Role of phloretin as a sensitizer to TRAIL-induced apoptosis in colon cancer

Phloretin is one of the apple polyphenols with anticancer activities. Since tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves important roles in inducing apoptosis, the present study examined the effect of phloretin on TRAIL-induced apoptosis in colon cancer cells. Treatment with both phloretin and TRAIL markedly suppressed the survival of cancer cells from several colon cancer cell lines compared with that of cells treated with either TRAIL or phloretin. Additionally, decreased numbers of colonies were observed following addition of phloretin and TRAIL. Furthermore, TRAIL- and phloretin-treated HT-29-Luc cells exhibited decreased luciferase activity. Increased apoptosis was observed in phloretin- and TRAIL-treated HT-29-Luc colon cancer cells, accompanying elevated levels of cleaved poly(ADP-ribose) polymerase, and caspase-3, −8 and −9. The expression levels of MCL1 apoptosis regulator BCL2 family member (Mcl-1) were decreased following addition of phloretin in colon cancer cells. In addition, overexpression of Mcl-1 in phloretin- and TRAIL-treated HT-29-Luc cells resulted in increased cell survival. Treatment of HT-29-Luc cells with a combination of cycloheximide (CHX) and phloretin led to a more prominent decrease in Mcl-1 expression compared with that in cells treated with CHX alone, while Mcl-1 expression was recovered by treatment with MG132. Binding of ubiquitin with Mcl-1 was verified using immunoprecipitation. Intraperitoneal injection of both TRAIL and phloretin into tumor xenografts was associated with a decreased tumor volume compared with that following injection with either TRAIL or phloretin. Overall, the present results suggest a synergistic effect of phloretin on TRAIL-induced apoptosis in colon cancer cells.     

Methodology in Conventional Head and Neck Reconstruction Following Robotic Cancer Surgery: A Bridgehead Robotic Head and Neck Reconstruction

PurposeRobotic head and neck surgery is widespread nowadays. However, in the reconstruction field, the use of robotic operations is not. This article aimed to examine methodologies for conventional head and neck reconstruction after robotic tumor surgery in an effort to obtain further options for future reconstruction manipulations.Materials and MethodsA retrospective review of all patients who received head and neck robot surgery and conventional reconstructive surgery between October 2016 and September 2021.ResultsIn total, 53 cases were performed. 67.9% of the tumors were greater than 4 cm. Regarding defect size, 47.2% of the lesions were greater than 8 cm. In terms of TNM stage, stage 3 disease was recorded in 26.4% and stage 4 in 52.8%. To make a deep and narrow field wider, we changed the patient’s posture in pre-op field, additional dissection was done. We used radial forearm flap mostly (62.2%).ConclusionConventional head and neck reconstruction after robotic ENT cancer surgery is possible. One key step is to secure additional space in the deep and narrow space left after robotic surgery. For this, we opted for a radial forearm flap mostly. This can be performed as a bridgehead to perform robotic head and neck reconstruction.     

Phenotype of Asthma-COPD Overlap in COPD and Severe Asthma Cohorts

BackgroundAsthma and chronic obstructive pulmonary disease (COPD) are airway diseases with similar clinical manifestations, despite differences in pathophysiology. Asthma-COPD overlap (ACO) is a condition characterized by overlapping clinical features of both diseases. There have been few reports regarding the prevalence of ACO in COPD and severe asthma cohorts. ACO is heterogeneous; patients can be classified on the basis of phenotype differences. This study was performed to analyze the prevalence of ACO in COPD and severe asthma cohorts. In addition, this study compared baseline characteristics among ACO patients according to phenotype.MethodsPatients with COPD were prospectively enrolled into the Korean COPD subgroup study (KOCOSS) cohort. Patients with severe asthma were prospectively enrolled into the Korean Severe Asthma Registry (KoSAR). ACO was defined in accordance with the updated Spanish criteria. In the COPD cohort, ACO was defined as bronchodilator response (BDR) ≥ 15% and ≥ 400 mL from baseline or blood eosinophil count (BEC) ≥ 300 cells/μL. In the severe asthma cohort, ACO was defined as age ≥ 35 years, smoking ≥ 10 pack-years, and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity < 0.7. Patients with ACO were divided into four groups according to smoking history (threshold: 20 pack-years) and BEC (threshold: 300 cells/μL).ResultsThe prevalence of ACO significantly differed between the COPD and severe asthma cohorts (19.8% [365/1,839] vs. 12.5% [104/832], respectively; P < 0.001). The percentage of patients in each group was as follows: group A (light smoker with high BEC) – 9.1%; group B (light smoker with low BEC) – 3.7%; group C (moderate to heavy smoker with high BEC) – 73.8%; and group D (moderate to heavy smoker with low BEC) – 13.4%. Moderate to heavy smoker with high BEC group was oldest, and showed weak BDR response. Age, sex, BDR, comorbidities, and medications significantly differed among the four groups.ConclusionThe prevalence of ACO differed between COPD and severe asthma cohorts. ACO patients can be classified into four phenotype groups, such that each phenotype exhibits distinct characteristics.     

