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Objective@#Side effects from the coronavirus disease-2019 (COVID-19) vaccine, such as pain, headache, nausea, and fatigue, have caused vaccine hesitancy. Research on the effects of psychological factors on COVID-19 vaccine side effects is insufficient. This study aims to investigate the effect of psychological factors on COVID-19 vaccination side effects. @*Methods@#We recruited a total of 226 individuals registered for the COVID-19 vaccine in Seoul, South Korea, for this study. Participants completed a pre-vaccination questionnaire, including the 5C antecedents of vaccination, and a survey of psychological factors (Patient Health Questionnaire–9 [PHQ-9], Generalized Anxiety Disorder–7, Somatic symptom amplification scale [SSAS], and Illness Attitude Scale [IAS]). After vaccination, participants completed an online questionnaire regarding vaccine side effects at 20 minutes, three days, and seven days after vaccination. We added a discrete set of hierarchical variables with vaccine side effects as the dependent variable to the hierarchical regression analysis: demographics for Model 1, 5C antecedents of vaccination for Model 2, and psychological factors for Model 3. @*Results@#Our results indicated that the risk factors for side effects 20 minutes after vaccination were young age, high PHQ, and SSAS scores. Risk factors for side effects three days after vaccination were young age, high constraints, and calculation, and the risk factor for side effects at seven days was a high IAS score. @*Conclusion@#Our study confirmed that there is a significant relationship between psychological factors and COVID-19 vaccine side effects in chronological order. Psychosocial factors should be examined when assessing side-effect reactions to the COVID-19 vaccine.
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Sleep deprivation or insomnia is one of the most common but neglected health conditions, with serious long-term consequences. In addition, insomnia is linked to poor work performance, impaired memory, and lack of concentration. Improving sleep quality is a crucial aspect of health care. Hypnotic agents, such as benzodiazepines, antidepressants, and antihistamines, are often used to enhance sleep quality; however, these medications often result in tolerance and dependence, resulting in withdrawal syndrome upon discontinuation. In recent years, studies have focused on natural and herbal therapies as alternative sleep aids to overcome the adverse effects of available sleep medications. Plant extracts contain phytochemicals that exert anxiolytic and sedative properties. This includes Passiflora incarnata (FSD-PI) and Lactuca sativa L. (FSD-LS) which can induce sleep. Herein, we assessed the effects of natural products, FSD-PI and FSD-LS, as well as their synergistic effects on pentobarbital sleep-induced ICR mice. We observed that natural extracts did not cause any behavioral changes capable of negative effects in mice. Furthermore, sleep duration was prolonged in pentobarbital-treated mice administered with FSD-LS (100 mg/kg). Our data suggest that FSD-LS may be a safe and effective sleep promoter.
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Background@#Disruptions of the intestinal epithelial barrier (IEB) are frequently observed in various digestive diseases, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). This study assessed the improvement in the IEB during the laxative activity of phlorotannin (Pt) harvested from Ecklonia cava in constipation by examining the changes in the expression of the regulatory proteins for the tight junction (TJ) and adherens junction (AJ), and inflammatory cytokines in Sprague Dawley (SD) rats with loperamide (Lm)-induced constipation after a Pt treatment. @*Results@#The Pt treatment induced laxative activity, including the improvement of feces-related parameters, gastrointestinal transit rate, and histological structure of the mid colon in Lm-treated SD rats. In addition, significant recovery effects were detected in the histology of IEB, including the mucus layer, epithelial cells, and lamina propria in the midcolon of Lm + Pt treated SD rats. The expression levels of E-cadherin and p120-catenin for AJ and the ZO-1, occludin, and Claudin-1 genes for TJ in epithelial cells were improved remarkably after the Pt treatment, but the rate of increase was different. Furthermore, the Pt treatment increased the expression level of several inflammatory cytokines, such asTNF-α, IL-6, IL-1β, IL-13, and IL-4 in Lm + Pt treated SD rats. @*Conclusions@#These results provide the first evidence that the laxative activity of Pt in SD rats with Lm-induced constipation phenotypes involve improvements in the IEB.
