The Clinical Features and Risk Factors of Subglottic Cysts in Children: A Clinical Experience Using the Spontaneous Respiration Technique

Objectives@#. Subglottic cysts (SGCs) are a rare cause of respiratory distress resulting from upper airway obstruction in infants and young children. Risk factors other than prematurity with a history of endotracheal intubation have not yet been well elucidated. Therefore, we aimed to describe the clinical features and analyze the risk factors of SGCs. @*Methods@#. We conducted a retrospective review of medical records of pediatric patients who underwent marsupialization for SGCs between January 2017 and March 2022. These records were then compared with those of controls with a history of neonatal intubation, with a case-to-control ratio of 1:3. @*Results@#. Eleven patients (eight boys and three girls) diagnosed with SGCs and 33 control patients (26 boys and seven girls) were included. All patients had a history of premature birth and neonatal intubation. Symptoms of SGCs appeared at a mean age of 8.2 months (range, 1–14 months) after extubation. The mean duration of intubation was 21.5 days (range, 2–90 days), and the intubation period was longer in patients with SGCs than in controls (21.5±24.8 days vs. 5.3±7.1 days; P<0.001). Furthermore, gestational age (28.3±4.2 weeks vs. 33.8±4.4 weeks; P=0.001) and birth weight (1,134.1±515.1 g vs. 2,178.2±910.1 g; P=0.001) were significantly lower in patients with SGCs than in controls. Multivariable analysis identified the intubation period as an independent risk factor. @*Conclusion@#. This study showed that gestational age, birth weight, and the intubation period were significantly associated with the development of SGCs. Pediatric patients presenting with progressive dyspnea who have the corresponding risk factors should undergo early laryngoscopy for the differential diagnosis of SGC.

Vocal Fold Leukoplakia: Updates in Diagnosis and Management

Vocal fold leukoplakia poses a challenge to otolaryngologists due to its various spectrum of pathologic diagnosis. The degree of dysplasia is associated with malignancy risk and the new 2017 WHO classification system changed from the 3-tier system to a 2-tier system consisting of low and high grades. Infections including candidiasis, cryptococcosis, and tuberculosis should also be included in the differential diagnosis. Efforts have been made to evaluate risks using endoscopic technologies such as narrow band imaging, and surgery is essential for histopathological diagnosis. Regarding management, it is important to make an accurate diagnosis and find a balance between oncologic safety and functional outcome.

The Clinical Implications of Simultaneous Bilateral Chronic Ear Surgery for Patients with Asymmetric Hearing / 대한이비인후과학회지

Background and Objectives@#Surgery for bilateral chronic otitis media (COM) is usually performed sequentially, not simultaneously. The main reason is to prevent iatrogenic bilateral conductive hearing loss during recovery period. However, with asymmetric hearing loss, the difference in patient inconvenience between sequential and simultaneous surgery may be the same. This study evaluates the efficacy of simultaneous COM surgery in patients with asymmetric hearing.Subjects Materials and Method From 2012 to 2018, 9 patients underwent simultaneous bilateral COM surgery. The period of patients’ hospital stay, the success rate of tympanoplasty, tolerability for operation, and hearing thresholds were analyzed statistically. @*Results@#For the 8 same-day surgery patients, the mean hospital period was 4.4±0.7 days, which was much shorter than that of sequential surgery (8 days). Tympanoplasty was successful in all patients without complications. In the better side, the preoperative/postoperative mean air conduction thresholds (AC) were 62.97±12.89 dB/47.81±19.07 dB (p=0.017), the bone conduction thresholds (BC) were 46.72±10.31 dB/37.66±16.99 dB (p=0.161) and the air-bone gaps (ABG) were 16.25±8.81 dB/10.16±7.78 dB (p=0.176). In the worse side, the preoperative/ postoperative mean AC were 86.56±18.22 dB/72.18±29.43 dB (p=0.035), BC were 53.28± 11.10 dB/48.13±18.41 dB (p=0.173), and ABG were 33.28±11.22 dB/24.06±14.80 dB (p=0.500). In both ear, the postoperative AC and BC were better than or equivocal to those of the preoperative value, and the result was similar with each of the unilateral ear audiological results. @*Conclusion@#Despite the fact that there is no complete consensus to date, simultaneous bilateral COM surgery can be an option when patients have asymmetric hearing loss. Simultaneous bilateral COM surgery could save time, cost, and lead to similar results with sequential surgery, so it could be a considerable surgical option for patients with bilateral COM.

