Relationship Between MicroRNA Signature and Arterial Stiffness in Patients With Ischemic Stroke

Background@#and Purpose We investigated whether circulating microRNAs (miRNAs) is associated with arterial stiffness in patients with acute ischemic stroke. @*Methods@#We recruited patients with acute ischemic stroke who were admitted to a university hospital stroke center and underwent carotid-femoral pulse wave velocity (cfPWV) measurement using SphygmoCor (AtCor Medical, Sydney, Australia) and brachial-ankle PWV using a volume-plethysmography device (VP-1000, Omron Colin, Komaki, Japan). Circulating miRNAs were measured in venous blood samples stored in EDTA. We selected five miRNAs (miR-17, miR-93, miR-450, miR-629, and let-7i) related to atherosclerosis based on a literature review. Pearson’s correlation analysis was applied to the correlations between miRNAs and arterial stiffness parameters. Finally, multivariable linear regression analysis was performed to identify the independent factors for cfPWV. @*Results@#This study included 70 patients (age=71.1±10.3 years [mean±SD], 29 females). The expression levels of miR-93 (r=-0.27, p=0.049) and let-7i ((r=-0.27, p=0.039) were inversely correlated with cfPWV. Multivariable linear regression analysis including age, hypertension, and estimated glomerular filtration rate showed that let-7i was independently related with cfPWV (standardized coefficient=-0.262, p=0.036). Correlation analysis indicated that let-7i was positively associated with visceral muscle Hounsfield units on computed tomography ((r=0.264, p=0.043). @*Conclusions@#The expression level of let-7i was independently related to arterial stiffness in patients with cerebral infarction, suggesting that it plays a pathophysiological role in atherosclerosis.

Efficacy and Safety of ClearCut™ Knife H-type in Endoscopic Submucosal Dissection for Gastric Neoplasms: A Multicenter, Randomized Trial

Purpose@#Endoscopic submucosal dissection (ESD) is an effective treatment for early gastrointestinal neoplasms. However, this is a time-consuming procedure requiring various devices. This study aimed to evaluate the efficacy and safety of the ClearCut™ Knife H-type, which is an integrated needle-tipped and insulated-tipped (IT) knife. @*Materials and Methods@#Between July 2020 and September 2021, 99 patients with gastric epithelial neoplasms scheduled for ESD at three tertiary care hospitals were randomly assigned to H-knife (ClearCut™ Knife H-type) or IT-knife (conventional IT knife) groups.Procedure times, therapeutic outcomes, and adverse events were analyzed. @*Results@#A total of 98 patients (50 in the H-knife group and 48 in the IT-knife group) were analyzed. The median total procedure time was 11.9 minutes (range, 4.4–47.2 minutes) in the H-knife group and 12.7 minutes (range, 5.2–137.7 minutes) in the IT-knife group (P=0.209).Unlike the IT-knife group, which required additional devices in all cases, no additional devices were used in the H-knife group (P<0.001). En-bloc resection was performed for all lesions in both groups. The incidence of adverse events was not significantly different between groups (4.0% in the H-knife group vs. 8.3% in the IT-knife group; P=0.431). @*Conclusions@#The newly developed hybrid device, the ClearCut™ Knife H-type, had comparable efficacy to the conventional IT knife for gastric ESD.

A Novel One-Step Knife Approach Can Reduce the Submucosal Injection Time of Endoscopic Submucosal Dissection: A SingleBlinded Randomized Multicenter Clinical Trials

