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Background: Interstitial lung abnormalities (ILAs) are associated with the risk of lung cancer and its mortality. However, the impact of ILA on treatment-related complications and survival in patients who underwent curative surgery is still unknown., Research Question: This study aimed to evaluate the significance of the presence of computed tomography-diagnosed ILA and histopathologically matched interstitial abnormalities on postoperative pulmonary complications (PPCs) and the long-term survival of patients who underwent surgical treatment for lung cancer., Study Design and Methods: A matched case-control study was designed to compare PPCs and mortality among 50 patients with ILA, 50 patients with idiopathic pulmonary fibrosis (IPF) and 200 controls. Cases and controls were matched by sex, age, smoking history, tumour location, the extent of surgery, tumour histology and pathological TNM stage., Results: Compared with the control group, the OR of the prevalence of PPCs increased to 9.56 (95% CI 2.85 to 32.1, p<0.001) in the ILA group and 56.50 (95% CI 17.92 to 178.1, p<0.001) in the IPF group. The 5-year overall survival (OS) rates of the control, ILA and IPF groups were 76% (95% CI 71% to 83%), 52% (95% CI 37% to 74%) and 32% (95% CI 19% to 53%), respectively (log-rank p<0.001). Patients with ILA had better 5-year OS than those with IPF (log-rank p=0.046) but had worse 5-year OS than those in the control group (log-rank p=0.002)., Conclusions: The presence of radiological and pathological features of ILA in patients with lung cancer undergoing curative surgery was associated with frequent complications and decreased survival., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) that results from an immune-mediated reaction involving various antigens in susceptible individuals. However, the clinical characteristics and outcomes of HP in South Korea are not well understood., Objectives: This study was conducted to identify the clinical characteristics and outcomes of HP in South Korea., Design: This is a retrospective observational study investigating patients with pathologically confirmed HP at our center, along with a comprehensive review of published HP cases in the Republic of Korea., Methods: This retrospective study analyzed 43 patients with pathologically proven HP at a single tertiary hospital in Korea between 1996 and 2020. In addition, case reports of HP published in Korea were collected. The clinical characteristics, etiologies, treatment, and outcomes of patients from our center, as well as case reports, were reviewed. Patients from our hospital were divided into fibrotic and nonfibrotic subtypes according to the ATS/JRS/ALAT guidelines., Results: Among 43 patients with biopsy-proven HP, 12 (27.9%) and 31 (72.1%) patients were classified into the fibrotic and nonfibrotic subtypes, respectively. The fibrotic HP group was older (64.6 ± 8.5 versus 55.2 ± 8.3, p  = 0.002) with less frequent complaints of fever (0% versus 45.2%, p  = 0.013) compared to the nonfibrotic HP group. The most common inciting antigen was household mold (21, 48.8%), followed by inorganic substances (6, 14.0%). Inciting antigens were not identified in eight (18.6%) patients. Treatment of corticosteroids was initiated in 34 (79.1%) patients. An analysis of 46 patients from Korea by literature review demonstrated that reported cases were relatively younger and drugs were the most common etiology compared to our cohort., Conclusion: The analysis of reported cases, as well as our cohort, showed that exposure history and clinical manifestations are heterogeneous for patients with HP in South Korea.

Background and Aims: In a recent randomized controlled trial, a double bare metal stent (DBS) showed better stent patency than single-layer metal stents. However, clear evidence comparing the efficacy of uncovered (UCDBS) and partially covered (PCDBS) DBSs for distal malignant biliary obstruction (MBO) is lacking. Therefore, we compared the clinical outcomes including stent patency of UCDBSs versus PCDBSs., Methods: A multicenter, randomized study was performed in patients with distal MBO. The primary endpoint was stent patency. Secondary endpoints were the proportion of patients with patent stents at 6 months, risk factors for stent dysfunction, overall survival, technical and clinical success rates of stent placement, and other adverse events (AEs)., Results: Among 258 included patients, 130 were randomly assigned to the PCDBS group and 128 to the UCDBS group. The mean duration of stent patency of the PCDBS (421.2 days; 95% confidence interval [CI], 346.7-495.7) was longer than that of the UCDBS (377.4 days; 95% CI, 299.7-455.0), although total stent dysfunction and stent dysfunction within 6 months were not different between groups. Multivariate analysis indicated that chemotherapy after stent placement was a significant factor for overall survival (hazard ratio, .570; 95% CI, .408-.796) and had a marginal impact on stent patency (hazard ratio, 1.569; 95% CI, .923-2.667). There were no remarkable differences in AEs, including pancreatitis, cholecystitis, and stent migration, between the 2 groups., Conclusions: The use of PCDBSs compared with UCDBSs in patients with distal MBO has unclear benefits regarding stent patency and overall survival, although PCDBSs have a lower rate of tumor ingrowth. (Clinical trial registration number: NCT02937246.)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Purpose: Hypoxaemia is a significant adverse event during endoscopic retrograde cholangiopancreatography (ERCP) under monitored anaesthesia care (MAC); however, no model has been developed to predict hypoxaemia. We aimed to develop and compare logistic regression (LR) and machine learning (ML) models to predict hypoxaemia during ERCP under MAC., Materials and Methods: We collected patient data from our institutional ERCP database. The study population was randomly divided into training and test sets (7:3). Models were fit to training data and evaluated on unseen test data. The training set was further split into k-fold (k=5) for tuning hyperparameters, such as feature selection and early stopping. Models were trained over k loops; the i-th fold was set aside as a validation set in the i-th loop. Model performance was measured using area under the curve (AUC)., Results: We identified 6114 cases of ERCP under MAC, with a total hypoxaemia rate of 5.9%. The LR model was established by combining eight variables and had a test AUC of 0.693. The ML and LR models were evaluated on 30 independent data splits. The average test AUC for LR was 0.7230, which improved to 0.7336 by adding eight more variables with an l 1 regularisation-based selection technique and ensembling the LRs and gradient boosting algorithm (GBM). The high-risk group was discriminated using the GBM ensemble model, with a sensitivity and specificity of 63.6% and 72.2%, respectively., Conclusion: We established GBM ensemble model and LR model for risk prediction, which demonstrated good potential for preventing hypoxaemia during ERCP under MAC., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

In the wake of the COVID-19 pandemic, lung disorders have become a major health concern for humans. Allergic asthma is the most prevalent form of asthma, and its treatments target the inflammation process. Despite significant developments in the diagnosis and management of allergic asthma, side effects are a major concern. Additionally, its extreme heterogeneity impedes the efficacy of the majority of treatments. Thus, newer, safer therapeutic substances, such as natural products, are desired. Citrus junos Tanaka has traditionally been utilized as an anti-inflammatory, sedative, antipyretic, and antitoxic substance. In this study, the protective effects of Citrus junos Tanaka peel extract (B215) against lung inflammation were examined, and efforts were made to understand the underlying protective mechanism using an HDM-induced lung inflammation murine model. The administration of B215 reduced immune cell infiltration in the lungs, plasma IgE levels, airway resistance, mucus hypersecretions, and cytokine production. These favorable effects alleviated HDM-induced lung inflammation by modulating the NF-κB signaling pathway. Hence, B215 might be a promising functional food to treat lung inflammation without adverse effects.

