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.

PURPOSE: The aim of this study was to classify the shapes of retromolar pads and assess their morphometric differences using a 3D model. MATERIALS AND METHODS: Two hundred fully edentulous or Kennedy Class I partially edentulous patients (400 retromolar pads) were enrolled. Scan data of the definitive mandibular casts produced through functional impressions were obtained using a 3D laser scanner. Seven parameters (transverse diameter, longitudinal diameter, transverse-contour length, longitudinal-contour length, longitudinal/transverse diameter ratio, longitudinal/transverse-contour length ratio, and angle of the retromolar pad line to the residual alveolar ridge line) were measured using image analysis software. Subsequently, the pads were classified according to the shape. Statistical analyses were performed using 95% confidence intervals. RESULTS: Classifying the retromolar pads into three shapes led to high intra-examiner reliability (Cronbach’s alpha = 0.933). The pear shape was the most common (56.5%), followed by oval/round (27.7%) and triangular (15.8%) shapes. There were no significant differences between the left and right sides according to the shape and no significant differences in any parameter according to age. The transverse diameter and longitudinal/transverse diameter ratio differed between sexes (P < .05). The triangular shape had a significantly different transverse diameter, transverse-contour length, longitudinal/transverse diameter ratio, and longitudinal/transverse-contour length ratio compared with the pear and oval/round shapes (P < .05). CONCLUSION From a clinical reliability standpoint, classifying retromolar pads into three shapes (oval/round, pear-shaped, and triangular) is effective. The differences in the sizes among the shapes were attributed to the transverse measurement values.

testing revealed that the patient was positive for HLA-DRB1*04, HLA-DRB1*12, HLA-DQB1*03, andHLA-DQB1*04. To the best of our knowledge, this is the first case of fulminant T1DM reported to occurimmediately after COVID-19 infection.

BACKGROUND/OBJECTIVES: A dietary restriction on the intake of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) has been reported to be effective in the treatment of gastrointestinal (GI) tract complications. Enteral nutrition (EN) is widely used for patients who cannot obtain their nutritional requirements orally, but many studies have reported EN complications, especially diarrhea, in up to 50% of patients. SUBJECTS/METHODS: We performed a single-center, non-randomized, controlled trial to determine the effects of a low-FODMAP enteral formula on GI complications in patients in intensive care units (ICUs). Patients in the ICU who needed EN (n = 66) were alternately assigned to the low-FODMAP group (n = 33) or the high-FODMAP group (n = 33). RESULTS: Anthropometric and biochemical parameters were measured, and stool assessment was performed using King's Stool Chart. We excluded patients who received laxatives, GI motility agents, proton pump inhibitors, antifungal agents, and antibiotics other than β-lactams. There were no differences in GI symptoms during 7 days of intervention, including bowel sound, abdominal distension, and vomiting between the 2 groups. However, diarrhea was more frequent in the high-FODMAP group (7/33 patients) than the lowFODMAP group (1/33 patients) (P = 0.044). CONCLUSIONS Our results suggest that a low-FODMAP enteral formula may be a practical therapeutic approach for patients who exhibit enteral formula complications. Our study warrants further randomized clinical trials and multicenter trials.

Nondystrophic myotonias and periodic paralyses are an important group of genetic skeletal muscle disorders characterized by dysfunction of ion channels that regulate cell membrane excitability. Mutations in the Sodium Voltage-Gated Channel Alpha Subunit 4 (SCN4A) gene are associated with a spectrum of a heterogeneous group of skeletal muscle such as sodium channel myotonia, paramyotonia congenita, hyperkalemic periodic paralysis, congenital myasthenia, and congenital myopathy. Gain of function mutations in SCN4A cause three muscle disorders with overlapping clinical phenotypes: myotonia, paramyotonia congenita, and hyperkalemic periodic paralysis. Here, we describe the clinical and genetic features of a new family with paramyotonia. The proband, an eight-year-old girl, began to experience muscle stiffness in her hands and limbs on exposure to exercise exercise at the age of four and presented with myotonia. She was initially misdiagnosed with myotonic dystrophy because of worsening weakness with significant elevation of serum creatinine kinase levels. Two other affected family members had paradoxical myotonia in the face and hands on exposure to cold muscle stiffness in her face, hands, and limbs on exposure to cold and showed grip myotonia on physical examination. A novel heterozygous in-frame insertion, c.3911_3912+1dupAGA, at the boundary between exon 21 and intron 21 of SCN4A was identified using whole exome sequencing. Our finding enhances our understanding of the genotype and phenotype of patients with paramyotonia congenita, caused by mutations in the SCN4A gene.