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Background@#Recombination activating gene2 (Rag2) knockout (KO) mice are used widely in various research fields, including vaccine development, transplantation studies, and hematopoiesis research, but few studies have compared their phenotypes. This study examined whether there were differences in the immunophenotypes between Rag2 KO mice derived from different sources. In particular, the changes in the organ weight, histological structure, and subpopulation of T and B cells were compared in the spleen and thymus of C57BL/6-Rag2em1hwl/Korl (Rag2/Korl KO) and B6.Cg-Rag2tm1.1Cgn/J (Rag2/J KO) mice. @*Results@#The weight of the spleen and thymus similarly decreased in the Rag2/Korl and Rag2/J KO mice compared to their wild type (WT) mice, even though the other organs were kept at the same weight. A slight difference between the Rag2/Korl and Rag2/J KO group were detected in the number of white blood cells (WBC), lymphocytes (LYM), red cell distribution width (RDW), and platelets (PLT). In addition, the white pulp of the spleen and the cortex region of the thymus decreased in both Rag2 KO mice compared to WT mice. On the other hand, significant differences in the number of CD8+ T and B cell subpopulations between WT and Rag2 KO mice were observed between Rag2/Korl and Rag2/J KO group, while the CD4+ T subpopulation was maintained similarly in both groups. @*Conclusions@#These results suggest that Rag2/Korl and Rag2/J KO mice exhibit similar immunophenotypes in the spleen and thymus except for the differences in the number of CD8+ T and B cell subpopulations.
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Objectives@#The purpose is to investigate personality characteristics according to reports of suicide risk among students in the 2nd step evaluation of the Student Emotional Behavior Test conducted in one district of Daegu in 2022. @*Methods@#A total of 99 students’ school level, gender, and rate of suicide risk reporting were investigated, and sub-factors of Personality Assessment Inventory-Adolescent (PAI-A) were compared according to suicide risk reporting. We also analyzed the factors that have the most significant influence on suicide risk reporting among PAI-A. @*Results@#There was no gender difference in suicide risk reporting, but there was a significant difference at the school level. Among the PAI-A clinical scales, significant differences between groups were found in somatic complaints (SOM), anxiety (ANX), anxiety-related disorder (ADR), depression (DEP), paranoia (PAR), borderline features (BOR), suicide ideation (SUI), nonsupport (NON) and treatment rejection (RXR). Suicide risk reporting was higher in high school students than middle school, and students with high scores of NON on the PAI-A. @*Conclusions@#Reports of suicide risk show differences in internalization factors of personality traits. This means that adolescents are more likely to report suicide risk as they frequently experience inherent negative emotions such as depression and anxiety or as their interpersonal relationships become strained. In addition, it can be said that identifying social networks and forming support resources are important factors in preventing self-harming or suicidal ideation that occur during early adolescence.
