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Purpose@#Among the characteristics of non-alcoholic fatty liver disease (NAFLD), hepatic steatosis is due to excessive fat accumulation and causes liver damage and lipotoxicity, which are associated with insulin resistance, endoplasmic reticulum (ER) stress, and apoptosis. Umbelliferone (UMB) has various powerful pharmacological properties, such as antioxidant, anti-hyperglycemic, anti-viral, and anti-inflammatory effects. However, the mechanism of action in hepatic steatosis and lipid-induced ER stress is still unclear. Thus, the efficacy of UMB in hepatic steatosis and palmitate (PA)-induced hepatocellular lipotoxicity was evaluated in the present study. @*Materials and Methods@#Male C57BL/6J mice (n=40) were divided into four groups: regular diet (RD), UMB-supplemented RD, high-fat diet (HFD), and UMB-supplemented HFD. All mice were fed orally for 12 weeks. In addition, the effects of UMB on lipotoxicity were investigated in AML12 cells treated with PA (250 μM) for 24 h; Western blot analysis was used to evaluate the changes in ER stress and apoptotic-associated proteins. @*Results@#Administration with UMB in HFD-fed mice reduced lipid accumulation and hepatic triglyceride (TG) as well as serum insulin and glucose levels. In AML12 cells, UMB treatment reduced lipid accumulation as indicated by decreases in the levels of lipogenesis markers, such as SREBP1, FAS, PPAR-γ, and ADRP. Furthermore, UMB reduced both oxidative stress and ER stress-related cellular apoptosis. @*Conclusion@#UMB supplementation ameliorated hepatic steatosis and improved insulin resistance by inhibiting lipid accumulation and regulating ER stress. These findings strongly suggest that UMB may be a potential therapeutic compound against NAFLD.
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Background/Aims@#Although anti-hepatitis C virus (HCV) assay is widely used to screen for HCV infection, it has a high false-positive (FP) rate in low-risk populations. We investigated the accuracy of anti-HCV signal-to-cutoff (S/CO) ratio to distinguish true-positive (TP) from FP HCV infection. @*Methods@#We retrospectively analyzed 77,571 patients with anti-HCV results. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of anti-HCV S/CO ratio in anti-HCV positive patients. @*Results@#Overall, 1,126 patients tested anti-HCV positive; 34.7% of patients were FP based on HCV RNA and/or recombinant immunoblot assay (RIBA) results. The age and sex-adjusted anti-HCV prevalence was 1.22%. We identified significant differences in serum aspartate transaminase and alanine transaminase levels, anti-HCV S/CO ratio, and RIBA results between groups (viremia vs. non-viremia, TP vs. FP). Using ROC curves, the optimal cutoff values of anti-HCV S/CO ratio for HCV viremia and TP were 8 and 5, respectively. The area under the ROC curve, sensitivity, specificity, positive and negative predictive values were 0.970 (95% CI, 0.959–0.982, p < 0.001), 99.7%, 87.5%, 87.4%, and 99.7%, respectively, for predicting HCV viremia at an anti-HCV S/CO ratio of 8 and 0.987 (95% CI, 0.980–0.994, p < 0.001), 95.3%, 94.7%, 97.1%, and 91.4%, respectively, for TP HCV infection at an anti-HCV S/CO ratio of 5. No patients with HCV viremia had an anti-HCV S/CO ratio below 5. @*Conclusions@#The anti-HCV S/CO ratio is highly accurate for discriminating TP from FP HCV infection and should be considered when diagnosing HCV infections.
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Computer-aided design–computer-aided manufacturing technology has been widely used in the manufacture of fixed prostheses including implants, but in the case of removable dentures, the analog method is still being used due to the errors such as a lack of fusion and over-fusion in selective laser meting process. With the recent development of CAD software, virtual surveying and framework design are made possible, and the designed file can be manufactured by milling or 3D printing. It replace the analog method of waxing and denture curing process and also can reduce the production time and cost. Therefore, this case is reported because good clinical results were obtained by digitally surveying on CAD software to produce a surveyed metal restoration and framework on maxillary and mandibular removable dentures.
