How Does Medical Policy on the Use of Prophylactic Antibiotics Affect Medical Costs, Length of Hospital Stay, and Antibiotic Use in Orthopedics?

Purpose@#The purpose of this study was to compare patients who had undergone spine surgery (SS) and hip arthroplasty surgery (HAS) and to analyze how medical policies drawn from “The Evaluation of the Appropriate Use of Prophylactic Antibiotics” have affected length of hospital stay (LOS), direct medical costs (DMC), and the duration of antibiotics use in Korea. @*Materials and Methods@#This retrospective nationwide study identified subjects from the Korean National Health Insurance Review and Assessment Service database from January, 2011 to December, 2018. Evaluation of HAS (control group) was implemented in 2007, and that for SS (case group) was conducted for the first time in 2014 (intervention time). In our comparative interrupted time series analysis, we compared DMC, LOS, and use of antibiotics between both groups. @*Results@#177468 patients who underwent SS and 89372 patients who underwent HAS were included in the study. In 2016, DMC increased for HAS, compared to SS, by 1.03 times (p=0.041). However, cost changes during other observational periods for SS were not higher than those for HAS (p>0.05). SS incurred a reduced LOS of 3% in the first 2 years (p<0.05). Thereafter, LOS changes in SS were not smaller than those in HAS. A decrease in the usage of total antibiotics and broad spectrum antibiotics was observed for 5 years. @*Conclusion@#This medical policy was effective in terms of reducing usage and duration of antibiotics use, especially in the first 2 years after the implementation of the policy.

Current status of imaging studies and application of clinical decision rules for pediatric blunt cervical spine injury

Purpose@#We investigated the current status of imaging studies for pediatric blunt cervical spine injury, and applied 3 clinical decision rules to children with blunt trauma of the head or neck in a pediatric emergency center in Korea. The rules included National Emergency X-Radiography Utilization Study (NEXUS) criteria, Canadian Cervical Spine Rule, and Pediatric Emergency Care Applied Research Network risk factors. @*Methods@#This was a retrospective study conducted on 399 children aged 15 years or younger who visited the center after the blunt trauma, and underwent cervical spine radiographs from January 2020 through December 2021. We examined the clinical characteristics per age groups (0-1, 2-5, 6-12, and 13-15 years). Using the 3 rules, we selected children with a potential need for imaging studies (PNI). For this purpose, we analyzed the absence of low-risk variables and the presence of high-risk variables. Predictive performances of the rules were measured for the imaging-confirmed cervical spine injury. @*Results@#The study population (n = 399) had a median age of 5.0 years (interquartile range, 2.0-9.0) and a 64.2% boys’ proportion. Fall (36.6%) was the most common injury mechanism. Two children had the cervical spine injuries. As per NEXUS criteria, Canadian Cervical Spine Rule, and Pediatric Emergency Care Applied Research Network risk factors, 72 (18.0%), 289 (72.4%), and 74 children (18.5%) were classified as those with PNI, respectively. Resultantly, 291 children (72.9%) were classified as having PNI whereas the other 108 (27.1%) were deemed to undergo unnecessary imaging. The 3 rules had nearly 100% sensitivity and negative predictive value, except a 50% sensitivity of NEXUS criteria. @*Conclusion@#Imaging studies can be minimized for children with blunt trauma of the head or neck who are deemed without PNI per the 3 current clinical decision rules. More elaborate criteria are needed to make a timely diagnosis.

Clinical Characteristics and Antibiotic Susceptibility of Staphylococcus lugdunensis Isolated from Skin Diseases: A Retrospective Single-Center Study / 대한피부과학회지

