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Primary esophageal melanoma is a rare disease with a poor prognosis. To date, 18 cases have been reported in Korea. Four patients visited the Chonnam National University Hwasun Hospital with dysphagia, followed by epigastric pain and discomfort, odynophagia, and weight loss. Esophagogastroduodenoscopy revealed a black pigmented polypoid mass, protruding mass, or black-pigmented flat lesions. Two patients had distant metastases and lymphadenopathies in imaging studies. Two patients underwent esophagectomy and intrathoracic esophagogastrostomy. One patient was treated with chemotherapy and interferon-alpha. The other patient declined further treatment. The routine histology using HE revealed brown-colored atypical melanocytes. Immunohistochemical staining exhibited strong reactivity for Melan-A, S-100, and HMB-45 proteins. The biopsy specimens were interpreted to be malignant melanoma. One patient had multiple distant metastases 13 months after surgery. The other patient had no recurrence for 33 months after surgery. The patient treated with chemotherapy and interferon-alpha showed disease progression in the follow-up examination. Primary esophageal melanoma in Korea is a rare disease characterized by aggressive behavior, early metastasis, and poor prognosis.

The relationship between cooling time (CT) variables and neurological outcomes is controversial. We evaluated the relationship between CT and neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM).We conducted a multicenter, prospective, and registry-based study of OHCA survivors treated with TTM. CT was defined as the time from restoration of spontaneous circulation to achievement of the target temperature. The primary outcome was a favorable neurological outcome at 6 months. Multilevel logistic regression analysis was performed to test the relationship between CT and the primary outcome.Overall, the favorable neurological outcome rates at 6 months were 29.8% in 937 patients. When CT was stratified into categories of 0-3, 3.1-6, 6.1-9, 9.1-12, and12 h, according to 3-h intervals, the primary outcome rates were 8.2%, 22.7%, 35.5%, 44.7%, and 44.5%, respectively (p 0.001). Significant differences were not found in multilevel logistic regression analysis; the adjusted odds ratios (95% confidence interval) of each category for the primary outcome compared to the 0-3-h group were 0.81 (0.32 to 2.04), 0.77 (0.30 to 2.01), 1.26 (0.43 to 3.68), and 1.06 (0.37 to 3.06).We did not find a relationship between CT and neurological outcomes at 6 months.

The von Frey filament test (vF) is a mainstay of clinical examination. However, its results can be affected by touch speed and other potentially confounding factors. Moreover, the differences between two adjacent filament levels are too large to detect subtle changes. Active vF (AvF) was developed to induce in-depth sensory change. The present study hypothesized that AvF produces different patterns of fingertip sensation; consequently, it could be used as a new assessment tool for neural impairment. The aim of the study was to provide preliminary normative comparative vF and AvF data. This study prospectively examined 32 healthy participants, using AvF and vF. The index and the fifth finger volar pad were examined using AvF and vF, without visual stimulation. The correlation between AvF and vF measurements was evaluated. In addition, differences according to innervation zone, right versus left hand, and gender, and the correlation between AvF values and subjects' age were analyzed. Mean AvF value was significantly higher and had greater variance than vF (111.3 ± 46.9 vs. 24.1 ± 9.8; P 0.01). The Spearman correlation coefficient between AvF and vF was 0.341. Values were similar in the index and fifth fingers and right and left hands. However, values were significantly different between women and men. The correlation between age and AvF values was 0.259. AvF provided more precise values, with continuous units for tactile sensation, excluding tester-dependent factors. Furthermore, AvF and vF values may not be correlated.

Advances in data collection (high-throughput shotgun metagenomics, transcriptomics, and metabolomics) and analysis (bioinformatics and multiomics) led to the realization that all mammals are metaorganisms, shaped not only by their own genome but also by the genomes of the microbes that colonize them. To date, most studies have focused on the bacterial microbiome, whereas curated databases for viruses, fungi, and protozoa are still evolving. Studies on the interdependency of microbial kingdoms and their combined effects on host physiology are just starting. Although it is clear that past and present exposure to commensals and pathogens profoundly affect human physiology, such exposure is lacking in standard preclinical models such as laboratory mice. Laboratory mouse colonies are repeatedly rederived in germ-free status and subjected to restrictive, pathogen-free housing conditions. This review summarizes efforts to bring the wild microbiome into the laboratory setting to improve preclinical models and their translational research value.

Background & Aims Non-alcoholic fatty liver disease (NAFLD), the hepatic correlate of the metabolic syndrome, is a major risk factor for hepatobiliary cancer (HBC). Although chronic inflammation is thought to be the root cause of all these diseases, the mechanism whereby it promotes HBC in NAFLD remains poorly understood. Herein, we aim to evaluate the hypothesis that inflammation-related dysregulation of the ESRP2-NF2-YAP/TAZ axis promotes HB carcinogenesis. Methods We use murine NAFLD models, liver biopsies from patients with NAFLD, human liver cancer registry data, and studies in liver cancer cell lines. Results Our results confirm the hypothesis that inflammation-related dysregulation of the ESRP2-NF2-YAP/TAZ axis promotes HB carcinogenesis, supporting a model whereby chronic inflammation suppresses hepatocyte expression of ESRP2, an RNA splicing factor that directly targets and activates NF2, a tumor suppressor that is necessary to constrain YAP/TAZ activation. The resultant loss of NF2 function permits sustained YAP/TAZ activity that drives hepatocyte proliferation and de-differentiation. Conclusion Herein, we report on a novel mechanism by which chronic inflammation leads to sustained activation of YAP/TAZ activity; this imposes a selection pressure that favors liver cells with mutations enabling survival during chronic oncogenic stress. Lay summary Non-alcoholic fatty liver disease (NAFLD) increases the risk of hepatobiliary carcinogenesis. However, the underlying mechanism remains unknown. Our study demonstrates that chronic inflammation suppresses hepatocyte expression of ESRP2, an adult RNA splicing factor that activates NF2. Thus, inactive (fetal) NF2 loses the ability to activate Hippo kinases, leading to the increased activity of downstream YAP/TAZ and promoting hepatobiliary carcinogenesis in chronically injured livers.

Background There are ongoing efforts to reduce CT radiation exposure for the diagnosis of appendicitis. Recent guidelines recommend using clinical scoring systems to triage patients who need imaging examinations. Purpose To determine whether patient triaging with scoring systems can reduce CT use without a loss of diagnostic accuracy in adolescents and young adults suspected of having appendicitis. Materials and Methods This retrospective study used data from a previous multicenter randomized controlled trial conducted between December 2013 and August 2016. Five scoring systems (adult appendicitis, appendicitis inflammatory response, modified Alvarado, Broek, and Christian scores) were used to categorize patients into low-, intermediate-, or high-probability groups. CT use was simulated for only the intermediate-probability group. The primary outcomes were CT reduction rate, sensitivity, and specificity. The CT reduction rate was defined as the proportion of patients in low- and high-probability groups who would not have to undergo CT among all patients. Sensitivity and specificity were calculated in the overall diagnostic pathway using each scoring system and subsequent CT. As a secondary analysis, to maintain the diagnostic accuracy to a level of when CT was used for all patients with suspected appendicitis, new cutoff values for probability group stratification targeting 97.6% sensitivity and 94.9% specificity were applied for each of the scoring systems. Results A total of 2888 patients (mean age ± standard deviation, 28 years ± 9; 1580 women and 1308 men) with suspected appendicitis were evaluated, of whom 1088 had and 1800 did not have appendicitis. The CT reduction rates of the five scoring systems ranged from 55.6% (1606 of 2888 patients) to 71.1% (2053 of 2888), but at the cost of sensitivity (range, 48.7% [530 of 1088] to 81.2% [883 of 1088]) and specificity (range, 79.0% [1422 of 1800] to 97.8% [1761 of 1800]). Targeting 97.6% sensitivity and 94.9% specificity, the CT reduction rates of all five scoring systems were 0% (0 of 2888). Conclusion Using clinical scoring systems in triaging patients for selective CT use led to a considerable loss of diagnostic accuracy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mellnick in this issue.