This phase I/II study evaluated the safety and efficacy of a new histone deacetylase (HDAC) inhibitor, ivaltinostat, in combination with gemcitabine and erlotinib for advanced pancreatic ductal adenocarcinoma (PDAC). Patients diagnosed with unresectable, histologically confirmed PDAC who had not undergone previous therapy were eligible. Phase I had a 3 + 3 dose escalation design to determine the maximum tolerable dose (MTD) of ivaltinostat (intravenously on days 1, 8 and 15) with gemcitabine (1000 mg/m 2 intravenously on days 1, 8 and 15) and erlotinib (100 mg/day, orally) for a 28-day cycle. In phase II, patients received a six-cycle treatment with the MTD of ivaltinostat determined in phase I. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), disease control rate (DCR) and progression-free survival (PFS). The MTD of ivaltinostat for the phase II trial was determined to be 250 mg/m 2 . In phase II, 24 patients were enrolled. The median OS and PFS were 8.6 (95% confidence interval [CI]: 5.3-11.2) and 5.3 months (95% CI: 3.7-5.8). Of the 16 patients evaluated for response, ORR and DCR were 25.0% and 93.8% with a median OS/PFS of 10.8 (95% CI: 8.3-16.7)/5.8 (95% CI: 4.6-6.7) months. Correlative studies showed that mutation burden detected by cfDNA and specific blood markers such as TIMP1, pro-MMP10, PECAM1, proMMP-2 and IGFBP1 were associated with clinical outcomes. Although the result of a small study, a combination of ivaltinostat, gemcitabine and erlotinib appeared to be a potential treatment option for advanced PDAC., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Prostate-only radiotherapy (PORT) is widely used as the definitive treatment for localized prostate cancer. Prostate cancer has an α/β ratio; therefore, radiotherapy (RT) with a large fraction size is biologically effective for tumor control. The current external beam RT technique for PORT has been improved from three-dimensional conformal RT to intensity-modulated, stereotactic body, and image-guided RTs. These methods are associated with reduced radiation exposure to normal tissues, decreasing urinary and bowel toxicity. Several trials have shown improved local control with dose escalation through the aforementioned methods, and the efficacy and safety of intensity-modulated and stereotactic body RTs have been proven. However, the management of RT in patients with prostate cancer has not been fully elucidated. As a clinician, there are several concerns regarding the RT volume and dose considering the patient's age and comorbidities. Therefore, this review aimed to discuss the radiobiological basis and external beam technical advancements in PORT for localized prostate cancer from a clinician's perspective., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflict of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer (PC) has been validated for pathological staging; however, its significance for clinical staging remains uncertain. We validated the prognostic performance and suitability of the current staging system for the clinical staging of PC. We identified 1043 patients from our PC registry who were staged by imaging according to the 8th edition staging system and conducted analysis, including overall survival (OS) comparison. Gradual prognostic stratification according to stage hierarchy yielded significant OS differences between stage groups, except between stage I and II (p = 0.193). A substage comparison revealed no survival differences between IB (T2N0) and IIA (T3N0), which were divided by the T3 criterion only (p = 0.278). A higher N stage had significantly shorter OS than a lower N stage (all pairwise p < 0.05). However, among the 150 patients who received upfront surgery, the pathological stage was more advanced than the clinical stage in 86 (57.3%), mostly due to a false-negative cN0 (70.9%). Our results suggest that the new definition of T3 and the number-based N criteria in the 8th edition AJCC staging system may be not adequate for clinical staging. Establishing separate criteria more suitable for clinical staging should be considered.

Hepatic alcohol clearance is a key factor to overcome alcohol hangovers, and over the period, alcohol hangovers may lead to inflammation and oxidative stress. Natural food products with high antioxidant and anti-inflammatory effects might contribute to hepatic alcohol clearance, a hypothesis in this study. The present study aimed to evaluate the influence of turmeric ( Curcuma longa L., Zingiberaceae ) is an herbal product having antioxidant and anti-inflammatory activities, on alcohol metabolism using binge alcohol drinking rat model. In vivo investigations revealed that pretreatment with turmeric extract enhanced alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities upon binge ethanol (3 g/kg). Additionally, pretreatment with turmeric extract regulated CYP2E1 activity and levels of reactive oxygen species (ROS), Bax, Bcl-2, and inflammatory mediators like IL-1β, IL-6, and TNF-α. Moreover, turmeric extract upregulated superoxide dismutase, catalase, and glutathione peroxidase activities in liver tissues. Together, these observations shed light on the potential beneficial effects of turmeric extract against acute liver toxicity. The results offer an alternative natural functional food product, turmeric extract, to prevent the negative implications of binge drinking., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

A man with a history of neurofibromatosis presented to our hospital with a soft palate mass. Since the patient had neurofibromatosis, we diagnosed the mass as a neurofibroma and planned annual regular follow-up without any treatment. Five months later, the patient visited our emergency department because of uncontrolled epistaxis, and the mass was enlarged to the extent of the airway obstruction. Endoscopic resection was performed and the tumor was confirmed to be a leiomyosarcoma. The malignant potential of the new lesion in a neurofibromatosis patient should be actively evaluated and treated, if required., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Some BTC types respond to pembrolizumab, but there are no known prognostic factors to predict its treatment benefits. In this study, we attempted to identify the prognostic factors associated with pembrolizumab as a second-line treatment for gemcitabine-refractory BTC. This retrospective and single tertiary-center study involved all the consecutive patients (n = 80) with refractory advanced BTC, who were diagnosed as programmed cell death ligand 1-positive and treated with pembrolizumab between August 2017 and February 2021. The overall survival (OS) was analyzed using Cox regression analysis. The median OS was 6.0 months [95% confidence interval (CI): 3.87−8.20]; median progression-free survival was 1.9 months (95% CI: 1.82−1.98); and the response rate was 15.9%. In the multivariate Cox regression analysis, the TB [adjusted hazard ratio (HR) = 2.286; 95% CI: 1.177−4.440; p = 0.015), albumin levels (adjusted HR = 0.392; 95% CI: 0.211−0.725; p = 0.003), ALP levels (adjusted HR = 1.938; 95% CI: 1.105−3.400; p = 0.021), and LMR (adjusted HR = 0.325; 95% CI: 0.173−0.609; p < 0.001) were identified as significant variables associated with the OS. High albumin levels and LMR and low ALP levels and TB were significantly associated with better OS in patients treated with pembrolizumab.

Objectives: Diseases of the middle ear can interfere with normal sound transmission, which results in conductive hearing loss. Since video pneumatic otoscopy (VPO) findings reveal not only the presence of middle ear effusions but also dynamic movements of the tympanic membrane and part of the ossicles, analyzing VPO images was expected to be useful in predicting the presence of middle ear transmission problems. Using a convolutional neural network (CNN), a deep neural network implementing computer vision, this preliminary study aimed to create a deep learning model that detects the presence of an air-bone gap, conductive component of hearing loss, by analyzing VPO findings., Design: The medical records of adult patients who underwent VPO tests and pure-tone audiometry (PTA) on the same day were reviewed for enrollment. Conductive hearing loss was defined as an average air-bone gap of more than 10 dB at 0.5, 1, 2, and 4 kHz on PTA. Two significant images from the original VPO videos, at the most medial position on positive pressure and the most laterally displaced position on negative pressure, were used for the analysis. Applying multi-column CNN architectures with individual backbones of pretrained CNN versions, the performance of each model was evaluated and compared for Inception-v3, VGG-16 or ResNet-50. The diagnostic accuracy predicting the presence of conductive component of hearing loss of the selected deep learning algorithm used was compared with experienced otologists., Results: The conductive hearing loss group consisted of 57 cases (mean air-bone gap = 25 ± 8 dB): 21 ears with effusion, 14 ears with malleus-incus fixation, 15 ears with stapes fixation including otosclerosis, one ear with a loose incus-stapes joint, 3 cases with adhesive otitis media, and 3 ears with middle ear masses including congenital cholesteatoma. The control group consisted of 76 cases with normal hearing thresholds without air-bone gaps. A total of 1130 original images including repeated measurements were obtained for the analysis. Of the various network architectures designed, the best was to feed each of the images into the individual backbones of Inception-v3 (three-column architecture) and concatenate the feature maps after the last convolutional layer from each column. In the selected model, the average performance of 10-fold cross-validation in predicting conductive hearing loss was 0.972 mean areas under the curve (mAUC), 91.6% sensitivity, 96.0% specificity, 94.4% positive predictive value, 93.9% negative predictive value, and 94.1% accuracy, which was superior to that of experienced otologists, whose performance had 0.773 mAUC and 79.0% accuracy on average. The algorithm detected over 85% of cases with stapes fixations or ossicular chain problems other than malleus-incus fixations. Visualization of the region of interest in the deep learning model revealed that the algorithm made decisions generally based on findings in the malleus and nearby tympanic membrane., Conclusions: In this preliminary study, the deep learning algorithm created to analyze VPO images successfully detected the presence of conductive hearing losses caused by middle ear effusion, ossicular fixation, otosclerosis, and adhesive otitis media. Interpretation of VPO using the deep learning algorithm showed promise as a diagnostic tool to differentiate conductive hearing loss from sensorineural hearing loss, which would be especially useful for patients with poor cooperation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 The Authors. Ear & Hearing is published on behalf of the American Auditory Society, by Wolters Kluwer Health, Inc.)