Therapeutic Outcome of Primary Snoring and Mild Obstructive Sleep Apnea and Clinical Suggestion for Treatment Approaches / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES@#The clinical significance and need for the treatment of primary snoring and mild obstructive sleep apnea have been recently questioned. In this study, we analyzed therapeutic outcome and the methods of treatment of such diseases.SUBJECTS AND METHOD: A retrospective review was conducted using the medical records of patients diagnosed with primary snoring or mild obstructive sleep apnea at a single institution from 2013 to 2015 through polysomnography or WATCHPAT.@*RESULTS@#Of the 18 patients (37%) with primary snoring, 13 patients (72.2%) underwent surgery, four patients (22.2%) were treated with surgery and mandibular advancement device, and one patient (5.6%) underwent automatic positive airway pressure therapy. Of the 78 patients (61%) with mild obstructive sleep apnea, 35 patients (44.8%) had surgery, 24 patients (30.8%) were treated with mandibular advancement device, 13 patients (16.7%) were treated with surgery and mandibular advancement device and 6 patients (7.7%) received automatic positive airway pressure therapy. For primary snoring, while Epworth Sleepiness Scale and Pittsburg Sleep Quality Index did not improve, the snoring visual analog scale decreased significantly. In patients with mild obstructive sleep apnea, Apnea-Hypopnea Index, snoring decibel, Epworth Sleepiness Scale, and Pittsburg Sleep Quality Index were significantly decreased after treatment and the lowest oxygen saturation was significantly increased after treatment.@*CONCLUSION@#For primary snoring, the direction of treatment should be determined in accordance with the presence of associated diseases related to sleep disturbance breathing. For mild obstructive sleep apnea, active treatment may be helpful.

Analysis of Sleep Questionnaires of Commercial Vehicle Operators in Korea / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES@#Obstructive sleep apnea (OSA) is highly prevalent in commercial vehicle operators (CMVOs). This study aimed to evaluate the poor sleep quality, daytime sleepiness, and the prevalence of self-reported OSA in CMVOs.SUBJECTS AND METHOD: We performed a retrospective review of the medical records of patients who visited a single institution with sleep problems from 2011 January to 2016 December. Among the patients, a total of 38 CMVOs was analyzed. Clinical information, questionnaires about sleep quality (Pittsburg sleep questionnaire, PSQI), excessive daytime sleepiness (Epworth sleepiness scale, ESS) and risk factors for OSA (STOP-Bang) were analyzed. The frequency of motor vehicle accidents and near accidents was assessed, and polysomnography (PSG) was used for OSA diagnosis purposes.@*RESULTS@#The mean age of the study population was 45.3±11.8 years. The average score of PSQI, ESS, and STOP-Bang were 6.75±4.22, 10.79±7.12, and 4.62±3.34, respectively. A significant association between near accidents and high-risk group of OSA was observed [odds ratio (OR)=2.73, 95% confidence interval (CI)=1.08–4.48]. Subjects with poor sleep quality showed significantly increased risk of near accidents (OR=2.34, 95% CI=1.01–3.56). Receiver operating characteristic curves of STOP-Bang questionnaire using apnea-hypopnea index (cut-off value=5) indicates that suspected OSA group predicted by STOP-Bang score was significantly correlated with OSA severity (area under curve=0.72, sensitivity 77.1%, specificity 59.4%).@*CONCLUSION@#Administration of STOP-Bang questionnaire before a PSG can identify high-risk subjects, supporting its further use in OSA screening of CMVOs.

Analysis of Sleep Questionnaires of Commercial Vehicle Operators in Korea / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea (OSA) is highly prevalent in commercial vehicle operators (CMVOs). This study aimed to evaluate the poor sleep quality, daytime sleepiness, and the prevalence of self-reported OSA in CMVOs. SUBJECTS AND METHOD: We performed a retrospective review of the medical records of patients who visited a single institution with sleep problems from 2011 January to 2016 December. Among the patients, a total of 38 CMVOs was analyzed. Clinical information, questionnaires about sleep quality (Pittsburg sleep questionnaire, PSQI), excessive daytime sleepiness (Epworth sleepiness scale, ESS) and risk factors for OSA (STOP-Bang) were analyzed. The frequency of motor vehicle accidents and near accidents was assessed, and polysomnography (PSG) was used for OSA diagnosis purposes. RESULTS: The mean age of the study population was 45.3±11.8 years. The average score of PSQI, ESS, and STOP-Bang were 6.75±4.22, 10.79±7.12, and 4.62±3.34, respectively. A significant association between near accidents and high-risk group of OSA was observed [odds ratio (OR)=2.73, 95% confidence interval (CI)=1.08–4.48]. Subjects with poor sleep quality showed significantly increased risk of near accidents (OR=2.34, 95% CI=1.01–3.56). Receiver operating characteristic curves of STOP-Bang questionnaire using apnea-hypopnea index (cut-off value=5) indicates that suspected OSA group predicted by STOP-Bang score was significantly correlated with OSA severity (area under curve=0.72, sensitivity 77.1%, specificity 59.4%). CONCLUSION: Administration of STOP-Bang questionnaire before a PSG can identify high-risk subjects, supporting its further use in OSA screening of CMVOs.