Pelvic radiation therapy (RT) is a common treatment for malignancies, including gynecological, genitourinary, and lower gastrointestinal tract cancers. However, chronic radiation proctitis (RP) is an unavoidable side effect, and its clinical presentation varies from asymptomatic to potentially life-threatening. This study evaluated the clinical characteristics and risk factors of chronic RP.Patients with chronic RP (212) following RT for various pelvic cancers between January 2015 and December 2021 were enrolled. Clinical characteristics of RP were analyzed retrospectively. Severity was graded according to the Radiation Therapy Oncology Group (RTOG) modified rectal toxicity score and Vienna rectoscopy score (VRS), and risk factors were statistically analyzed.The most common pelvic cancer observed was cervical cancer. The patients received three-dimensional conformal RT (3D-CRT), intensity-modulated RT, or a combination of 3D-CRT and intracavitary RT (ICR). Rectal bleeding occurred in 70 (33.0%) patients. Previous abdominopelvic surgery and total radiation dose significantly correlated with the RTOG score and VRS. Previous abdominopelvic surgery, ICR, and total radiation dose were associated with chronic hemorrhagic RP. All patients with chronic hemorrhagic RP were treated with argon plasma coagulation (APC). 91.4% of cases required 1-3 APC sessions to resolve the bleeding, with a mean of 1.7 sessions.Our results showed that previous abdominopelvic surgery and total radiation dose were significant risk factors related to chronic RP, while total radiation dose was related to chronic hemorrhagic RP. We also showed that APC was effective and safe for chronic hemorrhagic RP.

In the hemodynamic study, computational fluid dynamics (CFD) analysis has shown that high wall shear stress (WSS) is an important parameter in cerebral aneurysm formation. However, CFD analysis is not more realistic than fluid–structure interaction (FSI) analysis given its lack of considering the involvement of vascular structures. To investigate the relationship between the hemodynamic parameters and the aneurysm formation, the locations of high WSS and high strain were extracted from the CFD and FSI analyses, respectively. Then the distances between the aneurysm formation site and the locations of high WSS or high strain were calculated. A total of 37 intracranial paraclinoid aneurysms were enrolled for quantitative comparison. Additionally, the dura mater was modeled to facilitate realistic results in FSI analysis. The average distance from the location of the aneurysm formation site to the high strain (1.74 mm $$\pm $$ ± 1.04 mm) was smaller than the average distance to the high WSS (3.33 mm $$\pm $$ ± 1.18 mm). The presence of dura mater also influenced the findings in the aneurysm formation site. High strain extracted by FSI analysis is an important hemodynamic factor related to the formation of cerebral aneurysms. Strain parameter could help to predict the formation of aneurysms and elucidate the appropriate treatment.

Engulfment and cell motility 1 (ELMO1) plays a crucial role in the process of migration, chemotaxis, and metastasis of tumor cells. ELMO1 has been implicated in the pathogenesis of various cancers. However, the distinct function of ELMO1 in colorectal cancer (CRC) is unclear. We determined whether ELMO1 affects the oncogenic behavior of CRC cells and investigated its prognostic value in CRC patients.We investigated the impact of ELMO1 on tumor cell behavior using small interference RNA (siRNA) in CRC cell lines, including SW480 and DLD1. The expression of ELMO1 was investigated by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) in cancer tissues and sera obtained from CRC patients.ELMO1 knockdown suppressed tumor cell proliferation in SW480 and DLD1 cells. ELMO1 knockdown-induced apoptosis through up-regulation of caspase-3, -7, and PARP activities and down-regulation of the anti-apoptotic Mcl-1 protein. ELMO1 knockdown-induced cell-cycle arrest by decreasing cyclin D1, cyclin-dependent kinase 2, 4 and 6, and the 25C cell division cycle (CDC25C). ELMO1 knockdown suppressed tumor cell invasion and migration. The expression of E-cadherin was increased, while that of Vimentin and Claudin 1 decreased following ELMO1 knockdown. The phosphorylation levels of PDK1, Akt, and GSK-3β and were down-regulated after ELMO1 knockdown. The expression of ELMO1 was found up-regulated in cancer tissues and sera taken from CRC patients. ELMO1 expression was significantly associated with tumor stage, lymph node metastasis, distant metastases, and poor survival.ELMO1 mediates tumor progression by increasing tumor cell motility and inhibiting apoptosis in human CRC.

Objective We investigated whether purpurin inhibits various pathways of inflammation leading to atopic dermatitis. Introduction 1,2,4-Trihydroxyanthraquinone, commonly called purpurin, is an anthraquinone that is a naturally occurring red/yellow dye. Purpurin is a highly antioxidative anthraquinone and previous studies have reported antibacterial, anti-tumor, and anti-oxidation activities in cells and animals. However, the skin inflammatory inhibition activity mechanism study of purpurin has not been elucidated in vitro. Methods In this study, we investigated the anti-inflammatory activity of purpurin in HaCaT (human keratinocyte) cell lines stimulated with a mixture of tumor necrosis factor-alpha (TNF-α)/Interferon-gamma (IFN-γ). The inhibitory effect of Purpurin on cytokines (IL-6, IL-8, and IL-1β) and chemokine (TARC, MDC, and RANTES) was confirmed by ELISA and RT-qPCR. We investigated each signaling pathway and the action of inhibitors through western blots. Results The expression levels of cytokines and chemokines were dose-dependently suppressed by purpurin treatment in TNF-α/IFN-γ-induced HaCaT cells from ELISA and real-time PCR. Purpurin also inhibited protein kinase B (AKT), mitogen-activated protein kinase (MAPKs), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) activation in TNF-α/IFN-γ-stimulated HaCaT cells. Additionally, there was a synergistic effect when purpurin and inhibitor were applied together, and inflammation was dramatically reduced. Conclusion Therefore, these results demonstrate that purpurin exhibits anti-inflammatory and anti-atopic dermatitis activity in HaCaT cells.

Background Self-expandable metal stent (SEMS) placement is commonly used as a bridge to surgery (BTS) for left-sided malignant colorectal obstruction (MCO). However, the optimal time interval between BTS stenting and surgery for left-sided MCO is unclear, and the results of previous studies are conflicting. This study aimed to determine the differences in clinical outcomes according to the time interval between BTS stenting and surgery in left-sided MCO. Methods Data from 594 patients who underwent SEMS placement for MCO between January 2009 and December 2018 were reviewed. Among them, 148 patients who underwent SEMS placement as BTS treatment and curative surgery were enrolled. The enrolled patients were divided into three groups according to the interval between BTS stenting and surgery: group 1 (interval ≤2 weeks), group 2 (interval 2–3 weeks), and group 3 (interval >3 weeks). Results Group 2 and 3 patients underwent significantly higher rates of laparoscopic surgery than those in group 1 (83.7, 81.0 vs. 53.2 %, respectively; P=0.003, P=0.003, respectively). Also, rates of stoma formation directly after resection were significantly higher in group 1 compared to groups 2 and 3 (21.3 vs 2.3, 6.9%, respectively; P=0.008, P=0.043, respectively). Bridging interval had no effect on SEMS-related complications, resection-related complications, 90-day mortality, permanent stoma formation, 3-year disease-free survival, and 3-year overall survival. Conclusions A bridging interval of > 2 weeks between BTS stenting and surgery for left-sided MCO is preferable for lower stoma formation rates and higher rates of laparoscopic approach operation, with no difference in short-term and long-term outcomes including complication, mortality, and survival.

Mucosa-associated lymphoid tissue (MALT) lymphoma predominantly involves the gastrointestinal tract, with the stomach being the most commonly affected site. Colonic involvement is quite rare. Hence, the etiology, clinical characteristics, treatment, and outcome of colonic MALT lymphoma are not well established. This paper reports a case of MALT lymphoma of the transverse colon, presenting as a subepithelial tumor in a 50-year-old woman. The patient received 3,060 cGy in 17 fractions with external beam radiation therapy for three weeks. At 2 months after radiation therapy, a colonoscopy examination revealed complete resolution and a scar change of the lesion. The follow-up at 24 months revealed no evidence of tumor recurrence after radiation therapy.

