus using computed tomography. The involvement of posterior facet was revealed as more complicated than Essex-Lopresti classification. The principle purpose of treatment of calcaneal fractures are restoration of calcaneal height (Bohler angle), width, axis, anatomical reduction of joint and restoration of function through the stable fixation. Good visualization of joint and anatomical reduction could be achieved by extended lateral approach. But, skin problem could be occurred after of extended lateral approach.
Axis, Cervical Vertebra ; Calcaneus ; Depression ; Intra-Articular Fractures ; Joints ; Skin ; Tarsal Bones ; Tongue

PURPOSE: The purpose of this study was to examine the occurrence of toxic exposure cases in Korean emergency centers using a toxic exposure surveillance system-based report form and to provide guidelines for the prevention and treatment of toxic exposures. METHODS: We retrospectively reviewed the medical records of toxic exposure patients who had visited emergency centers from January 2009 to December 2009. Epidemiology data points for the toxic exposure cases included age, gender, type of exposure, number and kind of substances involved, reason and route of poison exposure, management of the patients in the emergency departments, and the clinical outcome. RESULTS: A total of 3,501 patients from 12 emergency departments were enrolled in the study. 50.0% of the total exposure patients were male and 63.0% of the total cases were fatal. Acute intoxication occurred in 91.3% of the total patients and suicidal intent was the most common (43.3%) reason for exposure. The most common route of exposure was ingestion (75.9%). Of the total cases, pesticides were involved in 26.3%, sedatives/hypnotics/antipsychotics were involved in 22.0%, and bites and envenomations were involved in 15.7%. CONCLUSION: We provided a database of patients who were admitted to emergency departments after poisoning incidents. We recommend that toxicology professionals develop a classification scheme for toxicants which is adequate for Korean domestic circumstances and initiate a toxic surveillance system for all types of exposures. With support of a psychiatric surveillance system for suicidal patients and establishment of social mediation for pesticide poisoning, major reductions in poison exposures can be achieved.
Bites and Stings ; Eating ; Emergencies ; Humans ; Male ; Medical Records ; Negotiating ; Pesticides ; Retrospective Studies ; Toxicology

CXC chemokine receptor 4 (CXCR4), which binds the stromal cell-derived factor-1 (SDF-1), has been shown to play a critical role in mobilizing the bone marrow (BM)-derived stem cells and inflammatory cells. We studied the effects of AMD3100, CXCR4 antagonist, on a murine bleomycin-induced pulmonary fibrosis model. Treatment of mice with AMD3100 in bleomycin-treated mice resulted in the decrease of SDF-1 in bronchoalveolar lavage (BAL) fluids at an early stage and was followed by the decrease of fibrocytes in the lung. AMD3100 treatment decreased the SDF-1 mRNA expression, fibrocyte numbers in the lung at an early stage (day 3) and CXCR4 expression at the later stage (day 7 and 21) after bleomycin injury. The collagen content and pulmonary fibrosis were significantly attenuated by AMD3100 treatment in later stage of bleomycin injury. AMD3100 treatment also decreased the murine mesenchymal and hematopoietic stem cell chemotaxis when either in the stimulation with bleomycin treated lung lysates or SDF-1 in vitro. In BM stem cell experiments, the phosphorylation of p38 MAPK which was induced by SDF-1 was significantly blocked by addition of AMD3100. Our data suggest that AMD3100 might be effective in preventing the pulmonary fibrosis by inhibiting the fibrocyte mobilization to the injured lung via blocking the SDF-1/CXCR4 axis.
Animals ; *Bleomycin ; Bronchoalveolar Lavage Fluid/chemistry ; Cell Movement/drug effects ; Cells, Cultured ; Chemokine CXCL12/chemistry/metabolism ; Cytoprotection/drug effects ; Down-Regulation/drug effects ; Drug Evaluation, Preclinical ; Female ; Heterocyclic Compounds/pharmacology/*therapeutic use ; Lung/drug effects/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Pulmonary Fibrosis/*chemically induced/*prevention & control ; Receptors, CXCR4/*antagonists & inhibitors/metabolism

BACKGROUND/AIMS: Few studies have investigated hepatitis A virus (HAV) seroepidemiology in Koreans with chronic liver disease (CLD). This study compared the prevalence of IgG anti-HAV between the general healthy population and patients with hepatitis B virus-related CLD (HBV-CLD), with the aim of identifying predictors of HAV prior exposure. METHODS: In total, 1,319 patients were recruited between June 2008 and April 2010. All patients were tested for IgG anti-HAV, hepatitis B surface antigen (HBsAg), and antibodies to hepatitis C virus. The patients were divided into the general healthy population group and the HBV-CLD group based on the presence of HBsAg. The seroprevalence of IgG anti-HAV was compared between these two groups. RESULTS: The age-standardized seroprevalence rates of IgG anti-HAV in the general healthy population and patients with HBV-CLD were 52.5% and 49.1%, respectively. The age-stratified IgG anti-HAV seroprevalence rates for ages < or =19, 20-29, 30-39, 40-49, 50-59, and > or =60 years were 14.3%, 11.2%, 45.5%, 90.5%, 97.6% and 98.3%, respectively, in the general healthy population, and 0%, 9.8%, 46.3%, 91.1%, 97.7%, and 100% in the HBV-CLD group. In multivariate analysis, age (<30 vs. 30-59 years: OR=19.339, 95% CI=12.504-29.911, P<0.001; <30 vs. > or =60 years: OR=1060.5, 95% CI=142.233-7907.964, P<0.001) and advanced status of HBV-CLD (OR=19.180, 95% CI=4.550-80.856, P<0.001) were independent predictors of HAV prior exposure. CONCLUSIONS: The seroprevalence of IgG anti-HAV did not differ significantly between the general-healthy-population and HBV-CLD groups. An HAV vaccination strategy might be warranted in people younger than 35 years, especially in patients with HBV-CLD.
Adolescent ; Adult ; Age Factors ; Aged ; Female ; Hepatitis A/complications/*epidemiology/prevention & control ; Hepatitis A Antibodies/*blood ; Hepatitis A virus/immunology ; Hepatitis B Surface Antigens/blood ; Hepatitis B, Chronic/*complications ; Humans ; Immunoglobulin G/*blood ; Male ; Middle Aged ; Republic of Korea ; Seroepidemiologic Studies ; Sex Factors ; Vaccination