Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background/Aims: Belching disorder (BD) is clinically distinct from gastroesophageal reflux disease (GERD) with belching. Supragastric belching (SGB) is closely associated with reflux episodes. This study investigates belch characteristics in association with reflux, compared between patients with BD and those who had GERD with belching. Methods: Impedance pH monitoring data from 10 patients with BD and 10 patients with GERD who exhibited belching were retrospectively analyzed. Belches were considered “isolated“ or “reflux-related” and acidicon-acidic. Belch characteristics were compared between patients with BD and those with GERD. Results: Symptomatic belches were more frequent in patients with BD than in patients with GERD (median, 160.5 vs 56.0, P < 0.05). SGB was the most common type in both groups; common subtypes comprised “isolated“ in patients with BD and “isolated during the reflux period” in patients with GERD. Reflux-related SGB was more common in patients with GERD than in BD (78.3% vs 45.2%, P < 0.005).Both “preceding belching” including the reflux period and acidic SGB were more common in patients with GERD than in BD (31.8% vs 8.6% and 38.1% vs 8.9%, both P < 0.05). Supragastric belch number positively correlated with all reflux episodes in patients with GERD (adjusted R2 = 0.572, P = 0.007). Conclusions BD is characterized by more belching, compared to GERD. SGB is more frequently associated with reflux in GERD than in BD; acidity may be related to GERD. In BD, SGB is typically non-acidic and unrelated to reflux. Distinct SGB characteristics may reflect different pathogenic mechanisms of reflux and associated symptoms.

Background/Aims: Belching disorder (BD) is clinically distinct from gastroesophageal reflux disease (GERD) with belching. Supragastric belching (SGB) is closely associated with reflux episodes. This study investigates belch characteristics in association with reflux, compared between patients with BD and those who had GERD with belching. Methods: Impedance pH monitoring data from 10 patients with BD and 10 patients with GERD who exhibited belching were retrospectively analyzed. Belches were considered “isolated“ or “reflux-related” and acidicon-acidic. Belch characteristics were compared between patients with BD and those with GERD. Results: Symptomatic belches were more frequent in patients with BD than in patients with GERD (median, 160.5 vs 56.0, P < 0.05). SGB was the most common type in both groups; common subtypes comprised “isolated“ in patients with BD and “isolated during the reflux period” in patients with GERD. Reflux-related SGB was more common in patients with GERD than in BD (78.3% vs 45.2%, P < 0.005).Both “preceding belching” including the reflux period and acidic SGB were more common in patients with GERD than in BD (31.8% vs 8.6% and 38.1% vs 8.9%, both P < 0.05). Supragastric belch number positively correlated with all reflux episodes in patients with GERD (adjusted R2 = 0.572, P = 0.007). Conclusions BD is characterized by more belching, compared to GERD. SGB is more frequently associated with reflux in GERD than in BD; acidity may be related to GERD. In BD, SGB is typically non-acidic and unrelated to reflux. Distinct SGB characteristics may reflect different pathogenic mechanisms of reflux and associated symptoms.

Background/Aims: We aimed to evaluate associations between comorbidities, peripheral neuropathy, and spontaneous internal anal sphincter relaxation (SAR) in patients with defecatory disorders. Methods: A patient was considered to exhibit SAR during high-resolution anorectal manometry (HR-ARM) when the nadir pressure is < 15 mmHg and the time from onset to relaxation was ≥ 15 seconds in the resting pressure frame. A case-control study was performed using HR-ARM data collected from 880 patients from January 2010 to May 2015. We identified 23 cases with SAR (median age 75 years; 15 females; 12 fecal incontinence and 11 constipation). We compared HR-ARM values, Charlson index comorbidity scores, neuropathy, and the prevalence of diseases that potentially cause neuropathy between controls and SAR patients. Each SAR case was compared to 3 controls. Controls were selected to match the age, gender, and examination year of each SAR case. Results: Compared to controls (26.1%), SAR patients (52.2%) exhibited a significantly higher frequency of fecal incontinence. SAR patients also had higher Charlson index scores (5 vs 4, P = 0.028). Nine of 23 SAR patients (39.1%) exhibited peripheral neuropathy— this frequency was higher than that for the control group (11.6%; P = 0.003). Diseases that potentially cause neuropathy were observed in 17 of 23 SAR cases and 32 of 69 controls (P = 0.022). Conclusions SAR develops in patients with constipation and fecal incontinence but is more common in patients with fecal incontinence. Our controlled observational study implies that SAR is associated with peripheral neuropathy and more severe comorbidities.