Approximately 70% of breast cancers are estrogen receptor (ER)-positive and treated with endocrine therapy. A commonly used treatment agent, tamoxifen, shows high efficacy for improving prognosis. However, approximately one-third of patients treated with tamoxifen develop resistance to this drug. Here, we investigated the function of general control non-derepressible 5 (GCN5) and its downstream effectors in tamoxifen-resistant (TamR) breast cancer. TamR-MCF7 breast cancer cells maintained high GCN5 levels due to its attenuated proteasomal degradation. GCN5 overexpression upregulated amplified in breast cancer 1 (AIB1) expression, resulting in decreased p53 stability and tamoxifen resistance. Conversely, the sensitivity of GCN5-AIB1-overexpressing MCF7 cells to tamoxifen was restored by forced p53 expression. An in vivo study demonstrated a positive correlation between GCN5 and AIB1 and their contribution to tamoxifen resistance. We concluded that GCN5 promotes AIB1 expression and tamoxifen resistance in breast cancer by reducing p53 levels, suggesting the utility of GCN5 and its downstream effectors as therapeutic targets to either prevent or overcome tamoxifen resistance in breast cancer.

Significance A major yet perplexing question in the field of necroptosis is the role and involvement of necroptosis in cancer cells. Many cancer cells have protective mechanisms against necroptosis, but the underlying mechanism remains elusive. We report findings of cross-talk and a regulatory pathway that exist between MYC, a potent oncogene, and RIPK3, a pivotal factor in necroptosis. We find that MYC pathway is downregulated upon necroptotic, while MYC inhibits TNF-α–induced necroptosis. The inhibitory effect of MYC on necroptosis is unexpected because no transcriptional activity by MYC is required. Mechanistically, a direct interaction between MYC and RIPK3 takes place in the cytosol, preventing RIPK1–RIPK3 complex formation. Finally, MYC depletion enhances antitumor activity of necroptosis-inducing agents in a xenograft model., The underlying mechanism of necroptosis in relation to cancer is still unclear. Here, MYC, a potent oncogene, is an antinecroptotic factor that directly suppresses the formation of the RIPK1–RIPK3 complex. Gene set enrichment analyses reveal that the MYC pathway is the most prominently down-regulated signaling pathway during necroptosis. Depletion or deletion of MYC promotes the RIPK1–RIPK3 interaction, thereby stabilizing the RIPK1 and RIPK3 proteins and facilitating necroptosis. Interestingly, MYC binds to RIPK3 in the cytoplasm and inhibits the interaction between RIPK1 and RIPK3 in vitro. Furthermore, MYC-nick, a truncated form that is mainly localized in the cytoplasm, prevented TNF-induced necroptosis. Finally, down-regulation of MYC enhances necroptosis in leukemia cells and suppresses tumor growth in a xenograft model upon treatment with birinapant and emricasan. MYC-mediated suppression of necroptosis is a mechanism of necroptosis resistance in cancer, and approaches targeting MYC to induce necroptosis represent an attractive therapeutic strategy for cancer.

Purpose We measured how much CO2 gas was used in urologic laparoscopic surgeries and studied whether the amount of gas was associated with postoperative pain. Materials and methods Four hundred sixty-three patients underwent urologic laparoscopic surgeries by a single surgeon. All surgeries were performed by a transperitoneal approach under a 15-mm Hg pneumoperitoneum using CO2 gas. The amount of CO2 was measured. Neuromuscular blockade with rocuronium was performed during the surgery and patient-controlled analgesia was also applied. Postoperative pain was assessed four times for 24 hours using a 10-point visual analogue scale. Results The mean laparoscopic time was 75.65±38.19 minutes and the mean amount of CO2 gas used was 415.70±190.68 L. The mean score on the postoperative pain scale was 6.37±1.48 for 12 hours (sum of measurements taken at 6 and 12 hours after the surgery) and 11.72±2.46 for 24 hours (sum of measurements at 6, 12, 18, and 24 hours). In the statistical analysis, there were no correlations between the amount of CO2 used and pain scores for 12 and 24 hours postoperatively. There were no correlations between laparoscopic time and pain scores for 12 or 24 hours postoperatively. There were also no correlations between operative method and pain scores for 12 or 24 hours postoperatively. Conclusions We recorded the amount of CO2 gas used for each laparoscopic surgery. There was no correlation between the amount of CO2 used and postoperative pain. The lack of correlation may have been because the surgery was performed under anesthesia with deep neuromuscular blockade.

Objectives: This study evaluated the incidence, risk factors, and clinical characteristics of complications of candidaemia in adults, with a focus on endophthalmitis, endocarditis, and osteoarticular infections. Methods: All patients ≥18 years old with candidaemia in two Korean tertiary hospitals from 2007 to 2016 were investigated. Complications of candidaemia were defined as the presence of endophthalmitis, endocarditis, or osteoarticular infections documented in patients with candidaemia. The clinical characteristics and risk factors for candidaemia with complications were analysed in the patients who underwent ophthalmological examinations. Results: Of 765 adult patients with candidaemia, 34 (4.4%) met the definition of complications, including endophthalmitis in 29 (3.8%), endocarditis in 4 (0.5%), and osteoarticular infections in 3 (0.4%). Of the 225 patients who underwent ophthalmological examinations, 29 (12.9%) had endophthalmitis. Candida albicans was an independent risk factor for complicated candidaemia (OR, 5.12; 95% CI, 2.17–12.09; P < 0.001). Although the mortality rate was no higher in complicated candidaemia, the duration of antifungal therapy was longer (23.1 ± 17.6 vs. 16.4 ± 10.8 days, P = 0.042), and 13 patients (39.3%) underwent additional procedures or surgery. Conclusions: Complications of candidaemia occurred in 4.4% of adult patients. C. albicans was an independent risk factor for complicated candidaemia in adults. Complications of candidaemia might need prolonged treatment and additional procedures or surgery. Therefore, careful evaluation and active treatment of candidaemia with complications should be encouraged. Keywords: Candidaemia, Complication, Candida albicans

Liver fibrosis is an excessive wound healing process that occurs in response to liver damage depending on underlying aetiologies. Currently, there are no effective therapies and FDA-approved therapeutics for the treatment of liver fibrosis except liver transplantation. Multipotent adipose-derived stem cells (ADSCs) have received significant attention as regenerative medicine for liver fibrosis owing to their advantages over stem cells with other origins. However, intrinsic limitations of stem cell therapies, such as cellular rejection and tumor formation, have impeded clinical applications of the ADSC-based liver therapeutics. To overcome these problems, the extracellular nanovesicles (ENVs) responsible for the therapeutic effect of ADSCs (A-ENVs) have shown considerable promise as cell-free therapeutics for liver diseases. However, A-ENVs have not been used for the treatment of intractable chronic liver diseases including liver fibrosis and cirrhosis. Therefore, in this study, we investigated the in vitro and in vivo antifibrotic efficacy of A-ENVs in thioacetamide-induced liver fibrosis models. A-ENVs significantly downregulated the expression of fibrogenic markers, such as matrix metalloproteinase-2, collagen-1, and alpha-smooth muscle actin. The systemic administration of A-ENVs led to high accumulation in fibrotic liver tissue and the restoration of liver functionality in liver fibrosis models through a marked reduction in α-SMA and collagen deposition. These results demonstrate the significant potential of A-ENVs for use as extracellular nanovesicles-based therapeutics in the treatment of liver fibrosis and possibly other intractable chronic liver diseases.

Brain metastases (BM) are the most common intracranial tumors, and their prevalence is increasing. High-resolution black-blood (BB) imaging was used to complement the conventional contrast-enhanced 3D gradient-echo imaging to detect BM. In this study, we propose an efficient deep learning algorithm (DLA) for BM detection in BB imaging with contrast enhancement scans, and assess the efficacy of an automatic detection algorithm for BM. A total of 113 BM participants with 585 metastases were included in the training cohort for five-fold cross-validation. The You Only Look Once (YOLO) V2 network was trained with 3D BB sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) images to investigate the BM detection. For the observer performance, two board-certified radiologists and two second-year radiology residents detected the BM and recorded the reading time. For the training cohort, the overall performance of the five-fold cross-validation was 87.95%, 24.82%, 19.35%, 14.48, and 18.40 for sensitivity, precision, F1-Score, the false positive average for the BM dataset, and the false positive average for the normal individual dataset, respectively. For the comparison of reading time with and without DLA, the average reading time was reduced by 20.86% in the range of 15.22–25.77%. The proposed method has the potential to detect BM with a high sensitivity and has a limited number of false positives using BB imaging.