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Background/Aims@#Patients with inflammatory bowel disease (IBD) are diagnosed with ankylosing spondylitis (AS) often. However, the disease course of patients with both IBD and AS is not well understood. This study aims to evaluate the effect of concomitant AS on IBD outcomes. @*Methods@#Among the 4,722 patients with IBD who were treated in 3 academic hospitals from 2004 to 2021, 55 were also diagnosed with AS (IBD-AS group). Based on patients’ electronic medical records, the outcomes of IBD in IBD-AS group and IBD group without AS (IBD-only group) were appraised. @*Results@#The proportion of patients treated with biologics or small molecule therapies was significantly higher in IBD-AS group than the proportion in IBD-only group (27.3% vs. 12.7%, P= 0.036). Patients with both ulcerative colitis and AS had a significantly higher risk of biologics or small molecule therapies than patients with only ulcerative colitis (P< 0.001). For univariable logistic regression, biologics or small molecule therapies were associated with concomitant AS (odds ratio, 4.099; 95% confidence interval, 1.863–9.021; P< 0.001) and Crohn’s disease (odds ratio, 3.552; 95% confidence interval, 1.590–7.934; P= 0.002). @*Conclusions@#Concomitant AS is associated with the high possibility of biologics or small molecule therapies for IBD. IBD patients who also had AS may need more careful examination and active treatment to alleviate the severity of IBD.
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Background@#Degenerative tendinopathy, a condition causing movement restriction due to high pain, highly impacts productivity and quality of life. The healing process is a complex phenomenon and involves a series of intra-cellular and inter-cellular processes. Proliferation and differentiation of the tenocyte is a major and essential process to heal degenerative tendinopathy. The recent development in microRNA (miRNA)-mediated reprogramming of the cellular function through specific pathways opened door for the development of new regenerative therapeutics. Based on information about gene expression and regulation of tendon injury and healing, we attempted to evaluate the combinatorial effect of selected miRNAs for better healing of degenerative tendinopathy. @*Methods@#The present study was designed to evaluate the combinatorial effect of two miRNAs (has-miR-140 and has-miR-135) in the healing process of the tendon. Publicly available information/data were retrieved from appropriate platforms such as PubMed.Only molecular data, directly associated with tendinopathies, including genes/proteins and miRNAs, were used in this study. The miRNAs involved in tendinopathy were analyzed by a Bioinformatics tools (e.g., TargetScan, miRDB, and the RNA22v2). Interactive involvement of the miRNAs with key proteins involved in tendinopathy was predicted by the Insilco approach. @*Results@#Based on information available in the public domain, tendon healing-associated miRNAs were predicted to explore their therapeutic potentials. Based on computation analysis, focusing on the potential regulatory effect on tendon healing, the miR-135 and miR-140 were selected for this study. These miRNAs were found as key players in tendon healing through Rho-associated coiled-coil containing protein kinase 1 (ROCK1), IGF-1/PI3K/Akt, PIN, and Wnt signaling pathways. It was also predicted that these miRNAs may reprogram the cells to induce proliferation and differentiation activity. Many miRNAs are likely to regulate genes important for the tendinopathy healing process, and the result of this study allows an approach for miRNA-mediated regeneration of the tenocyte for tendon healing. Based on computational analysis, the role of these miRNAs in different pathways was established, and the results provided insights into the combinatorial approach of miRNA-mediated cell reprogramming. @*Conclusions@#In this study, the association between miRNAs and the disease was evaluated to correlate the tendinopathy genes and the relevant role of different miRNAs in their regulation. Through this study, it was established that the synergistic effect of more than one miRNA on directed reprogramming of the cell could be helpful in the regeneration of damaged tissue. It is anticipated that this study will be helpful for the design of miRNA cocktails for the orchestration of cellular reprogramming events.
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Purpose@#The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC). @*Materials and Methods@#In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety. @*Results@#Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates. @*Conclusion@#Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).
