Flos magnoliae constituent fargesin has an anti-allergic effect via ORAI1 channel inhibition

Flos magnoliae (FM), the dry flower buds of Magnolia officinalis or its related species, is a traditional herbal medicine commonly used in Asia for symptomatic relief of and treating allergic rhinitis, headache, and sinusitis. Although several studies have reported the effects of FM on store-operated calcium entry (SOCE) via the ORAI1 channel, which is essential during intracellular calcium signaling cascade generation for T cell activation and mast cell degranulation, the effects of its isolated constituents on SOCE remain unidentified. Therefore, we investigated which of the five major constituents of 30% ethanoic FM (vanillic acid, tiliroside, eudesmin, magnolin, and fargesin) inhibit SOCE and their physiological effects on immune cells. The conventional whole-cell patch clamp results showed that fargesin, magnolin, and eudesmin significantly inhibited SOCE and thus human primary CD4 + T lymphocyte proliferation, as well as allergen-induced histamine release in mast cells. Among them, fargesin demonstrated the most potent inhibitory effects not only on ORAI1 (IC 50 = 12.46 ± 1.300 μM) but also on T-cell proliferation (by 87.74% ± 1.835%) and mast cell degranulation (by 20.11% ± 5.366%) at 100 μM. Our findings suggest that fargesin can be a promising candidate for the development of therapeutic drugs to treat allergic diseases.

Nootkatol prevents ultraviolet radiation-induced photoaging via ORAI1 and TRPV1 inhibition in melanocytes and keratinocytes

Skin photoaging occurs due to chronic exposure to solar ultraviolet radiation (UV), the main factor contributing to extrinsic skin aging. Clinical signs of photoaging include the formation of deep, coarse skin wrinkles and hyperpigmentation.Although melanogenesis and skin wrinkling occur in different skin cells and have different underlying mechanisms, their initiation involves intracellular calcium signaling via calcium ion channels. The ORAI1 channel initiates melanogenesis in melanocytes, and the TRPV1 channel initiates MMP-1 production in keratinocytes in response to UV stimulation. We aimed to develop a drug that may simultaneously inhibit ORAI1 and TRPV1 activity to help prevent photoaging. We synthesized nootkatol, a chemical derivative of valencene. TRPV1 and ORAI1 activities were measured using the whole-cell patch-clamp technique. Intracellular calcium concentration [Ca2+ ] i was measured using calcium-sensitive fluorescent dye (Fura-2 AM). UV-induced melanin formation and MMP-1 production were quantified in B16F10 melanoma cells and HaCaT cells, respectively. Our results indicate that nootkatol (90 μM) reduced TRPV1 current by 94% ± 2% at –60 mV and ORAI1 current by 97% ± 1% at –120 mV. Intracellular calcium signaling was significantly inhibited by nootkatol in response to ORAI1 activation in human primary melanocytes (51.6% ± 0.98% at 100 μM). Additionally, UV-induced melanin synthesis was reduced by 76.38% ± 5.90% in B16F10 melanoma cells, and UV-induced MMP-1 production was reduced by 59.33% ± 1.49% in HaCaT cells. In conclusion, nootkatol inhibits both TRPV1 and ORAI1 to prevent photoaging, and targeting ion channels may be a promising strategy for preventing photoaging.

Flos magnoliae constituent fargesin has an anti-allergic effect via ORAI1 channel inhibition

Flos magnoliae (FM), the dry flower buds of Magnolia officinalis or its related species, is a traditional herbal medicine commonly used in Asia for symptomatic relief of and treating allergic rhinitis, headache, and sinusitis. Although several studies have reported the effects of FM on store-operated calcium entry (SOCE) via the ORAI1 channel, which is essential during intracellular calcium signaling cascade generation for T cell activation and mast cell degranulation, the effects of its isolated constituents on SOCE remain unidentified. Therefore, we investigated which of the five major constituents of 30% ethanoic FM (vanillic acid, tiliroside, eudesmin, magnolin, and fargesin) inhibit SOCE and their physiological effects on immune cells. The conventional whole-cell patch clamp results showed that fargesin, magnolin, and eudesmin significantly inhibited SOCE and thus human primary CD4 + T lymphocyte proliferation, as well as allergen-induced histamine release in mast cells. Among them, fargesin demonstrated the most potent inhibitory effects not only on ORAI1 (IC 50 = 12.46 ± 1.300 μM) but also on T-cell proliferation (by 87.74% ± 1.835%) and mast cell degranulation (by 20.11% ± 5.366%) at 100 μM. Our findings suggest that fargesin can be a promising candidate for the development of therapeutic drugs to treat allergic diseases.