The coronavirus disease 2019 (COVID-19) pandemic situation is a state that has had a great impact on the medical system and society. To respond to the pandemic situation, various methods, such as a pre-triage system, are being implemented in the emergency medical field. However, there are insufficient studies on the effects of this pandemic situation on patients visiting the emergency department (ED), especially those with cardio/cerebrovascular diseases (CVD)We performed a retrospective analysis of a cohort of patients from April 2020 to December 2020 (April 2020 was when the pre-triage system was established) compared to a parallel comparison patient cohort from 2019. The primary outcome was in-hospital mortality. CVD was defined by the patient's final diagnosis.During the same period, the number of patients who had visited the ED after COVID-19 had decreased to 79.1% of the number of patients who had visited the ED before COVID-19. The overall patient mortality and the mortality in the patients cardiovascular disease had both increased, while the mortality from cerebrovascular disease did not increase. Meanwhile, the ED length of stay had increased in all patients but did not increase in the patients with cardiovascular disease.As with prior studies conducted in other regions, in our study, the total number of ED visits were decreased compared to before COVID-19. The overall mortality had increased, particularly in the patients with cardiovascular disease.

We report a deep learning-based emotion recognition method using EEG data collected while applying cosmetic creams. Four creams with different textures were randomly applied, and they were divided into two classes, “like (positive)” and “dislike (negative)”, according to the preference score given by the subject. We extracted frequency features using well-known frequency bands, i.e., alpha, beta and low and high gamma bands, and then we created a matrix including frequency and spatial information of the EEG data. We developed seven CNN-based models: (1) inception-like CNN with four-band merged input, (2) stacked CNN with four-band merged input, (3) stacked CNN with four-band parallel input, and stacked CNN with single-band input of (4) alpha, (5) beta, (6) low gamma, and (7) high gamma. The models were evaluated by the Leave-One-Subject-Out Cross-Validation method. In like/dislike two-class classification, the average accuracies of all subjects were 73.2%, 75.4%, 73.9%, 68.8%, 68.0%, 70.7%, and 69.7%, respectively. We found that the classification performance is higher when using multi-band features than when using single-band feature. This is the first study to apply a CNN-based deep learning method based on EEG data to evaluate preference for cosmetic creams.

This study aimed to evaluate the prevalence of left main or triple vessel coronary artery disease (CAD) in comatose out-of-hospital cardiac arrest (OHCA) survivors and assessed their outcome based on the revascularization strategy. This multicenter, retrospective, observational registry-based study was conducted at 9 Korean tertiary care hospitals. Adult comatose OHCA survivors with left main or triple vessel CAD documented by immediate (≤ 2 h) coronary angiography after return of spontaneous circulation between 2011 and 2019 were included. The primary outcome was neurologically intact survival at 1-month. Among 727 OHCA patients, 150 (25%) had left main or triple vessel CAD and underwent complete (N = 32), incomplete (N = 78), and no immediate (N = 40) revascularization, respectively. The rate of neurologically intact survival at 1 month was significantly different among the groups (53%, 32%, and 23% for complete, incomplete, and no immediate revascularization groups, respectively; P = 0.02). After adjustment using the inverse probability of treatment weighting, complete revascularization was associated with neurologically intact survival at 1 month (odds ratio, 2.635; P = 0.01). Left main or triple vessel CAD is not uncommon in OHCA patients. The complete revascularization was associated with better outcome. Further clinical trials to confirm the best revascularization strategy are needed.

Mammography is the initial examination to detect breast cancer symptoms, and quality control of mammography devices is crucial to maintain accurate diagnosis and to safeguard against degradation of performance. The objective of this study was to assist radiologists in mammography phantom image evaluation by developing and validating an interpretable deep learning model capable of objectively evaluating the quality of standard phantom images for mammography.A total of 2,208 mammography phantom images were collected for periodic accreditation of the scanner from 1,755 institutions. The dataset was randomly split into training (1,808 images) and testing (400 images) datasets with subgroups (76 images) for the multi-reader study. To develop an interpretable model that contains two deep learning networks in series, five processing steps were performed: mammography phantom detection, phantom object detection, post-processing, score evaluation, and a report with a comment about ambiguous results.For phantom detection, the accuracy and mean intersection over union (mIOU) were 1.00 and 0.938 in the test dataset, respectively. During phantom object detection, a total of 6,369 out of 6,400 objects were detected as the correct object class, and the accuracy and mIOU were 0.995 and 0.813, respectively. The predicted score for each object showed a consensus of 97.40% excluding ambiguous points and 59.10% for ambiguous points of the groups.The interpretable deep learning model using large-scale data from multiple centers shows high performance and reasonable object scoring, successfully validating the reliability and feasibility of mammography phantom image quality management.

Gut microbiota comprise microorganisms residing in the gastrointestinal tract. Some of these microbiota are implicated in the progression of colorectal cancer (CRC). Here, we highlight studies on the effects of meat intake and fermented foods on characteristics of gut microbiota that can influence colitis-associated factors underlying CRC. Gut microbiota can influence the development and progression of CRC, through influencing factors such as secretion of toxins; enzymes for activating carcinogenesis (including β-glucuronidase, β-glucosidase, azoreductase, nitroreductase, and alcohol dehydrogenase); hydrogen sulfide generation; generation of reactive oxygen species and inflammation; secondary bile salt transformation; and products of protein fermentation. Additionally, some studies that the composition of gut microbiota (probiotics) or prebiotics plays an important role in the production of short chain fatty acids, inactivation enzymes for carcinogenesis, antioxidant activities, and inhibition of pathogen colonization. In this review, we discuss various explanatory mechanisms of the relationship between the multifactorial role of the gut microbiota and the development of CRC. Moreover, this review provides fundamental information on dietary fermented food and the gut microbiota, which is helpful for healthy people and those with CRC alike.

This study aims to examine sex-specific differences in body composition and lower extremity fat distribution and their association with physical performance among healthy older adults. The pilot study comprises 40 subjects (20 men and 20 women) matched by age and body mass index. The participants undergo dual-energy X-ray absorptiometry, magnetic resonance imaging, and proton magnetic resonance spectroscopy (1H-MRS) to assess body composition and lower extremity fat distribution. 1H-MRS is used to measure the extramyocellular lipid (EMCL) and intramyocellular lipid (IMCL) contents of the lower leg muscles (soleus and tibialis anterior) at the maximum circumference of the calf after overnight fasting. The tibialis anterior IMCL, as assessed by 1H-MRS, is negatively associated with the five-times sit-to-stand test scores (rs = 0.518, p = 0.023) in men, while the soleus IMCL content is negatively associated with the timed up-and-go test scores (rs = 0.472, p = 0.048) in women. However, the soleus EMCL content is positively associated with the five-times sit-to-stand test scores (rs = −0.488, p = 0.040) in women, but this association is not statistically significant in men. This study shows an inverse correlation between IMCL content and physical performance in healthy older individuals and lower leg muscle-specific IMCL based on sex differences. Furthermore, our results suggest that greater EMCL content in the soleus and calf subcutaneous fat might affect physical performance positively in women but not men.

Subacute thyroiditis (SAT) is a painful thyroiditis that often requires steroid therapy. Here, we report the first case of severe SAT in a patient who received the first dose of mRNA coronavirus disease 2019 (COVID-19) vaccination. A 34-year-old man without a viral prodrome felt a lump when swallowing 5 days after his first dose of mRNA-1273 (Moderna) vaccination. Ten days after vaccination, the patient visited the hospital and was advised to rest and take nonsteroidal anti-inflammatory drugs. He revisited the hospital 10 days later as symptoms aggravated with anterior neck pain, headache, fatigue, muscle weakness, and weight loss. Thyroid hormone levels and inflammatory markers were consistent with thyrotoxicosis. A thyroid ultrasound scan revealed typical SAT findings. His symptoms rapidly improved after receiving prednisone. A week later, the patient successfully completed his second dose of the vaccine. The thyroid function test results were nearly normal 1 month after the completion of the vaccination. We report this case to raise awareness of the occurrence of SAT after COVID-19 vaccination. As the risk of COVID-19 outweighs the minor risks of the vaccine, managing the side effects of the first vaccine dose is crucial to complete COVID-19 vaccination.