In human colorectal cancer (CRC), TP53 is one of the most important driver genes. Immunohistochemistry (IHC) has been used most often to assess the variational status of TP53. Recently, next-generation sequencing (NGS) of the TP53 gene has increased. However, to our knowledge, a comparison between TP53 status evaluated by IHC and NGS has not been studied. Therefore, the primary aim of this study was to compare the clinical effect of TP53 status evaluated by IHC and NGS in patients with CRC. The secondary aim was to investigate the correlation between expression of p53 by IHC and variational status of TP53 by NGS. We performed immunohistochemical staining of p53 and sequencing of TP53 by NGS in 204 human samples of CRC. We then analyzed the correlation between variational status of TP53 and p53 expression, along with their prognostic impact in CRC patients. There was significant correlation between p53 expression and TP53 variation, TP53 variation and higher N stage, and positive p53 expression and higher N stage. Positive IHC expression of p53 was significantly associated with overall survival (OS) of CRC patients by univariate analysis and was revealed as an independent prognostic factor by multivariate analysis. Additionally, the nonsense/frameshift p53 expression pattern showed a significantly better prognosis than the wild type and missense p53 expression patterns. However, the variational status of TP53 was not significant in OS of CRC patients. These results suggest that IHC expression of p53 protein correlates with variation status of TP53 and expression of p53 protein rather than variation status of TP53 has more significant impact on the OS of CRC patients., (© 2022. The Author(s).)

Background and Aim: This study investigated the administration of combination therapy, allogeneic natural killer (NK) cells and pembrolizumab in the treatment of advanced biliary tract cancer to determine the safety and tolerability (phase 1) and the efficacy and safety (phase 2a)., Methods: Forty patients (phase 1, n = 6; phase 2a, n = 34) were enrolled between December 2019 and June 2021. The patients received highly activated allogeneic NK cells ("SMT-NK") on weeks 1 and 2 and pembrolizumab on week 1. This 3-week schedule (one cycle) was repeated until confirmed disease progression, intolerable adverse events (AEs), patient withdrawal, or finishing the maximum treatment schedule. The tumor response was evaluated after every three cycles., Results: In phase 1, four patients (66.7%) experienced seven AEs, but no severe AE was observed. In phase 2a, 126 AEs occurred in 29 patients (85.3%). Severe AEs (≥grade 3) were reported in 16 patients (47.1%). The overall response rate (ORR) was 17.4% in the full analysis set and 50.0% in the per-protocol set., Conclusions: SMT-NKs plus pembrolizumab resulted in no severe AEs directly related to the drug combination. The combination therapy also exerted antitumor activity with improved efficacy compared to the recent monotherapy with pembrolizumab in patients with advanced biliary tract cancer.

Background and Study Aims: Fatty pancreas is a potential risk factor for acute pancreatitis; however, whether it is also a risk factor for post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been evaluated. We aimed to determine the impact of fatty pancreas on the development of PEP., Methods: We analyzed the data of patients who underwent abdominal computed tomography (CT) scan and sequential therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Fatty change in the pancreas was evaluated based on pancreatic attenuation of unenhanced image on CT scan. The risk of fatty pancreas for the development of PEP was evaluated using a logistic regression model., Results: Of a total of 858 patients included in the study, 354 (41.3%) had fatty pancreas, while 504 (58.7%) did not have fatty pancreas. PEP developed in 28 patients (7.9%) in the fatty pancreas group and in 13 patients (2.6%) in the no fatty pancreas group. Fatty pancreas was significantly associated with the development of PEP (odds ratio [OR] [95% confidence interval [CI]] 2.38 [1.16-4.87]). A history of acute pancreatitis, female sex, difficult cannulation, and endoscopic papillary balloon dilation were also risk factors for the development of PEP. The risk for moderate-to-severe PEP development tended to be higher in the fatty pancreas group than in the no fatty pancreas group (OR [95% CI] 5.61 [0.63-49.62])., Conclusions: Fatty pancreas is a significant risk factor for the development of PEP. Clinicians need to be aware of the risk of fatty pancreas for the development of PEP prior to performing ERCP., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The ability to accurately predict the prognosis and intervention requirements for treating highly infectious diseases, such as COVID-19, can greatly support the effective management of patients, especially in resource-limited settings. The aim of the study is to develop and validate a multimodal artificial intelligence (AI) system using clinical findings, laboratory data and AI-interpreted features of chest X-rays (CXRs), and to predict the prognosis and the required interventions for patients diagnosed with COVID-19, using multi-center data. In total, 2282 real-time reverse transcriptase polymerase chain reaction-confirmed COVID-19 patients’ initial clinical findings, laboratory data and CXRs were retrospectively collected from 13 medical centers in South Korea, between January 2020 and June 2021. The prognostic outcomes collected included intensive care unit (ICU) admission and in-hospital mortality. Intervention outcomes included the use of oxygen (O2) supplementation, mechanical ventilation and extracorporeal membrane oxygenation (ECMO). A deep learning algorithm detecting 10 common CXR abnormalities (DLAD-10) was used to infer the initial CXR taken. A random forest model with a quantile classifier was used to predict the prognostic and intervention outcomes, using multimodal data. The area under the receiver operating curve (AUROC) values for the single-modal model, using clinical findings, laboratory data and the outputs from DLAD-10, were 0.742 (95% confidence interval [CI], 0.696−0.788), 0.794 (0.745−0.843) and 0.770 (0.724−0.815), respectively. The AUROC of the combined model, using clinical findings, laboratory data and DLAD-10 outputs, was significantly higher at 0.854 (0.820−0.889) than that of all other models (p < 0.001, using DeLong’s test). In the order of importance, age, dyspnea, consolidation and fever were significant clinical variables for prediction. The most predictive DLAD-10 output was consolidation. We have shown that a multimodal AI model can improve the performance of predicting both the prognosis and intervention in COVID-19 patients, and this could assist in effective treatment and subsequent resource management. Further, image feature extraction using an established AI engine with well-defined clinical outputs, and combining them with different modes of clinical data, could be a useful way of creating an understandable multimodal prediction model.

Dysarthria may present during the natural course of many degenerative neurological conditions. Hypokinetic and ataxic dysarthria are common in movement disorders and represent the underlying neuropathology. We developed an artificial intelligence (AI) model to distinguish ataxic dysarthria and hypokinetic dysarthria from normal speech and differentiate ataxic and hypokinetic speech in parkinsonian diseases and cerebellar ataxia. We screened 804 perceptual speech analyses performed in the Samsung Medical Center Neurology Department between January 2017 and December 2020. The data of patients diagnosed with parkinsonian disorders or cerebellar ataxia were included. Two speech tasks (numbering from 1 to 50 and reading nine sentences) were analyzed. We adopted convolutional neural networks and developed a patch-wise wave splitting and integrating AI system for audio classification (PWSI-AI-AC) to differentiate between ataxic and hypokinetic speech. Of the 395 speech recordings for the reading task, 76, 112, and 207 were from normal, ataxic dysarthria, and hypokinetic dysarthria subjects, respectively. Of the 409 recordings of the numbering task, 82, 111, and 216 were from normal, ataxic dysarthria, and hypokinetic dysarthria subjects, respectively. The reading and numbering task recordings were classified with 5-fold cross-validation using PWSI-AI-AC as follows: hypokinetic dysarthria vs. others (area under the curve: 0.92 ± 0.01 and 0.92 ± 0.02), ataxia vs. others (0.93 ± 0.04 and 0.89 ± 0.02), hypokinetic dysarthria vs. ataxia (0.96 ± 0.02 and 0.95 ± 0.01), hypokinetic dysarthria vs. none (0.86 ± 0.03 and 0.87 ± 0.05), and ataxia vs. none (0.87 ± 0.07 and 0.87 ± 0.09), respectively. PWSI-AI-AC showed reliable performance in differentiating ataxic and hypokinetic dysarthria and effectively augmented data to classify the types even with limited training samples. The proposed fully automatic AI system outperforms neurology residents. Our model can provide effective guidelines for screening related diseases and differential diagnosis of neurodegenerative diseases., Competing Interests: The authors have declared that no competing interests exist.