Background@#Staphylococcus lugdunensis is an emerging pathogen in skin and soft tissue infections. However, until recently, the role of S. lugdunensis as a skin pathogen remained underrated. @*Objective@#The purpose of this study was to investigate the clinical characteristics and antibiotic susceptibility of S.lugdunensis isolated from skin diseases. @*Methods@#This is a retrospective chart review of 48 cases in which S. lugdunensis was isolated from bacterial skin cultures between 2016 and 2021. @*Results@#Among the 48 patients, the mean age was 41.0 years, 54.2% were male, and 12.5% of the patients had immunosuppressive diseases. Nearly 87.4% of infections occurred below the waist and the dominant sources of isolation were epidermal cyst (31.3%) and hidradenitis suppurativa (29.2%). The rate of resistance of S. lugdunensis against β-lactam antibiotics were as follows: penicillin, 83.3%; oxacillin, 37.5%; and methicillin, 29.2%. @*Conclusion@# S. lugdunensis is emerging as one of the primary pathogens of skin infections. When S. lugdunensis is isolated, dermatologists should consider that it is not just a component of the skin flora but can also be a pathogen. If S. lugdunensis is identified as the cause of infection, it should be managed with appropriate antibiotic therapy.

Incidence and Clinical Course of Acute Endophthalmitis after Idiopathic Epiretinal Membrane Surgery with Microincision Vitrectomy

Purpose@#To investigate the incidence and clinical course of acute endophthalmitis after idiopathic epiretinal membrane (iERM) surgery employing microincision vitrectomy (MIVS). @*Methods@#We retrospectively reviewed the medical records of eyes with acute endophthalmitis developing after iERM surgery via 23- or 25-gauge MIVS from 2011 to 2021. The incidence, culture-positive rate (and responsible bacteria), final visual acuity (VA), and factors affecting poor visual outcomes were assessed. @*Results@#Acute endophthalmitis developed in 20 of the 12,921 eyes (0.15%) after MIVS. Of these, 14 of 3,180 eyes treated via iERM (0.44%, one per 227 procedures) developed endophthalmitis; the incidence ratio (iERM versus non-iERM) was 7.1 (p < 0.001, 95% confidence interval [CI] = 2.6-22.7). At least one sclerotomy remained unsutured in all eyes after iERM surgery. Thirteen eyes (92.9%) were given intravitreal antibiotic injections after emergency vitrectomy, and one eye was treated with intravitreal antibiotic injection alone. Staphylococcus epidermidis was cultured from four eyes (28.6%); three strains were methicillin-resistant. All final VAs were not better than the initial VAs; the average VA decreased from 20/42 to 20/259 (p < 0.001). Six eyes (42.9%) attained legal blindness status (final VA < 20/200); Macular invasion was a unique risk factor for such blindness (p = 0.020, odds ratio = 35.0, 95% CI = 1.7-703.0). @*Conclusions@#Acute endophthalmitis developing after iERM surgery with MIVS was more common than such endophthalmitis after other retinal surgery. Approximately 40% of the former patients became legally blind, and the risk was higher in eyes with macular involvement of endophthalmitis.

Association of Pre- and Perinatal Risk Factors With Tourette Syndrome or Chronic Tic Disorders in a Korean School-Age Population

Objectives@#Tic disorders are highly heritable; however, growing evidence suggests that environmental factors play a significant role in their pathogenesis. Studies on these factors have been inconsistent, with conflicting results. Therefore, this study aimed to examine the associations of pre- and perinatal exposure to Tourette syndrome (TS) or chronic tic disorders (CTD) in Korean school-aged children. @*Methods@#This case-control study used data from a large prospective cohort study. The primary outcome was TS/CTD diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria and Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean Version. Demographic, pre-, and perinatal information was obtained from the maternal questionnaires. Data between the TS/CTD and control groups were compared using the chi-squared or Student’s t-test, as appropriate. Two-step logistic regression analyses were used to test the association between TS/CTD and pre- and perinatal risk factors. @*Results@#We included of 223 children (78 with TS/CTD and 145 controls). Significant differences in the demographic data between the two groups were observed. The male sex ratio, mean parental age, parental final education level, and family history of tics were included as confounders. In the final adjusted multivariable model, TS/CTD was significantly associated with antiemetic exposure during pregnancy (odds ratio [OR]=16.61, 95% confidence interval [CI] 1.49–185.22, p=0.02) and medically assisted reproduction (OR=7.89, 95% CI 2.28–27.28, p=0.01). @*Conclusion@#Antiemetic exposure and medically assisted reproduction are significantly associated with the risk of TS/CTD. These results should be replicated in future prospective and gene-by-environment studies.