Nootkatol prevents ultraviolet radiation-induced photoaging via ORAI1 and TRPV1 inhibition in melanocytes and keratinocytes

Skin photoaging occurs due to chronic exposure to solar ultraviolet radiation (UV), the main factor contributing to extrinsic skin aging. Clinical signs of photoaging include the formation of deep, coarse skin wrinkles and hyperpigmentation.Although melanogenesis and skin wrinkling occur in different skin cells and have different underlying mechanisms, their initiation involves intracellular calcium signaling via calcium ion channels. The ORAI1 channel initiates melanogenesis in melanocytes, and the TRPV1 channel initiates MMP-1 production in keratinocytes in response to UV stimulation. We aimed to develop a drug that may simultaneously inhibit ORAI1 and TRPV1 activity to help prevent photoaging. We synthesized nootkatol, a chemical derivative of valencene. TRPV1 and ORAI1 activities were measured using the whole-cell patch-clamp technique. Intracellular calcium concentration [Ca2+ ] i was measured using calcium-sensitive fluorescent dye (Fura-2 AM). UV-induced melanin formation and MMP-1 production were quantified in B16F10 melanoma cells and HaCaT cells, respectively. Our results indicate that nootkatol (90 μM) reduced TRPV1 current by 94% ± 2% at –60 mV and ORAI1 current by 97% ± 1% at –120 mV. Intracellular calcium signaling was significantly inhibited by nootkatol in response to ORAI1 activation in human primary melanocytes (51.6% ± 0.98% at 100 μM). Additionally, UV-induced melanin synthesis was reduced by 76.38% ± 5.90% in B16F10 melanoma cells, and UV-induced MMP-1 production was reduced by 59.33% ± 1.49% in HaCaT cells. In conclusion, nootkatol inhibits both TRPV1 and ORAI1 to prevent photoaging, and targeting ion channels may be a promising strategy for preventing photoaging.

Luteolin reduces fluid hypersecretion by inhibiting TMEM16A in interleukin-4 treated Calu-3 airway epithelial cells

Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl– and HCO3 – is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calciumactivated Cl– channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SPEtOH- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

Gardenia jasminoides extract and its constituent, genipin, inhibit activation of CD3/CD28 co-stimulated CD4+ T cells via ORAI1 channel

Gardenia jasminoides (GJ) is a widely used herbal medicine with antiinflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJEtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJEtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJHEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJHEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited IORAI1 and interleukin-2 production in CD3/ CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4+ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

Luteolin reduces fluid hypersecretion by inhibiting TMEM16A in interleukin-4 treated Calu-3 airway epithelial cells

Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl– and HCO3 – is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calciumactivated Cl– channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SPEtOH- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

Gardenia jasminoides extract and its constituent, genipin, inhibit activation of CD3/CD28 co-stimulated CD4+ T cells via ORAI1 channel

Gardenia jasminoides (GJ) is a widely used herbal medicine with antiinflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJEtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJEtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJHEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJHEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited IORAI1 and interleukin-2 production in CD3/ CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4+ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

Surgical Strategy for T2 Gallbladder Cancer: Nationwide Multicenter Survey in Korea

BACKGROUND: Although all guidelines suggest that T2 gallbladder (GB) cancer should be treated by extended cholecystectomy (ECx), high-level scientific evidence is lacking because there has been no randomized controlled trial on GB cancer. METHODS: A nationwide multicenter study between 2000 and 2009 from 14 university hospitals enrolled a total of 410 patients with T2 GB cancer. The clinicopathologic findings and long-term follow-up results were analyzed after consensus meeting of Korean Pancreas Surgery Club. RESULTS: The 5-year cumulative survival rate (5YSR) for the patients who underwent curative resection was 61.2%. ECx group showed significantly better 5YSR than simple cholecystectomy (SCx) group (65.4% vs. 54.0%, P = 0.016). For N0 patients, there was no significant difference in 5YSR between SCx and ECx groups (68.7% vs. 73.6%, P = 0.173). Systemic recurrence was more common than locoregional recurrence (78.5% vs. 21.5%). Elevation of cancer antigen 19-9 level preoperatively and lymph node (LN) metastasis were significantly poor prognostic factors in a multivariate analysis. CONCLUSION: ECx including wedge resection of GB bed should be recommended for T2 GB cancer. Because systemic recurrence was more common and recurrence occurred more frequently in patients with LN metastasis, postoperative adjuvant therapy should be considered especially for the patients with LN metastasis.