Background Since vaccines against COVID-19 became available, rare breakthrough infections have been reported despite their high efficacies. Purpose To evaluate the clinical and imaging characteristics of patients with COVID-19 breakthrough infections and compare them with those of unvaccinated patients with COVID-19. Materials and Methods In this retrospective multicenter cohort study, the authors analyzed patient (aged ≥18 years) data from three centers that were registered in an open data repository for COVID-19 between June and August 2021. Hospitalized patients with baseline chest radiographs were divided into three groups according to their vaccination status. Differences between clinical and imaging features were analyzed using the Pearson χ 2 test, Fisher exact test, and analysis of variance. Univariable and multivariable logistic regression analyses were used to evaluate associations between clinical factors, including vaccination status and clinical outcomes. Results Of the 761 hospitalized patients with COVID-19, the mean age was 47 years and 385 (51%) were women; 47 patients (6%) were fully vaccinated (breakthrough infection), 127 (17%) were partially vaccinated, and 587 (77%) were unvaccinated. Of the 761 patients, 412 (54%) underwent chest CT during hospitalization. Among the patients who underwent CT, the proportions without pneumonia were 22% of unvaccinated patients (71 of 326), 30% of partially vaccinated patients (19 of 64), and 59% of fully vaccinated patients (13 of 22) ( P < .001). Fully vaccinated status was associated with a lower risk of requiring supplemental oxygen (odds ratio [OR], 0.24 [95% CI: 0.09, 0.64; P = .005]) and lower risk of intensive care unit admission (OR, 0.08 [95% CI: 0.09, 0.78; P = .02]) compared with unvaccinated status. Conclusion Patients with COVID-19 breakthrough infections had a significantly higher proportion of CT scans without pneumonia compared with unvaccinated patients. Vaccinated patients with breakthrough infections had a lower likelihood of requiring supplemental oxygen and intensive care unit admission. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Schiebler and Bluemke in this issue.

The current study investigated the anti-neuroinflammatory effects and mechanisms of astragalin (Ast) and isoquercitrin (Que) isolated from chamchwi ( Aster scaber Thunb.) in the lipopolysaccharide (LPS)-activated microglia and hippocampus of LPS induced mice. LPS induced increased cytotoxicity, nitric oxide (NO) production, antioxidant activity, reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS) expression, the release of pro-inflammatory cytokines, protein kinase B phosphorylation, and mitogen-activated protein kinases (MAPK) phosphorylation in LPS-treated microglial cells. Intraperitoneal injection of LPS also induced neuroinflammatory effects in the murine hippocampus. Ast and Que significantly reduced LPS-induced production of NO, iNOS, and pro-inflammatory cytokines in the microglia and hippocampus of mice. Therefore, anti-inflammatory effects on MAPK signaling pathways mediate microglial cell and hippocampus inflammation. In LPS-activated microglia and hippocampus of LPS-induced mice, Ast or Que inhibited MAPK kinase phosphorylation by extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 signaling proteins. Ast and Que inhibited LPS-induced ROS generation in microglia and increased 1,1-diphenyl-2-picrylhydrazyl radical scavenging. In addition, LPS treatment increased the heme oxygenase-1 level, which was further elevated after Ast or Que treatments. Ast and Que exert anti-neuroinflammatory activity by down-regulation of MAPKs signaling pathways in LPS-activated microglia and hippocampus of mice.

Abstract: Basaloid squamous cell carcinoma (SCC) is very rare subtype of SCC of the lung and it is important to distinguish basaloid to other subtypes of SCCs, since the prognosis of basaloid subtype is considered poorer than that of other non-basaloid subtypes of SCCs. Aim of this study was to assess computed tomography (CT) findings of basaloid SCC of the lung in 12 patients.From January 2016 to April 2021, 12 patients with surgically proven basaloid SCC of the lung were identified. CT findings were analyzed, and the imaging features were compared with histopathologic reports. Clinical and demographic features were also analyzed.Axial location of the tumor was central in 5 patients, while 7 was in peripheral. Of the 7 patients whose tumors were located in the peripheral, margin of the tumor were smooth (n  = 2), lobulated (n  = 2), or spiculated (n  = 3). After contrast injection, net enhancement value ranged from 15.8 to 71.8 HU (median, 36.4 HU). Endobronchial growth were seen in 5 patients and these patients accompanied obstructive pneumonia or atelectasis. Internal profuse necrosis, cavitation, or calcifications were not seen.On CT, basaloid squamous cell presents as solitary nodule or mass with moderate enhancement. Tumor was located either peripheral or central compartment of the lung and cavitation was absent., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Antibiotic-resistant Cutibacterium acnes and dysbiosis of the skin microbiome are of increasing concern in acne treatment. Enterococcus faecalis, a widely used probiotic, has shown benefits for acne treatment by exerting antimicrobial activity against C. acnes. Therefore, this study aimed to investigate the efficacy and safety of an E. faecalis CBT SL-5-extract-containing lotion in patients with mild-to-moderate acne. Twenty patients were enrolled in this randomized, placebo-controlled, split-face comparative study. Patients were treated with E. faecalis lotion on one side of the face and a vehicle lotion on the other side for 4 weeks. The efficacy outcome measures included improvement in the investigators' assessment of acne severity, patient satisfaction, changes in skin parameters and diversity of the skin microbiome. The investigators' assessment score was significantly improved on the test side compared to the control side, after 2 weeks (p = 0.009) and 6 weeks (p < 0.0005). However, TEWL and skin hydration were not significantly different between the two groups. The phylogenetic diversity of the skin microbiota decreased over time in the skin samples of test side. In conclusion, E. faecalis CBT SL-5 extract can be a feasible and well-tolerated option for improving acne severity and skin microbiome dysbiosis in mild-to-moderate acne patients., (© 2022. The Microbiological Society of Korea.)

Background: Parkinsonian diseases and cerebellar ataxia among movement disorders, are representative diseases which present with distinct pathological gaits. We proposed a machine learning system that can differentiate Parkinson's disease (PD), cerebellar ataxia and progressive supranuclear palsy Richardson syndrome (PSP-RS) based on postural instability and gait analysis., Methods: We screened 1467 gait (GAITRite) and postural instability (Pedoscan) analyses performed in Samsung Medical Center from January 2019 to December 2020. PD, probable PSP-RS, and cerebellar ataxia (i.e., probable MSA-C, hereditary ataxia, and sporadic adult-onset ataxia) were included in the study. The gated recurrent units for GaitRite and the deep neural network for Pedoscan were applied. The enhanced weight voting ensemble (EWVE) method was applied to incorporate the two modalities., Results: We included 551 PD, 38 PSP-RS, 113 cerebellar ataxia and among them, 71 were MSA-C. Pedoscan-based and Gait-based model showed high sensitivity but low specificity in differentiating atypical parkinsonism from PD. The EWVE showed significantly improved specificity and reliable performance in differentiation between PD vs. ataxia patients (AUC 0.974 ± 0.036, sensitivity 0.829 ± 0.217, specificity 0.969 ± 0.038), PD vs. MSA-C (AUC 0.975 ± 0.020, sensitivity 0.823 ± 0.162, specificity 0.932 ± 0.030) and PD vs. PSP-RS (AUC 0.963 ± 0.028, sensitivity 0.555 ± 0.157, specificity 0.936 ± 0.031)., Conclusion: We proposed reliable Pedoscan-based, Gait-based and EWVE model in differentiating gait disorders by integrating information from gait and postural instability. This model can provide diagnosis guidelines to primary caregivers and assist in differential diagnosis of PD from atypical parkinsonism for neurologists., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, the protective functions of bacteria-free conditioned media from Bifidobacterium and Lactobacillus species against ultraviolet radiation-induced skin ageing and associated cellular damage were investigated. The effects of ultraviolet radiation-induced reactive oxygen species production were suppressed by all conditioned media; particularly, the loss of cell viability and downregulation of collagen gene expression were significantly reversed by the conditioned media from B. longum and B. lactis . Further exa mination of potential anti-pigmentation effects revealed that the B. lactis -derived conditioned media significantly inhibited tyrosinase activity and alpha-melanocyte-stimulating hormone-induced melanin production in human epidermal melanocytes. Further, the conditioned media suppressed the phosphorylation of extracellular signal- related kinase, which functions as an upstream regulator of melanogenesis. Therefore, B. lactis -derived conditioned media can potentially protect against cellular damage involved in skin-ageing processes., (© 2022 Yoo Kyung Hong et al., published by Sciendo.)