Background/Aims: Our study aims to characterize esophageal motor function; evaluate the relationships among esophagogastroduodenoscopy (EGD), high-resolution manometry (HRM), and 24-hour esophageal multichannel intraluminal impedance monitoring combined with pHmetry (MII-pH); and elucidate the determinants of esophageal symptom perception in South Koreans with systemic sclerosis (SSc). Methods: We reviewed prospectively collected HRM (n = 46), EGD (n = 41), and MII-pH (n = 37) data from 46 consecutive patients with SSc (42 females; mean age 50.1 years) who underwent esophageal tests between June 2013 and September 2018. Results: The most common HRM diagnosis was normal (39.1%), followed by ineffective esophageal motility (23.9%) and absent contractility (21.7%). Erosive esophagitis was observed in 12.2% of total SSc patients, with a higher frequency in patients with absent contractility than those with normal motility (44.5% vs 0.0%, P = 0.01). Pathologic acid exposure was observed in 6 patients (20.0%) and positive symptom association in 18 patients (60.0%) in MII-pH tests of symptomatic patients. The proportion of SSc patients with esophageal symptoms not explained by reflux or mucosal or motor esophageal abnormalities was 33.0%. Conclusions Esophageal involvement among South Koreans with SSc was characterized by heterogeneous motility patterns, with a higher prevalence of normal motility and lower prevalence of erosive esophagitis. Reflux hypersensitivity or functional heartburn might be partly attributed to the perception of esophageal symptoms in SSc patients who have neither gastroesophageal reflux disease nor esophageal dysmotility.

BACKGROUND: Atelosteogenesis type I (AO-I) is a rare lethal skeletal dysplastic disorder characterized by severe short-limbed dwarfism and dislocated hips, knees, and elbows. AO-I is caused by mutations in the filamin B (FLNB) gene; however, several other genes can cause AO-like lethal skeletal dysplasias. METHODS: In order to screen all possible genes associated with AO-like lethal skeletal dysplasias simultaneously, we performed whole-exome sequencing in a female newborn having clinical features of AO-I. RESULTS: Exome sequencing identified a novel missense variant (c.517G>A; p.Ala173Thr) in exon 2 of the FLNB gene in the patient. Sanger sequencing validated this variant, and genetic analysis of the patient's parents suggested a de novo occurrence of the variant. CONCLUSIONS: This study shows that exome sequencing can be a useful tool for the identification of causative mutations in lethal skeletal dysplasia patients.
Exome ; Female ; Filamins/chemistry/*genetics ; Gene Frequency ; Heterozygote ; Humans ; Infant, Newborn ; Mutation, Missense ; Osteochondrodysplasias/*genetics/pathology/radiography ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA

PURPOSE: Globular adiponectin (gAd) is a type of adipocytokine, which is mainly produced by adipose tissue. It has been reported that gAd acts as a pro- as well as an anti-inflammatory factor. Interleukin (IL)-6 and IL-8 are pro-inflammatory cytokines. To investigate the role of gAd on periodontal tissues, the expression of adiponectin receptor 1 (AdipoR1) and the effect of gAd on the expression of IL-6 and IL-8 were investigated in periodontal ligament (PDL) and gingival fibroblasts. METHODS: PDL and gingival fibroblasts were cultured from human periodontal tissues. gAd derived from Escherichia coli and murine myeloma cells were used. The expression of AdipoR1 was estimated by reverse transcription-polymerase chain reaction and western blot. The expression of cytokines was measured by enzyme-linked immunosorbent assay. RESULTS: PDL and gingival fibroblasts expressed both mRNA and protein of AdipoR1. gAd derived from E. coli increased the production of IL-6 and IL-8, but polymyxin B, an inhibitor of lipopolysaccharide (LPS), inhibited IL-6 and IL-8 production induced by gAd in both types of cells. gAd derived from murine myeloma cells did not induce IL-6 and IL-8 production in those cells. gAd derived from E. coli contained higher levels of LPS than gAd derived from murine myeloma cells. LPS increased production of IL-6 and IL-8 in PDL and gingival fibroblasts, but pretreatment of cells with gAd derived from murine myeloma cells did not inhibit LPS-induced IL-6 and IL-8 expression. CONCLUSIONS: Our results suggest that PDL and gingival fibroblasts express AdipoR1 and that gAd does not act as a modulator of IL-6 and IL-8 expression in PDL and gingival fibroblasts.
Adiponectin ; Adipose Tissue ; Blotting, Western ; Cytokines ; Escherichia coli ; Fibroblasts ; Humans ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Periodontal Ligament ; Polymyxin B ; Receptors, Adiponectin ; RNA, Messenger