Mitochondrial dysfunction reduces the activity of KIR2.1 K⁺ channel in myoblasts via impaired oxidative phosphorylation

Myoblast fusion depends on mitochondrial integrity and intracellular Ca²⁺ signaling regulated by various ion channels. In this study, we investigated the ionic currents associated with [Ca²⁺]i regulation in normal and mitochondrial DNA-depleted (ρ0) L6 myoblasts. The ρ0 myoblasts showed impaired myotube formation. The inwardly rectifying K⁺ current (I(Kir)) was largely decreased with reduced expression of KIR2.1, whereas the voltage-operated Ca²⁺ channel and Ca²⁺-activated K⁺ channel currents were intact. Sustained inhibition of mitochondrial electron transport by antimycin A treatment (24 h) also decreased the I(Kir). The ρ0 myoblasts showed depolarized resting membrane potential and higher basal [Ca²⁺]ᵢ. Our results demonstrated the specific downregulation of I(Kir) by dysfunctional mitochondria. The resultant depolarization and altered Ca²⁺ signaling might be associated with impaired myoblast fusion in ρ0 myoblasts.

Awareness and attitude on international emergency medicine: a resident survey

OBJECTIVE: International emergency medicine (IEM) is a rapidly growing field in emergency medicine (EM). However, there are few studies of the interest and attitude of EM residents on this subject in Korea. The aim of this study was to assess the awareness of IEM and determine feasibility of adoption as an EM residency program. METHODS: A structured on/off-line survey was distributed to all current first to third grade EM residents in Korea (year 2016–2017). Ninety-two hospitals with residency programs and 463 residents were identified as potential survey candidates. The survey consisted of 20 questionnaires including binary yes/no and multiple choice questions. RESULTS: The response rate was 37.1% (172/463). The proportion of residents who have interest in IEM was 62.8% (108/172); 76.2% (131/172) respondents answered that they wanted to participate in IEM/global health activities during their residency. Approximately two thirds (68.6%, 118/172) reported that they plan to participate in any IEM activity even after graduation. More than half (56.4%, 97/172) agreed that the inclusion of IEM/global health training in their residency might be necessary and it may help them to guide their future careers after their training (68.6%, 118/172). A total of 144 respondents (83.7%) indicated lack of time during their residency mostly, absence of an IEM program (47.1%, 81/172), and lack of information on IEM (31.4%, 54/172). CONCLUSION: IEM is of interest to Korean EM residents. On the other hand, formal education and training offered to residents is limited in Korea. Korean Society of Emergency Medicine should start discussions on how to adopt a global IEM agenda, and reflect on a resident training program.

Activation of transient receptor potential vanilloid 3 by the methanolic extract of Schisandra chinensis fruit and its chemical constituent γ-schisandrin

Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel with modest permeability to calcium ions. It is involved in intracellular calcium signaling and is therefore important in processes such as thermal sensation, skin barrier formation, and wound healing. TRPV3 was initially proposed as a warm temperature sensor. It is activated by synthetic small-molecule chemicals and plant-derived natural compounds such as camphor and eugenol. Schisandra chinensis (Turcz.) Baill (SC) has diverse pharmacological properties including antiallergic, anti-inflammatory, and wound healing activities. It is extensively used as an oriental herbal medicine for the treatment of various diseases. In this study, we investigated whether SC fruit extracts and seed oil, as well as four compounds isolated from the fruit can activate the TRPV3 channel. By performing whole-cell patch clamp recording in HEK293T cells overexpressing TRPV3, we found that the methanolic extract of SC fruit has an agonistic effect on the TRPV3 channel. Furthermore, electrophysiological analysis revealed that γ-schisandrin, one of the isolated compounds, activated TRPV3 at a concentration of 30 µM. In addition, γ-schisandrin (~100 µM) increased cytoplasmic Ca²⁺ concentrations by approximately 20% in response to TRPV3 activation. This is the first report to indicate that SC extract and γ-schisandrin can modulate the TRPV3 channel. This report also suggests a mechanism by which γ-schisandrin acts as a therapeutic agent against TRPV3-related diseases.