Background: Sternal osteomyelitis (OM) after median sternotomy is the rarest form of deep sternal wound infections (DSWIs). A retrospective study was implemented to evaluate the incidence and potential risk factors of sternal OM after median sternotomy., Methods: We analyzed 3,410 consecutive patients who underwent cardiothoracic surgery via median sternotomy from January 2005 to December 2019 at our institution. A sternal OM and control group without any sign of wound infections after median sternotomy were selected. Comparisons of the variables between the two groups were performed using the Student's t -test and Fisher's exact tests. The association of potential risk factors with sternal OM was tested by logistic regression analysis., Results: A total of 16 patients (0.47%) had sternal OM after median sternotomy. None of the variables were different between the sternal OM patients and the control group including body mass index (BMI), diabetes mellitus (DM), hypertension (HTN), left ventricle (LV) function, transfusion, operation time, cardiopulmonary bypass (CPB) time and intensive care unit and ventilator days. By univariate analysis, none of the variables were associated with an increased risk of sternal OM., Conclusions: The incidence of sternal OM after median sternotomy in our institution was 0.47% and there was no correlation between the known risk factors of DSWI and sternal OM in our study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1694/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Objectives: To evaluate radiologic and histologic correlations for interstitial lung abnormalities (ILAs) and to investigate radiologic or pathologic features contributing to disease progression and mortality., Methods: From 268 patients who underwent surgical lung biopsy between January 2004 and April 2019, 45 patients with incidentally detected ILA and normal pulmonary function were retrospectively included. CT features were classified as subpleural fibrotic or non-fibrotic, and changes in ILA over at least 2 years of follow-up were evaluated. Histologic findings were categorized as definite, probable, indeterminate, or alternative diagnosis for usual interstitial pneumonia (UIP) patterns. Overall and progression-free survival were calculated using the Kaplan-Meier method, and the Cox proportional hazard method was used to examine predictors for ILA progression and survival., Results: Among 36 subpleural fibrotic ILA subjects, 25 (69%) showed definite or probable UIP patterns, and 89% (8/9) of subpleural non-fibrotic ILA subjects showed an indeterminate or alternative diagnosis for UIP pattern on histopathology. On the radiologic-pathologic correlation, reticular opacity of fibrotic ILA was correlated with patchy involvement of fibrosis, and ground-glass attenuation of non-fibrotic ILA corresponded to diffuse interstitial thickening. The median progression time of ILA was 54 months, and fibrotic ILA increased the likelihood of progression (hazard ratio, 2.42; p = 0.017). The median survival time of ILA subjects was 123 months, and fibrotic ILA was associated with an increased risk of death (hazard ratio, 9.22; p = 0.025)., Conclusions: Subpleural fibrotic ILAs are associated with pathologic UIP patterns, and it is important to recognize subpleural fibrotic ILA on CT to predict disease progression and mortality., Key Points: • In total, 69% of subpleural fibrotic ILA showed definite or probable UIP patterns, while 11% of subpleural non-fibrotic ILA showed definite or probable UIP patterns. • Subpleural fibrotic ILA was associated with an increased rate of progression (hazard ratio, 2.42; p = 0.017), and the median progression-free time was 40 months. • Subpleural fibrotic ILA had an increased risk of death (hazard ratio, 9.22; p = 0.025), and the median survival time was 86 months., (© 2021. The Author(s), under exclusive licence to European Society of Radiology.)

FOLFIRINOX (oxaliplatin, leucovorin, irinotecan, and 5-fluorouracil) is a first-line chemotherapy for metastatic pancreatic cancer (PC). Chemotherapy-induced neutropenia is one of the most serious adverse events associated with advanced PC. Although UGT1A1 polymorphisms are associated with the metabolism of irinotecan, their role as surrogate markers for FOLFIRINOX-induced neutropenia has not been confirmed. We investigated risk factors for FN-in particular, UGT1A1 polymorphisms-in PC patients receiving FOLFIRINOX, using a single-center cohort registry. To investigate the association between UGT1A1 polymorphisms and FN, we divided patients into three groups based on the predicted UGT1A1 phenotype: extensive metabolizer (EM) vs. intermediate metabolizer (IM) vs. poor metabolizer (PM). A total of 154 patients (FN group ( n = 31) vs. non-FN group ( n = 123)) receiving first-line FOLFIRINOX were identified between December 2017 and July 2020. The Cox regression analysis showed that female sex (HR: 2.20; p = 0.031), Eastern Cooperative Oncology Group performance status = 1 (HR: 2.83; p = 0.008), UGT1A1 IM (HR: 4.30; p = 0.004), and UGT1A1 PM (HR: 4.03; p = 0.028) were statistically significant risk factors for FN. We propose that UGT1A1 is the strongest predictive factor for FN and that this gene should be screened prior to the administration of chemotherapy.

Background: This study aims to develop artificial intelligence (AI) system to automatically classify patients with maxillary sinus fungal ball (MFB), chronic rhinosinusitis (CRS), and healthy controls (HCs)., Methods: We collected 512 coronal image sets from ostiomeatal unit computed tomography (OMU CT) performed on subjects who visited a single tertiary hospital. These data included 254 MFB, 128 CRS, and 130 HC subjects and were used for training the proposed AI system. The AI system takes these 1024 sets of half CT images as input and classifies these as MFB, CRS, or HC. To optimize the classification performance, we adopted a 3-D convolutional neural network of ResNet 18. We also collected 64 coronal OMU CT image sets for external validation, including 26 MFB, 18 CRS, and 20 HCs from subjects from another referral hospital. Finally, the performance of the developed AI system was compared with that of the otolaryngology resident physicians., Results: Classification performance was evaluated using internal 5-fold cross-validation (818 training and 206 internal validation data) and external validation (128 data). The area under the receiver operating characteristic over the internal 5-fold cross-validation and the external validation was 0.96 ±0.006 and 0.97 ±0.006, respectively. The accuracy of the internal 5-fold cross-validation and the external validation was 87.5 ±2.3% and 88.4 ±3.1%, respectively. As a result of performing a classification test on external validation data from six otolaryngology resident physicians, the accuracy was obtained as 84.6 ±11.3%., Conclusions: This AI system is the first study to classify MFB, CRS, and HC using deep neural networks to the best of our knowledge. The proposed system is fully automatic but performs similarly to or better than otolaryngology resident physicians. Therefore, we believe that in regions where otolaryngology specialists are scarce, the proposed AI will perform sufficiently effective diagnosis on behalf of doctors., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Early detection and classification of bone tumors in the proximal femur is crucial for their successful treatment. This study aimed to develop an artificial intelligence (AI) model to classify bone tumors in the proximal femur on plain radiographs., Methods: Standard anteroposterior hip radiographs were obtained from a single tertiary referral center. A total of 538 femoral images were set for the AI model training, including 94 with malignant, 120 with benign, and 324 without tumors. The image data were pre-processed to be optimized for training of the deep learning model. The state-of-the-art convolutional neural network (CNN) algorithms were applied to pre-processed images to perform three-label classification (benign, malignant, or no tumor) on each femur. The performance of the CNN model was verified using fivefold cross-validation and was compared against that of four human doctors., Results: The area under the receiver operating characteristic (AUROC) of the best performing CNN model for the three-label classification was 0.953 (95% confidence interval, 0.926-0.980). The diagnostic accuracy of the model (0.853) was significantly higher than that of the four doctors (0.794) (P = 0.001) and also that of each doctor individually (0.811, 0.796, 0.757, and 0.814, respectively) (P<0.05). The mean sensitivity, specificity, precision, and F1 score of the CNN models were 0.822, 0.912, 0.829, and 0.822, respectively, whereas the mean values of four doctors were 0.751, 0.889, 0.762, and 0.797, respectively., Conclusions: The AI-based model demonstrated high performance in classifying the presence of bone tumors in the proximal femur on plain radiographs. Our findings suggest that AI-based technology can potentially reduce the misdiagnosis of doctors who are not specialists in musculoskeletal oncology., Competing Interests: The authors have declared that no competing interests exist.