Total Knee Replacement After Arthroscopic Meniscectomy in Knee Osteoarthritis: A Nationwide Population-Based Cohort Study

Background@#Recent studies raise concerns that arthroscopic meniscectomy (AM) for degenerative tear may be detrimental to the maintenance of the joint structure. This study was performed to examine the rate of total knee replacement (TKR) among patients with knee osteoarthritis (OA) who underwent AM for meniscal tears and compare this rate with those who did not. @*Methods@#A retrospective cohort study was conducted using the National Health Insurance Database of South Korea. Among knee OA patients aged 50–79, those who were treated with AM due to meniscal damage from 2007 to 2009 were selected as the AM group while those not treated with AM despite the presence of meniscal damage were selected as control group. Both were matched based on a propensity score and followed-up until the earliest occurrence of:TKR, death, or 10 years. Cox proportional hazards models were used to compare the outcome. @*Results@#A total of 36,974 patients were included in AM groups and non-AM group after 1:1 matching. TKR occurred in 9.62% and 7.64% in AM and non-AM groups with the average duration after meniscectomy of 5.88 ± 2.77 and 5.50 ± 2.94 years, respectively. After adjustment for baseline confounders, the TKR rate in the AM group was calculated to be 25% higher than that in the non-AM group (subdistribution hazard ratio, 1.25; 95% confidence interval, 1.16–1.34). The mortality rate was 5.20%, which did not significantly differ between groups. @*Conclusion@#OA patients who underwent AM for the meniscal injury had higher incidence of TKR up to 10 years of follow-up than the non-operated group. The greater TKR utilization observed in patients undergoing AM merits caution when treating OA patients with meniscal injury.

Suicidal Ideation, Depression, and Insomnia in Parent Survivors of Suicide: Based on Korean Psychological Autopsy of Adolescent Suicides

Background@#This study aims to evaluate suicidal ideation, depression, and insomnia among parent survivors of adolescents who died by suicide and their relevant risk factors using psychological autopsy results from South Korea. @*Methods@#The participants were 42 parent survivors (10 fathers and 32 mothers) of 35 adolescents who died by suicide. We used the Patient Health Questionnaire-9 and the Korean version of the Insomnia Severity Index to evaluate the mental health of the bereaved parents. We used the Korean Psychological Autopsy Checklist for Adolescents, the Korean Beck Depression Inventory, the Korean Version of the Barratt Impulsiveness Scale-II, and the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime-Korean versions to evaluate the mental health of deceased adolescents before their deaths. @*Results@#The results showed that many parent survivors of suicide had developed clinically significant suicidal ideation, depression, and insomnia (75.6%, 73.2%, and 42.9%, respectively). Furthermore, the higher the incidence of traumatic events experienced by the deceased adolescents, the higher the severity of depression and insomnia experienced by surviving parents. @*Conclusion@#We should pay attention that parent survivors of suicide can suffer mental disorders after their offspring's death. In future studies, long-term follow-up studies with larger samples need to generalize our findings and clarify the causal relationship.

Intravenous Versus Perineural Dexamethasone for Reducing Rebound Pain After Interscalene Brachial Plexus Block: A Randomized Controlled Trial