Radiographic basal ganglia abnormalities secondary to nonketotic hyperglycemia with unusual clinical features

A 77-year-old woman was admitted to a local clinic for altered consciousness and presented with a suspected basal ganglion hemorrhage detected on brain computed tomography. The patient was stuporous, but her vital signs were stable. Her initial blood glucose was 607 mg/dL, and a hyperdense lesion was found in the right basal ganglion on brain computed tomography. T1-weighted magnetic resonance imaging revealed high signal intensity in the right basal ganglion. Electroencephalography showed no seizure activity. The patient was treated with a fluid infusion, and serum glucose level was controlled with insulin. The patient gradually recovered consciousness and was alert within 24 hours as serum glucose level normalized. The basal ganglion lesion caused by hyperglycemia was not accompanied by involuntary limb movement. This is the first report of a patient presenting with decreased consciousness and typical neural radiographic changes associated with nonketotic hyperglycemia but without movement abnormalities.

Selective Cannabinoid Receptor-1 Agonists Regulate Mast Cell Activation in an Oxazolone-Induced Atopic Dermatitis Model

BACKGROUND: Many inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation. However, the endogenous modulators for mast cell activation and the underlying mechanism have yet to be elucidated. Endogenous cannabinoids such as palmitoylethanolamide (PEA) and N-arachidonoylethanolamine (anandamide or AEA), were found in peripheral tissues and have been proposed to possess autacoid activity, implying that cannabinoids may downregulate mast cell activation and local inflammation. OBJECTIVE: In order to investigate the effect of cannabinoid receptor-1 (CB1R) agonists on mast cell activation, AEA-derived compounds were newly synthesized and evaluated for their effect on mast cell activation. METHODS: The effects of selected compounds on FcepsilonRI-induced histamine and beta-hexosaminidase release were evaluated in a rat basophilic leukemia cell line (RBL-2H3). To further investigate the inhibitory effects of CB1R agonist in vivo, an oxazolone-induced atopic dermatitis mouse model was exploited. RESULTS: We found that CB1R inhibited the release of inflammatory mediators without causing cytotoxicity in RBL-2H3 cells and that CB1R agonists markedly and dose-dependently suppressed mast cell proliferation indicating that CB1R plays an important role in modulating antigen-dependent immunoglobulin E (IgE)-mediated mast cell activation. We also found that topical application of CB1R agonists suppressed the recruitment of mast cells into the skin and reduced the level of blood histamine. CONCLUSION: Our results indicate that CB1R agonists down-regulate mast cell activation and may be used for relieving inflammatory symptoms mediated by mast cell activation, such as atopic dermatitis, psoriasis, and contact dermatitis.

Utility of the Rapid Emergency Medicine Score (REMS) for Predicting Hospital Mortality in Severely Injured Patients

PURPOSE: We evaluated the power of the Rapid Emergency Medicine Score (REMS) for predicting hospital mortality in trauma patients. Then, we compared the REMS with two other scoring systems, the Emergency Trauma Score (EMTRAS) and the Injury Severity Score (ISS) for predicting prognosis. METHODS: We examined data from a prospectively collected registry in a single trauma center from January 2010 to November 2011. Patients enrolled in the registry were trauma patients who were predicted to have an ISS>15 or who required urgent multiple surgical consultations as soon as possible. Pediatric patients (<18-years-old) who were referred after initial care or death on arrival, and those with injuries due to burns, asphyxia, or drowning were excluded. The study population was divided into two subgroups according to hospital mortality, and the differences in clinical characteristics and calculated scores were examined. The odds ratio (OR) of REMS for predicting In-hospital mortality was calculated and the prognostic power of the three scoring systems for predicting hospital mortality by drawing receiver operating characteristic (ROC) curves was compared. RESULTS: A total of 103 patients were included in the analysis. Of these, 44 died during hospitalization. All three prognostic scores were significantly higher in the hospital mortality subgroup. The OR of the REMS for predicting hospital mortality was 1.35 (p<0.001). The areas under the ROC curves of the REMS, EMTRAS, and ISS were 0.815 (95% confidence interval [CI], 0.727-0.884), 0.872 (95% CI, 0.793-0.930), and 0.693 (95% CI, 0.595-0.780), respectively. The area under the ROC curve of the REMS was not different from that of the EMTRAS or ISS. CONCLUSION: The REMS showed good prognostic power for predicting hospital mortality in severely injured patients. Consecutive prospective studies are warranted to determine the utility of this scoring system for trauma patients.

