Promoter-Specific Variants in NeuroD1 and H3K4me3 Coincident Regions and Clinical Outcomes of Small Cell Lung Cancer

Background@#Neurogenic differentiation 1 (NeuroD1) is a representative small cell lung cancer (SCLC) transcription regulator involved in the carcinogenesis and behavior of SCLC.Histone modifications play an important role in transcription, and H3 lysine 4 trimethylation (H3K4me3) is primarily associated with promoter regions. @*Methods@#We investigated the association between single nucleotide polymorphisms (SNPs) in NeuroD1 and H3K4me3 coincident regions, selected using ChIP sequencing (ChIP-seq), and the clinical outcomes of 261 patients with SCLC. @*Results@#Among 230 SNPs, two were significantly associated with both the chemotherapy response and overall survival (OS) of patients with SCLC. RNF145 rs2043268A>G was associated with worse chemotherapy response and OS (under a recessive model, adjusted odds ratio [aOR], 0.50, 95% confidence interval [CI], 0.26–0.94, P = 0.031, and adjusted hazard ratio [aHR], 1.88, 95% CI, 1.38–2.57, P G was also associated with worse chemotherapy response and OS (under a dominant model, aOR, 0.47, 95% CI, 0.23–0.99, P = 0.046, and aHR, 2.03, 95% CI, 1.47–2.82, P G and CINP rs762105A>G were associated with clinical outcomes in patients with SCLC and also affected the promoter activity of each gene.

Prognostic Implication of Volumetric Quantitative CT Analysis in Patients with COVID-19: A Multicenter Study in Daegu, Korea

Objective@#Lung segmentation using volumetric quantitative computed tomography (CT) analysis may help predict outcomes of patients with coronavirus disease (COVID-19). The aim of this study was to investigate the relationship between CT volumetric quantitative analysis and prognosis in patients with COVID-19. @*Materials and Methods@#CT images from patients diagnosed with COVID-19 from February 18 to April 15, 2020 were retrospectively analyzed. CT with a negative finding, failure of quantitative analysis, or poor image quality was excluded. CT volumetric quantitative analysis was performed by automated volumetric methods. Patients were stratified into two risk groups according to CURB-65: mild (score of 0–1) and severe (2–5) pneumonia. Outcomes were evaluated according to the critical event-free survival (CEFS). The critical events were defined as mechanical ventilator care, ICU admission, or death.Multivariable Cox proportional hazards analyses were used to evaluate the relationship between the variables and prognosis. @*Results@#Eighty-two patients (mean age, 63.1 ± 14.5 years; 42 females) were included. In the total cohort, male sex (hazard ratio [HR], 9.264; 95% confidence interval [CI], 2.021–42.457; p = 0.004), C-reactive protein (CRP) (HR, 1.080 per mg/dL;95% CI, 1.010–1.156; p = 0.025), and COVID-affected lung proportion (CALP) (HR, 1.067 per percentage; 95% CI, 1.033– 1.101;p < 0.001) were significantly associated with CEFS. CRP (HR, 1.164 per mg/dL; 95% CI, 1.006–1.347; p = 0.041) was independently associated with CEFS in the mild pneumonia group (n = 54). Normally aerated lung proportion (NALP) (HR, 0.872 per percentage; 95% CI, 0.794–0.957; p = 0.004) and NALP volume (NALPV) (HR, 1.002 per mL; 95% CI, 1.000–1.004;p = 0.019) were associated with a lower risk of critical events in the severe pneumonia group (n = 28). @*Conclusion@#CRP in the mild pneumonia group; NALP and NALPV in the severe pneumonia group; and sex, CRP, and CALP in the total cohort were independently associated with CEFS in patients with COVID-19.

The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea

Background@#Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. @*Methods@#We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. @*Results@#Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease. @*Conclusion@#DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.

Acute Hyperglycemic Crises with Coronavirus Disease-19: Case Reports

Since the first case was contracted by coronavirus disease-19 (COVID-19) in Daegu, Korea in February 2020, about 6,800 cases and 130 deaths have been reported on April 9, 2020. Recent studies have reported that patients with diabetes showed higher mortality and they had a worse prognosis than the group without diabetes. In poorly controlled patients with diabetes, acute hyperglycemic crises such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) also might be precipitated by COVID- 19. Thus, intensive monitoring and aggressive supportive care should be needed to inadequately controlled patients with diabetes and COVID-19 infection. Here, we report two cases of severe COVID-19 patients with acute hyperglycemic crises in Korea.