Background/Aims@#Endoscopic submucosal dissection (ESD) is a curative treatment modality for early gastric neoplasms; however, ESD can be a time-consuming process. To overcome this pitfall, we developed the one-step knife (OSK) approach, which combines an endoscopic knife and injection needle on a single sheath. We aimed to evaluate whether this approach could reduce the ESD procedure time. @*Methods@#This single-blinded randomized multicenter trial at four tertiary hospitals from June 2019 to June 2020 included patients aged 19 to 85 years undergoing ESD. Patients were randomly assigned to two groups (OSK or conventional knife [CK]). The injection time, total procedure time, resected specimen size, submucosal fluid amount, degree of device satisfaction, and adverse events were evaluated and compared between groups. @*Results@#Fifty-one patients were analyzed (OSK: 25 patients and CK: 26 patients). No baseline differences were observed between groups, with the exception of a higher portion of males in the OSK group. The mean injection time was significantly reduced in the OSK group (39.0 seconds) compared to that in the CK group (87.5 seconds, p<0.001). A decrease of more than 10 minutes in the total procedure time (18.0 minutes vs 28.1 minutes, p=0.055) in the OSK group compared to the CK group was observed. Second-look esophagogastroduodenoscopy revealed two delayed bleeding cases in the OSK group that were easily controlled by endoscopic hemostasis. @*Conclusions@#OSK reduced the injection time and showed a decrease in total procedure time compared with the CK approach. OSK can be a feasible tool for ESD, especially in difficult cases.

Eradication Rate Using a First-line Triple Therapy for Helicobacter pylori Infection in Yeongdong, Gangwon Province, Korea

Background/Aims@#The eradication success rate of Helicobacter pylori (H. pylori) infection with a first-line standard triple therapy (STT) has been decreasing in Korea. However, treatment outcomes of H. pylori infection in Yeongdong, Gangwon Province have been scarcely reported. This study aimed to investigate the treatment outcomes of H. pylori infection in a single tertiary care hospital with regional characteristics. @*Materials and Methods@#From July 2018 to June 2019, a total of 592 patients who underwent STT consisting of a proton pump inhibitor, amoxicillin, and clarithromycin for 7 to 14 days as a first-line H. pylori eradication therapy were included. Demographic data and treatment outcomes were retrospectively reviewed using medical records. @*Results@#The median age of 592 patients was 58 years (range 23 to 86) and 329 patients (55.6%) were men. The indication for eradication therapy included chronic atrophic gastritis (57.9%), peptic ulcer disease (19.6%), and gastric neoplasm after endoscopic resection (5.9%). Most patients (92.2%) received a 7-day course of STT. Eradication rate of STT was 64.0% (379/592). Rescue therapy was performed in 146 patients, and the final eradication rate reached 85.6% (507/592). @*Conclusions@#Eradication rate of STT in Yeongdong area of Gangwon Province was unsatisfactory, warranting the consideration of a first-line eradication regimen other than STT.

The comprehensive on-demand 3D bio-printing for composite reconstruction of mandibular defects / 대한악안면성형재건외과학회지

Background@#The mandible is a functional bio-organ that supports facial structures and helps mastication and speaking. Large mandible defects, generally greater than 6-cm segment loss, may require composite tissue reconstruction such as osteocutaneous-vascularized free flap which has a limitation of additional surgery and a functional morbidity at the donor site. A 3D bio-printing technology is recently developed to overcome the limitation in the composite reconstruction of the mandible using osteocutaneous-vascularized free flap.ReviewScaffold, cells, and bioactive molecules are essential for a 3D bio-printing. For mandibular reconstruction, materials in a 3D bio-printing require mechanical strength, resilience, and biocompatibility. Recently, an integrated tissue and organ printing system with multiple cartridges are designed and it is capable of printing polymers to reinforce the printed structure, such as hydrogel. @*Conclusion@#For successful composite tissue reconstruction of the mandible, biologic considerations and components should be presented with a comprehensive on-demand online platform model of customized approaches.

Romosozumab in Postmenopausal Korean Women with Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study

Background@#This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis. @*Methods@#Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤–2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months. @*Results@#At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary efficacy endpoint) between the romosozumab (9.5%) and placebo (–0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P<0.001). The difference in the LS mean percent change from baseline was also significant for total hip and femoral neck BMD (secondary efficacy endpoints). After treatment with romosozumab, the percent change from baseline in procollagen type 1 N-terminal propeptide transiently increased at months 1 and 3, while that in C-terminal telopeptide of type 1 collagen showed a sustained decrease. No events of cancer, hypocalcemia, injection site reaction, positively adjudicated atypical femoral fracture or osteonecrosis of the jaw, or positively adjudicated serious cardiovascular adverse events were observed. At month 9, 17.6% and 2.9% of patients in the romosozumab group developed binding and neutralizing antibodies, respectively. @*Conclusion@#Treatment with romosozumab for 6 months was well tolerated and significantly increased lumbar spine, total hip, and femoral neck BMD compared with placebo in Korean postmenopausal women with osteoporosis (ClinicalTrials.gov identifier NCT02791516).