Serial blood concentration of polyethoxylated tallow amine and clinical presentations in acute herbicide poisoning

<正>1Department of Emergency Medicine, Chungnam National University Hospital, Daejeon 35015, South Korea2Department of Emergency Medicine, College of Medicine, Chungnam National University, Daejeon 35015, South Korea3Forensic Toxicology Division, National Forensic Service, Daejeon 34054, South Korea4Department of Emergency Medicine, Chungbuk National University Hospital, Cheongju 28644, South Korea Corresponding Author:Wonjoon Jeong, Email:gardenjun@hanmail.net     

Associations of Emergency Department Visits for Asthma with Precipitation and Temperature on Thunderstorm Days: A Time-Series Analysis of Data from Louisiana,USA, 2010–2012

Background: Studies of thunderstorm asthma to understand risk factors using high-resolution climate data and asthma outcomes on a large scale are scarce. Moreover, thunderstorm asthma is not well studied in the United States.Objectives: We examined whether climate parameters involved in thunderstorms are associated with emergency department (ED) visits for acute asthma attacks in the United States.Methods: We analyzed 63,789 asthma-related, daily ED visits for all age groups, and thunderstorm-associated climate data in Louisiana during 2010 through 2012. We performed time-series analyses using quasi-Poisson regression models with natural cubic splines of date, parish, holiday, day of week, season, daily maximum concentrations of ozone (O3) and fine particulate matter [PM ≤2.5μm in aerodynamic diameter (PM2.5)], and daily mean pressure, precipitation, and temperature. Because of a significant interaction effect between temperature and lightning days on asthma-related visits, we performed stratified analyses by days with/without lightning or thunderstorm (defined by any lightning and precipitation).Results: On thunderstorm days, higher asthma-related ED visits were associated with higher daily mean precipitation [relative risk (RR)=1.145 per 1g/m2/s (95% CI: 1.009, 1.300)] and lower daily mean temperature [RR=1.011 per 1°C change (1.000–1.021)] without carry-over effect to the next non-thunderstorm day. These higher risks were found mainly among children and adults <65 years of age. We observed similar results on lightning days. However, we did not find similar associations for non-thunderstorm or non-lightning days. Daily maximum O3 and PM2.5 levels were not significantly associated with asthma ED visits on thunderstorm days.Discussion: Higher precipitation and lower temperature on thunderstorm days appear to contribute to asthma attacks among people with asthma, suggesting they should consider taking precautions during thunderstorms. EDs should consider preparing for a potential increase of asthma-related visits and ensuring sufficient stock of emergency medication and supplies for forecasted severe thunderstorm days. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP10440","term_id":"372009825","term_text":"EHP10440"}}EHP10440     

Surgical management in a severe OSA patient diagnosed with Stickler syndrome

Stickler syndrome is a genetic disorder of connective tissue. One of the major symptoms associated with this disorder is an oro-facial malformation, which may cause a submucous cleft or a complete cleft of the hard palate. A 32-year-old man diagnosed with Stickler syndrome and a submucosal cleft palate (SMCP) visited our hospital with a chief complaint of excessive daytime sleepiness. The patient was diagnosed with severe obstructive sleep apnea (OSA), and administration of a polysomnography test revealed an apnea-hypopnea index (AHI) of 30.9 events/hour (h). Auto-titrating continuous positive airway pressure was initiated to control the OSA symptoms and subsequently the patient showed some improvement. However, due to continuous velopharyngeal insufficiency symptoms, intravelar veloplasty was performed. Three months after surgery, the AHI had decreased to 12.4 events/h. Recent studies have described a greater risk for OSA in individuals with cleft palate, than in the general population. The present case demonstrates surgical success in a patient with OSA and SMCP, suggesting that palatal surgery may be considered an optional surgical treatment for OSA patients with SMCP.     