A solitary fibrous tumor (STF) is a relatively unusual neoplasm first described as a distinctive tumor arising from pleura. Some reports have shown that STF also affect extrathoracic regions. A 70-year-old woman was referred to our hospital for surgical treatment of an incidentally discovered thigh mass. We performed complete removal of the tumor. It was a soft tissue tumor with muscle indentation but without invasion to the surrounding muscles. The resected specimen was 7.0x6.3x5.2 cm. Histologically, the tumor was composed of a haphazard proliferation of spindle cells and epitheloid cells with hypercellularity and high mitotic activity. Immunohistochemistry showed positive immunoreactivity for CD34, CD99, bcl-2 protein, CD117, vimentin, smooth muscle actin and epithelial membrane antigen. We report, herein, on a rare case of malignant SFT in the thigh region along with a review of the literature.
Actins ; Aged ; Female ; Humans ; Immunohistochemistry ; Mucin-1 ; Muscle, Smooth ; Muscles ; Pleura ; Solitary Fibrous Tumors ; Thigh ; Vimentin

INTRODUCTION: Bone resorption is a unique function of osteoclasts. Osteoclasts are a specialized macrophage polykaryon whose differentiation is regulated principally by macrophage colony-stimulating factors, receptor activator of nuclear factor kappaB ligand (RANK) ligand, osteoprotegerin (OPG), and interleukins (IL). Reflecting the integrin-mediated signals, osteoclasts develop a specialized cytoskeleton that allows it to establish an isolated micro-environment between itself and the bone, wherein matrix degradation occurs by a process involving proton transport. The levels of IL-1, IL-6, OPG, and prostaglandin E2 (PGE2) expression were evaluated to study the correlations between dental implant teeth and the adjacent teeth. MATERIALS AND METHODS: The exudate of the gingival crevice acquired from dental implants, adjacent teeth, opposite teeth and contralateral teeth of 24 patients. RESULTS: 1. The levels of IL-1, IL-6, OPG and PGE2 expression in dental implant teeth were higher than those of the contralateral teeth. 2. IL-1 revealed a higher expression level in the adjacent teeth than in dental implant teeth. 3. The dental implant teeth and adjacent teeth did not show a remarkable difference in the level of IL-1 expression. 4. All the other cytokines were strongly expressed in the dental implant compared to the adjacent teeth. CONCLUSION: These results suggest that there might be close correlation between dental implant teeth and adjacent teeth in terms of the expressions of cytokines that affect the development and regulation of osteoclasts.
Bone Resorption ; Cytokines ; Cytoskeleton ; Dental Implants ; Dinoprostone ; Exudates and Transudates ; Humans ; Interleukin-1 ; Interleukin-6 ; Interleukins ; Macrophage Colony-Stimulating Factor ; Macrophages ; Osteoclasts ; Osteoprotegerin ; Protons ; RANK Ligand ; Tooth

The majority of cystic masses in the lateral neck are benign entities, and these entities include branchial cyst. Occult papillary thyroid carcinoma can occasionally present with regional lymph node metastasis. However, cystic metastasis from occult papillary thyroid carcinoma is a very rare condition. We present here a case of a cystic neck mass as the sole initial clinical manifestation of metastatic occult papillary thyroid carcionoma.
Branchioma ; Lymph Nodes ; Neck* ; Neoplasm Metastasis ; Thyroid Gland* ; Thyroid Neoplasms*