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Purpose@#This retrospective study aimed to determine the number of times the ultrasound-guided attenuation parameter (UGAP) should be measured during the evaluation of hepatic steatosis. @*Methods@#Patients with suspected nonalcoholic fatty liver disease who underwent two UGAP repetition protocols (six-repetition [UGAP_6] and 12-repetition [UGAP_12]) and measurement of the controlled attenuation parameter (CAP) using transient elastography between October 2020 and June 2021 were enrolled. The mean attenuation coefficient (AC), interquartile range (IQR)/median, and coefficient of variance (CV) of the two repetition protocols were compared using the paired t test. Moreover, the diagnostic performances of UGAP_6 and UGAP_12 were compared using the area under the receiver operating characteristic (AUROC) curve, considering the CAP value as a reference standard. @*Results@#The study included 160 patients (100 men; mean age, 50.9 years). There were no significant differences between UGAP_6 and UGAP_12 (0.731±0.116 dB/cm/MHz vs. 0.734±0.113 dB/cm/MHz, P=0.156) and mean CV (7.6±0.3% vs. 8.0±0.3%, P=0.062). However, the mean IQR/median of UGAP_6 was significantly lower than that of UGAP_12 (8.9%±6.0% vs. 9.8%±5.2%, P=0.012). In diagnosing the hepatic steatosis stage, UGAP_6 and UGAP_12 yielded comparable AUROCs (≥S1, 0.908 vs. 0.897, P=0.466; ≥S2, 0.883 vs. 0.897, P=0.126; S3, 0.832 vs. 0.834, P=0.799). @*Conclusion@#UGAP had high diagnostic performance in diagnosing hepatic steatosis, regardless of the number of repetitions (six repetitions vs. 12 repetitions), with maintained reliability. Therefore, six UGAP measurements seem sufficient for evaluating hepatic steatosis using UGAP.
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Neonatal tension pneumothorax is life-threatening. A tension pneumothorax on the right side was detected on a newborn boy weighing 2,380 g, who was born at 35 weeks of gestation. Given the unavailability of an on-duty thoracic surgeon and appropriately sized chest tubes in the neonatal intensive care unit, an emergency physician performed closed thoracostomy using two 7-French latex catheters. Immediately after the re-expansion of the right lung, left tension pneumothorax was newly detected. Two more 7-French latex catheters were inserted, relieving the left lesion. We consider that the right pneumothorax occurred due to the mixture of spontaneous rupture of the subpleural blebs and barotrauma during the initial positive pressure ventilation, while the left lesion did due to the high-flow oscillatory ventilation. Despite the limited availability of devices in the present case, a favorable outcome was achieved by the use of alternative catheters, which were chosen by the emergency physician.
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Objective@#Cyclin-dependent kinase inhibitor (CDKN)2A/B homozygous deletion is a key molecular marker of isocitrate dehydrogenase (IDH)-mutant astrocytomas in the 2021 World Health Organization. We aimed to investigate whether qualitative and quantitative MRI parameters can predict CDKN2A/B homozygous deletion status in IDH-mutant astrocytomas. @*Materials and Methods@#Preoperative MRI data of 88 patients (mean age ± standard deviation, 42.0 ± 11.9 years; 40 females and 48 males) with IDH-mutant astrocytomas (76 without and 12 with CDKN2A/B homozygous deletion) from two institutions were included. A qualitative imaging assessment was performed. Mean apparent diffusion coefficient (ADC), 5th percentile of ADC, mean normalized cerebral blood volume (nCBV), and 95th percentile of nCBV were assessed via automatic tumor segmentation.Logistic regression was performed to determine the factors associated with CDKN2A/B homozygous deletion in all 88 patients and a subgroup of 47 patients with histological grades 3 and 4. The discrimination performance of the logistic regression models was evaluated using the area under the receiver operating characteristic curve (AUC). @*Results@#In multivariable analysis of all patients, infiltrative pattern (odds ratio [OR] = 4.25, p = 0.034), maximal diameter (OR = 1.07, p = 0.013), and 95th percentile of nCBV (OR = 1.34, p = 0.049) were independent predictors of CDKN2A/B homozygous deletion. The AUC, accuracy, sensitivity, and specificity of the corresponding model were 0.83 (95% confidence interval [CI], 0.72–0.91), 90.4%, 83.3%, and 75.0%, respectively. On multivariable analysis of the subgroup with histological grades 3 and 4, infiltrative pattern (OR = 10.39, p = 0.012) and 95th percentile of nCBV (OR = 1.24, p = 0.047) were independent predictors of CDKN2A/B homozygous deletion, with an AUC accuracy, sensitivity, and specificity of the corresponding model of 0.76 (95% CI, 0.60–0.88), 87.8%, 80.0%, and 58.1%, respectively. @*Conclusion@#The presence of an infiltrative pattern, larger maximal diameter, and higher 95th percentile of the nCBV may be useful MRI biomarkers for CDKN2A/B homozygous deletion in IDH-mutant astrocytomas.