Objective: Gastrointestinal (GI) cancer patients often experience severe malnutrition during cancer therapies due to gastrointestinal dysfunctions including poor digestion and absorption as well as tumor-associated anorexia. In this study, we performed a randomized clinical trial to determine the efficacy of oral nutrition supplement (ONS) enriched with omega-3 fatty acids on nutritional status, quality of life (QOL), and pro-inflammatory indices., Methods: Patients diagnosed with GI cancers were recruited and screened for eligibility. A total of 58 patients were randomly allocated to either the control group (n=27) or the experimental group (n=31). The intervention group received 200 ml ONS twice a day while the control group received routine care. Anthropometrics, Patient-Generated Subjective Global Assessment (PG-SGA) score, QOL score and nutrient intake data were collected at baseline, week 4 and week 8. Blood was drawn for biochemical assessments. Nine patients from each group dropped out of the study Forty patients (18 control patients and 22 intervention patients) completed the study., Results: This study showed that ONS intervention improved PG-SGA scores in the intervention group (p<0.01). Scores of physical functioning score and role functioning were declined only in the control group and the difference between week 8 and baseline for role functioning was significant (p<0.001). Fatigue score was steadily decreased in the experiment group, and the differences between week 8 and baseline was significant between two groups (p<0.02). However, no statistically significant improvement in biochemical markers of nutritional status and pro-inflammatory cytokine concentrations were found. These results suggests that ONS intervention for 8 weeks improves PG-SGA scores and QOL scores in patients undergoing cancer therapy.

In this study, a bamboo stick board with rotary-cut bamboo veneers was successfully fabricated. Additionally, vacuum heat (VH) treatment, which is a popular thermal modification method, was used to modify bamboo sticks. Therefore, the effects of different VH treatment temperatures on the dimensional stability and flexural properties of bamboo stick boards with and without bamboo veneers were investigated. For all boards, as the temperature increased to 220 °C, the thickness change rate and equilibrium moisture content decreased, and the flexural properties increased. The results exhibited that VH treatment improved the dimensional stability and flexural properties of the boards. Furthermore, the board with veneers had lower flexural properties and higher thickness swelling after water absorption than the board without veneers (BSB). The results indicated that bamboo veneer caused low flexural properties and high thickness swelling of the board compared to the BSB. However, the bamboo veneer played an aesthetic role in the appearance of the bamboo stick board.

Background/aims: Sphincterotomes are essential for endoscopic sphincterotomy (EST) and can also be used for cannulation in ERCP. A domestic new pull-type sphincterotome (Optimos™, Taewoong, Goyang, Korea) provides acceptable technical feasibility and safety, but there are no comparison results. Thus, this study compared the clinical performance and safety of Optimos™ sphincterotome to a conventional sphincterotome (CleverCut3™, Olympus, Tokyo, Japan) in patients who underwent ERCP., Methods: From April 2021 to July 2021, a randomized prospective comparative study was conducted on 104 consecutive patients who underwent ERCP in three medical centers. The primary endpoint was the clinical performance and safety of sphincterotomes during ERCP., Results: One hundred and four patients were assigned randomly to the Optimos™ group (n=51) or CleverCut3™ group (n=53). All demographic characteristics did not differ between the groups except the BMI. The technical success rate for cannulation, performance of EST, and total procedure time were similar in the two groups. The adverse events did not differ, even though two cases of post-ERCP pancreatitis occurred in CleverCut3™. On the other hand, in questionnaire analysis, CleverCut™ showed a better user's convenience (median [interquartile range] 4.0 [3.0-4.0] vs. 3.0 [3.0-4.0], p=0.013) and manipulability (median [interquartile range], 4.0 [3.0-4.0] vs. 3.0 [3.0-4.0], p=0.039) than Optimos™, even though the other profiles did not reveal any differences., Conclusions: New domestic pull-type sphincterotome can offer comparable clinical performance and safety profiles to conventional sphincterotome, but it needs refinements to increase the user's convenience and manipulability. Further improvement and innovation will be required to advance domestic medical devices.

Lactic acid bacteria present in Kimchi, such as Leuconostoc mesenteroides (Lm), Latilactobacillus curvatus (Lc), and Lactiplantibacillus plantarum (Lp) produce extracellular vesicles (ECVs) that modulate immune responses. The ECVs of probiotic Kimchi bacteria are abbreviated as LmV, LcV, and LpV. Treatment of macrophages (RAW264.7) with ECVs (LmV, LcV, and LpV) increased the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin-6 (IL-6). Immunostimulatory effects exerted on the RAW264.7 cells were stronger after treatments with LmV and LcV than with LpV. Treatment of mice with LcV (1 mg/kg, orally) induced splenocyte proliferation and subsequent production of both NO and cytokines (INF-γ, TNF-α, IL-4, and IL-10). Furthermore, pre-treatment of macrophages and microglial cells with ECVs prior to LPS stimulation significantly attenuated the production of NO and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Therefore, ECVs (LmV, LcV, and LpV) prevent inflammatory responses in the LPS-stimulated microglial cells by blocking the extracellular signal-regulated kinase (Erk) and p38 signaling pathways. These results showed that LmV, LcV, and LpV from Kimchi probiotic bacteria safely exert immunomodulatory effects.

Background/aims: : Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC., Methods: We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC: 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 1:3 propensity score matching (PSM) was performed to reduce selection bias., Results: Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis., Conclusions: We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.

We evaluated the proportion of BRCA 1 / 2 germline mutations in Korean patients with sporadic pancreatic ductal adenocarcinoma (PDAC) and its effect on the chemotherapeutic response of FOLFIRINOX. This retrospective study included patients who were treated at two tertiary hospitals between 2012 and 2020, were pathologically confirmed to have PDAC, and had undergone targeted next-generation sequencing-based germline genetic testing. Sixty-six patients were included in the study (24 men; median age 57.5 years). In the germline test, BRCA 1 / 2 pathogenic mutations were found in nine patients (9/66, 13%, BRCA 1 , n = 3; BRCA 2 , n = 5; and BRCA 1 / 2 , n = 1). There was no significant difference in the baseline characteristics according to BRCA mutation positivity. Among patients who underwent FOLFIRINOX chemotherapy, patients with a BRCA 1 / 2 mutation showed a higher overall response rate than those without a BRCA 1 / 2 mutation (71.4% vs. 13.9%, p = 0.004). Patients with a germline BRCA 1 / 2 mutation showed longer progression-free survival than those without a BRCA 1 / 2 mutation, without a significant time difference (18 months vs. 10 months, p = 0.297). Patients with a BRCA 1 / 2 mutation in the germline blood test had a higher response rate to FOLFIRINOX chemotherapy in PDAC. The high proportion of BRCA 1 / 2 germline mutations and response rate supports the need for germline testing in order to predict better treatment response.