Risk Factors of Outcomes of COVID-19 Patients in Korea: Focus on Early Symptoms

BackgroundCoronavirus disease 2019 (COVID-19) has spread around the globe, and it is important to determine the risk factors of death in the general population. Our study aimed to determine the risk factors of death and severe illness requiring supplemental oxygen therapy based on the demographic and clinical characteristics of COVID-19 patients in Korea.MethodsIn this study, we used data provided by the Korea Disease Control and Prevention Agency (KDCA) and analyzed a total of 5,068 patients with COVID-19, excluding 19 pregnant women and 544 individuals with missing data. We performed logistic regression analysis to determine the impact of early symptoms on survival and severe disease. Logistic regression models included sex, age, number of comorbidities, symptoms on admission, blood pressure, heart rate, and body temperature as explanatory variables, and death and oxygen therapy as outcome variables.ResultsLogistic regression analyses revealed that the male sex, older age (≥ 60 years), higher number of comorbidities, presence of symptoms on admission, heart rate ≥ 120 bpm, and body temperature ≥ 37.5°C presented with higher risk of in-hospital death and oxygen therapy requirement. Conversely, rhinorrhea and headache were associated with a low risk of death and oxygen therapy requirement. The findings showed that cough, sputum, and fever were the most common symptoms on admission, while 25.3% of patients with COVID-19 were asymptomatic.ConclusionCOVID-19 patients with high-risk early symptoms on admission, such as dyspnea and altered mental status, and those without low-risk symptoms of rhinorrhea and headache should be included in priority treatment groups.     

Microsurgical anatomy of the facial nerve

The facial nerve connections and pathways from the cortex to the brainstem are intricate and complicated. The extra‐axial part of the facial nerve leaves the lateral part of the pontomedullary sulcus and enters the temporal bone through the internal acoustic meatus. In the temporal bone, the facial nerve branches into fibers innervating the glands and tongue. After it emerges from the temporal bone it supplies various facial muscles. It contains a motor, general sensory, special sensory, and autonomic components. The physician needs comprehensive knowledge of the anatomy and courses of the facial nerve to diagnose and treat lesions and diseases of it so that surgical complications due to facial nerve injury can be avoided. This review describes the microsurgical anatomy of the facial nerve and illustrates its anatomy in relation to the surrounding bone, connective, and neurovascular structures.     

Analysis of Characteristics and Mortality in Cardiac Arrest Patients by Hospital Level: a Nationwide Population-based Study

BackgroundSurvival and post-cardiac arrest care vary considerably by hospital, region, and country. In the current study, we aimed to analyze mortality in patients who underwent cardiac arrest by hospital level, and to reveal differences in patient characteristics and hospital factors, including post-cardiac arrest care, hospital costs, and adherence to changes in resuscitation guidelines.MethodsWe enrolled adult patients (≥ 20 years) who suffered non-traumatic cardiac arrest from 2006 to 2015. Patient demographics, insurance type, admission route, comorbidities, treatments, and hospital costs were extracted from the National Health Insurance Service database. We categorized patients into tertiary hospital, general hospital, and hospital groups according to the level of the hospital where they were treated. We analyzed the patients'' characteristics, hospital factors, and mortalities among the three groups. We also analyzed post-cardiac arrest care before and after the 2010 guideline changes. The primary end-point was 30 days and 1 year mortality rates.ResultsThe tertiary hospital, general hospital, and hospital groups represented 32.6%, 49.6%, and 17.8% of 337,042 patients, respectively. The tertiary and general hospital groups were younger, had a lower proportion of medical aid coverage, and fewer comorbidities, compared to the hospital group. Post-cardiac arrest care, such as percutaneous coronary intervention, targeted temperature management, and extracorporeal membrane oxygenation, were provided more frequently in the tertiary and general hospital groups. After adjusting for age, sex, insurance type, urbanization level, admission route, comorbidities, defibrillation, resuscitation medications, angiography, and guideline changes, the tertiary and general hospital groups showed lower 1-year mortality (tertiary hospital vs. general hospital vs. hospital, adjusted odds ratios, 0.538 vs. 0.604 vs. 1; P < 0.001). After 2010 guideline changes, a marked decline in atropine use and an increase in post-cardiac arrest care were observed in the tertiary and general hospital groups.ConclusionThe tertiary and general hospital groups showed lower 30 days and 1 year mortality rates than the hospital group, after adjusting for patient characteristics and hospital factors. Higher-level hospitals provided more post-cardiac arrest care, which led to high hospital costs, and showed good adherence to the guideline change after 2010.