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Objective@#To evaluate treatment patterns and healthcare resource utilization (HCRU) after initiating biologic disease-modifying antirheumatic drugs (bDMARDs) in Korean patients with rheumatoid arthritis (RA). @*Methods@#Patients newly diagnosed with RA in 2014 were identified and followed up on using the Korean National Health Insurance Database until 2018. The initial line of therapy (LOT) or LOT1 included patients treated with conventional DMARDs (cDMARD). Patients who started a bDMARD were assigned to LOT2 bDMARD. Those who moved from a bDMARD to a Janus kinase inhibitor were assigned to LOT3. Analyzed outcomes were treatment patterns and HCRU in LOT2 bDMARD. @*Results@#The most prescribed initial bDMARD was a tumor necrosis factor inhibitor. Seventy-five percent of patients had changes in treatment after starting a bDMARD, such as addition/removal or switch of a DMARD, and transition to LOT3. For the first and second changes in LOT2 bDMARD, adding a cDMARD to a bDMARD was more common than switching to another bDMARD (7.98% vs. 2.93% for the first change, and 17.10% vs. 6.51% for the second change). Tocilizumab was the most common bDMARD that was switched to. Forty-eight percent of patients had at least one hospitalization after initiating bDMARDs. Of these patients, 64.3% were admitted due to RA-related reasons. @*Conclusion@#This real-world study provides information on treatment characteristics of RA patients in Korea after starting a bDMARD. In contrary to guidelines, cDMARD addition was more often than bDMARD switches in daily clinical practice.
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Objective@#Depression in Parkinson’s disease (PD) affects the quality of life of patients. Postural instability and gait disturbance are associated with the severity and prognosis of PD. We investigated the association of depression with axial involvement in early-stage PD patients. @*Methods@#This study involved 95 PD patients unexposed to antiparkinsonian drugs. After a baseline assessment for depression, the subjects were divided into a depressed PD group and a nondepressed PD group. Analyses were conducted to identify an association of depression at baseline with the following outcome variables: the progression to Hoehn and Yahr scale (H-Y) stage 3, the occurrence of freezing of gait (FOG), levodopa-induced dyskinesia, and wearing-off. The follow-up period was 53.40 ± 16.79 months from baseline. @*Results@#Kaplan–Meier survival curves for H-Y stage 3 and FOG showed more prominent progression to H-Y stage 3 and occurrences of FOG in the depressed PD group than in the nondepressed PD group (log-rank p = 0.025 and 0.003, respectively). Depression in drug-naïve, early-stage PD patients showed a significant association with the progression to H-Y stage 3 (hazard ratio = 2.55; 95% confidence interval = 1.32–4.93; p = 0.005), as analyzed by Cox regression analyses. In contrast, the occurrence of levodopa-induced dyskinesia and wearing-off did not differ between the two groups (log-rank p = 0.903 and 0.351, respectively). @*Conclusion@#Depression in drug-naïve, early-stage PD patients is associated with an earlier occurrence of postural instability. This suggests shared nondopaminergic pathogenic mechanisms and potentially enables the prediction of early development of postural instability.
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Objective@#Associations between various metabolic conditions and Parkinson’s disease (PD) have been previously identified in epidemiological studies. We aimed to investigate the causal effect of lipid levels, type 2 diabetes mellitus (T2DM), and body mass index (BMI) on PD in a Korean population via Mendelian randomization (MR). @*Methods@#Two-sample MR analyses were performed with inverse-variance weighted (IVW), weighted median, and MR-Egger regression approaches. We identified genetic variants associated with lipid concentrations, T2DM, and BMI in publicly available summary statistics, which were either collected from genome-wide association studies (GWASs) or from meta-analyses of GWAS that targeted only Korean individuals or East Asian individuals, including Korean individuals. The outcome dataset was a GWAS on PD performed in a Korean population. @*Results@#From previous GWASs and meta-analyses, we selected single nucleotide polymorphisms as the instrumental variables. Variants associated with serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, as well as with T2DM and BMI, were selected (n = 11, 19, 17, 89, and 9, respectively). There were no statistically significant causal associations observed between the five exposures and PD using either the IVW, weighted median, or MR-Egger methods (p-values of the IVW method: 0.332, 0.610, 0.634, 0.275, and 0.860, respectively). @*Conclusion@#This study does not support a clinically relevant causal effect of lipid levels, T2DM, and BMI on PD risk in a Korean population.
