Fibrotic Burden Determines Cardiovascular Risk among Subjects with Metabolic Dysfunction-Associated Fatty Liver Disease

Background/AimsMetabolic dysfunction associated fatty liver disease (MAFLD) has recently been introduced to compensate for the conventional concept of nonalcoholic fatty liver disease (NAFLD). We explored whether fibrotic burden determines the risk of atherosclerotic cardiovascular disease (ASCVD) among subjects with MAFLD.MethodsWe recruited 9,444 participants from the Korea National Health and Nutrition Examination Survey (2008 to 2011). Liver fibrosis was identified using the fibrosis-4 (FIB-4) index and NAFLD fibrosis score. The 10-year ASCVD risk score (>10%) was used to determine a high probability ASCVD risk. For sensitivity analysis, propensity score matching was assessed to subjects with aged 40 to 75 years free from ASCVD.ResultsThe prevalence of MAFLD was 38.0% (n=3,592). The ASCVD risk scores stratified in quartile were positively correlated to MAFLD and FIB-4 defined-significant liver fibrosis (p for trend <0.001). Individuals with both MAFLD and FIB-4 defined-significant liver fibrosis had a greater chance of high probability ASCVD risk (odds ratio [OR]=2.40; p<0.001) than those without MAFLD. The impact of MAFLD on high probability ASCVD risk was greater than that of significant liver fibrosis (OR=4.72 for MAFLD vs OR=1.88 for FIB-4 defined-significant liver fibrosis; all p<0.001). Among participants with MAFLD, low muscle mass enhanced the risk of significant liver fibrosis (OR=1.56 to 2.43; p<0.001). When NAFLD fibrosis score was applied to define significant liver fibrosis, similar findings were observed.ConclusionsIndividuals with MAFLD had a substantial ASCVD risk compared to those without MAFLD. Accompanying significant liver fibrosis further enhanced the risk of ASCVD among subjects with MAFLD.     

Clinical Features and Long-term Prognosis of Crohn’s Disease in Korea: Results from the Prospective CONNECT Study

Background/AimsThe prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD.MethodsPatients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019).ResultsA total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35; 95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection.ConclusionsThe prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.     

Automated and manual microscopic analyses for leukocyte differential counts in exudative pleural effusions: Real-world disagreement and clinical application

Differential leukocyte counts of pleural fluid are routinely recommended for the early diagnosis and management of exudative pleural effusions. Rapid automated cellular analysis agrees strongly with standard manual microscopic counts and has become a reality in many clinical laboratories. However, discordant results sometimes observed between automated and manual analyses raise concern about using automated analysis to aid prompt differential diagnosis. This study aimed to evaluate the real-world disagreement between automated and manual leukocyte analyses in exudative pleural effusions and to investigate whether the discordant results occur in specific cellular ranges or randomly. We conducted a retrospective study of patients who were diagnosed with parapneumonic pleural effusions (PPE), tuberculous pleural effusions (TPE), and malignant pleural effusions (MPE) between September 2018 and December 2020. Differential and predominant leukocyte counts were performed using an automated XN-350 analyzer with a two-part differential count consisting of polymorphonuclear (PMN) and mononuclear (MN) leukocytes and a manual method with Wright-stained cytospin slides. We compared the two methods on cases of 109 PPEs, 50 TPEs, and 116 MPEs. Although the overall correlation between the two methods for differential leukocyte counts was excellent, there were etiologic variations; MPEs showed a lower correlation compared to PPEs and TPEs. Automated-PMN predominance almost corresponded to manual cytospin-neutrophilic predominance. In contrast, ~10% of the automated-MN predominance did not correspond with the cytospin-lymphocytic predominance. These discrepancies occurred most in the automated-MN% range of 51% to 60%, followed by 61% to 70%. The PMN% range ≥50% and <30% on the automated analysis reliably corresponds to the neutrophilic and lymphocytic predominance, respectively. However, the MN% range of 51% to 70% may not coincide with lymphocytic predominance on manual cytospin analysis. This range leaves the potential cause of exudative pleural effusions open.     

Prospective genomically guided identification of “early/evolving” and “undersampled” IDH-wildtype glioblastoma leads to improved clinical outcomes