Aim: Several studies have reported favorable outcomes of nonspecific interstitial pneumonia (NSIP); however, its prognosis and prognostic factors remain unclear. This study aimed to determine the outcomes of fibrotic NSIP and the prognostic factors for progression, relapse, and survival., Methods: In this retrospective study, we reviewed the clinical data of 204 patients diagnosed with fibrotic NSIP by surgical lung biopsy at Samsung Medical Center. The factors associated with survival and disease progression or relapse were determined using Cox proportional hazard analysis., Results: The median age of patients was 54 years and 67 (33%) patients were male. Also, 47 patients (23%) were current or ex-smokers. In all, 141 (69%) patients were diagnosed with idiopathic NSIP, while 63 (31%) patients were associated with connective tissue diseases. Progression or relapse was observed in 100 (49%) patients. The 5-year and 10-year survival rates were 94.6% and 90.4%, respectively. The factors associated with disease progression and relapse were diffusing capacity for carbon monoxide (DLco) <60% [adjusted hazard ratio (HR), 1.739; 95% confidence interval (CI), 1.036-2.921; p  = 0.036], bronchoalveolar lavage (BAL) lymphocyte >15% (adjusted HR, 0.592; 95% CI, 0.352-0.994; p  = 0.047), and treatment with corticosteroid and azathioprine (adjusted HR, 0.556; 95% CI, 0.311-0.955; p  = 0.048). Disease progression or relapse was associated with mortality (adjusted HR, 7.135; 95% CI, 1.499-33.971; p  = 0.014)., Conclusion: Preserved lung function, BAL lymphocytosis, and treatment with corticosteroids and azathioprine were associated with lower risks of disease progression and relapse, which were risk factors for mortality.

Background: Cancer stem cells (CSCs) are implicated in carcinogenesis, cancer progression, and recurrence. Several biomarkers have been described for pancreatic ductal adenocarcinoma (PDAC) CSCs; however, their function and mechanism remain unclear., Method: In this study, secretome analysis was performed in pancreatic CSC-enriched spheres and control adherent cells for biomarker discovery. Glutaredoxin3 (GLRX3), a novel candidate upregulated in spheres, was evaluated for its function and clinical implication., Results: PDAC CSC populations, cell lines, patient tissues, and blood samples demonstrated GLRX3 overexpression. In contrast, GLRX3 silencing decreased the in vitro proliferation, migration, clonogenicity, and sphere formation of cells. GLRX3 knockdown also reduced tumor formation and growth in vivo. GLRX3 was found to regulate Met/PI3K/AKT signaling and stemness-related molecules. ELISA results indicated GLRX3 overexpression in the serum of patients with PDAC compared to that in healthy controls. The sensitivity and specificity of GLRX3 for PDAC diagnosis were 80.0 and 100%, respectively. When GLRX3 and CA19-9 were combined, sensitivity was significantly increased to 98.3% compared to that with GLRX3 or CA19-9 alone. High GLRX3 expression was also associated with poor disease-free survival in patients receiving curative surgery., Conclusion: Overall, these results indicate GLRX3 as a novel diagnostic marker and therapeutic target for PDAC targeting CSCs., (© 2021. The Author(s).)

Aim: Sirtuin 2 (SIRT2) is a NAD+-dependent deacetylase involved in various biological functions via deacetylation of proteins, including histone protein. Hepatic fat accumulation from aging and excess caloric intake contribute to development of non-alcoholic fatty liver disease. The study aim was to elucidate the role of SIRT2 in lipid metabolism homeostasis., Materials and Methods: SIRT2 +/+ (C57BL/6) and SIRT2 -/- were randomly assigned to normal diet or high-fat diet (HFD) groups and fed for 6 weeks. Histological features of the livers were evaluated by hematoxylin and eosin and Masson's trichrome staining, and the levels of selected factors were determined by quantitative reverse transcription-polymerase chain reaction and western blot analysis., Key Findings: Although the SIRT2 -/- mice were viable, their livers exhibited higher glycogen accumulation, and skeletal muscle showed features of increased metabolic demand. The SIRT2 -/- mice attenuated HFD-induced weight gain, visceral adipose tissue formation, and fat accumulation in the liver in which the expressions of genes involved in metabolic substrate transport were modified. Additionally, the hepatocellular senescence and upregulated cell-cycle factors upon HFD intake in SIRT2 -/- livers suggested a role of SIRT2 in gene expression during abnormal metabolism. Moreover, the fibrotic phenotype of liver tissue without fat accumulation and the increased expression of genes involved in liver fibrosis in the HFD-fed SIRT2 -/- mice indicated that SIRT2 had a role in hepatocyte and hepatic stellate cell activation., Significance: Our results indicated that SIRT2 has a critical role in regulating lipid metabolic homeostasis and in sustaining liver integrity by modulating related gene expression., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Endoscopic biliary stenting (EBS) with a fully covered, self-expandable metallic stent (FC-SEMS) and plastic stent (PS) is safe and efficient for biliary anastomotic strictures (ASs) after a deceased donor liver transplantation. Limited studies have investigated the use of FC-SEMSs for biliary strictures post-living donor liver transplantation (LDLT). We compared the resolution rate of biliary ASs post-LDLT and the 12-month recurrence rates post-stent removal between EBS with an FC-SEMS, PS, and percutaneous transhepatic biliary drainage (PTBD)., Methods: Patients with biliary ASs after an LDLT (mean age: 57.3 years, 76.1% men) hospitalized between 2014 and 2017 were enrolled. Endoscopic retrograde cholangiopancreatography (ERCP) was repeated every 3-4 months. Patients were followed-up for at least 1-year post-stent removal., Results: Of the 75 patients enrolled, 16, 20, and 39 underwent EBS with an FC-SEMS, PS, and PTBD, respectively. Median follow-up period was 39.2 months. Fewer ERCP procedures were needed in the FC-SEMS group than in the PS group (median, 2 vs. 3; P = 0.20). Median stent indwelling periods were 4.7, 9.3, and 5.4 months in the FC-SEMS, PS, and PTBD groups, respectively (P = 0.006). The functional resolution rate was lower in the PS group (16/20) than in the FC-SEMS (16/16) or PTBD (39/39) group (P = 0.005). The radiologic resolution rate was higher in the FC-SEMS group (16/16) than in the PS group (14/20) (P = 0.07). The 12-month recurrence rates showed no significant differences (FC-SEMS, 4/16; PS, 3/16; PTBD, 6/39; P = 0.66). The rates of complications during treatment differed significantly between the groups (P = 0.04). Stent migration occurred in 1 (6.3%) and 5 (25.0%) patients in the FC-SEMS and PS groups, respectively (P = 0.59)., Conclusions: EBS with an FC-SEMS is comparable with EBS with a PS or PTBD in terms of biliary stricture resolution and 12-month recurrence rates. The use of FC-SEMSs is potentially effective and safe for biliary AS resolution after LDLT., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Development of effective therapeutics for mitigating the COVID-19 pandemic is a pressing global need. Neutralizing antibodies are known to be effective antivirals, as they can be rapidly deployed to prevent disease progression and can accelerate patient recovery without the need for fully developed host immunity. Here, we report the generation and characterization of a series of chimeric antibodies against the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Some of these antibodies exhibit exceptionally potent neutralization activities in vitro and in vivo, and the most potent of our antibodies target three distinct non-overlapping epitopes within the RBD. Cryo-electron microscopy analyses of two highly potent antibodies in complex with the SARS-CoV-2 spike protein suggested they may be particularly useful when combined in a cocktail therapy. The efficacy of this antibody cocktail was confirmed in SARS-CoV-2-infected mouse and hamster models as prophylactic and post-infection treatments. With the emergence of more contagious variants of SARS-CoV-2, cocktail antibody therapies hold great promise to control disease and prevent drug resistance., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Related to this work, the Institute of Cellular and Organismic Biology, Academia Sinica have filed a patent application on which HCW, YLL, MHT, and STDH are named as inventors. The other authors declare no conflict of interest.

Lactiplantibacillus plantarum, previously named "Lactobacillus plantarum," is found in a wide variety of environments exhibiting a high level of intraspecies genetic diversity. To investigate the strain diversity, we performed comparative genomic analyses of the 54 complete genome sequences. The results revealed that L. plantarum subsp. plantarum was split into three lineages, A, B and C. Of the genes beneficial for probiotic activity, only those associated with the biosynthesis of plantaricin (Pln), an L. plantarum-specific bacteriocin, were found to be significantly different among the lineages. The genes related to the biosynthesis of plnE/F were conserved throughout the three lineages, whereas the outgroups did not possess any Pln-producing genes. In lineage C, the deepest and ancestral type branch, plnE/F genes, were well conserved. In lineage B, loss of gene function was observed due to mobile elements in the pln loci. In lineage A, most strains were predicted to produce more than one type of Pln by possessing diverse Pln-encoding genes. These results showed the presence of functional diversity arising from the trifurcating evolution in L. plantarum subsp. plantarum and demonstrated that Pln is an indicator for differentiating the three lineages., (© 2021. The Author(s).)