Hematological Parameters Predicting Complications of Caustic Ingestion: A Retrospective Study

PURPOSE: In addition to chemical burn of the alimentary tract, caustic ingestion can cause severe complications including esophageal perforation, airway edema, esophageal stricture, and death. Hematological parameters have been reported to be useful inflammatory markers predicting prognoses in various clinical situations where oxidative stress is increased. We hypothesized that hematological parameters might be useful for prediction of complications after caustic ingestion. METHODS: We performed a retrospective analysis of patients admitted to our Emergency Department after caustic ingestion. The numbers of leukocytes, neutrophils, lymphocytes, and monocytes, and the neutrophil-lymphocyte ratio were compared between uncomplicated and complicated patient groups. Receiver operating characteristic curve analysis was performed for parameters that differed between the two groups. Subgroup analysis was performed according to the substance ingested, thus acid or alkali. RESULTS: Thirty-seven patients were included in our study and eight had complications. Leukocyte, neutrophil counts, and the neutrophil-lymphocyte ratio of the complicated group were higher than those of the uncomplicated group. The areas under the receiver operating characteristic curves of leukocyte counts, neutrophil counts, and the neutrophil- lymphocyte ratio, were 0.819, 0.832, and 0.750, respectively. The cut-off values of these parameters for prediction of complications were 12 060/uL, 9607/uL, and 2.72, respectively. In subgroup analysis, the leukocyte and neutrophil counts, and the neutrophil-lymphocyte ratio of complicated patients who had ingested alkali were higher than those of the uncomplicated group. CONCLUSION: Leukocyte counts, neutrophil counts, and the neutrophil-lymphocyte ratio might serve as useful predictors of complications after ingestion of caustic substances.

Radiation Exposure through Private Health Examinations in Korea

BACKGROUND: Due to the increase in general health examination centers, health examination programs are becoming more diversified in Korea. Some of the general health examination tests, such as computed tomography, result in substantial levels of radiation exposure. However, the amount of radiation exposure from these examinations has not been studied in Korea. Thus, the aim of this study was to investigate the level of radiation exposure from general health examinations. METHODS: Through the Korean Hospitals Association website and portal sites, 296 general health examination facilities were included in the study. The information about whether radiation-related tests are included in the health examination program of each facility was collected from their internet website. The radiation exposure dose for each test was obtained from the Database Construction Report by the Korean Institute of Nuclear Safety. RESULTS: The mean base exposure dose of health examination programs from 296 health facilities was 2.49+/-2.50 mSv. The mean maximum exposure dose was 14.82+/-9.55 mSv (maximum 40.1 mSv). The maximum exposure dose was the highest at university-associated hospitals (21.63+/-7.54 mSv) and lowest at hospitals with < or =30 beds (7.84+/-7.64 mSv). The contribution of computed tomography on the maximum exposure dose was the highest of all examinations (72%). CONCLUSIONS: This study verified that examinees are exposed to substantial levels of radiation during general health examinations. It is necessary to establish evidence-based screening programs considering radiation exposure during general health examinations.