Since the implementation of the nationwide coronavirus disease 2019 (COVID-19) vaccination campaign, emergency departments (EDs) have had an increasing number of patients reporting postvaccination cardiovascular adverse effects. We investigated the clinical features of patients who visited the ED for cardiovascular adverse reactions after COVID-19 mRNA vaccination.We conducted a retrospective observational study in two EDs. Patients with cardiovascular adverse reactions after COVID-19 mRNA vaccination who visited EDs between June 1, 2021, and October 15, 2021, were selected. The clinical data of these patients were collected by reviewing medical records.Among 683 patients, 426 (62.4%) were female. The number of patients in their 20s was the highest (38.9% of males, 28.2% of females) (Most patients who visited the ED with cardiovascular adverse reactions were discharged from the ED, but some were admitted for other medical diseases as well as adverse vaccine reactions. Therefore, further surveillance and a differential diagnosis of cardiovascular adverse events after COVID-19 mRNA vaccination should be considered by emergency physicians.

Background Sepsis is a series of organ failures caused by dysregulated responses to infection. Risk factors for sepsis are multiple comorbidities, a poor nutrition status, and limited mobility. The primary purpose of the study was to determine whether ambulation ability with albumin and C-reactive protein are predictive of 28-day mortality of elderly patients with sepsis. Methods This was a retrospective observational study using a multicentre-based registry of elderly patients between November 2016 and February 2017. The inclusion criteria were a patient ≥65 years and a diagnosis of sepsis and exclusion criteria were a patient with covariates of ambulation ability such as central nervous system diseases, or malignancy. The area under the receiver operating characteristic curve of prediction models were calculated and compared. The survival rates according to the ambulation ability were estimated and compared by the log-rank test. Results 2291 patients ≥65 years visited with infectious diseases. 496 subjects with central nervous system diseases, 710 subjects with malignancy and 817 subjects with a Sequential Organ Failure Assessment score ≤ 1 were excluded. Ultimately, 278 subjects were included in the primary analysis. 133 (47.8%) subjects were male and the median age was 78 years. 228 (82%) subjects could ambulate independently before morbidity and 28 (10.1%) subjects expired in 28 days. In the inability to ambulate and C-reactive protein to albumin ratio model, the area under the curve predicting 28-day mortality was 0.761 with no significant difference from the Sequential Organ Failure Assessment score (0.859, p = 0.097) and the estimated survival rate on 28th day according to the ability to ambulate showed a significant difference (hazard ratio = 1.212, p Conclusion The premorbid ambulation ability with albumin and C-reactive protein can be combined to predict 28-day mortality in elderly patients with sepsis.

Purpose To assess the performance of the post-cardiac arrest (CA) prognostication strategy algorithm recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) in 2020. Methods This was a retrospective analysis of the Korean Hypothermia Network Prospective Registry 1.0. Unconscious patients without confounders at day 4 (72–96 h) after return of spontaneous circulation (ROSC) were included. The association between the prognostic factors included in the prognostication strategy algorithm, except status myoclonus and the neurological outcome, was investigated, and finally, the prognostic performance of the prognostication strategy algorithm was evaluated. Poor outcome was defined as cerebral performance categories 3–5 at 6 months after ROSC. Results A total of 660 patients were included in the final analysis. Of those, 108 (16.4%) patients had a good neurological outcome at 6 months after CA. The 2020 ERC/ESICM prognostication strategy algorithm identified patients with poor neurological outcome with 60.2% sensitivity (95% CI 55.9–64.4) and 100% specificity (95% CI 93.9–100) among patients who were unconscious or had a GCS_M score ≤ 3 and with 58.2% sensitivity (95% CI 53.9–62.3) and 100% specificity (95% CI 96.6–100) among unconscious patients. When two prognostic factors were combined, any combination of prognostic factors had a false positive rate (FPR) of 0 (95% CI 0–5.6 for combination of no PR/CR and poor CT, 0–30.8 for combination of No SSEP N20 and NSE 60). Conclusion The 2020 ERC/ESICM prognostication strategy algorithm predicted poor outcome without an FPR and with sensitivities of 58.2–60.2%. Any combinations of two predictors recommended by ERC/ESICM showed 0% of FPR.

We have developed a cell penetrating peptide (CPP) system with high selectivity and penetrability at nanomolar concentrations with a combination of an HER2-selective affibody, ZHER2:342 (ZHER2), and a dimeric α-helical leucine- and lysine-rich peptide, LK-2. ZHER2 and LK-2 are linearly fused together and expressed in a prokaryotic system to create the LK-2-ZHER2 protein, which can successfully distinguish and penetrate HER2-overexpressing cancer cells at nanomolar concentrations. LK-2-ZHER2 has the ability to intracellularly deliver doxorubicin as a conjugate form to enhance its anti-cancer effect on HER2-overexpressing breast cancer cells with a great selectivity. The selective penetrability was confirmed in vitro, in 3D spheroids, and in in vivo models. LK-2-ZHER2 has the capability to overcome the weak points of current CPPs, such as poor penetrability at low concentrations and a lack of selectivity, by combining powerful CPP and affibody sequences.

Background The association of body mass index with outcome in patients treated with targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) is unclear. The purpose of this study was to examine the effect of body mass index (BMI) on neurological outcomes and mortality in resuscitated patients treated with TTM after OHCA. Methods This multicenter, prospective, observational study was performed with data from 22 hospitals included in the Korean Hypothermia Network KORHN-PRO registry. Comatose adult patients treated with TTM after OHCA between October 2015 and December 2018 were enrolled. The BMI of each patient was calculated and classified according to the criteria of the World Health Organization (WHO). Each group was analyzed in terms of demographic characteristics and associations with six-month neurologic outcomes and mortality after cardiac arrest (CA). Results Of 1,373 patients treated with TTM identified in the registry, 1,315 were included in this study. One hundred two patients were underweight (BMI 2), 798 were normal weight (BMI 18.5–24.9 kg/m2), 332 were overweight (BMI 25–29.9 kg/m2), and 73 were obese (BMI ≥ 30 kg/m2). The higher BMI group had younger patients and a greater incidence of diabetes and hypertension. Six-month neurologic outcomes and mortality were not different among the BMI groups (p = 0.111, p = 0.234). Univariate and multivariate analyses showed that BMI classification was not associated with six-month neurologic outcomes or mortality. In the subgroup analysis, the underweight group treated with TTM at 33°C was associated with poor neurologic outcomes six months after CA (OR 2.090, 95% CI 1.010–4.325, p = 0.047), whereas the TTM at 36°C group was not (OR 0.88, 95% CI 0.249–3.112, p = 0.843). Conclusions BMI was not associated with six-month neurologic outcomes or mortality in patients surviving OHCA. However, in the subgroup analysis, underweight patients were associated with poor neurologic outcomes when treated with TTM at 33°C.

CD47 is an immunoregulatory protein that is found on the cell surface and plays significant roles in cellular functions such as proliferation, apoptosis, migration, and immune homeostasis. CD47 is overexpressed in various human cancers and is associated with tumor development, progression, and poor prognosis. In this study, we analyzed the expression of CD47 to determine whether it affected the oncogenic behavior of colorectal cancer (CRC) and investigated the prognostic value of CD47 expression in patients with CRC. We investigated 468 patients with CRC who underwent curative surgery and examined the expression of CD47 in tumor and lymph node tissues by performing RT-PCR and immunohistochemistry. Apoptosis, proliferation, angiogenesis, and lymphangiogenesis were determined via a TUNEL assay and immunohistochemical staining for Ki-67, CD34, and D2-40. CD47 expression was increased in human CRC tumors and metastatic lymph nodes compared with normal colorectal mucosa and non-metastatic lymph node tissues. CD47 expression was significantly associated with perineural invasion, lymphovascular invasion, cell differentiation, cancer stage, depth of invasion, lymph node metastasis, distant metastasis, and poor survival. The mean apoptotic index and microvessel density value of CD47-positive tumors were significantly higher than those of CD47-negative tumors. However, no significant difference was observed between CD47 expression and Ki-67 labeling index or lymphatic vessel density. These results indicate that CD47 mediated the progression of CRC by inducing tumor cell apoptosis and angiogenesis.