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Background@#Targeted risk population has been highly vaccinated against pneumococcal diseases in South Korea. Despite this, the pneumococcal serotype distribution is evolving, which impedes efficient roll-out of vaccines. @*Methods@#This prospective cohort study included patients aged ≥ 19 years with communityacquired pneumonia (CAP) from five university hospitals in South Korea between September 2018 and July 2021. The outcomes of interest were the demographic and clinical characteristics of patients with CAP, pneumococcal serotype distribution, and risk factors of 30-day mortality in patients with pneumococcal CAP (pCAP). Considering the high seroprevalence, we analyzed the clinical characteristics of serotype 3 pCAP. @*Results@#A total of 5,009 patients hospitalized with CAP was included (mean age ± standard deviation, 70.3 ± 16.0 years; 3,159 [63.1%] men). Streptococcus pneumoniae was the leading causative agent of CAP (11.8% overall, 17.7% in individuals aged < 65 years with chronic medical conditions). Among the 280 serotyped Streptococcus pneumococcus, serotype 3 was the most common (10.0%), followed by serotypes 19A (8.9%), 34 (8.9%), and 35B (8.9%).Non-vaccine serotypes (serotype 35B [13.9%] and 34 [12.0%]) were the most prevalent in 108 individuals vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23).Serotype 3 was prevalent, irrespective of PPSV23 vaccination status, and more common in individuals with chronic lung disease (P = 0.008). Advanced age (adjusted odds ratio [aOR], 1.040; 95% confidence interval [CI], 1.011–1.071), long-term care facility residence (aOR, 2.161; 95% CI, 1.071–4.357), and bacteremia (aOR, 4.193; 95% CI, 1.604–10.962) were independent risk factors for 30-day mortality in patients with pCAP. PPSV23 vaccination reduced the risk of mortality (aOR, 0.507; 95% CI, 0.267–0.961). @*Conclusion@#Serotype 3 and 19A were still the most common serotypes of pCAP in South Korea despite the national immunization program of 13-valent pneumococcal conjugated vaccine in children and PPSV23 in old adults. PPSV23 vaccination might reduce the risk of mortality in patients with pCAP.
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Background@#Phthalates and bisphenol A (BPA) are endocrine-disrupting chemicals and may cause immunological disorders in children. Therefore, according to the region, we investigated urinary phthalates and BPA levels and the relationship between urinary phthalate, aeroallergen sensitization, and eosinophil count during the coronavirus disease 2019 pandemic. @*Methods@#In total, 203 schoolchildren (134 residential and 69 industrial) aged 7–10 years were enrolled between July 2021 and July 2022. The BPA, metabolites of four high-molecularweight phthalates (Σ4HMWP) and three low-molecular-weight phthalates (Σ3LMWP), were measured in the urine samples. Total eosinophil count and transepidermal water loss (TEWL) were also measured along with the skin prick test. @*Results@#The two groups had no differences in terms of BPA. The industrial group had significantly more plastic container usage, and there was a difference in the Σ3LMWP (P < 0.001) between the two groups but no difference in the Σ4HMWP (P = 0.234). The quartiles of urinary Σ4HMWP and Σ3LMWP (P < were not associated with the total eosinophil count, vitamin D level, or TEWL. After adjusting for cofactors, the quartiles of urinary Σ4HMWP and Σ3LMWP were significantly associated with total eosinophil count (P < 0.001) but not with aeroallergen sensitization or vitamin D. @*Conclusion@#Exposure to phthalates was significantly associated with eosinophil count but not with aeroallergen sensitization or vitamin D. Therefore, reducing the use of plastic containers may effectively prevent exposure to phthalates and reduce Th2 cell-mediated inflammation in children.
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Objective@#: Cubital tunnel syndrome, the most common ulnar nerve entrapment neuropathy, is usually managed by simple decompression or anterior transposition. One of the concerns in transposition is damage to the nerve branches around the elbow. In this study, the location of ulnar nerve branches to the flexor carpi ulnaris (FCU) was assessed during operations for cubital tunnel syndrome to provide information to reduce operation-related complications. @*Methods@#: A personal series (HJY) of cases operated for cubital tunnel syndrome was reviewed. Cases managed by transposition and location of branches to the FCU were selected for analysis. The function of the branches was confirmed by intraoperative nerve stimulation and the location of the branches was assessed by the distance from the center of medial epicondyle. @*Results@#: There was a total of 61 cases of cubital tunnel syndrome, among which 31 were treated by transposition. Twenty-one cases with information on the location of branches were analyzed. The average number of ulnar nerve branches around the elbow was 1.8 (0 to 3), only one case showed no branches. Most of the cases had one branch to the medial head, and one other to the lateral head of the FCU. There were two cases having branches without FCU responses (one branch in one case, three branches in another). The location of the branches to the medial head was 16.3±8.6 mm distal to the medial epicondyle (16 branches; range, 0 to 35 mm), to the lateral head was 19.5±9.5 mm distal to the medial epicondyle (19 branches; range, -5 to 30 mm). Branches without FCU responses were found from 20 mm proximal to the medial condyle to 15 mm distal to the medial epicondyle (five branches). Most of the branches to the medial head were 15 to 20 mm (50% of cases), and most to the lateral head were 15 to 25 mm (58% of cases). There were no cases of discernable weakness of the FCU after operation. @*Conclusion@#: In most cases of cubital tunnel syndrome, there are ulnar nerve branches around the elbow. Although there might be some cases with branches without FCU responses, most branches are to the FCU, and are to be saved. The operator should be watchful for branches about 15 to 25 mm distal to the medial epicondyle, where most branches come out.