A Case of COVID-19 with Acute Myocardial Infarction and Cardiogenic Shock

A 60-year-old male patient with coronavirus disease-2019 showed new onset ST-segment elevation in V1–V2 leads on electrocardiogram and cardiac enzyme elevation in intensive care unit. He had a history of type 2 diabetes mellitus, hypertension, and dyslipidemia. He was receiving mechanical ventilation and veno-venous extracorporeal membrane oxygenation treatment for severe hypoxia. Two-D echocardiogram showed regional wall motion abnormalities. We performed primary percutaneous coronary intervention for acute myocardial infarction complicating cardiogenic shock under hemodynamic support. He expired on the 16th day of admission because of cardiogenic shock and multi-organ failure. Active surveillance and intensive treatment strategy are important for saving lives of COVID-19 patients with acute myocardial infarction.

Control of Anthracnose and Gray Mold in Pepper Plants Using Culture Extract of White-Rot Fungus and Active Compound Schizostatin

Fungi produce various secondary metabolites that have beneficial and harmful effects on other organisms. Those bioactive metabolites have been explored as potential medicinal and antimicrobial resources. However, the activities of the culture filtrate (CF) and metabolites of white-rot fungus (Schizophyllum commune) have been underexplored. In this study, we assayed the antimicrobial activities of CF obtained from white-rot fungus against various plant pathogens and evaluated its efficacy for controlling anthracnose and gray mold in pepper plants. The CF inhibited the mycelial growth of various fungal plant pathogens, but not of bacterial pathogens. Diluted concentrations of CF significantly suppressed the severity of anthracnose and gray mold in pepper fruits. Furthermore, the incidence of anthracnose in field conditions was reduced by treatment with a 12.5% dilution of CF. The active compound responsible for the antifungal and disease control activity was identified and verified as schizostatin. Our results indicate that the CF of white-rot fungus can be used as an eco-friendly natural product against fungal plant pathogens. Moreover, the compound, schizostatin could be used as a biochemical resource or precursor for development as a pesticide. To the best of our knowledge, this is the first report on the control of plant diseases using CF and active compound from white-rot fungus. We discussed the controversial antagonistic activity of schizostatin and believe that the CF of white-rot fungus or its active compound, schizostatin, could be used as a biochemical pesticide against fungal diseases such as anthracnose and gray mold in many vegetables.

A Case of Multiple Endocrine Neoplasia Type 1 in Type 2 Diabetes Mellitus with Poor Glycemic Control / 임상당뇨병

The primary causes of uncontrolled diabetes are poor life-style, infection, ischemic heart disease and inappropriate usage of oral anti-diabetic agents and insulin. Supplementary causes are stroke, acute pancreatitis and endocrine diseases. Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant syndrome characterized by primary hyperparathyroidism, pituitary neoplasia, and foregut lineage neuroendocrine tumors, and is associated with increased glucose levels. We present a case of a 69-year-old woman who had polyuria, polydipsia, weight loss and hyperglycemia over 6 months. She had hypertrophy of the face, hand, and foot, and active bleeding and large folds were observed in the stomach and duodenum upon esophagogastroduodenoscopy. She also had high levels of IGF-1 and gastrin and got the failure of growth hormone suppression after an oral glucose load (75 g). These findings suggested a diagnosis of acromegaly and gastrinoma, which was clinically diagnosed along with MEN 1. The patient improved glycemic control and symptoms after being treated with somatostatin analogues and insulin therapy over a 5-month follow-up period. Here, we report a case of MEN 1 in type 2 diabetes mellitus with a poorly controlled blood glucose level. Clinicians should consider endocrine disease in patients with poor glycemic control in diabetes.

A Case of Teratoma of Thyroid Gland in Adolescence

Benign teratomas of the thyroid are very rare in adolescence and adults. In this review, we report a case of 14-year-old Korean girl with huge neck mass. She presented with anterior neck enlargement and compression symptom which was rapidly aggravated in 2 months. In physical examination, enlarged and firm right thyroid lobe was palpated and laboratory test of thyroid function was normal. In ultrasonography, right lobe was mainly occupied with a solid nodule size of 44×23×25 mm, showing markedly inhomogeneous hypoechogenicity. As fine needle aspiration cytology was non-diagnostic, lobectomy was done. Histological examination demonstrated that the tumor is benign thyroid teratoma composed of tissue from all three germ layers. When large thyroid nodule is detected in adolescence and malignancy could not be ruled out, final diagnosis should be made with surgical resection. And we should at least attentive for possibility of teratomas when ultrasonographic findings are suspicious.

Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea

BACKGROUND: Diabetic cardiac autonomic neuropathy (CAN) is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV). METHODS: In this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41) received α-lipoic acid (ALA) at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34) received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes. RESULTS: Most of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by −3.97 ms in the placebo group (P=0.06). The power spectrum of the low frequency (LF) band in the standing position increased by 15.77 ms² in the ALA group, whereas it declined by −15.04 ms² in the placebo group (P=0.08). The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by −0.42 in the placebo group (P=0.06). There were no differences between the two groups regarding rates of adverse events. CONCLUSION: Although a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.

Acute Aortic Dissection in a Patient with Pheochromocytoma / 대한내과학회지

Pheochromocytomas are neoplasms of the adrenal gland that are derived from chromaffin cells. One of the most important features of this tumor is that it can synthesize and release catecholamines such as norepinephrine and epinephrine. Due to this, arterial hypertension is one of the most common manifestations of the tumor. Although arterial hypertension is a substantial risk factor for aortic dissection, aortic dissection is actually a rare manifestation of pheochromocytoma. Here, we report a patient with pheochromocytoma who presented with acute type B aortic dissection.

Unilateral noncystic renal dysplasia in a Sprague Dawley rat / 동물의과학연구지

Renal dysplasia is a developmental disorder of the renal parenchyma involving anomalous differentiation. It is characterized by persistent metanephric ducts surrounded by primitive mesenchyme, fetal or immature glomeruli, fetal or immature tubules, interstitial fibrosis, and dysontogenic metaplasia involving tissues such as cartilage. Renal dysplasia has been rarely reported in rats. Here, we observed a small left kidney in a rat used in a short-term repeat toxicity study. The rat showed no clinical signs throughout the study. All parameters, including those reflecting kidney functions, were normal upon hematological examination and urinalysis. Grossly, the kidney was small (5 x 8 mm) and its surface appeared normal. Histological examination revealed that the cortex and medulla were poorly demarcated and contained immature/atrophic glomeruli, immature renal tubules, and mesenchymal cells. The cortex contained immature glomeruli, atrophic glomeruli with cystic dilatation of Bowman's capsular space, and some atypical tubules. Primitive metanephric tubules in the medulla were larger in diameter than normal collecting ducts, lined by a tall columnar epithelium with pale cytoplasm and basal nucleus, and surrounded by loose mesenchymal cells. Occasional tubules contained pale eosinophilic homogenous material in the lumen. Thus, this was diagnosed as a case of renal dysplasia on the basis of histologic features and is the first reported case of renal dysplasia in Sprague Dawley rats.

An Adult Case of Fisher Syndrome Subsequent to Mycoplasma pneumoniae Infection

Reported herein is an adult case of Fisher syndrome (FS) that occurred as a complication during the course of community-acquired pneumonia caused by Mycoplasma pneumoniae. A 38-yr-old man who had been treated with antibiotics for serologically proven M. pneumoniae pneumonia presented with a sudden onset of diplopia, ataxic gait, and areflexia. A thorough evaluation including brain imaging, cerebrospinal fluid examination, a nerve conduction study, and detection of serum anti-ganglioside GQ1b antibody titers led to the diagnosis of FS. Antibiotic treatment of the underlying M. pneumoniae pneumonia was maintained without additional immunomodulatory agents. A complete and spontaneous resolution of neurologic abnormalities was observed within 1 month, accompanied by resolution of lung lesions.

A Case of Community-Acquired Methicillin-Resistant Staphylococcus aureus Pneumonia / 대한내과학회지

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has received considerable attention in recent years as the cause of infections in individuals in the community who do not have traditional risk factors for MRSA infection, such as hospitalization or contact with healthcare services. CA-MRSA strains have different molecular and antimicrobial susceptibilities, as compared to hospital-associated MRSA. Although CA-MRSA strains are primarily associated with skin and soft tissue infections, they can cause more invasive infections, such as severe community-acquired pneumonia. Reports on CA-MRSA pneumonia in Korea are sparse. Therefore, we report a case of CA-MRSA pneumonia with molecular typing of the MRSA isolate.