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Peritoneal seeding of hepatocellular carcinoma (HCC) is incurable and has poor prognosis. A 68-year-old man underwent surgical resection for a 3.5 cm single nodular HCC at the tip of segment 3 and transarterial chemoembolization for a 1.5 cm-sized recurrent HCC at the tip of segment 6. 3 months later, an increasing 1 cm pelvic nodule on the rectovesical pouch warranted radiotherapy. Although it stabilized, a new 2.7 cm-sized peritoneal nodule in the right upper quadrant (RUQ) omentum appeared 3.5 years after radiotherapy. Hence, omental mass and small bowel mesentery mass excision were performed. 3 years later, recurrent peritoneal metastases in the RUQ omentum and rectovesical pouch progressed. 33 cycles of atezolizumab and bevacizumab treatment elicited stable disease response. Finally, laparoscopic left pelvic peritonectomy was performed without tumor recurrence. Herein, we present a case of HCC with peritoneal seeding that was successfully treated with surgery after radiotherapy and systemic therapy, leading to complete remission.
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Background@#The purpose of this study was to identify the prevalence of posttraumatic embitterment disorder (PTED) among soldiers, and examine its relation to stress, depression, self-esteem, impulsiveness, and suicidal ideation. @*Methods@#The subjects of this study were 200 soldiers and 197 control subjects, a total of 397 persons. Measurement tools used included the PTED self-rating scale, Stress Response Inventory, Beck Depression Inventory, Rosenberg Self-Esteem Inventory, Barratt Impulsiveness Scale, and Beck Scale of Suicide Ideation.Result: The major findings of the analysis are as follows: first, 11.5% of the soldiers were in the risk group for PTED, and 4% of them had PTED. Second, PTED in the soldiers was significantly associated with a number of variables such as their educational background, stress, depression, self-esteem, impulsiveness, and suicidal ideation, while it was not significantly associated with age. Third, through the hierarchical multiple regression analysis, it was found that academic background, stress, and depression had a statistically significant positive effect on the incidence of PTED in the soldiers. @*Conclusion@#In order to prevent and effectively intervene in PTED in soldiers, there is a need for interventional efforts focused on depression and stress related to negative life events.
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Background@#Information on the effectiveness of nirmatrelvir/ritonavir against the omicron is limited. The clinical response and viral kinetics to therapy in the real world need to be evaluated. @*Methods@#Mild to moderate coronavirus disease 2019 (COVID-19) patients with risk factors for severe illness were prospectively enrolled as a treatment group with nirmatrelvir/ritonavir therapy versus a control group with supportive care. Serial viral load and culture from the upper respiratory tract were evaluated for seven days, and clinical responses and adverse reactions were evaluated for 28 days. @*Results@#A total of 51 patients were analyzed including 40 in the treatment group and 11 in the control group. Faster symptom resolution during hospitalization (P= 0.048) was observed in the treatment group. Only minor adverse reactions were reported in 27.5% of patients. The viral load on Day 7 was lower in the treatment group (P = 0.002). The viral culture showed a positivity of 67.6% (25/37) vs. 100% (6/6) on Day 1, 0% (0/37) vs. 16.7 (1/6) on Day 5, and 0% (0/16) vs. 50.0% (2/4) on Day 7 in the treatment and control groups, respectively. @*Conclusions@#Nirmatrelvir/ritonavir against the omicron was safe and resulted in negative viral culture conversion after Day 5 of treatment with better symptomatic resolution.