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Background@#The treatment outcomes of patients with multidrug/rifampin-resistant (MDR/RR) tuberculosis (TB) are important indicators that reflect the current status of TB management and identify the key challenges encountered by TB control programs in a country. @*Methods@#We retrospectively evaluated the treatment outcomes as well as predictors of unfavorable outcomes in patients with MDR/RR-TB notified from 2011 to 2017, using an integrated TB database. @*Results@#A total of 7,226 patients with MDR/RR-TB were included. The treatment success rate had significantly increased from 63.9% in 2011 to 75.1% in 2017 (P < 0.001). Among unfavorable outcomes, the proportion of patients who failed, were lost to follow up, and were not evaluated had gradually decreased (P< 0.001). In contrast, TB-related death rate was not significantly changed (P= 0.513), while the non-TB related death rate had increased from 3.2% in 2011 to 11.1% in 2017 (P < 0.001). Older age, male sex, immigrants, low household income, previous history of TB treatment, and comorbidities were independent predictors of unfavorable outcomes. Of the 5,308 patients who were successfully treated, recurrence occurred in 241 patients (4.5%) at a median 18.4 months (interquartile range, 9.2–32.4) after completion treatment. @*Conclusion@#The treatment outcomes of patients with MDR/RR-TB has gradually improved but increasing deaths during treatment is an emerging challenge for MDR-TB control in Korea. Targeted and comprehensive care is needed for vulnerable patients such as the elderly, patients with comorbidities, and those with low household incomes.
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The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.
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Purpose@#Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC. @*Materials and Methods@#Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed. @*Results@#From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines. @*Conclusion@#We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.
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Major depressive disorder is a leading cause of disability in more than 280 million people worldwide. Monoamine-based antidepressants are currently used to treat depression, but delays in treatment effects and lack of responses are major reasons for the need to develop faster and more efficient antidepressants. Studies show that ketamine (KET), a PCP analog, produces antidepressant effects within a few hours of administration that lasts up to a week. However, the use of KET has raised concerns about side effects, as well as the risk of abuse. 4 -F-PCP analog is a novel PCP analog that is also an NMDA receptor antagonist, structurally similar to KET, and might potentially elicit similar antidepressant effects, however, there has been no study on this subject yet. Herein, we investigate whether 4-F-PCP displays antidepressant effects and explored their potential therapeutic mechanisms. 4-F-PCP at 3 and 10 mg/kg doses showed antidepressant-like effects and repeated treatments maintained its effects. Furthermore, treatment with 4-F-PCP rescued the decreased expression of proteins most likely involved in depression and synaptic plasticity. Changes in the excitatory amino acid transporters (EAAT2, EAAT3, EAAT4) were also seen following drug treatment. Lastly, we assessed the possible side effects of 4-F-PCP after long-term treatment (up to 21 days). Results show that 4-F-PCP at 3 mg/kg dose did not alter the cognitive function of mice. Overall, current findings provide significant i
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Purpose@#The strategy of latent tuberculosis infection (LTBI) treatment in household tuberculosis (TB) contacts has been expanding in South Korea. However, there is little evidence of the cost-effectiveness of LTBI treatment in patients over 35 years of age. This study aimed to evaluate the cost-effectiveness of LTBI treatment among household TB contacts in different age groups in South Korea. @*Materials and Methods@#An age-structured model of TB was developed based on the reports from the Korea Disease Control and Prevention Agency and the National Health Insurance Service. Quality-adjusted life-years (QALY) and the averted number of TBrelated deaths were