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.

PURPOSE: We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. MATERIALS AND METHODS: A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). CONCLUSION: We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT.
Adenocarcinoma* ; Carcinoma, Endometrioid ; Chemoradiotherapy ; Chemoradiotherapy, Adjuvant ; Disease-Free Survival ; Endometrial Neoplasms ; Female ; Humans ; Multivariate Analysis ; Neoplasm Metastasis ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Risk Factors

BACKGROUND AND OBJECTIVES: We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients. SUBJECTS AND METHODS: Patients who met inclusion criteria were randomized to receive 1 of the following 2-month drug regimens: valsartan 160 mg plus rosuvastatin 20 mg, valsartan 160 mg plus placebo, or rosuvastatin 20 mg plus placebo. The primary efficacy variables were change in sitting diastolic blood pressure (sitDBP) and sitting systolic blood pressure (sitSBP), and percentage change in low-density lipoprotein-cholesterol (LDL-C) in the combination, valsartan, and rosuvastatin groups. Adverse events (AEs) during the study were analyzed. RESULTS: A total of 354 patients were screened and 123 of them were finally randomized. Changes of sitDBP by least squares mean (LSM) were -11.1, -7.2, and -3.6 mm Hg, respectively, and was greater in the combination, as compared to both valsartan (p=0.02) and rosuvastatin (p<0.001). Changes of sitSBP by LSM were -13.2, -10.8, and -4.9 mm Hg, and was greater in the combination, as compared to rosuvastatin (p=0.006) and not valsartan (p=0.42). Percentage changes of LDL-C by LSM were -52, -4, and -47% in each group, and was greater in the combination, as compared to valsartan (p<0.001), similar to rosuvastatin (p=0.16). Most AEs were mild and resolved by the end of the study. CONCLUSION: Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability, as compared to valsartan monotherapy. Its lipid lowering effect was similar to rosuvatatin monotherapy.
Blood Pressure ; Drug Therapy, Combination ; Humans ; Least-Squares Analysis ; Rosuvastatin Calcium ; Valsartan

Quetiapine is an atypical antipsychotic that is frequently used to manage delirium in geriatric patients. Acute pancreatitis associated with quetiapine has rarely been reported. A 70-year-old male presented with severe abdominal pain a few hours after taking a dose of quetiapine prescribed for delirium. Despite the lack of risk factors of pancreatitis in his medical history, the patient had a slight increase of serum lipase and amylase levels. His general condition improved on discontinuation of quetiapine. A month later, quetiapine was readministered for the recurrence of delirium. Subsequently, the patient developed the same symptom with a significant increase in serum pancreatic enzyme levels, confirming that quetiapine induced the pancreatitis. We reported the first case of quetiapine-induced pancreatitis in Korea, together with a review of the literature.
Abdominal Pain ; Aged* ; Amylases ; Delirium ; Humans ; Korea ; Lipase ; Male ; Pancreatitis* ; Recurrence ; Risk Factors ; Quetiapine Fumarate

In this article, on page 230, Fig. 2A needs to be corrected.

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