Background: Autosomal dominant giant platelet syndrome (GPS) is characterized by thrombocytopenia, giant platelets, and Döhle-like inclusion bodies in leukocytes.Previous studies suggest relatively preserved platelet structure and function, implicating impaired megakaryocyte fragmentation. This study aimed to identify myosin heavy chain 9 (MYH9) mutations in Korean patients with GPS and to define the associated clinical, molecular and functional characteristics. Methods: After detailed personal and family history taking, peripheral blood smears were reviewed for platelet size, count, and leukocyte inclusions. MYH9 mutations were analyzed in peripheral blood mononuclear cells by direct sequencing of selected exons or complementary DNA (cDNA). Computer-assisted structural modeling was performed to evaluate the functional consequences of identified mutations. Results: Twenty-two affected individuals from six unrelated families were diagnosed with hereditary macrothrombocytopenia consistent with GPS. The median platelet count was 59,000/L, and the mean platelet volume was markedly increased (17.8 fL). Platelets ranged from approximately half to 1.5 times the size of red blood cells.Döhle-like inclusions were observed in 25-33% of leukocytes in four families. Extrahematologic manifestations included hearing impairment (family with Ile1816Val) and renal involvement, ranging from mild proteinuria to chronic renal failure requiring renal transplantation (family with Lys373Asn). Five families harbored MYH9 mutations—Arg1933Ter, Trp33Cys (novel), Lys373Asn, Ile1816Val, and Arg1165Cys—located in exons 40, 1, 10, 37, and 26, respectively; mutations segregated with affected status.Biochemical analysis revealed decreased MYH9 in soluble fractions with increased insoluble pellets; Trp33Cys and Lys373Asn produced aberrant approximately 140 kDa bands in addition to the normal 224 kDa band. Modeling localized Trp33Cys to the proximal myosin head region implicated in actin interaction. Conclusion Five GPS-associated MYH9 mutations were identified, including a novel Trp33Cys variant. Altered MYH9 solubility and disturbed protein–protein interactions may contribute to disease pathogenesis.

Background and Objectives: Studies investigating the correlation between papillary thyroid carcinoma (PTC) tumor size and the prevalence of the B-type Raf kinase (BRAF) mutation have yielded conflicting results. Therefore, we evaluated the prevalence of BRAF mutation according to tumor size in a large cohort of PTC patients to clarify this association. Materials and Methods: We retrospectively analyzed 6,438 patients with surgically diagnosed classic PTC between January 2009 and December 2017 at Samsung Medical Center, Seoul, Republic of Korea.During the study period, BRAF mutation testing was attempted on all fine-needle aspiration specimens, except for a small number of inadequate specimens. All other histologic subtypes were excluded. The prevalence of BRAF mutation was assessed based on tumor size, and further analyzed by age group and sex according to tumor size. Results: The overall prevalence of BRAF mutation was 79.2%. When PTCs ≤1 cm were excluded, the prevalence was 77.2%. The prevalence significantly decreased with increasing tumor size (p for trend ＜0.001). It was significantly higher in men than in women (p=0.013), but did not differ by age. The inverse correlation between tumor size and prevalence was prominent in patients aged 20-49 years but was less distinct in those aged 50 years and older. Conclusion In this large cohort of patients with PTC, the prevalence of BRAF mutation significantly decreased with increasing tumor size. These findings suggest that BRAF mutation is enriched in smaller surgically treated classic PTCs and may provide a hypothesis-generating clue regarding its role in early PTC development, although selection bias cannot be excluded.

The over-the-scope clip (OTSC) system is a powerful full-thickness suturing device used for closing refractory bleeding, perforations, and fistulas in gastrointestinal diseases, offering greater force than conventional clips. Here, we report two cases of pancreatobiliary disease treated using OTSC. The first case involved the successful OTSC ligation of a colonic fistula caused by necrotizing pancreatitis, and the second was a duodenal perforation due to stent migration, which was also successfully treated with OTSC. These cases indicate that OTSC can be beneficial for pancreatobiliary diseases, potentially eliminating the need for surgery when endoscopic treatment is successful.

Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

The over-the-scope clip (OTSC) system is a powerful full-thickness suturing device used for closing refractory bleeding, perforations, and fistulas in gastrointestinal diseases, offering greater force than conventional clips. Here, we report two cases of pancreatobiliary disease treated using OTSC. The first case involved the successful OTSC ligation of a colonic fistula caused by necrotizing pancreatitis, and the second was a duodenal perforation due to stent migration, which was also successfully treated with OTSC. These cases indicate that OTSC can be beneficial for pancreatobiliary diseases, potentially eliminating the need for surgery when endoscopic treatment is successful.

Background: Human herpesvirus 6 (HHV-6) encephalitis is a rare but serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). This study investigated the incidence, clinical features, and long-term neurological sequelae of HHV-6 encephalitis in pediatric and adolescent HSCT recipients. Methods: We retrospectively reviewed 92 patients who were younger than 20 years of age at the time of undergoing allogeneic HSCT between January 2015 and December 2024. HHV-6 encephalitis was diagnosed based on neurological symptoms and the detection of HHV-6 DNA in cerebrospinal fluid using multiplex polymerase chain reaction. Patients with HHV-6 encephalitis were followed for a median of six years (range, 4.5-8.5 years) to assess long-term neurological outcomes. Results: Three patients (3.2%) developed HHV-6 encephalitis between 15 and 26 days post-transplantation, coinciding with neutrophil engraftment. Clinical presentation included fever, seizures, altered consciousness, and short-term memory loss.Neuroimaging revealed high signal intensity lesions in the limbic system. Despite prompt antiviral therapy with foscarnet and initial viral clearance, all patients developed significant long-term neurological sequelae, including persistent cognitive impairment, epilepsy (two with refractory seizures), and memory disturbances. One patient continues to require assistance with activities of daily living, while two others face challenges reintegrating into school and society. Conclusion HHV-6 encephalitis following allogeneic HSCT in pediatric and adolescent patients can lead to severe and lasting neurological impairment, despite timely antiviral therapy. These long-term sequelae substantially affect quality of life and impose ongoing healthcare and societal burdens. Multidisciplinary long-term care is essential, and further research is warranted to improve prevention and treatment strategies.

The over-the-scope clip (OTSC) system is a powerful full-thickness suturing device used for closing refractory bleeding, perforations, and fistulas in gastrointestinal diseases, offering greater force than conventional clips. Here, we report two cases of pancreatobiliary disease treated using OTSC. The first case involved the successful OTSC ligation of a colonic fistula caused by necrotizing pancreatitis, and the second was a duodenal perforation due to stent migration, which was also successfully treated with OTSC. These cases indicate that OTSC can be beneficial for pancreatobiliary diseases, potentially eliminating the need for surgery when endoscopic treatment is successful.

Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

The over-the-scope clip (OTSC) system is a powerful full-thickness suturing device used for closing refractory bleeding, perforations, and fistulas in gastrointestinal diseases, offering greater force than conventional clips. Here, we report two cases of pancreatobiliary disease treated using OTSC. The first case involved the successful OTSC ligation of a colonic fistula caused by necrotizing pancreatitis, and the second was a duodenal perforation due to stent migration, which was also successfully treated with OTSC. These cases indicate that OTSC can be beneficial for pancreatobiliary diseases, potentially eliminating the need for surgery when endoscopic treatment is successful.

The over-the-scope clip (OTSC) system is a powerful full-thickness suturing device used for closing refractory bleeding, perforations, and fistulas in gastrointestinal diseases, offering greater force than conventional clips. Here, we report two cases of pancreatobiliary disease treated using OTSC. The first case involved the successful OTSC ligation of a colonic fistula caused by necrotizing pancreatitis, and the second was a duodenal perforation due to stent migration, which was also successfully treated with OTSC. These cases indicate that OTSC can be beneficial for pancreatobiliary diseases, potentially eliminating the need for surgery when endoscopic treatment is successful.