Olfactory and Gustatory Dysfunction in a COVID-19 Patient with Ankylosing Spondylitis Treated with Etanercept: Case Report

The neurologic manifestations concerning coronavirus disease 2019 (COVID-19) are highly penetrated. Anosmia and ageusia are one of the common acute neurologic symptoms, which develop in the early stage of COVID-19. However, it is not reported that how immunosuppressive agents affect these symptoms. We report olfactory and gustatory dysfunctions in a patient with ankylosing spondylitis (AS) treated with etanercept during COVID-19. A 53-year-old female showing AS controlled with tumor necrosis factor-α inhibitor, etanercept, had been diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, presenting cough and rhinorrhea. One month after diagnosis, she complained about hyposmia and hypogeusia two days before the seronegative conversion of SARS-CoV-2, which were confirmed by a neurological examination. We speculate that the etanercept may have delayed the development of olfactory and gustatory dysfunction in the patient.

A case of IgG4-related disease associated with psoriasis-like skin rash and hypereosinophilic syndrome

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is newly recognized immune-mediated and fibroinflammatory conditions with various organ involvements. Any organs can be involved, but the pancreas, salivary gland, lymph nodes, and orbit are known to be commonly involved organs. A 54-year-old man presented with complaint of psoriasis like skin rash developed 4 years prior to admission. Although he had been treated for skin rash, the extent of skin lesions increased as well as hypereosinophilia, and multiple lymphadenopathies were newly developed. The patient was diagnosed with IgG4-RD by serum IgG4 levels and histologic examination of the inguinal lymph node. One month after treatment with steroid and azathioprine, his skin rash and lymphadenopathies resolved with improvement and eosinophil count was within the normal range. We herein report a case of a IgG4-RD patient associated with psoriasis-like skin rash and hypereosinophilic syndrome.

A Case of Rapid Progressive Neurosyphilis in Patient with Ankylosing Spondylitis Who Is Treating Anti-interleukin 17A Monoclonal Antibody, Secukinumab

Anti-interleukin 17A agent, secukinumab is remarkably effective for treating patients with ankylosing spondylitis. However, the main safety concern of secukinumab is an increased risk of infection. Generally, neurosyphilis occurs a few years after the primary syphilitic infection. Rare cases of progressing to neurosyphilis with a much lower latency were reported. We report a case of rapid progressive neurosyphilis involving hearing loss in both ears in a patient with ankylosing spondylitis who was treated with secukinumab.

An Esophageal Squamous Cell Carcinoma with Lymph Node Metastasis Presenting as a Small Subepithelial Tumor

A subepithelial tumor-like esophageal carcinoma is rare. We report a case of an esophageal squamous cell carcinoma with lymph node metastasis presenting as a small subepithelial tumor. A 68-year-old man presented to our hospital complaining of hoarseness since last three months. Endoscopic examination revealed a 1 cm hard and fixed subepithelial tumor with surface erosion in the lower esophagus. A biopsy specimen was obtained using conventional forceps, and histopathological evaluation revealed few atypical squamous epithelial cells. Subsequent EUS demonstrated a homogeneous hypoechoic lesion in the deep mucosal layer. A CT scan of the chest showed a 3 cm mass in the right upper paratracheal area. EUS-guided fine needle biopsy of the lesion led to the diagnosis of squamous cell carcinoma with lymph node metastasis.

Ascending Colon Cancer with Pathologically Confirmed Tumor Thrombosis of Superior Mesenteric Vein: A Case Report

Colon cancer is very rarely accompanied by tumor thrombosis of the superior mesenteric vein (SMV). A 46-year-old patient had been diagnosed with SMV tumor thrombosis related to colon cancer without hepatic metastasis and underwent right hemicolectomy with SMV tumor thrombectomy. Tumor thrombosis was pathologically confirmed as metastatic colon cancer. There has been no recurrence for 12 months with 12 cycles of adjuvant-chemotherapy.