BACKGROUND: Diabetes mellitus (DM) is the most common chronic metabolic disorder with an increasing prevalence worldwide. According to a previous study, physicians' treatment patterns or patients' behaviors change when they become aware of the risk for cardiovascular (CV) disease in patients with DM. However, there exist controversial reports from previous studies in the impact of physicians' behaviors on the patients' quality of life (QoL) improvements. So we investigate the changes in QoL according to physicians and patients' behavioral changes after the awareness of CV risks in patients with type 2 DM. METHODS: Data were obtained from a prospective, observational study where 799 patients aged ≥40 years with type 2 DM were recruited at 24 tertiary hospitals in Korea. Changes in physicians' behaviors were defined as changes in the dose/type of antihypertensive, lipid-lowering, and anti-platelet therapies within 6-month after the awareness of CV risks in patients. Changes in patients' behaviors were based on lifestyle modifications. Audit of Diabetes Dependent Quality of Life comprising 19-life-domains was used. RESULTS: The weighted impact score change for local or long-distance journey (P=0.0049), holidays (P=0.0364), and physical health (P=0.0451) domains significantly differed between the two groups; patients whose physician's behaviors changed showed greater improvement than those whose physician's behaviors did not change. CONCLUSION This study demonstrates that changes in physicians' behaviors, as a result of perceiving CV risks, improve QoL in some domains of life in DM patients. Physicians should recognize the importance of understanding CV risks and implement appropriate management.

The term dopa-responsive dystonia (DRD) is used to describe a group of neurometabolic disorders, which are characterized by dystonia, and are typically associated with diurnal fluctuations and respond to levodopa treatment. Autosomal dominant DRD (DYT5a, MIM# 128230) is caused by a heterozygous mutation in the GTP cyclohydrolase 1 (GCH1) gene (MIM# 600225). GCH1 encodes an enzyme, which is involved in the biosynthesis of tetrahydrobiopterin, an essential co-factor for tyrosine hydroxylase. Herein, we report the case of a 16-year-old girl who was diagnosed with DYT5a. She exhibited additional unusual clinical features, including intellectual disability, depression, multiple skeletal anomalies, and short stature, which are not commonly observed in patients with DYT5a. The patient harbored a heterozygous missense variant, c.539A>C, p.Gln180Pro, in the GCH1 gene, which was identified by targeted gene panel analysis using next-generation sequencing.

Tatton-Brown-Rahman Syndrome (TBRS), an overgrowth syndrome caused by heterozygous mutation of DNMT3A, first was described in 2014. Approximately 60 DNMT3A variants, including 32 missense variants, have been reported, with most missense mutations located on the DNMT3A functional domains. Autosomal dominant inheritance by germ-line mutation of DNMT3A has been reported, but vertical transmission within a family is extremely rare. Herein, we report the first Korean family with maternally inherited TBRS due to the novel heterozygous DNMT3A variant c.118G>C p.(Glu40Gln), located outside the main functional domain and identified by multigene panel sequencing. The patient and her mother had typical clinical features, including tall stature during childhood, macrocephaly, intellectual disability, and characteristic facial appearance. TBRS shows milder dysmorphic features than other overgrowth syndromes, potentially leading to underdiagnosis and underestimated prevalence; thus, targeted multigene panel sequencing including DNMT3A will be a useful tool in cases of overgrowth and unexplained mild intellectual disability for early diagnosis and genetic counseling.
Early Diagnosis ; Genetic Counseling ; Germ-Line Mutation ; Growth Disorders ; High-Throughput Nucleotide Sequencing ; Humans ; Intellectual Disability ; Megalencephaly ; Mothers ; Mutation, Missense ; Prevalence ; Sequence Analysis, DNA ; Wills

Smith-Kingsmore syndrome (SKS; OMIM 616638), also known as macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (MINDS; ORPHA 457485), is a rare autosomal dominant disorder, the prevalence of which is not known. It is caused by a heterozygous germline mutation in MTOR (OMIM 601231). Ten different MTOR germline mutations in 27 individuals have been reported in the medical literature to date. These were all gain-of-function missense variants, and about half of the 27 individuals had c.5395G>A p.(Glu1799Lys) in MTOR. Here, I report for the first time a Korean patient with the heterozygous germline mutation c.5395G>A p.(Glu1799Lys) in MTOR. It was found to be a de novo mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing. The patient showed typical clinical features of SKS, including macrocephaly/megalencephaly; moderate intellectual disability; seizures; behavioral problems; and facial dysmorphic features of curly hair, frontal bossing, midface hypoplasia, and hypertelorism.
Databases, Genetic ; Germ-Line Mutation ; Hair ; Humans ; Hypertelorism ; Intellectual Disability ; Megalencephaly ; Prevalence ; Problem Behavior ; Seizures ; Thorax