BackgroundGenomic profiling studies of diffuse gliomas have led to new improved classification schemes that better predict patient outcomes compared to conventional histomorphology alone. One example is the recognition that patients with IDH-wildtype diffuse astrocytic gliomas demonstrating lower-grade histologic features but genomic and/or epigenomic profile characteristic of glioblastoma typically have poor outcomes similar to patients with histologically diagnosed glioblastoma. Here we sought to determine the clinical impact of prospective genomic profiling for these IDH-wildtype diffuse astrocytic gliomas lacking high-grade histologic features but with molecular profile of glioblastoma.MethodsClinical management and outcomes were analyzed for 38 consecutive adult patients with IDH-wildtype diffuse astrocytic gliomas lacking necrosis or microvascular proliferation on histologic examination that were genomically profiled on a prospective clinical basis revealing criteria for an integrated diagnosis of “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV” per cIMPACT-NOW criteria.ResultsWe identified that this diagnosis consists of two divergent clinical scenarios based on integration of radiologic, histologic, and genomic features that we term “early/evolving” and “undersampled” glioblastoma, IDH-wildtype. We found that prospective genomically guided identification of early/evolving and undersampled IDH-wildtype glioblastoma resulted in more aggressive patient management and improved clinical outcomes compared to a biologically matched historical control patient cohort receiving standard-of-care therapy based on histomorphologic diagnosis alone.ConclusionsThese results support routine use of genomic and/or epigenomic profiling to accurately classify glial neoplasms, as these assays not only improve diagnostic classification but critically lead to more appropriate patient management that can improve clinical outcomes.     

Low-Frequency Noise Characteristics in HfO2-Based Metal-Ferroelectric-Metal Capacitors

The transport mechanism of HfO₂-based metal-ferroelectric-metal (MFM) capacitors was investigated using low-frequency noise (LFN) measurements for the first time. The current–voltage measurement results revealed that the leakage behavior of the fabricated MFM capacitor was caused by the trap-related Poole–Frenkel transport mechanism, which was confirmed by the LFN measurements. The current noise power spectral densities (S_I) obtained from the LFN measurements followed 1/f noise shapes and exhibited a constant electric field (E) × S_I/I² noise behavior. No polarization dependency was observed in the transport characteristics of the MFM capacitor owing to its structural symmetry.     

The Prevalence of Clostridium difficile Colitis and Effect on All-Cause Mortality in Elderly Patients after Hip Fracture Surgery: A Korean Nationwide Cohort Study

BackgroundThis study aimed to investigate the prevalence of Clostridium difficile colitis (CDC) in elderly patients with hip fractures using a nationwide cohort database and to analyze the effect of CDC on the all-cause mortality rate after hip fracture.MethodsThis retrospective nationwide study identified subjects from the Korean National Health Insurance Service-Senior cohort. The subjects of this study were patients who were over 65 years old and underwent surgical treatment for hip fractures from January 1, 2002, to December 31, 2015. The total number of patients included in this study was 10,158. The diagnostic code used in this study was A047 of the International Classification of Diseases, 10th revision for identifying CDC. Procedure codes for C. difficile culture or toxin assay were BY021 and BY022. CDC patients were defined as follows: patients treated with oral vancomycin or metronidazole over 10 days and patients with procedure codes BY021 and BY022 or diagnostic code A047 after hip fracture. Incidence date (index date, time zero) of hip fracture for analyzing risk of all-cause mortality was defined as the date of discharge. A generalized estimating equation model with Poisson distribution and logarithmic link function was used for estimating adjusted risk ratios and 95% confidence intervals to assess the association between CDC and cumulative mortality risk.ResultsThe prevalence of CDC during the hospitalization period in the elderly patients with hip fractures was 1.43%. Compared to the non-CDC group, the CDC group had a 2.57-fold risk of 30-day mortality after discharge, and a 1.50-fold risk of 1-year mortality after discharge (p < 0.05).ConclusionsThe prevalence of CDC after hip fracture surgery in elderly patients was 1.43%. CDC after hip fracture in the elderly patients significantly increased the all-cause mortality rate after discharge.     

Anti-adhesion agent to prevent of post-operative adhesion and fibrosis after vasectomy: a study using a rat model

BackgroundPost-vasectomy pain syndrome (PVPS) is difficult to treat. Direct damage to the vas deferens, inflammation, compression of nerves through fibrotic adhesions, and congestion of the epididymis are known to cause PVPS. The purpose of this study was to evaluate whether the application of anti-adhesion agents after vasectomy can reduce the degree of adhesion and fibrosis in a rat model.MethodsIn the study, 11 Sprague-Dawley rats (22 vas deferens) from each group were evaluated. In the experimental group, surgery was terminated after applying the anti-adhesion agent; this was not applied in the control group. After 14 days of vasectomy, the scrotum was dissected to evaluate the degree of gross adhesion at the vasectomy site. Histological examination of the surrounding tissues, including the vas deferens and the spermatic cord, was also performed.ResultsAdhesions were not observed in 72.73% (16/22) rats from the experimental group, in which the anti-adhesion agent was applied; in contrast, the incidence of adhesions in the control group was 100%. There was a statistically significant relationship between the distribution of grades for adhesion and anti-adhesion agent (chi-square, P<0.001). On classification of fibrosis and inflammation, application of the anti-adhesion agent was significantly associated with lower grade inflammation and fibrosis compared to that of the control group (chi-square, P=0.001). The rate of intact muscle structure was 90.91% (20/22) in the experimental group, and 36.36% (8/22) in the control group, and the application of the anti-adhesion agent demonstrated significant association with preservation of intact muscle structure (chi-square, P<0.001).ConclusionsThe application of an anti-adhesion agent after vasectomy prevented the development of adhesion, fibrosis, and inflammation reaction and further reduced structural destruction.     