estimated along with discounted costs for a measure of incremental cost-effectiveness ratios. @*Results@#The number of cumulative active TB cases would decrease by 1564 and 7450 under the scenario of LTBI treatment for those aged <35 years and <70 years, respectively, relative to the no-treatment scenario. The treatment strategies for patients aged 0 to <35 years, <55 years, <65 years, and <70 years would add 397, 1482, 3782, and 8491 QALYs at a cost of $660, $5930, $4560, and $2530, respectively, per QALY. For the averted TB-related deaths, LTBI treatment targeting those aged 0 to <35 years, <55 years, <65 years, and <70 years would avert 7, 89, 155, and 186 deaths at a cost of $35900, $99200, $111100, and $115700 per deaths, respectively, in 20 years. @*Conclusion@#The age-specific expansion policy of LTBI treatment not only for those under 35 years of age but also for those under 65 years of age among household contacts was cost-effective in terms of QALYs and averted TB deaths.
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Background@#Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting. @*Methods@#The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included. @*Results@#The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success). @*Conclusion@#A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.
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There are many reports of subacute thyroiditis (SAT) that occurred after the coronavirus disease 2019 (COVID-19), but no such case has been reported in Korea. Moreover, the simultaneous occurrence of SAT and Graves’ disease (GD) is rare. Here, we describe a patient who developed SAT and GD after the second episode of COVID-19. A 27-year-old woman with no known history of thyroid disease presented with fever, upper respiratory tract symptoms, and painful neck swelling. Thyroid function tests revealed thyrotoxicosis, and thyroid ultrasound showed heterogeneous echogenicity of enlarged thyroid glands. Her initial clinical presentation was consistent with SAT after viral infection, with typical neck tenderness and spontaneous improvement of thyrotoxicosis without antithyroid drug use. However, this case had some atypical features, such as an elevated thyroid-stimulating immunoglobulin level, relapse of thyrotoxicosis in short-term follow-up, and increased Tc-99m pertechnetate uptake, suggesting the coexistence of GD. About two months after methimazole (15 mg/day) was prescribed, she was lost to follow up again. We report the first case of unusual co-occurrence of SAT and GD following COVID-19.
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Objective@#: The use of indocyanine green videoangiography (ICG-VA) to assess blood flow in the brain during cerebrovascular surgery has been increasing. Clinical studies on ICG-VA have predominantly focused on qualitative analysis. However, quantitative analysis numerical modelling for time profiling enables a more accurate evaluation of blood flow kinetics. In this study, we established a multiple exponential modified Gaussian (multi-EMG) model for quantitative ICG-VA to understand accurately the status of cerebral hemodynamics. @*Methods@#: We obtained clinical data of cerebral blood flow acquired the quantitative analysis ICG-VA during cerebrovascular surgery. Varied asymmetric peak functions were compared to find the most matching function form with clinical data by using a nonlinear regression algorithm. To verify the result of the nonlinear regression, the mode function was applied to various types of data. @*Results@#: The proposed multi-EMG model is well fitted to the clinical data. Because the primary parameters—growth and decay rates, and peak centres and heights—of the model are characteristics of model function, they provide accurate reference values for assessing cerebral hemodynamics in various conditions. In addition, the primary parameters can be estimated on the curves with partially missed data. The accuracy of the model estimation was verified by a repeated curve fitting method using manipulation of missing data. @*Conclusion@#: The multi-EMG model can possibly serve as a universal model for cerebral hemodynamics in a comparison with other asymmetric peak functions. According to the results, the model can be helpful for clinical research assessment of cerebrovascular hemodynamics in a clinical setting.