Therapeutic Outcome of Primary Snoring and Mild Obstructive Sleep Apnea and Clinical Suggestion for Treatment Approaches / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The clinical significance and need for the treatment of primary snoring and mild obstructive sleep apnea have been recently questioned. In this study, we analyzed therapeutic outcome and the methods of treatment of such diseases. SUBJECTS AND METHOD: A retrospective review was conducted using the medical records of patients diagnosed with primary snoring or mild obstructive sleep apnea at a single institution from 2013 to 2015 through polysomnography or WATCHPAT. RESULTS: Of the 18 patients (37%) with primary snoring, 13 patients (72.2%) underwent surgery, four patients (22.2%) were treated with surgery and mandibular advancement device, and one patient (5.6%) underwent automatic positive airway pressure therapy. Of the 78 patients (61%) with mild obstructive sleep apnea, 35 patients (44.8%) had surgery, 24 patients (30.8%) were treated with mandibular advancement device, 13 patients (16.7%) were treated with surgery and mandibular advancement device and 6 patients (7.7%) received automatic positive airway pressure therapy. For primary snoring, while Epworth Sleepiness Scale and Pittsburg Sleep Quality Index did not improve, the snoring visual analog scale decreased significantly. In patients with mild obstructive sleep apnea, Apnea-Hypopnea Index, snoring decibel, Epworth Sleepiness Scale, and Pittsburg Sleep Quality Index were significantly decreased after treatment and the lowest oxygen saturation was significantly increased after treatment. CONCLUSION: For primary snoring, the direction of treatment should be determined in accordance with the presence of associated diseases related to sleep disturbance breathing. For mild obstructive sleep apnea, active treatment may be helpful.

Resistance to the c-Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells.

Investigation of the mechanisms of resistance to targeted therapies is essential as resistance acquired during treatment may lead to relapse or refractoriness to the therapy. Our previous study identified the small molecule KRC-108 as a result of efforts to find an anticancer agent with c-Met-inhibitory activity. In the present study, the changes accompanying resistance to KRC-108 were investigated in the gastric cancer cell line MKN-45 and its KRC-108-resistant clones by western blot and immunofluorescence analyses. Increased expression of the c-Met protein was observed in KRC-108-resistant cells compared with that of the parental cells, and the phosphorylation of c-Met also increased in cell lines resistant to KRC-108. Resistance to the c-Met inhibitor was associated with cell morphological changes: MKN-45 parental cells, which had a round and poorly differentiated morphology, were altered to exhibit an epithelial cell-like phenotype in KRC-108-resistant clones. Consistent with the transition to an epithelial morphology, the expression of E-cadherin was increased in resistant cells. Using immunoprecipitation, an interaction between E-cadherin and the c-Met protein was observed in the KRC-108-resistant cells. Immunohistochemical analysis of human gastric carcinoma tissues revealed the co-expression of E-cadherin and c-Met. These results suggest that the epithelial transition in KRC-108-resistant cells is mediated by recruiting E-cadherin to c-Met protein. Thus, the present study identified a mechanism used by cancer cells to confer resistance to anticancer agents.

Transcriptional regulation of Niemann-Pick C1-like 1 gene by liver receptor homolog-1.

Factors that modulate cholesterol levels have major impacts on cardiovascular disease. Niemann-Pick C1-like 1 (NPC1L1) functions as a sterol transporter mediating intestinal cholesterol absorption and counter-balancing hepatobiliary cholesterol excretion. The liver receptor homolog 1 (LRH-1) had been shown to regulate genes involved in hepatic lipid metabolism and reverse cholesterol transport. To study whether human NPC1L1 gene is regulated transcriptionally by LRH-1, we have analyzed evolutionary conserved regions (ECRs) in HepG2 cells. One ECR was found to be responsive to the LRH-1. Through deletion studies, LRH-1 response element was identified and the binding of LRH-1 was demonstrated by EMSA and ChIP assays. When SREBP2, one of several transcription factors which had been shown to regulate NPC1L1 gene, was co-expressed with LRH-1, synergistic transcriptional activation resulted. In conclusion, we have identified LRH-1 response elements in NPC1L1 gene and propose that LRH-1 and SREBP may play important roles in regulating NPC1L1 gene.

Effect of alpha-tocopherol supplementation during boar semen cryopreservation on sperm characteristics and expression of apoptosis related genes.