Objectives: We conducted an in vitro investigation of the activity of rifamycins against planktonic and biofilm states of Staphylococcus aureus and Staphylococcus epidermidis isolates from patients with prosthetic joint infections (PJIs), characterised their rpoB gene mutations, and analysed the clinical outcomes of rifampicin-resistant isolates. Methods: A total of 110 staphylococcal isolates were collected from patients with PJI. Antimicrobials tested using the broth microdilution method included rifampicin, rifabutin, rifapentine and rifaximin. We evaluated rpoB gene mutations to identify rifampicin resistance mechanisms. Clinical outcomes were assessed in rifampicin-resistant isolates. Results: The 110 staphylococcal isolates included 85 S. aureus (55% methicillin-resistant) and 25 S. epidermidis (100% methicillin-resistant). Seven S. aureus isolates and two S. epidermidis isolates were resistant to rifampicin [minimum inhibitory concentration (MIC) ≥2 μg/mL] and these isolates exhibited rpoB gene mutations. Among the 78 rifampicin-susceptible S. aureus isolates and 23 S. epidermidis isolates, 76 S. aureus isolates (97.4%) and all S. epidermidis isolates (100%) were highly susceptible (MIC ≤ 0.06 μg/mL) to other rifamycins. The minimum biofilm bactericidal concentrations for ≥50% of isolates (MBBC50) to rifampicin, rifabutin, rifapentine and rifaximin were 4, 1, 2 and 4 μg/mL for S. aureus and 1, 0.125, 0.25 and 0.5 μg/mL for S. epidermidis, respectively, among rifampicin-susceptible isolates. Among nine patients bearing rifampicin-resistant isolates, only three (33%) had successful outcomes. Conclusion: Rifamycins other than rifampicin show promising antistaphylococcal activity, including antibiofilm activity. Rifamycin-resistant staphylococci exhibit rpoB gene mutations.

Highlights • There are virus carriers in the asymptomatic population • The duration of viral shedding may be short in asymptomatic carriers • Fourteen days of isolation after diagnosis may be sufficient in entirely asymptomatic cases, From 71 laboratory-confirmed cases, we found three presymptomatic patients and 10 entirely asymptomatic infections. In two of the three incubation period patients, the viral titer in the presymptomatic period was very high (Ct value 35 RT-PCR within 14 days after diagnosis. Patients who have COVID-19 may already be infectious before there are symptoms, and 14 days of isolation after diagnosis may be sufficient in entirely asymptomatic cases.

BACKGROUND Dix-Hallpike (DH) test is sometimes done in a modified or reduced manner in a clinical setting. However, there has been no study that evaluated the reliability of this modified test. OBJECTIVES The purposes of this study were to determine whether the efficacy of a modified DH test, named the 'pillow under shoulders' test, was equivalent to the standard DH test and to assess the difference in patient discomfort between the two methods. METHODS Randomized controlled study at three academic referral hospitals, conducted in compliance with the CONSORT statement. Patients suspected for BPPV based on symptoms were randomly assigned to Group A or Group B. Patients in Group A received a standard DH test initially, followed by a modified DH test with a pillow under shoulders. Patients in Group B also received the two tests, but in the reverse order. The diagnostic results of both tests and patients' subjective scoring for uneasiness (discomfort, pain, anxiety) were statistically analyzed. RESULTS McNemar's test and Kappa statistics showed a statistically equivalent diagnostic value between standard and modified DH tests (Cohen's kappa = 0.823 and McNemar P = 0.18). The modified DH test had high sensitivity (95.5%) and fairly good specificity (87.9%). There was no statistical significance in the patients' subjective scoring for uneasiness between the two methods, although most patients reported less inconvenience after the modified DH test compared to the standard DH test. CONCLUSIONS The modified version of the standard DH test, the 'pillow under shoulders' method, may be a reliable, comfortable option to diagnose vertical canal BPPV. We suggest that this method can be used when head hanging is not feasible or sufficient for the standard DH test.

Thrombocytopenia is common and associated with mortality in critically ill patients. However, the time course of platelet counts and its association with the neurologic outcome after out-of-hospital cardiac arrest (OHCA) are not well known. The purpose of this study is to describe the time course of platelet counts in relation to the neurologic outcome in patients undergoing targeted temperature management (TTM) after CA.Review of consecutive patients receiving TTM after out-of-hospital CA between 2009 and 2016. The blood sample was collected daily until 7 days. The primary outcome was poor neurologic outcome at 6 months after CA defined as Cerebral Performance Category of 3-5 and secondary outcome was mortality at 6 months.A total of 261 consecutive patients treated with TTM after OHCA between 2009 and 2016. One hundred seventy-five patients (67.0%) had poor neurologic outcomes 6 months after CA. The changes in the platelet counts over time between the good and poor outcome groups were statistically significant (p 0.001). The platelet counts declined during TTM in both groups. The platelet counts recovered to the normal range at the end of the first week in the good neurologic outcome group. However, the platelet counts remained low in the poor outcome group. Low platelet counts on the 7th day were associated with poor neurologic outcomes (aOR 0.975, 95% CI, 0.961-0.989) and mortality at 6 months (aOR 0.986, 95% CI, 0.975-0.997) after adjusting for covariates.The changes in platelet counts in OHCA patients have a biphasic pattern that is significantly different in patients with good neurologic outcomes and those with poor neurologic outcomes at 6 months. A low platelet count 7 days after CA was associated with a poor neurologic outcome and mortality at 6 months.

Purpose We present surgical techniques and operative results of laparoscopic reconstruction for patients with retrocaval ureter (RCU) and review similar papers. Materials and methods Ten patients with RCU were enrolled in this study from April 2005 to January 2017. The mean age of 7 males and 3 females was 40.5 years old. The chief complaint was flank pain in 6 patients; the remaining patients were detected incidentally. All patients showed hydronephrosis and typical S-shaped deformity of the ureter on imaging studies. Five patients showed obstructed patterns on the renal scans. Two surgeons performed laparoscopic ureteroureterostomies with transperitoneal approaches including excision of the compressed ureter. Double-J ureteral stents were inserted intraoperatively. The operative and follow-up results were checked and compared with published papers. Results All laparoscopic reconstructions were successfully completed without conversion to open surgery. The mean operative time was 199.6 minutes. The estimated blood loss was 154.4 mL. No operative complications were encountered. There were no obstruction and symptom after the mean follow-up of 40.7 months. We found 7 papers from PubMed, which had more than five cases of laparoscopic reconstruction of RCU. We reviewed and summarized the clinical and operative parameters. Conclusions Our results show that transperitoneal laparoscopic ureteroureterostomy with excision of the compressed ureter is a safe and effective treatment for RCU. Data from published papers and ours summarize clinical parameters of RCU, and suggest that the laparoscopic reconstruction can be considered as the standard treatment for it.

Self-expandable metal stent (SEMS) placement is commonly used for palliation of left-sided malignant colorectal obstruction (MCO). However, right-sided MCO is usually treated surgically. Recent studies that compared palliative SEMS insertion and emergency surgery in right-sided MCOs have reported conflicting results. This study aimed to compare the effectiveness of palliative SEMS placement in left-sided MCOs and right-sided MCOs and to investigate the predictive factors for clinical success and risk factors for complications. Data from 469 patients who underwent palliative SEMS placement for MCO at 6 hospitals in the Honam province of South Korea between 2009 and 2018 were reviewed. Among them, 69 patients with right-sided MCO and 400 patients with left-sided MCO who underwent SEMS placement for palliative purposes were enrolled. Clinical success, overall survival, complications, and predictive factors for clinical success and risk factors for complications were included as the main outcome measures. The clinical success rates were 97.1% (65/67) in right-sided MCO patients and 88.2% (353/400) in left-sided MCO patients. Complications including stent migration, tumor ingrowth, outgrowth, perforation, bacteremia/fever, and bleeding occurred in 10.1% (7/69) of right-sided MCO patients and 19.9% (79/400) of left-sided MCO patients. The mean overall survival of right-sided MCO was 28.02 months and 18.23 months for left-sided MCO. In multivariate logistic regression analysis, T3 stage tumors and the use of uncovered stents were significant factors for the clinical success of SEMS. The use of covered stents and performance status score of 0 to 2 were independent significant risk factors for complications. Palliative SEMS placement in right-sided MCO showed better clinical success rates than left-sided MCO. The use of uncovered stents is recommended for higher clinical success rates and lower complication rates.