Vessel Wall Changes on Serial High-Resolution MRI and the Use of Cilostazol in Patients With Adult-Onset Moyamoya Disease

Background and PurposeThe natural course of adult-onset moyamoya disease (MMD) is unknown, and there is no medical treatment that halts its progression. We hypothesized that progressive shrinkage of large intracranial arteries occurs in adult-onset MMD, and that cilostazol inhibits this process.MethodsSerial high-resolution magnetic resonance imaging (HR-MRI) was performed on 66 patients with MMD: 30 patients received cilostazol, 21 received other antiplatelets, and 15 received no antiplatelets or had poor compliance to them. Serial HR-MRI was performed (interval between MRI scans: 29.67±18.02 months, mean±SD), and changes in outer diameter, luminal stenosis, and vascular enhancement were measured. Factors affecting HR-MRI changes were evaluated, including vascular risk factors and the ring finger protein 213 gene variant.ResultsThe progression of stenosis to occlusion, recurrent ischemic stroke, and the development of new stenotic segments were observed in seven, seven, and three patients, respectively. Serial HR-MRI indicated that the degree of stenosis increased with negative remodeling (outer diameter shrinkage). Patients who received cilostazol presented significantly larger outer diameters and lower degrees of stenosis compared with other groups (p=0.005 and p=0.031, respectively). After adjusting for clinical and genetic factors, only cilostazol use was independently associated with negative remodeling (odds ratio=0.29, 95% confidence interval=0.10–0.84, p=0.023). While vascular enhancement was observed in most patients (61 patients), the progression of enhancement or the occurrence of new vascular enhancement was rarely observed on follow-up HR-MRI (6 and 1 patients, respectively).ConclusionsAdult-onset MMD induces progressive shrinkage of large intracranial arteries, which cilostazol treatment may prevent. Further randomized clinical trials are warranted.Trial registrationClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT02074111","term_id":"NCT02074111"}}NCT02074111.     

丹参通络解毒汤联合内皮祖细胞移植对心肌缺血再灌注损伤大鼠促血管新生作用的研究

目的探讨丹参通络解毒汤(DSTLJD)联合内皮祖细胞(endothelial progenitor cells, EPCs)移植对心肌缺血再灌注损伤(ischemic reperfusion injury, IRI)模型大鼠促血管新生作用的影响及其机制。方法采用密度梯度离心法及差数贴壁法分离和培养EPCs,采用免疫荧光法鉴定EPCs。通过结扎左冠状动脉左前降支的方法建立IRI模型,采用随机数字表法分为SH组(假手术组)、IRI组(模型组)、EPCs组(EPCs移植组)、DSTLJD组(丹参通络解毒汤组)、DSTLJD+EPCs组(丹参通络解毒汤+EPCs移植),每组10只。4周后,采用HE染色法观察心肌组织的病理形态,用免疫组化法测定各组大鼠心肌微血管计数(microvessel count, MVC)、心肌微血管密度(microvessel density, MVD),并检测各组大鼠血管内皮生长因子(vascular endothelial growth factor, VEGF)、碱性成纤维生长因子(basic fibroblast growth factor, bFGF)的蛋白表...     

The Impact of Masticatory Function on Cognitive Impairment in Older Patients: A Population-Based Matched Case-Control Study

PurposeThe aim of this study was to investigate the association between the changes in masticatory function and cognitive impairment by analyzing longitudinal data of older Korean patients.Materials and MethodsPatients aged over 60 years with dental records between 2005 to 2010 (baseline; T1) and 2014 to 2020 (follow-up; T2) were selected in a single medical center. Based on the dementia diagnosis after T2, the cohort was classified into two groups, the dementia group (n=122) and the control group (n=366). Changes in masticatory function were calculated using the total functional tooth unit (T-FTU) in both groups. The incidence of tooth extraction (%) and the subsequent rehabilitation during the observation period were also evaluated.ResultsIn the dementia group, T-FTU significantly decreased from T1 to T2 (9.81±2.78 to 9.11±3.16, respectively, p=0.008), while no significant change was observed in the control group. During the mean observation period of 9 years, significantly more teeth were extracted and neglected to be prosthetically restored in the dementia group than in the control group. Regression analysis revealed that the number of missing teeth neglected [odds ratio (OR)=1.195, 95% confidence interval (CI)=1.025–1.393, p=0.023] and previous alcohol consumption (OR=4.445, 95% CI=1.831–1.795, p=0.001) were the most significant risk factors of dementia.ConclusionThere might be a causative relationship between the neglected missing dentition and the onset of dementia.