Assessing Safety Attitudes among Healthcare Providers after a Hospital-Wide High-Risk Patient Care Program

PURPOSE: Cardiopulmonary resuscitation (CPR) is commonly performed in high-risk, high intensity situations and is therefore a good procedure around which to develop and implement safety culture strategies in the hospital. The purpose of this study was to evaluate the impact of a hospital-wide quality improvement program on the management of sudden cardiac arrests by assessing healthcare providers' attitudes towards patient safety. MATERIALS AND METHODS: This study was designed as a prospective cohort study at a single academic medical center. The comprehensive hospital-based safety program included steps to identify areas of hazard, partner units with the Resuscitation Committee, and to conduct a Safety Attitudes Questionnaire (SAQ). The SAQ evaluated 35 questions in seven domains to assess changes in patient safety culture by comparing the results before and after the hospital-wide high risk patient care improvement program. RESULTS: The response rates of the pre- and post-SAQ survey were 489 out of 1121 (43.6%) and 575 out of 1270 (45.3%), respectively. SAQ survey responses revealed significant improvement in all seven domains of the questionnaire (p-values of 0.006 and lower). In a subgroup analysis, doctors and nurses showed improvement in five domains. Both doctors and nurses did not show improvement in the "sharing information" domain. CONCLUSION: A hospital-wide quality improvement program for high-risk, high reliability patient care involving CPR care was shown to be associated with a change in healthcare providers' attitudes towards patient safety. Through an immersive and active program on CPR care, change in healthcare providers' attitudes towards patient safety was initiated.

A comparison between surgical resection and radiofrequency ablation in the treatment of hepatocellular carcinoma

PURPOSE: The aim of this study was to compare the therapeutic effects of radiofrequency ablation (RFA) and hepatic resection (HR) with regards to procedural morbidity, mortality, overall survival (OS) and disease-free survival (DFS) rates in hepatocellular carcinoma (HCC) patients. METHODS: Retrospective studies were performed based on the medical records of 129 patients who underwent curative HR, and 57 who patients received RFA for HCC, between 2005 and 2009. The inclusion criteria of HCC were the presence of three or fewer nodules 3 cm or less in diameter or a single nodule of 5 cm or less. RESULTS: The 1-, 3- and 5-year OS rates in the HR group were 91.3%, 78.8%, and 64.9%, compared to 94.4%, 74.0%, and 74.0% in the RFA group, with no significant difference between the two groups (P = 0.725). The estimated 1- and 3-year DFS rates were 70.0% and 53.0% in the HR group and 65.2% and 24.7% in the RFA group, respectively. The DFS rates of HR group were significantly higher than RFA group (P = 0.015). Multivariate analysis identified that recurrence (P = 0.036) and portal hypertension (P = 0.036) were associated with OS and that portal hypertension (P = 0.048) and increased serum alpha-FP (P = 0.008) were the factors significantly associated with DFS. CONCLUSION: HCC within Milan criteria should consider hepatectomy as the primary treatment if the patient's liver function and general conditions are good enough to undergo surgical operation. But in that RFA revealed similar overall survival to HR, RFA can be an alternative therapy for patients who are eligible for surgical resection.

Impact of lymph node ratio as a valuable prognostic factor in gallbladder carcinoma, focusing on stage IIIB gallbladder carcinoma / 대한외과학회지

PURPOSE: It is increasingly being recognized that the lymph node ratio (LNR) is an important prognostic factor for gallbladder carcinoma patients. The present study evaluated predictors of tumor recurrence and survival in a large, mono-institutional cohort of patients who underwent surgical resection for gallbladder carcinoma, focusing specifically on the prognostic value of lymph node (LN) status and of LNR in stage IIIB patients. METHODS: Between 2004 and 2011, 123 patients who underwent R0 radical resection for gallbladder carcinoma at the Chonnam National University Hwasun Hospital were reviewed retrospectively. Patients were staged according to the American Joint Committee on Cancer 7th edition, and prognostic factors affecting disease free survival, such as age, sex, comorbidity, body mass index, presence of preoperative symptoms, perioperative blood transfusion, postoperative complications, LN dissection, tumor size, differentiation, lymph-vascular invasion, perineural invasion, T stage, presence of LN involvement, N stage, numbers of positive LNs, LNR and implementation of adjuvant chemotherapy, were statistically analyzed. RESULTS: LN status was an important prognostic factor in patients undergoing curative resection for gallbladder carcinoma. The total number of LNs examined was implicated with prognosis, especially in N0 patients. LNR was a powerful predictor of disease free survival even after controlling for competing risk factors, in curative resected gallbladder cancer patients, and especially in stage IIIB patients. CONCLUSION: LNR is confirmed as an independent prognostic factor in curative resected gallbladder cancer patients, especially in stage IIIB gallbladder carcinoma.