Boar semen is extremely vulnerable to cold shock and sensitive to peroxidative damage due to high content of unsaturated fatty acids in the phospholipids of the plasma membrane and the relatively low antioxidant capacity of seminal plasma. The present study evaluated the influence of alpha-tocopherol supplementation at various concentrations in the boar semen extender during cryopreservation on post-thawed sperm motility characteristics (total sperm motility, MOT; local motility, LCM; curvilinear velocity, VCL; straight linear velocity, VSL; and average path velocity, VAP), sperm qualities (viability, acrosomal integrity and apoptosis), expression of stress protein (HSP70), and the expression of pro-apoptotic (Bax and Bak) and anti-apoptotic (Bcl-2l and Bcl-xl) genes. Semen collected from 10 Duroc boars was cryopreserved in lactose-egg yolk buffer supplemented with various concentrations of alpha-tocopherol (0, 100, 200, 400, 600 and 800 microM) using the straw-freezing procedure and stored at -196 degrees C for a minimum period of one month. In frozen-thawed groups, sperm motility was significantly (P<0.05) lower than that of fresh sperm. In fresh sperm, HSP70 immunoreactivity expression was observed in the equatorial region, but in frozen-thawed groups, expressions were mostly observed in the sperm head. Higher apoptosis rates were observed in 600 and 800 microM alpha-tocopherol supplemented frozen-thawed groups. In alpha-tocopherol supplemented frozen-thawed groups immediately after thawing, the expression was similar to that of fresh group. But after incubation at 37 degrees C for 3h, the expression in 200 and 800 microM alpha-tocopherol supplemented groups was higher than that of others. Expression of pro-apoptotic genes was significantly higher and anti-apoptotic genes was significantly (P<0.01) lower in alpha-tocopherol supplemented frozen-thawed groups compared to fresh sperm group. In conclusion, alpha-tocopherol, supplemented at 200 microM concentration in boar semen extender during cryopreservation had a positive effect on post-thawed sperm survivability.

BCAR3 regulates EGF-induced DNA synthesis in normal human breast MCF-12A cells.

BCAR3 (breast cancer anti-estrogen resistance 3) is a signal transducer containing an SH2 domain, a proline/serine-rich domain and a GDP-exchange factor homologous domain, whose role in signaling pathways is currently unclear. Furthermore, BCAR3 is implicated in anti-estrogen resistance of breast cancer cells. In the present study, we investigated the functional role of BCAR3 in a mitogenic signaling pathway of EGF in non-tumorigenic human breast epithelial MCF-12A cells. Microinjection of an anti-BCAR3 antibody, siRNAs targeting BCAR3 and an SH2 domain of BCAR3 inhibited EGF-induced DNA synthesis. Direct association of BCAR3 with activated EGF receptor and Cas was observed. Lastly, microinjection of a BCAR3 expression plasmid induced DNA synthesis. These findings suggest that the BCAR3 protein, through its SH2 domain, is involved in the signaling pathways of EGF leading to cell cycle progression, and that BCAR3 itself is part of a mitogenic signaling pathway.

Enhanced development of porcine embryos cloned from bone marrow mesenchymal stem cells.

In the present study, we have characterized an isolated population of porcine bone marrow mesenchymal stem cells (MSCs) for multilineage commitment and compared the developmental potential of cloned embryos with porcine MSCs and fetal fibroblasts (FFs). MSCs exhibited robust alkaline phosphatase activity and later transformed into mineralized nodules following osteoinduction. Furthermore, MSCs underwent adipogenic and chondrogenic differentiation by producing lipid droplets and proteoglycans, respectively. Primary cultures of FFs from a female fetus at ~30 day of gestation were established. Donor cells at 3-4 passage were employed for nuclear transfer (NT). Cell cycle analysis showed that the majority of MSCs in confluence were in the G0/G1 stage. Cumulus-oocyte complexes were matured and fertilized in vitro (IVF) as control. The cleavage rate was significantly (P<0.05) higher in IVF than in NT embryos with MSCs and FFs (84.54.6% vs. 52.25.4% and 50.85.2%, respectively). However, blastocyst rates in IVF and NT embryos derived from MSCs (20.62.5% and 18.43.0%) did not differ, but were significantly (P<0.05) higher than NT derived from FFs (9.52.1%). Total cell number and the ratio of ICM to total cells among blastocysts cloned from MSCs (34.45.2 and 0.380.08, respectively) were significantly (P<0.05) higher than those from FFs (22.65.5 and 0.180.12, respectively). Proportions of TUNEL positive cells in NT embryos from FFs (7.31.8%) were significantly (P<0.05) higher than in MSCs (4.61.3%) and IVF (2.50.9%). The results clearly demonstrate that multipotent bone marrow MSCs have a greater potential as donor cells than FFs in achieving enhanced production of cloned porcine embryos.