BackgroundDendritic cells (DCs) are specialized antigen-presenting cells known to bridge innate and adaptive immune reactions. However, the relationship between circulating DCs and Orientia tsutsugamushi infection is unclear. Therefore, this study aimed to examine the level and function of plasmacytoid DCs (pDCs) and conventional DCs (cDCs), two subsets of circulating DCs, in scrub typhus patients.MethodsThe study included 35 scrub typhus patients and 35 healthy controls (HCs). pDC and cDC levels, CD86 and CD274 expression, and cytokine levels were measured using flow cytometry.ResultsCirculating pDC and cDC levels were found to be significantly reduced in scrub typhus patients, which were correlated with disease severity. The patients displayed increased percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs in the peripheral blood. The alterations in the levels and surface phenotypes of pDCs and cDCs were recovered in the remission state. In addition, the production of interferon (IFN)-α and tumor necrosis factor (TNF)-α by circulating pDCs, and interleukin (IL)-12 and TNF-α by circulating cDCs was reduced in scrub typhus patients. Interestingly, our in vitro experiments showed that the percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs were increased in cultures treated with cytokines including IFN-γ, IL-12, and TNF-α.ConclusionsThis study demonstrates that circulating pDCs and cDCs are numerically deficient and functionally impaired in scrub typhus patients. In addition, alterations in the expression levels of surface phenotypes of pDCs and cDCs could be affected by pro-inflammatory cytokines.

Rationale: Rectal inflammatory myofibroblastic tumor (IMT) is an extremely rare mesenchymal tumor characterized by a mixture of spindle-shaped myofibroblasts or fibroblasts and inflammatory infiltration of lymphocytes and plasma cells. To date, only 8 cases of rectal IMT have been reported. Herein, we report an additional case of rectal IMT in a 28-year-old woman. Patient concerns: A 28-year-old woman presented with abdominal pain and hematochezia. Diagnoses: Colonoscopy showed a 3.0-cm subepithelial tumor with central ulceration, covered by white exudate in the rectum. Rectal magnetic resonance imaging revealed a 4.0 × 3.0-cm-sized well-defined subepithelial tumor in the right wall of the rectum, with suspicious right perirectal fat infiltration. Interventions: Laparoscopic anterior resection was performed. Microscopic examination of the surgical specimen revealed bland-looking spindle cells intermingled with lymphoplasma cells. Immunohistochemistry and fluorescence in situ hybridization showed anaplastic lymphoma kinase positivity and anaplastic lymphoma kinase positivity rearrangement. Rectal IMT was confirmed based on histological, immunohistochemical, and fluorescence in situ hybridization findings. The patient was doing well without evidence of tumor recurrence 1 year after the surgery. Lessons: Rectal IMT, despite its rarity, should be considered in the differential diagnosis of rectal cancer. Second, an accurate histopathologic diagnosis and complete surgical resection can be the most important approaches to offer a chance for the cure of rectal IMT.

Endocrine therapy is used to treat estrogen receptor (ER)-positive breast cancer. Tamoxifen is effective against this cancer subtype. Nonetheless, approximately 30% of patients treated with tamoxifen acquire resistance, resulting in therapeutic challenges. NR4A1 plays key roles in processes associated with carcinogenesis, apoptosis, DNA repair, proliferation, and inflammation. However, the role of NR4A1 in tamoxifen-resistant ER-positive breast cancer has not yet been elucidated. Here, we propose that NR4A1 is a promising target to overcome tamoxifen resistance. NR4A1 gene expression was downregulated in tamoxifen-resistant MCF7 (TamR) cells compared to that in MCF7 cells. Kaplan-Meier plots were used to identify high NR4A1 expression correlated with increased survival rates in patients with ER-positive breast cancer following tamoxifen treatment. Gain and loss of function experiments showed that NR4A1 restores sensitivity to tamoxifen by regulating cell proliferation, migration, invasion, and apoptosis. NR4A1 localized to the cytoplasm enhanced the expression of apoptotic factors. In silico and in vitro analyses revealed that NR4A1 enhanced responsiveness to tamoxifen by suppressing ERK signaling in ER-positive breast cancer, suggesting that the NR4A1/ERK signaling axis modulates tamoxifen resistance. These results indicate that NR4A1 could be a potential therapeutic target to overcome tamoxifen resistance in ER-positive breast cancer.

Background/aim ER-positive breast cancer patients commonly undergo endocrine therapy with drugs such as tamoxifen. Despite tamoxifen being a highly effective drug, long-term treatment results in resistance in one-third of the patients. Although many explanations for the development of tamoxifen resistance have been put forward, a clearly defined underlying mechanism is still lacking. Materials and methods The expression level of HOXB5 was evaluated between MCF7 breast cancer cells and tamoxifen-resistant MCF7 (TAMR) cells by RT-PCR. Then, the effect of HOXB5 on invasion and migration abilities as well as on cancer stemness were investigated through 3D culture and spheroid formation assay. Results In this study, we provide evidence that HOXB5 is up-regulated in TAMR cells. EGFR is concurrently overexpressed, and the EGFR signaling cascade is activated, resulting in migratory and invasive phenotypes in TAMR cells compared to MCF7 cells. However, HOXB5 knockdown in TAMR cells resulted in the de-activation of the EGFR signaling pathway, less aggressive phenotypes and restoration of sensitivity to tamoxifen treatment. More interestingly, TAMR cells expressed higher levels of stem cell markers, and as a result, their enhanced stemness allowed for a better formation of spheroids than MCF7 cells. When HOXB5 was overexpressed in MCF7 cells, they were able to form a larger number of spheroids as in TAMR cells. Conclusion HOXB5 is one of the key factors involved in tumor aggression and progression in tamoxifen-resistant breast cancer cells.

3,4,5‑Trihydroxycinnamic acid (THCA) exhibits anti‑inflammatory activity in acute or chronic inflammatory disorders, such as acute lung injury and asthma. The present study investigated the anti‑inflammatory activity of THCA in a tumor necrosis factor‑α/interferon‑γ (TI) mixture‑stimulated human keratinocyte cell line. The results of ELISA and reverse transcription‑quantitative PCR revealed that THCA reduced the secretion and mRNA expression levels of interleukin (IL)‑6; IL‑8; thymus and activation‑regulated chemokine; macrophage‑derived chemokine; regulated upon activation, normal T cell expressed and secreted; and monocyte chemoattractant protein‑1 in TI mixture‑stimulated HaCaT cells. In addition, the results of western blot analysis demonstrated that THCA exerted inhibitory activity on the activation of AKT, ERK and nuclear factor‑κB in TI mixture‑stimulated HaCaT cells. Furthermore, THCA upregulated the expression levels of heme oxygenase‑1 and NAD(P)H:quinone oxidoreductase 1, and the activation of nuclear factor erythroid 2‑related factor 2 in HaCaT cells. These results demonstrated that THCA may exhibit anti‑inflammatory activity in activated HaCaT cells.

Background/aim To present the variations in the target delineation and the planning results of intensity-modulated radiation therapy (IMRT) for breast cancers. Patients and methods We requested the target volumes and organs at risk delineation for two cases of left breast cancers, and evaluated the IMRT plans including the supraclavicular and internal mammary node irradiation. Results Twenty-one institutions participated in this study. Differences in the planning target volume among institutions reached up to three-times for breast-conserving surgery (BCS) case and five-times for mastectomy case. Mean heart doses ranged from 3.3 to 24.1 Gy for BCS case and from 5.0 to 26.5 Gy for mastectomy case. Ipsilateral lung volumes receiving more than 20 Gy ranged from 4.7 to 57.4% for BCS case and from 16.4 to 55.5% for mastectomy case. Conclusion There were large variations in the target delineation and planning results of IMRT for breast cancers among institutions. Considering the increased use of breast IMRT, more standardized protocols are needed.