Case of Renal Microaneurysms and Multiple Renal Infarctions in a Patient with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic inflammatory, heterogeneous autoimmune disease characterized by autoantibody production and the potential involvement of almost every organ system. Although vasculitis usually confined to small vessels is a fairly common feature of SLE, ischemic vasculitis with an aneurysm is an uncommon feature. In particular, renal arterial microaneurysms and multiple renal infarctions are very rarely reported in patients with SLE. Furthermore, to the best of the authors' knowledge, there is no report on renal arterial microaneurysms associated with SLE in Korea. Here, this paper presents a case of renal microaneurysms and multiple renal infarctions in a 41-year-old woman with SLE.

A Case of Small Hepatocellular Carcinoma Who Showed Complete Response by Combined Therapy of Transarterial Chemoembolization and Stereotactic Body Radiotherapy

In hepatocellular carcinoma (HCC), surgical resection or local ablation therapy is limited because of severe liver dysfunction or tumor location. Transarterial chemoembolization (TACE) has beed used widely as palliative treatment. Stereotactic Body Radiotherapy (SBRT) is a more recent and effective treatment for early stage HCC. We report a case with small HCC with complete response by TACE combined with SBRT.

Comparison of volatile organic compounds between cigarette smoke condensate (CSC) and extract (CSE) samples

Cigarette smoke is a major risk factor for several diseases, including chronic obstructive pulmonary and cardiovascular diseases. The toxicity of the cigarette smoke can be determined in vitro. The cytotoxicity test of the cigarette smoke is commonly conducted using the cigarette smoke condensate (CSC) and cigarette smoke extract (CSE). The CSC and CSE methods are well known for sampling of the particles and water-soluble compounds in the cigarette smoke, respectively. In this study, the CSC and CSE were analyzed by using a gas chromatography-mass spectrometry (GC-MS) system equipped with a wax column for separation of the volatile organic compounds. The cytotoxic effect of the CSC and CSE were evaluated thoroughly by comparing the analytical results of the CSC and CSE samples. The total concentration of the volatile organic compounds detected in the CSC sample was similar to that in the CSE sample based on the peak area. Except for the dimethyl sulfoxide solvent, nicotine had the highest concentration in the CSC sample, while acetonitrile had the highest concentration in the CSE sample. The compositions were as follows: (1) CSC sample: 55.8% nicotine, 18.0% nicotyrine, 3.20% 1,2,3-propanetriol, triacetate, 1.28% ethyl chloride, 1.22% phenol, etc. and (2) CSE sample: 18.7% acetonitrile, 18.0% acetone, 12.5% 2-hydroxy-2-methyl-propanenitrile, 8.98% nicotine, 5.86% nicotyrine, etc. In this manner, to accurately examine the cytotoxicity of the cigarette smoke using CSC or CSE, the components and their concentrations in the CSC and CSE samples should be considered.

Comparison of volatile organic compounds between cigarette smoke condensate (CSC) and extract (CSE) samples

Cigarette smoke is a major risk factor for several diseases, including chronic obstructive pulmonary and cardiovascular diseases. The toxicity of the cigarette smoke can be determined in vitro. The cytotoxicity test of the cigarette smoke is commonly conducted using the cigarette smoke condensate (CSC) and cigarette smoke extract (CSE). The CSC and CSE methods are well known for sampling of the particles and water-soluble compounds in the cigarette smoke, respectively. In this study, the CSC and CSE were analyzed by using a gas chromatography-mass spectrometry (GC-MS) system equipped with a wax column for separation of the volatile organic compounds. The cytotoxic effect of the CSC and CSE were evaluated thoroughly by comparing the analytical results of the CSC and CSE samples. The total concentration of the volatile organic compounds detected in the CSC sample was similar to that in the CSE sample based on the peak area. Except for the dimethyl sulfoxide solvent, nicotine had the highest concentration in the CSC sample, while acetonitrile had the highest concentration in the CSE sample. The compositions were as follows: (1) CSC sample: 55.8% nicotine, 18.0% nicotyrine, 3.20% 1,2,3-propanetriol, triacetate, 1.28% ethyl chloride, 1.22% phenol, etc. and (2) CSE sample: 18.7% acetonitrile, 18.0% acetone, 12.5% 2-hydroxy-2-methyl-propanenitrile, 8.98% nicotine, 5.86% nicotyrine, etc. In this manner, to accurately examine the cytotoxicity of the cigarette smoke using CSC or CSE, the components and their concentrations in the CSC and CSE samples should be considered.