Background@#Interscalene brachial plexus block (ISB) is a common regional technique to manage acute postoperative pain for arthroscopic rotator cuff tear repair. However, rebound pain may compromise its overall benefit. Our aim was to investigate the primary hypothesis that perineural and intravenous dexamethasone have different effects on rebound pain after resolution of ISB for arthroscopic rotator cuff tear repair. @*Methods@#Patients aged ≥ 20 years scheduled for elective arthroscopic rotator cuff tear repair under general anesthesia with preoperative ISB were included. The participants were randomized to receive dexamethasone either perineurally (perineural group) or intravenously (intravenous group). In the perineural group, patients received ISB with 12 mL of 0.5% ropivacaine containing 5 mg of dexamethasone; simultaneously, 1 mL of 0.9% normal saline was administered intravenously. In the intravenous group, patients received ISB with 12 mL of 0.5% ropivacaine; simultaneously, 1 mL of dexamethasone 5 mg was administered intravenously. The primary outcome was the difference in the pain score (0–10 on numeric rating scale) between before and after ISB resolution. The secondary outcomes were the incidence of rebound pain; onset, duration, and intensity of rebound pain; time to the first analgesic request; and pain-related sleep disturbance. @*Results@#A total of 71 patients were randomized to either perineural group (n = 36) or intravenous group (n = 35). After block resolution, pain scores increased significantly more in the perineural group (mean ± standard deviation, 4.9 ± 2.1) compared to the intravenous group (4.0 ± 1.7, P = 0.043). The duration of ISB was more prolonged in the perineural group (median [interquartile range], 19.9 [17.2–23.1] hours) than the intravenous group (15.1 [13.7–15.9] hours, P < 0.001). The incidence of rebound pain and pain-related sleep disturbance during the first postoperative week was significantly higher in the perineural group than in the intravenous group (rebound pain: 44.4% vs. 20.0%, P = 0.028; sleep disturbance: 55.6% vs. 25.7%, P = 0.011). The duration and intensity of rebound pain were similar between the two groups. @*Conclusion@#Although perineural dexamethasone provided longer postoperative analgesia, intravenous dexamethasone was more beneficial in reducing pain increase after ISB resolution, incidence of rebound pain, and pain-related sleep disturbance.

Contrast-Enhanced Ultrasonography for the Evaluation of Crohn’s Disease in Pediatric Patients

Background@#Contrast-enhanced ultrasonography (CEUS) of the bowel wall has been suggested as an alternative imaging modality for the follow-up of children with Crohn’s disease. To demonstrate the feasibility and clinical usefulness of CEUS in the estimation of Crohn’s disease activity in children with endoscopy as the reference standard.Method: In this prospective study, 30 pediatric patients with Crohn’s disease (24 males and 6 females; median age 14 years) underwent CEUS from December 2020 to August 2021.The simple endoscopic score for Crohn’s disease, pediatric Crohn’s disease activity index, serologic inflammatory markers, fecal calprotectin and CEUS perfusion parameters were assessed and compared between the inactive and active group based on endoscopic findings. @*Results@#CEUS was performed successfully in all 30 patients. Two patients showed mild adverse side effects such as temporary dysosmia. The active Crohn’s disease group showed higher erythrocyte sedimentation rate (mm/hr) (13.0 vs. 2.0, P = 0.003), C-reactive protein (mg/dL) (4.7 vs. 0.55, P = 0.018) and fecal calprotectin (mcg/g) (1,503 vs. 237.5, P = 0.005). Among the quantitative parameters for CEUS, the mean gradient to the peak value was higher in the active group (1.18 vs. 0.93, P = 0.034). The sensitivity and specificity of the mean gradient to the peak value for predicting active Crohn’s disease was 55.6% and 83.3%, respectively, with a cut-off of 1.09 (P = 0.015). @*Conclusion@#CEUS can be a safe and specific diagnostic modality for Crohn’s disease activity in children. Among quantitative CEUS parameters, the mean gradient to the peak value could be used to differentiate active and inactive Crohn’s disease.

Two Cases of Multiple Ossicular Chain Disruption After Penetrating Injury and Tympanic Membrane Healing

Ossicular chain disruption is a typical consequence of temporal bone trauma. However, it can also occur as a result of direct trauma to the ossicular chain due to penetrating injuries. Hearing loss, dizziness, and facial nerve damage could also occur after penetrating middle ear injuries. Multiple ossicular chain disruption is a rare traumatic ossicular complication caused by direct penetrating lesions in the external auditory canal. We present two cases of multiple ossicular disruptions (dislocation of the incudostapedial and malleoincudal joints) after ear-pick injuries, both of which resulted in conductive hearing loss. The condition improved after delayed surgical intervention (ossiculoplasty).