Background: FAM83H was originally reported to be essential for dental enamel formation. However, FAM83H has recently been implicated in tumorigenesis and tumor progression. Analysis of a publicly available gene expression database revealed a significant correlation between FAM83H and Nectin1 mRNA expression and bladder urothelial carcinoma (BUC). Therefore, we investigated the association between FAM83H and Nectin1 expression levels and the survival and recurrence of BUC in BUC patients using a tissue microarray., Methods: We performed immunohistochemical staining of FAM83H and Nectin1 in 165 human BUC tissue sections, and analyzed the prognostic significance of FAM83H and Nectin1 expression., Results: Both FAM83H and Nectin1 were mainly expressed in the cytoplasm, and their expression was significantly associated. FAM83H expression was significantly correlated with higher histologic grade, higher T stage, higher TNM stage, and recurrence. Nectin1 expression was significantly associated with higher histologic grade and recurrence. Univariate analysis showed FAM83H expression and Nectin1 expression were significantly associated with worse overall survival (OS) and shorter relapse-free survival (RFS) of BUC patients. In multivariate analysis, levels of FAM83H and Nectin1 were independent indicators of shorter survival of BUC patients., Conclusions: Our results suggest that FAM83H and Nectin1 are important in the progression of BUC, and that expression patterns of these two proteins can be used as prognostic indicators of survival in BUC patients., (© 2021. The Author(s).)

Background: Digital tomosynthesis (DTS) is an imaging technique with benefits in reconstructing sequential cross-sectional images. We evaluated the diagnostic performance of DTS for silicone airway stents and stent-related complications in patients who underwent bronchoscopic intervention., Methods: This retrospective study included patients who underwent bronchoscopic intervention after chest radiography (CXR) and DTS examinations from September 2013 to August 2020. The interval between CXR, DTS, and bronchoscopic intervention was a maximum of 10 days. CXR and DTS images were evaluated using a bronchoscopic view as a reference. We calculated the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for assessing the diagnostic performance., Results: The total CXR, DTS, and bronchoscopic intervention-matching datasets comprised 213 cases from 119 patients and, silicone stents were present in 167 of them. The ability of DTS to detect silicone stents was better than that of CXR (sensitivity, 92.8% vs. 71.3%, P<0.001). Of the 167 cases with silicone stents, 53 experienced stent migration and 121 experienced stent obstructions due to granulation tissue or fibrosis. The sensitivity for detecting stent migration was also higher with DTS than with CXR (45.3% vs. 24.5%, P=0.025). The sensitivity for detecting the stent obstruction was better with DTS than with CXR (64.5% vs. 19.0%, P<0.001)., Conclusions: DTS was more sensitive and accurate in revealing silicone airway stents and silicone stent-related complications than CXR. However, there were limitations in confirming stent migration and obstruction with DTS due to granulation tissue growth and fibrosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jtd-21-1032). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

The achievement of the pathologic complete response (pCR) has been considered a metric for the success of neoadjuvant chemotherapy (NAC) and a powerful surrogate indicator of the risk of recurrence and long-term survival. This study aimed to develop a multimodal deep learning model that combined clinical information and pretreatment MR images for predicting pCR to NAC in patients with breast cancer. The retrospective study cohort consisted of 536 patients with invasive breast cancer who underwent pre-operative NAC. We developed a deep learning model to fuse high-dimensional MR image features and the clinical information for the pretreatment prediction of pCR to NAC in breast cancer. The proposed deep learning model trained on all datasets as clinical information, T1-weighted subtraction images, and T2-weighted images shows better performance with area under the curve (AUC) of 0.888 as compared to the model using only clinical information (AUC = 0.827, P < 0.05). Our results demonstrate that the multimodal fusion approach using deep learning with both clinical information and MR images achieve higher prediction performance compared to the deep learning model without the fusion approach. Deep learning could integrate pretreatment MR images with clinical information to improve pCR prediction performance., (© 2021. The Author(s).)

Background: Recently, the analysis of endolymphatic hydropses (EHs) via inner ear magnetic resonance imaging (MRI) for patients with Ménière disease has been attempted in various studies. In addition, artificial intelligence has rapidly been incorporated into the medical field. In our previous studies, an automated algorithm for EH analysis was developed by using a convolutional neural network. However, several limitations existed, and further studies were conducted to compensate for these limitations., Objective: The aim of this study is to develop a fully automated analytic system for measuring EH ratios that enhances EH analysis accuracy and clinical usability when studying Ménière disease via MRI., Methods: We proposed the 3into3Inception and 3intoUNet networks. Their network architectures were based on those of the Inception-v3 and U-Net networks, respectively. The developed networks were trained for inner ear segmentation by using the magnetic resonance images of 124 people and were embedded in a new, automated EH analysis system-inner-ear hydrops estimation via artificial intelligence (INHEARIT)-version 2 (INHEARIT-v2). After fivefold cross-validation, an additional test was performed by using 60 new, unseen magnetic resonance images to evaluate the performance of our system. The INHEARIT-v2 system has a new function that automatically selects representative images from a full MRI stack., Results: The average segmentation performance of the fivefold cross-validation was measured via the intersection of union method, resulting in performance values of 0.743 (SD 0.030) for the 3into3Inception network and 0.811 (SD 0.032) for the 3intoUNet network. The representative magnetic resonance slices (ie, from a data set of unseen magnetic resonance images) that were automatically selected by the INHEARIT-v2 system only differed from a maximum of 2 expert-selected slices. After comparing the ratios calculated by experienced physicians and those calculated by the INHEARIT-v2 system, we found that the average intraclass correlation coefficient for all cases was 0.941; the average intraclass correlation coefficient of the vestibules was 0.968, and that of the cochleae was 0.914. The time required for the fully automated system to accurately analyze EH ratios based on a patient's MRI stack was approximately 3.5 seconds., Conclusions: In this study, a fully automated full-stack magnetic resonance analysis system for measuring EH ratios was developed (named INHEARIT-v2), and the results showed that there was a high correlation between the expert-calculated EH ratio values and those calculated by the INHEARIT-v2 system. The system is an upgraded version of the INHEARIT system; it has higher segmentation performance and automatically selects representative images from an MRI stack. The new model can help clinicians by providing objective analysis results and reducing the workload for interpreting magnetic resonance images., (©Chae Jung Park, Young Sang Cho, Myung Jin Chung, Yi-Kyung Kim, Hyung-Jin Kim, Kyunga Kim, Jae-Wook Ko, Won-Ho Chung, Baek Hwan Cho. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 21.09.2021.)

Background: The prognostic significance of PIK3CA mutations in colorectal cancer (CRC) remains controversial. Recently, an association between programmed death ligand-1 (PD-L1) and PIK3CA mutations has been reported. The study presented here was conducted to investigate the effect of PIK3CA mutations on the prognosis of CRC patients and the association between PIK3CA mutations and PD-L1., Methods: PIK3CA mutations were analyzed by targeted next-generation sequencing using formalin-fixed paraffin-embedded specimens from 224 primary CRC patients. PD-L1 expression was evaluated by immunohistochemical staining., Results: PIK3CA mutations and PD-L1 expression were detected in 21.4% and 10.3% of CRC patients, respectively. PIK3CA mutations were significantly correlated with right-side colon cancer (P=0.011) and were correlated inversely with lymph node metastasis (P=0.026), distant metastasis (P=0.047), and high TNM stage (P=0.036). In univariate analysis, PIK3CA mutations were correlated with longer relapse-free survival in CRC patients. PD-L1 expression was correlated significantly with PIK3CA mutations (P<0.001)., Conclusions: PIK3CA mutations were associated with favorable prognostic factors, longer relapse-free survival, and expression of PD-L1. Further investigation is needed to identify whether PIK3CA mutations are a good prognostic factor. Additionally, further studies are needed to understand the mechanisms behind the correlation between PIK3CA mutations and PD-L1 expression., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-2315). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)