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Background@#and Purpose Excess or insufficient sleep, irregular sleep-wake patterns, and an extreme early or late chronotypes adversely impact physical and mental health. Changes in sleep characteristics should therefore be tracked, and factors that contribute to poor sleep should be identified. We investigated the changes in sleep patterns among South Korean adults during 2009–2018. @*Methods@#Using data of a representative sample of South Korean adults from the 2009 (n= 2,658, 48.5% males; age=44.5±15.0 years old [mean±standard deviation], age range=19–86 years) and 2018 (n=2,389, 49.1% males; age=47.9±16.3 years, age range=19–92 years) Korean Headache-Sleep Study, we explored changes in sleep timing, sleep duration, chronotype, and social jetlag (SJL). Logistic regression analysis was used to examine the association between average sleep duration and depression. @*Results@#From 2009 to 2018, bedtimes were advanced by 10 and 25 min on workdays and free days, respectively. Meanwhile, wake-up times were advanced by 13 min and delayed by 12 min on workdays and free days, respectively. The average sleep duration significantly decreased from 7.45 h to 7.13 h. The prevalence of short sleep duration (<7 h) increased, whereas that of long sleep duration (≥8 h) decreased. A circadian preference toward eveningness and SJL increased. The prevalence of depression increased from 4.6% to 8.4%, and there were significant reverse J-shaped and U-shaped associations between average sleep duration and depression in 2009 and 2018, respectively. @*Conclusions@#Changes in sleep patterns and the association between sleep duration and depressive mood were determined from a representative sample of the South Korean adult population. Interventions to modify sleep behaviors might improve public health.
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Purpose@#Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy. @*Materials and Methods@#We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA. @*Results@#Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker. @*Conclusion@#Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.
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Background@#The exact definition of sensitive skin is not established yet. Since its high prevalence and significant influence on quality of life, it has become an important topic of research. Among various ingredients, conditioned media from umbilical cord blood-derived mesenchymal stem cells (UCB-MSC-CM) can be a promising source for the treatment of sensitive skin. @*Objective@#We evaluated the efficacy and safety of UCB-MSC-CM on patients with sensitive skin. @*Methods@#We designed a randomized, single blinded, prospective, split-face comparison study and enrolled thirty patients. All patients underwent nonablative fractional laser over the entire face before UCB-MSC-CM or normal saline was applied. Each facial area was randomly assigned to undergo treatment with either UCB-MSC-CM or normal saline. We performed three sessions at two-week intervals, and final results were assessed on six weeks after the last session. As an outcome measure, we evaluated a five-point global assessment scale, transepidermal water loss (TEWL), erythema index (EI) and Sensitive Scale-10. Twenty seven subjects were included in final analysis. @*Results@#The treated side exhibited greater improvement compared to the untreated side based on a five-point global assessment scale. TEWL, EI of the treated side were significantly lower than those of the untreated side throughout study period. Sensitive Scale-10 was significantly improved after treatment. @*Conclusion@#The application of UCB-MSC-CM resulted in improved skin barrier function and reduced inflammatory responsiveness, which could provide beneficial effect on sensitive skin.
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The mentalis muscle is a paired muscle originating from the alveolar bone of the mandible. This muscle is the main target muscle for botulinum neurotoxin (BoNT) injection therapy, which aims to treat cobblestone chin caused by mentalis hyperactivity. However, a lack of knowledge on the anatomy of the mentalis muscle and the properties of BoNT can lead to side effects, such as mouth closure insufficiency and smile asymmetry due to ptosis of the lower lip after BoNT injection procedures. Therefore, we have reviewed the anatomical properties associated with BoNT injection into the mentalis muscle.An up-to-date understanding of the localization of the BoNT injection point according to mandibular anatomy leads to better injection localization into the mentalis muscle. Optimal injection sites have been provided for the mentalis muscle and a proper injection technique has been described. We have suggested optimal injection sites based on the external anatomical landmarks of the mandible. The aim of these guidelines is to maximize the effects of BoNT therapy by minimizing the deleterious effects, which can be very useful in clinical settings.