Extracellular vesicles (EVs) are essential mediators in intercellular communication that have emerged as natural therapeutic nanomedicines for the treatment of intractable diseases. Their therapeutic applications, however, have been limited by unpredictable in vivo biodistribution after systemic administration. To control the in vivo fate of EVs, their surfaces should be properly edited, depending on the target site of action. Herein, based on bioorthogonal copper‐free click chemistry (BCC), surface‐edited EVs were prepared by using metabolically glycoengineered cells. First, the exogenous azide group was generated on the cellular surface through metabolic glycoengineering (MGE) using the precursor. Next, PEGylated hyaluronic acid, capable of binding specifically to the CD44‐expressing cells, was labelled as the representative targeting moiety onto the cell surface by BCC. The surface‐edited EVs effectively accumulated into the target tissues of the animal models with rheumatoid arthritis and tumour, primarily owing to prolonged circulation in the bloodstream and the active targeting mechanism. Overall, these results suggest that BCC combined with MGE is highly useful as a simple and safe approach for the surface modification of EVs to modulate their in vivo fate.

Cancer is a well-recognized cause of fever, which is related to cytokines produced by malignant cells. Prostate cancer presenting with fever and other inflammatory markers as a paraneoplastic syndrome rarely occurs.We describe the case of high fever and lower-urinary tract symptoms that progressed 1 month prior to presentation. A 78-year-old man had been diagnosed with prostate cancer 8 months ago. He received androgen deprivation therapy with leuprolide acetate 22.5 mg for every 3 months. Castration-resistant prostate cancer was diagnosed due to elevated prostate specific antigen (1639 ng/mL) and cancer fever.The patient received docetaxel-based systemic chemotherapy 50 mg/mm2 biweekly. Naproxen 500 mg was administered twice a day.After one cycle of systemic chemotherapy, the patient had no major side effects, no more fever was observed, and the systemic condition improved.Differentiating cancer-related fever from infection-related fever is important for appropriate patient management. In this case, fever appeared as the first symptom of castration-resistant prostate cancer and was managed by naproxen and resolved with systemic chemotherapy.

Purpose We analysed the prognostic value of somatosensory, brainstem auditory and visual evoked potentials (SSEPs, BAEPs and VEPs, respectively) for outcome prediction in cardiac arrest patients with targeted temperature management (TTM) and assessed whether BAEP and VEP measurements conferred added value to SSEP measurements. Methods Cases with SSEPs and VEPs or BAEPs were reviewed in a TTM registry. We focused on whether the following responses were clearly discernible: N20 for SSEPs, V for BAEPs, and P100 for VEPs. Each type of evoked potential was classified as absent, present or indeterminable. Neurological outcomes after 6 months were dichotomized as good (Cerebral Performance Category [CPC] 1–2) or poor (CPC 3–5). Results From 185 patients, 185 SSEPs, 172 BAEPs and 178 VEPs were included. None of the patients with a good outcome had absent SSEP, BAEP or VEP responses. Absent SSEP, BAEP and VEP responses yielded sensitivities of 42.3% (95% confidence interval [CI], 33.7–51.3%), 9.4% (95% CI, 4.6–16.7%) and 54.4% (95% CI, 46.0–62.5%) for poor outcomes, respectively. For the overall cohort, the addition of VEP measurements improved the sensitivities of single SSEP measurements (65.8% [95% CI, 57.7–73.3%] versus 36.2% [95% CI, 28.6–44.4%] and multimodal prognostication using SSEPs, brainstem reflex and brain computed tomography (75.7% [95% CI, 68.0–82.3%] versus 60.5% [95% CI, 52.3–68.4%]). Conclusions The prognostic value of VEPs was comparable to that of SSEPs, but the use of BAEPs was limited due to their low sensitivity. Additional VEP measurements can reduce prognostic uncertainty.

Predictive studies of acute respiratory distress syndrome (ARDS) in patients with coronavirus disease 2019 (COVID-19) are limited. In this study, the predictors of ARDS were investigated and a score that can predict progression to ARDS in patients with COVID-19 pneumonia was developed. All patients who were diagnosed with COVID-19 pneumonia between February 1, 2020, and May 15, 2020, at five university hospitals in Korea were enrolled. Their demographic, clinical, and epidemiological characteristics and the outcomes were collected using the World Health Organization COVID-19 Case Report Form. A logistic regression analysis was performed to determine the predictors for ARDS. The receiver operating characteristic (ROC) curves were constructed for the scoring model. Of the 166 patients with COVID-19 pneumonia, 37 (22.3%) patients developed ARDS. The areas under the curves for the infiltration on a chest X-ray, C-reactive protein, neutrophil/lymphocyte ratio, and age, for prediction of ARDS were 0.91, 0.90, 0.87, and 0.80, respectively (all P < 0.001 ). The COVID-19 ARDS Prediction Score (CAPS) was constructed using age (≥60 years old), C-reactive protein (≥5 mg/dL), and the infiltration on a chest X-ray (≥22%), with each predictor allocated 1 point. The area under the curve of COVID-19 ARDS prediction score (CAPS) for prediction of ARDS was 0.90 (95% CI 0.86–0.95; P < 0.001 ). It provided 100% sensitivity and 75% specificity when the CAPS score cutoff value was 2 points. CAPS, which consists of age, C-reactive protein, and the area of infiltration on a chest X-ray, was predictive of the development of ARDS in patients with COVID-19 pneumonia.

Rationale: Uterine arteriovenous malformation (UVM), which can be congenital or acquired, is a relatively rare disorder that can cause life-threatening hemorrhage. Acquired UVM occurs predominantly after previous uterine procedures; rarely, it may occur after a hysterectomy. Although the best treatment option for UVM remains controversial, transcatheter arterial embolization (TAE) has recently been introduced as a safe and effective treatment. Patient concerns: A 34-year-old woman who underwent hysterectomy for uncontrolled postpartum bleeding continued to have hemoperitoneum. Diagnosis: Two days after surgery, massive hemoperitoneum was identified on computed tomography scan, and acquired UVM was diagnosed by angiography. Interventions: The patient was successfully treated using TAE with an n-Butyl cyanoacrylate. Outcomes: After embolization, hemodynamic stability was achieved. A day after embolization, hemoglobin was 10.2 g/dL, and the patient was discharged from the hospital 4 days thereafter. Lessons: Although the overall incidence of acquired UVM after hysterectomy is low, bleeding from acquired UVM should be considered as one of the differential diagnoses in the immediate postpartum period, especially when the clinical symptoms do not correlate with the amount of blood loss. A high index of suspicion, prompt diagnosis and intervention, and a multidisciplinary approach in the management were the elements of a successful outcome in this case.

The ability to incorporate a desired functionality into proteins of interest in a site-specific manner can provide powerful tools for investigating biological systems and creating therapeutic conjugates. However, there are not any universal methods that can be applied to all proteins, and it is thus important to explore the chemical strategy for protein modification. In this paper, we developed a new reactive peptide tag/probe pair system for site-specific covalent protein labeling. This method relies on the recognition-driven reaction of a peptide tag and a molecular probe, which comprises the lysine-containing short histidine tag (KH6 or H6K) and a binuclear nickel (II)- nitrilotriacetic acid (Ni2+-NTA) complex probe containing a lysine-reactive N-acyl-N-alkyl sulfonamide (NASA) group. The selective interaction of the His-tag and Ni2+-NTA propeles a rapid nucleophilic reaction between a lysine residue of the tag and the electrophilic NASA group of the probe by the proximity effect, resulting in the tag-site-specific functionalization of proteins. We characterized the reactive profile and site-specificity of this method using model peptides and proteins in vitro, and demonstrated the general utility for production of a nanobody-chemical probe conjugate without compromising its binding ability.