Applications of Bioinspired Platforms for Enhancing Immunomodulatory Function of Mesenchymal Stromal Cells

Mesenchymal stromal cells (MSCs) have attracted scientific and medical interest due to their self-renewing properties, pluripotency, and paracrine function. However, one of the main limitations to the clinical application of MSCs is their loss of efficacy after transplantation in vivo. Various bioengineering technologies to provide stem cell niche-like conditions have the potential to overcome this limitation. Here, focusing on the stem cell niche microenvironment, studies to maximize the immunomodulatory potential of MSCs by controlling biomechanical stimuli, including shear stress, hydrostatic pressure, stretch, and biophysical cues, such as extracellular matrix mimetic substrates, are discussed. The application of biomechanical forces or biophysical cues to the stem cell microenvironment will be beneficial for enhancing the immunomodulatory function of MSCs during cultivation and overcoming the current limitations of MSC therapy.

Additional Clinical Benefit of Agomelatine Treatment for Major Depressive Disorder in Naturalistic Treatment Setting

Objective@#This study tried to observe additional benefit of agomelatine (AGO) treatment for major depressive disorder (MDD) in routine practice. @*Methods@#Retrospective chart review (n = 63) was conducted for additional benefit of combination with or switching to AGO in MDD patients without full remission. The primary endpoint was the mean change of Clinical Global Impression-Clinical Benefit (CGI-CB) total scores from baseline to the endpoint. Additional secondary endpoints were also collected. @*Results@#The changes of CGI-CB (Z = −3.073, p = 0.002) and Montgomery-Åsberg Depression Rating Scale (Z = −3.483, p ＜ 0.001) total scores were significantly decreased from baseline to the endpoint, respectively. At the endpoint, the remission rate was 22.6% (n = 18) and 28.6% of patient had improvement in CGI-CB total scores at the endpoint.No significant adverse events were observed. @*Conclusion@#This study has shown additional benefit of AGO treatment as combination or switching agent for MDD patients without full remission in routine practice. However, adequately-powered and well-controlled studies are necessary for generalization of the present findings.

Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity

Background/Aims@#To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis. @*Methods@#This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography. @*Results@#Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67, P<0.001; women: OR=1.59, 95% CI 1.40–1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02–1.50, P=0,028; women: OR=1.23, 95% CI 1.04–1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43–4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44–4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53–6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51–6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors. @*Conclusions@#In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.

Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIPin-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype. @*Materials and Methods@#Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort. @*Results@#Among 78 of a total of 395 patients (19.7%), 50 had bZIPin-f CEBPA, and 28 had non-bZIPin-f CEBPA. In the multivariate analysis, patients with NPM1mut, those with bZIPin-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITDmut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIPin-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITDpos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPAdm), bZIPin-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIPin-f CEBPA. Of 50 patients with bZIPin-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIPin-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838). @*Conclusion@#Only bZIPin-f CEBPA was associated with favorable outcomes in patients with CEBPAdm. However, some mutations accompanying bZIPin-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIPin-f CEBPA.

Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). @*Materials and Methods@#Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. @*Results@#Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. @*Conclusion@#CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

Recent advances in diagnosis and therapy in systemic mastocytosis

Mastocytosis is a heterogeneous neoplasm characterized by accumulation of neoplastic mast cells in various organs. There are three main types: cutaneous mastocytosis (CM), systemic mastocytosis (SM), and mast cell sarcoma. CM mainly affects children and is confined to the skin, whereas SM affects adults and is characterized by extracutaneous involvement, with or without cutaneous involvement. Most cases of SM have an indolent clinical course; however, some types of SM have aggressive behavior and a poor prognosis. Recent advances in the understanding of the molecular changes in SM have changed the diagnosis and treatment of aggressive and advanced SM subtypes. The International Consensus Classification and World Health Organization refined the diagnostic criteria and classification of SM as a result of accumulation of clinical experience and advances in molecular diagnostics. Somatic mutations in the KIT gene, most frequently KIT D816V, are detected in 90% of patients with SM. Expression of CD30 and any KIT mutation were introduced as minor diagnostic criteria after the introduction of highly sensitive screening methods. SM has a wide spectrum of clinical features, and only a few drugs are effective at treating advanced SM. Currently, the mainstay of SM treatment is limited to the management of chronic symptoms related to release of mast cell mediators. Small-molecule kinase inhibitors targeting the KIT-downstream and KIT-independent pathways were recently approved for treating advanced SM. I describe recent advances in diagnosis of SM, and review the currently available and emerging therapeutic options for SM management.