Interrater Reliability among Endoscopists: Diagnosis of Laryngopharyngeal Reflux Based on the Reflux Finding Score Determined by Upper Endoscopy

BACKGROUND/AIMS: Laryngopharyngeal reflux (LPR) is an extraesophageal manifestation of gastroesophageal reflux disease. Endoscopic assessment of LPR is needed for convenient diagnosis and documentation of treatment efficacy. The aim of this study was to investigate the interrater reliability of LPR among endoscopists based on endoscopic laryngeal images. MATERIALS AND METHODS: Nineteen endoscopists participated in this study. Before the test, they completed an intensive education program by an otorhinolaryngologist on the reflux finding score (RFS), which is a validated laryngoscopic assessment of LPR. A total of 100 endoscopic laryngeal images were used for 3 tests of RFS. Cohen's and Fleiss' kappa coefficients were used to determine the degree of interrater agreement in the diagnosis of LPR. RESULTS: In the first test, the mean of Cohen's kappa coefficients for LPR diagnosis between the otorhinolaryngologist and each of the 19 endoscopists was 0.3. In the second test, after additional education, the mean kappa value was 0.32. Fleiss' kappa coefficients for diagnosis of LPR among the 19 endoscopists in the first and second tests were 0.30 and 0.26, respectively. CONCLUSIONS: A short-term education program for endoscopists did not result in an improvement of accuracy in the diagnosis of LPR. Further studies using advanced educational programs for endoscopists are required.

Risk of Herpes Zoster in Patients with Rheumatoid Arthritis Undergoing Biologic Disease-Modifying Therapy

OBJECTIVE: Rheumatoid arthritis (RA) patients suffer from an increased risk of herpes zoster (HZ) partially due to immunosuppressant medications. This study investigated HZ in RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs), as compared with conventional DMARDs (cDMARDs). METHODS: This retrospective case series study assembled record information of 277 RA patients who received bDMARDs after failure of at least one cDMARDs at Seoul National University Hospital between August 2003 and February 2015. Following capture of baseline information and identification of HZ episodes, crude HZ incidence rates per 100 patient-years (95% confidence intervals) were calculated. RESULTS: For 718 treatment courses, 277 (38.6%) comprised cDMARDs, 66 (9.2%) infliximab, 175 (24.4%) etanercept, 95 (13.2%) adalimumab, 9 (1.3%) golimumab, 41 (5.7%) rituximab, 31 (4.3%) abatacept, and 24 (3.3%) tocilizumab. There were 37 HZ episodes, 16 during cDMARD treatment courses, and 21 accompanying bDMARDs, two with infliximab, eight with etanercept, five with adalimumab, and three each with rituximab and abatacept. The crude HZ incidence rate per 100 patient-years was 2.4 (1.4∼3.9) for cDMARDs, 2.2 (0.3∼7.9) for infliximab, 1.8 (0.8∼3.6) for etanercept, 3.7 (1.2∼8.4) for adalimumab, 3.9 (0.8∼11.0) for rituximab, and 8.5 (1.8∼23.1) for abatacept. CONCLUSION: We conclude that bDMARDs do not always increase the risk of HZs in RA patients, although HZ rates vary for different bDMARDs.