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Background@#Our study evaluated the prevalence and pattern of T-score discordance between the spine and hip in Korean patients with atypical femoral fracture (AFF) and femur neck fracture (FNF). @*Methods@#A total of 49 patients (all women) who were treated for AFF and 1:3 matched 147 female patients with FNF were included from January 2012 to August 2022. A discordance of more than 1.5 between lumbar spine and femur neck bone mineral density (BMD) was defined as a difference and divided into 3 groups: lumbar low (LL; lumbar BMD is less than femur neck BMD), no discordance (ND), and femur neck low (FL; femur neck BMD is less than lumbar BMD). We compared the prevalence and pattern of discordance between 2 groups, and the associated risk factors of T-score discordance among the subjects were evaluated using regression analysis. @*Results@#The prevalence of discordance was significantly higher in patients with AFF (51%) than in those with FNF (25.2%; p<0.001). LL discordance was found in 46.9% of the patients with AFF but only 4.8% in those with FNF. Conversely, FL discordance was found in 4.1% of the patients with AFF and 20.4% in those with FNF, respectively. No specific risk factor was found as T-score discordance in the 2 groups. @*Conclusions@#Clinicians should be aware that the pattern of T-score discordance can vary depending on the location of osteoporotic fractures. In addition, a longitudinal study would be necessary to verify the pattern of T-score discordance related to the osteoporotic fracture location.
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The incidence of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide, including Asia. Most patients with NAFLD-related HCC are at a much-advanced stage and older age at the time of diagnosis than those with virus-related HCC because they have not undergone HCC surveillance. This review provides an overview of the mechanism of hepatocarcinogenesis in NAFLD, preventive strategies for NAFLDrelated HCC, and strategies for the surveillance of patients with NAFLD.
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Purpose@#Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. @*Materials and Methods@#Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. @*Results@#A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. @*Conclusion@#Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.
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Purpose@#Breast cancer brain metastases (BCBM) may involve subtypes that differ from the primary breast cancer lesion. This study aimed to develop a radiomics-based model that utilizes preoperative brain MRI for multiclass classification of BCBM subtypes and to investigate whether the model offers better prediction accuracy than the assumption that primary lesions and their BCBMs would be of the same subtype (non-conversion model) in an external validation set. @*Materials and Methods@#The training and external validation sets each comprised 51 cases (102 cases total). Four machine learning classifiers combined with three feature selection methods were trained on radiomic features and primary lesion subtypes for prediction of the following four subtypes: 1) hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, 2) HR+/HER2+, 3) HR-/HER2+, and 4) triple-negative. After training, the performance of the radiomics-based model was compared to that of the non-conversion model in an external validation set using accuracy and F1-macro scores. @*Results@#The rate of discrepant subtypes between primary lesions and their respective BCBMs were 25.5% (n=13 of 51) in the training set and 23.5% (n=12 of 51) in the external validation set. In the external validation set, the accuracy and F1-macro score of the radiomics-based model were significantly higher than those of the non-conversion model (0.902 vs. 0.765, p=0.004; 0.861 vs. 0.699, p=0.002). @*Conclusion@#Our radiomics-based model represents an incremental advance in the classification of BCBM subtypes, thereby facilitating a more appropriate personalized therapy.
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BACKGROUND@#To achieve optimal bone marrow engraftment during bone marrow transplantation, migration of donor bone marrow cells (BMCs) toward the recipient’s bone marrow is critical. Despite the enhanced engraftment of BMCs by co-administration of mesenchymal stem cells (MSCs), the efficiency can be variable depending on MSC donor. The purpose of this study is to examine the functional heterogeneity of tonsil-derived MSCs (TMSCs) and to identify a marker to evaluate efficacy for the enhancement of BMC migration. @*METHODS@#To examine the donor-to-donor variation of TMSCs in potentiating BMC migration, we isolated TMSCs from 25 independent donors. Transcriptome of TMSCs and proteome of conditioned medium derived from TMSC were analyzed. @*RESULTS@#Enhanced BMC migration by conditioned medium derived from TMSCs was variable depending on TMSC donor. The TMSCs derived from 25 donors showed distinct expression profiles compared with other cells, including fibroblasts, adipose-derived MSCs and bone marrow–derived MSCs. TMSCs were distributed in two categories: high- and low-efficacy groups for potentiating BMC migration. Transcriptome analysis of TMSCs and proteome profiles of conditioned medium derived from TMSCs revealed higher expression and secretion of matrix metalloproteinase (MMP) 1 in the high-efficacy group. MMP1 knockdown in TMSCs abrogated the supportive efficacy of conditioned medium derived from TMSC cultures in BMC migration. @*CONCLUSION@#These data suggest that secreted MMP1 can be used as a marker to evaluate the efficacy of TMSCs in enhancing BMC migration. Furthermore, the strategy of analyzing transcriptomes and proteomes of the MSCs may be useful to set the standard for donor variation.