A Case of Multicentric Castleman's Disease Presenting with Follicular Bronchiolitis / 결핵및호흡기질환

Multicentric Castleman's disease (CD) is a rare atypical lymphoproliferative disorder, which is characterized by various systemic manifestations. Some patients with multicentric CD may have concomitant lung parenchymal lesions, for which lymphoid interstitial pneumonia (LIP) is known to be the most common pathologic finding. Follicular bronchiolitis and LIP are considered to be on the same spectrum of the disease. We describe a case of multicentric CD with pulmonary involvement, which was pathologically proven as follicular bronchiolitis.

Acute gastrointestinal dilation in laboratory rhesus monkeys in the Korea National Primate Research Center / 한국실험동물학회지

Acute gastrointestinal dilation is a medical condition in which the stomach and intestine become overstretched by excessive gas content. In laboratory monkeys, cases of bloating involving gastrointestinal dilation are rarely seen, and the cause thereof is not clearly defined. Two rhesus monkeys in the Korea National Primate Research Center were found to suffer from acute gastrointestinal dilation. One of the monkeys showed severe gastric bloating after recovering from general anesthesia with isoflurane, where after it died suddenly. During necropsy, severe congestion of the lung was observed. The other monkey showed gastrointestinal dilation and died after treatment. During necropsy, severe dilation of the large intestine was observed. Severe congestion was detected in small and large intestines. Histopathologically, erythrocytes were found to fill the alveoli and alveolar capillaries of the lung. In stomach, epithelial cells were found to be sloughed from the mucosal layer, and erythrocytes were found to fill the blood vessels of the submucosal and mucosal layers. In small and large intestines, epithelial cells were also found to be sloughed from the mucosal layer, and inflammatory cells were found to have infiltrated in the submucosa (only large intestine) and mucosa. Microbiologically, Enterococcus faecalis and the pathogenic Staphylococcus haemolyticus, which do not form gas in the gastrointestinal tract, were detected in the gastrointestinal contents of both monkeys. These results suggest that the cause of the acute gastrointestinal dilation in these monkeys was not infection by gas-forming bacteria, but rather multiple factors such as diet, anesthesia, and excessive water consumption.

Rectal Prolapse Associated with Recurrent Diarrhea in a Laboratory Cynomolgus Monkey (Macaca fascicularis) / 한국실험동물학회지

Rectal prolapse is a protrusion of one or more layers of the rectum through the anus. A 5-year-old laboratory cynomolgus monkey who had suffered from recurrent diarrhea died after surgical resection of a prolapsed rectum. On examination, the prolapsed rectum was a cylinder-shaped tissue whose surface was moist and dark red with a small amount of hemorrhage. Histologically, the rectum was characterized by a segmental to diffuse cellular infiltration in the submucosa and muscle layers. Inflammation in the rectum resulted in irritation of the myenteric plexus, which could cause hypermotility of the intestines, leading to chronic diarrhea. Rectal prolapse would result in economical loss or death of laboratory animals. However, rectal prolapse in the laboratory monkey could be easily overlooked because diarrhea or other symptoms resulting from rectal prolapse could be sometimes misunderstood as a primary problem. Therefore, researchers should suspect rectal prolapse if intestinal symptoms in the laboratory monkey are untreatable.

Surgical Approach to the Oral Cavity: Techniques, Advantages and Disadvantages of Pull Through Approach / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The pull-through approach is one of the surgical approaches for oral cavity cancer, but the reports on its surgical experiences, indications, advantages and disadvantages are lacking. PATIENTS AND METHODS: Fourteen patients of oral cavity and base of tongue cancer who had been treated with the pull-through approach at Severance Hospital from 1994 to 2000 were evaluated retrospectively using their surgical records and pathological reports. All patients had excision of primary tumor and bilateral neck dissection. RESULTS: Total glossectomy was performed with the pull-through approach in four cases of oral cavity or base of tongue cancer. Partial glossectomy or excision of floor of mouth was done with this approach in ten cases of oral cavity cancer. In three patients, partial mandibulectomy was combined with primary extirpation without lip-splitting incision. In all but one case, primary tumor and neck specimen could be removed en bloc. Surgical margins were negative in all cases. Postoperative cosmetic results were satisfactory. CONCLUSIONS: The pull-through approach is one of the useful surgical approach to oral cavity cancer. Especially, the pull-through excision is the choice of approach for total glossectomy. This approach is indicated in most of the oral cavity and the floor of mouth carcinoma with anterior location. It is contraindicated in patients with tumor extended to posterior part of tongue or oropharynx. En bloc excision of intraoral tumor and neck nodes without splitting lower lip or mandible is the major advantage of this approach.

