Targeted Panel Sequencing Identifies an Intronic c.5225-3C>G Variant of the FBN1 Gene Causing Sporadic Marfan Syndrome with Annuloaortic Ectasia.

Marfan syndrome (MFS) is a hereditary connective tissue disease whose clinical severity varies widely. Mutations of the FBN1 gene encoding fibrillin-1 are the most common genetic cause of Marfanoid habitus; however, about 10% of MFS patients are unaware of their genetic defects. Herein, we report a Korean patient with MFS and annuloaortic ectasia caused by an intronic c.5225-3C>G variant of the FBN1 gene identified by targeted panel sequencing. The reverse transcription analysis of FBN1 revealed that the intron 43 sequence from positions c.5297-1516 to c.5297-1 was retained at the coding sequence as a consequence of the c.5225-3C>G variant enhancing a cryptic splice acceptor site (c.5297-1518_5297-1517AG) in intron 43. The retained sequence of the part of intron 43 caused the same effect as insertion mutation (NM_000138.5:c.5297_c.5298ins5297-1516_5297-1), resulting in a frameshift mutation resulting in p.Ile1767Trpfs*3. The patient underwent an urgent modified Bentall operation with a 29 mm mechanical valve for annuloaortic ectasia and severe aortic valve regurgitation. This report emphasizes the need for functional investigations into the diagnostic workflows of certain diseases or gene panels with suspected high rates of intronic variants and potential pathogenic effects. Hence, further descriptions of individuals with intronic variants causing alternative splicing expected to have pathogenic effects at different transcript levels are crucial for improving our understanding.

Hyperglycemia and Hypoglycemia Are Associated with In-Hospital Mortality among Patients with Coronavirus Disease 2019 Supported with Extracorporeal Membrane Oxygenation.

Metabolic abnormalities, such as preexisting diabetes or hyperglycemia or hypoglycemia during hospitalization aggravated the severity of COVID-19. We evaluated whether diabetes history, hyperglycemia before and during extracorporeal membrane oxygenation (ECMO) support, and hypoglycemia were risk factors for mortality in patients with COVID-19. This study included data on 195 patients with COVID-19, who were aged ≥19 years and were treated with ECMO. The proportion of patients with diabetes history among nonsurvivors was higher than that among survivors. Univariate Cox regression analysis showed that in-hospital mortality after ECMO support was associated with diabetes history, renal replacement therapy (RRT), and body mass index (BMI) < 18.5 kg/m2. Glucose at admission >200 mg/dL and glucose levels before ventilator >200 mg/dL were not associated with in-hospital mortality. However, glucose levels before ECMO >200 mg/dL and minimal glucose levels during hospitalization <70 mg/dL were associated with in-hospital mortality. Multivariable Cox regression analysis showed that glucose >200 mg/dL before ECMO and minimal glucose <70 mg/dL during hospitalization remained risk factors for in-hospital mortality after adjustment for age, BMI, and RRT. In conclusion, glucose >200 mg/dL before ECMO and minimal glucose level <70 mg/dL during hospitalization were risk factors for in-hospital mortality among COVID-19 patients who underwent ECMO.

Dieckol, isolated from Ecklonia stolonifera, induces apoptosis in human hepatocellular carcinoma Hep3B cells.

Phlorotannins have been reported to demonstrate several biological properties, including antioxidant activity, and activities useful in the treatment of diabetic complications and in chemoprevention of several vascular diseases. In this study, we focused on the apoptosis induced by dieckol, a marine algal phlorotannin isolated from Ecklonia stolonifera, on human hepatocellular carcinoma (HCC) Hep3B cells. Dieckol reduced the numbers of viable cells and increased the numbers of apoptotic cells in a dose-dependent manner. Immunoblotting analysis revealed that dieckol increased the expression levels of cleaved caspases-3, 7, 8, and 9, and cleaved poly(ADP-ribose) polymerase. Dieckol increased the permeability of mitochondrial membranes and the release of cytochrome c from mitochondria into the cytosol with apoptosis-inducing factor. In addition, dieckol induced increased expression of truncated Bid and Bim. The results indicate that dieckol induces apoptosis via the activation of both death receptor and mitochondrial-dependent pathways in HCC Hep3B cells.

Mid- to Long-term Results of Surgical Treatment of ASD in Patients over 60 Years Old.

BACKGROUND: There is controversy about the benefit of surgical correction of an atrial septal defect (ASD) in patients over 60 years old. The purpose of this study was to determine whether surgical treatment is beneficial in those 60 years of age or older. MATERIALS AND METHODS: We reviewed the clinical course of 57 patients (mean age: 63.54±5.59 years) diagnosed with an isolated secundum ASD after the age of 60. The 24 patients (group A) who underwent surgical repair were compared with the 33 patients (group B) who were treated non-surgically. The mean follow-up period was 6.8±4.5 years. RESULTS: One operative death, 5 late deaths (20.8%) in group A, and 9 deaths (27.3%) in group B occurred in the study period. Symptomatic improvement was noted in 18 patients (75%) of group A after surgery. However 13 patients (39.4%) of group B showed symptomatic improvement during the follow-up period (p=0.012). The incidence of new atrial arrhythmia of the two groups was significantly different (16.7% vs 36.7%, p=0.038). The actuarial 10 year survival rate was 79% in group A and 73% in group B. CONCLUSION: Although surgical correction of ASD did not increase survival in patients over 60 years old, the surgical outcomes of ASD showed low operative mortality and resulted in symptomatic improvement in the majority of these patients. This study has shown the benefits of surgical closure of ASD even in advanced age in comparison to medical treatment.

Pilomatrix Carcinoma in the Chest Wall Around an Eloesser Open Window - A case report -.

Pilomatrix carcinoma originates in the matrix cell and is marked by exophytic growing and common local recurrence. There is no established treatment for wide local invasion and metastasis of the pilomatrix besides wide surgical resection. We report a case of rapidly progressive pilomatrix carcinoma, which arose around an Eloesser open window with direct invasion to the adjacent tissue.