Licochalcone D Inhibits Skin Epidermal Cells Transformation through the Regulation of AKT Signaling Pathways

Cell transformation induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the cancer preventive efficacy of licochalcone D (LicoD), a chalcone derivative in licorice extract, in EGF and TPA-induced transformed skin keratinocyte cells. LicoD effectively suppressed EGF-induced cell proliferation and anchorage-independent colony growth. EGF and TPA promoted the S phase of cell cycle, while LicoD treatment caused G1 phase arrest and down-regulated cyclin D1 and up-regulated p21 expression associated with the G1 phase. LicoD also induced apoptosis and increased apoptosis-related proteins such as cleaved-caspase-3, cleaved-caspase-7, and Bax (Bcl-2-associated X protein). We further investigated the effect of LicoD on the AKT signaling pathway involved in various cellular processes and found decreased p-AKT, p-GSK3β, and p-NFκB expression. Treatment with MK-2206, an AKT pharmacological inhibitor, suppressed EGF-induced cell proliferation and transformed colony growth. In conclusion, this study demonstrated the potential of LicoD as a preventive agent for skin carcinogenesis.

A Bivalent Inactivated Vaccine Prevents Enterovirus 71 and Coxsackievirus A16 Infections in the Mongolian Gerbil

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

A case of vocal cord dysfunction diagnosed in a 10-year-old girl with recurrent wheezing and dyspnea

Vocal cord dysfunction is one of the causes of dyspnea and is characterized by paradoxical closure of the vocal cords. The paradoxical movement of the vocal cords produces the limitation of airflow, resulting dyspnea, chest tightening, hoarseness, stridor, or wheezing. These findings are similar to those of other upper airway obstruction diseases or asthma; therefore, a high index of suspicion and clear differential diagnosis are required. Here, we discuss a case of vocal cord dysfunction aged 10 years that presented recurrent wheezing and dyspnea. The abnormal movement of the vocal cords was observed by fiberoptic laryngotracheobronchoscopy, which was correlated with stridor during respiration. Repeated episodic symptoms were controlled by the multidisciplinary team approach; however, surgical treatment was needed to stabilize the symptom.

Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography

Background@#The association of myosteatosis measured using visual muscular quality map in computed tomography (CT) with nonalcoholic fatty liver disease (NAFLD), its severity, and fibrosis was analyzed in a large population. @*Methods@#Subjects (n=13,452) with abdominal CT between 2012 and 2013 were measured total abdominal muscle area (TAMA) at L3 level. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, NAMA/TAMA, and LAMA/BMI. NAFLD and its severity were assessed by ultrasonography, and liver fibrosis was measured by calculating the NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB-4) scores. @*Results@#According to multiple logistic regression analyses, as quartiles of SMA/BMI, NAMA/BMI, and NAMA/TAMA increased, the odds ratios (ORs) for NAFLD decreased in each sex (P for trend <0.001 for all). The ORs of moderate/severe NAFLD were significantly higher in the Q1 group than in the Q4 group for SMA/BMI, NAMA/BMI, and NAMA/TAMA in men. The ORs of intermediate/high liver fibrosis scores assessed by NFS and FIB-4 scores increased linearly with decreasing quartiles for SMA/BMI, NAMA/BMI, and NAMA/TAMA in each sex (P for trend <0.001 for all). Conversely, the risk for NAFLD and fibrosis were positively associated with LAMA/BMI quartiles in each sex (P for trend <0.001 for all). @*Conclusion@#A higher proportion of good quality muscle was associated with lower risks of NAFLD and fibrosis.