Vestibular rehabilitation in incompletely compensated acute unilateral vestibular loss / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Vestibular rehabilitation has been recommended as the treatment of choice for patients with persisting dizziness due to vestibular dysfunction, since surgery is seldom appropriate and the available pharmacological treatments are not curative and can have undesirable side-effects. This study investigated the effects f vestibular rehabilitation therapy on recovery following acute unilateral vestibular loss. MATERIALS AND METHODS: Twenty-four patients were randomly assigned to two groups of either with-treatment or without treatment. The outcome measures included equilibrium scores in dynamic posturography, motion sensitivity quotient (MSQ), and dizziness handicap inventory (DHI). RESULTS: When individual comparison measures were compared, equilibrium score results at the end of the 8-week treatment period revealed improvement of postural control in the group who received vestibular rehabilitation therapy. The DHI and MSQ results revealed less motion sensitivity and dizziness handicap, but not the acquired statistical significance compared with the non-treatment group. CONCLUSION: This results suggest that after acute unilateral vestibular loss, most patients can effectively utilize the central compensation mechanisms to recover from such an injury, but the vestibular rehabilitation therapy could provide a more rapid and complete recovery for these patients.

Expression of MUC5AC and MUC8 mRNA in human nasal mucosa / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: MUC5AC is known to be a major secretory mucin in goblet cells of the mucosa of human lower respiratory tract. But in our preliminary study, we found that the levels of MUC8 mRNAs were significantly increased in the biopsy specimens of the nasal polyps whereas other mucin genes were not. This suggests the possibility that MUC8 might be one of the major overexpressed mucins in the nasal polyps. The purpose of this study is to investigate the cellular location of MUC5AC and MUC8 mRNA. Material and methods : Normal posterior ethmoid mucosa and the polyp tissue were fixed in 4% paraformaldehyde and were hybridized with the RNA riboprobe for MUC8 and the oligonucleotide probe for MUC5AC in the presence of digoxigenin (DIG). RESULT: In the normal posterior ethmoid mucosa, MUC 5AC mRNA and MUC8 mRNA were barely expressed in the epithelium and the submucosal glands. In the polyp epithelium, the expression of MUC 5AC mRNA was localized in the cytoplasm of goblet cells and the expression of MUC8 mRNA was strongly localized in the nucelus of the goblet cells, and weakly localized in the cytoplasm of the goblet cells. MUC8 mRNA was also expressed in low levels in the nucleus of the submucosal glands. CONCLUSION: MUC8 mRNA is localized mainly in the nucleus of goblet cells and is one of the major mucin genes overexpressed in goblet cells of thnasal polyp.

Occult Neck Metastasis in Larynx and Hypopharynx Squamous Cell Carcinomas Confirmed with Simultaneous Bilateral Elective Neck Dissection / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Neck metastasis is one of the most important prognostic factor in treating head and neck squamous cell carcinomas. Recently, elective neck dissection has been widely accepted for accurate pathologic staging and elective treatment of neck. Occult metastasis rate of laryngeal and hypopharyngeal cancer varies widely depending upon authors. However, occult metastasis rate confirmed with simultaneous bilateral elective dissection is rare. MATERIALS AND METHODS: Fifty patients (100 necks) who underwent surgery for laryngeal and hypopharyngeal squamous cell carcinomas as an initial treatment from 1992 to 1997 were evaluated. All had bilateral elective neck dissection at the time of surgery for the primary treatment. Charts and pathologic reports were reviewed. RESULT: Occult neck metastasis rate by primary site were as follows. Supraglottis ipsilateral 40% (8/20) contralateral 15% (3/20), glottis ipsilateral 18% (4/22), contralateral 0% (0/22), hypopharynx ipsilateral 88% (7/8), contralateral 25% (2/8). CONCLUSION: Supraglottic and hypopharyngeal cancer may need elective neck treatment bilaterally. Contralateral neck occult metastasis from glottic cancer was minimal.