Spontaneous Regression of Hyperplastic Gastric Polyps

Although gastric hyperplastic polyps are recognized as benign lesions, there is concern regarding carcinomatous changes in the polyps, depending on their size. If the polyp size is larger than 1.0~2.0 cm, endoscopic resection is usually recommended. Gastric hyperplastic polyps easily undergo changes in their shape and size over time. However, spontaneous regression of hyperplastic polyps is very rare. We present a recent case wherein gastric hyperplastic polyps disappeared spontaneously. We present the case along with a literature review.

Poloxamer 407 Hydrogels for Intravesical Instillation to Mouse Bladder: Gel-Forming Capacity and Retention Performance

PURPOSE: Poloxamer 407 (P407) thermo-sensitive hydrogel formulations were developed to enhance the retention time in the urinary bladder after intravesical instillation. MATERIALS AND METHODS: P407 hydrogels (P407Gels) containing 0.2 w/w% fluorescein isothiocyanate dextran (FD, MW 4 kDa) as a fluorescent probe were prepared by the cold method with different concentrations of the polymer (20, 25, and 30 w/w%). The gel-forming capacities were characterized in terms of gelation temperature (G-Temp), gelation time (G-Time), and gel duration (G-Dur). Homogenous dispersion of the probe throughout the hydrogel was observed by using fluorescence microscopy. The in vitro bladder simulation model was established to evaluate the retention and drug release properties. P407Gels in the solution state were administered to nude mice via urinary instillation, and the in vivo retention behavior of P407Gels was visualized by using an in vivo imaging system (IVIS). RESULTS: P407Gels showed a thermo-reversible phase transition at 4℃ (refrigerated; sol) and 37℃ (body temperature; gel). The G-Temp, G-Time, and G-Dur of FD-free P407Gels were approximately 10℃–20℃, 12–30 seconds, and 12–35 hours, respectively, and were not altered by the addition of FD. Fluorescence imaging showed that FD was spread homogenously in the gelled P407 solution. In a bladder simulation model, even after repeated periodic filling-emptying cycles, the hydrogel formulation displayed excellent retention with continuous release of the probe over 8 hours. The FD release from P407Gels and the erosion of the gel, both of which followed zero-order kinetics, had a linear relationship (r²=0.988). IVIS demonstrated that the intravesical retention time of P407Gels was over 4 hours, which was longer than that of the FD solution ( < 1 hour), even though periodic urination occurred in the mice. CONCLUSIONS: FD release from P407Gels was erosion-controlled. P407Gels represent a promising system to enhance intravesical retention with extended drug delivery.

CTLA4-CD28 chimera gene modification of T cells enhances the therapeutic efficacy of donor lymphocyte infusion for hematological malignancy

Donor lymphocyte infusion (DLI) followed by hematopoietic stem cell transplantation has served as an effective prevention/treatment modality against the relapse of some hematologic tumors, such as chronic myeloid leukemia (CML). However, the therapeutic efficacies of DLI for other types of leukemia, including acute lymphocytic leukemia (ALL), have been limited thus far. Therefore, we examined whether increasing the reactivity of donor T cells by gene modification could enhance the therapeutic efficacy of DLI in a murine model of ALL. When a CTLA4-CD28 chimera gene (CTC28) in which the intracellular signaling domain of CTLA4 was replaced with the CD28 signaling domain was introduced into CD4 and CD8 T cells in DLI, the graft-versus-tumor (GVT) effect was significantly increased. This effect was correlated with an increased expansion of donor CD8 T cells in vivo, and the depletion of CD8 T cells abolished this effect. The CD8 T cell expansion and the enhanced GVT effect were dependent on the transduction of both CD4 and CD8 T cells with CTC28, which emphasizes the role of dual modification in this therapeutic effect. The CTC28-transduced T cells that expanded in vivo also exhibited enhanced functionality. Although the potentiation of the GVT effect mediated by the CTC28 gene modification of T cells was accompanied by an increase of graft-versus-host disease (GVHD), the GVHD was not lethal and was mitigated by treatment with IL-10 gene-modified third-party mesenchymal stem cells. Thus, the combined genetic modification of CD4 and CD8 donor T cells with CTC28 could be a promising strategy for enhancing the therapeutic efficacy of DLI.