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Abstract Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.

Abstract Differentiating clinical stages based solely on positive findings from amyloid PET is challenging. We aimed to investigate the neuroanatomical characteristics at the whole-brain level that differentiate prodromal Alzheimer’s disease (AD) from cognitively unimpaired amyloid-positive individuals (CU A+) in relation to amyloid deposition and regional atrophy. We included 45 CU A+ participants and 135 participants with amyloid-positive prodromal AD matched 1:3 by age, sex, and education. All participants underwent 18F-florbetaben positron emission tomography and 3D structural T1-weighted magnetic resonance imaging. We compared the standardized uptake value ratios (SUVRs) and volumes in 80 regions of interest (ROIs) between CU A+ and prodromal AD groups using independent t-tests, and employed the least absolute selection and shrinkage operator (LASSO) logistic regression model to identify ROIs associated with prodromal AD in relation to amyloid deposition, regional atrophy, and their interaction. After applying False Discovery Rate correction at

Background/Aims Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. Methods This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10–100 ng/mL, 100–500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. Results This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. Conclusion High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.

Abstract Temporal parameters during swallowing are analyzed for objective and quantitative evaluation of videofluoroscopic swallowing studies (VFSS). Manual analysis by clinicians is time-consuming, complicated and prone to human error during interpretation; therefore, automated analysis using deep learning has been attempted. We aimed to develop a model for the automatic measurement of various temporal parameters of swallowing using deep learning. Overall, 547 VFSS video clips were included. Seven temporal parameters were manually measured by two physiatrists as ground-truth data: oral phase duration, pharyngeal delay time, pharyngeal response time, pharyngeal transit time, laryngeal vestibule closure reaction time, laryngeal vestibule closure duration, and upper esophageal sphincter opening duration. ResNet3D was selected as the base model for the deep learning of temporal parameters. The performances of ResNet3D variants were compared with those of the VGG and I3D models used previously. The average accuracy of the proposed ResNet3D variants was from 0.901 to 0.981. The F1 scores and average precision were 0.794 to 0.941 and 0.714 to 0.899, respectively. Compared to the VGG and I3D models, our model achieved the best results in terms of accuracy, F1 score, and average precision values. Through the clinical application of this automatic model, temporal analysis of VFSS will be easier and more accurate.

Abstract The purpose of this study was to clarify the association between improvement of spasticity in hemiplegic patient’s upper extremity with Botulinum toxin injection and improvement in postural balance and gait function. For this prospective cohort study, sixteen hemiplegic stroke patients with upper extremity spasticity were recruited. The plantar pressure with gait parameters, postural balance parameters, Modified Ashworth Scale, and Modified Tardieu Scale were evaluated before, 3 weeks and 3 months after Botulinum toxin A (BTxA) injection. Spasticity of hemiplegic upper extremity before, and after BTxA injection were significantly changed. Plantar pressure overload in affected side was reduced after BTxA injection. The mean X-speed and the horizontal distance decreased in postural balance analysis with eyes-opened test. Improvement in hemiplegic upper extremity spasticity showed positive correlation with gait parameters. In addition, improvement in hemiplegic upper extremity spasticity was positively correlated with change in balance parameters in postural balance analysis with eyes-closed and dynamic tests. This study focused on the effect of stroke patient’s hemiplegic upper extremity spasticity on their gait and balance parameters and identified that the BTxA injection on hemiplegic patient’s spastic upper extremity improve postural balance and gait function.

Abstract Background Recurrence is common in glioblastoma multiforme (GBM) because of the infiltrative, residual cells in the tumor margin. Standard therapy for GBM consists of surgical resection followed by chemotherapy and radiotherapy, but the median survival of GBM patients remains poor (~ 1.5 years). For recurrent GBM, anti-angiogenic treatment is one of the common treatment approaches. However, current anti-angiogenic treatment modalities are not satisfactory because of the resistance to anti-angiogenic agents in some patients. Therefore, we sought to identify novel prognostic biomarkers that can predict the therapeutic response to anti-angiogenic agents in patients with recurrent glioblastoma. Methods We selected patients with recurrent GBM who were treated with anti-angiogenic agents and classified them into responders and non-responders to anti-angiogenic therapy. Then, we performed proteomic analysis using liquid-chromatography mass spectrometry (LC–MS) with formalin-fixed paraffin-embedded (FFPE) tissues obtained from surgical specimens. We conducted a gene-ontology (GO) analysis based on protein abundance in the responder and non-responder groups. Based on the LC–MS and GO analysis results, we identified potential predictive biomarkers for anti-angiogenic therapy and validated them in recurrent glioblastoma patients. Results In the mass spectrometry-based approach, 4957 unique proteins were quantified with high confidence across clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic patterns (n = 269 proteins) between responders and non-responders. The GO term enrichment analysis revealed a cluster of genes related to immune cell-related pathways (e.g., TMEM173, FADD, CD99) in the responder group, whereas the non-responder group had a high expression of genes related to nuclear replisome (POLD) and damaged DNA binding (ERCC2). Immunohistochemistry of these biomarkers showed that the expression levels of TMEM173 and FADD were significantly associated with the overall survival and progression-free survival of patients with recurrent GBM. Conclusions The candidate biomarkers identified in our protein analysis may be useful for predicting the clinical response to anti-angiogenic agents in patients with recurred GBM.

Abstract In brain magnetic resonance imaging (MRI), white matter hyperintensity (WMH) is a commonly encountered finding and is known to reflect cerebral small vessel disease. The aim of our study was to investigate the association of coronary artery calcium (CAC) with WMH and elucidate the relationship between WMH and atherosclerotic risk factors in a large-scale healthy population. This retrospective study included 1337 individuals who underwent brain MRI and CAC scoring computed tomography at healthcare centers affiliated with a tertiary hospital. Cerebral WMH was defined as Fazekas score greater than 2 on brain MRI. Intracranial artery stenosis (ICAS) was also assessed and determined to be present when stenosis was more than 50% on angiography. The associations of risk factors, CAC score, and ICAS with cerebral WMH were assessed by multivariable regression analysis. In multivariable analysis, categories of higher CAC scores showed increased associations with both periventricular and deep WMHs in a dose-dependent relationship. The presence of ICAS was also significantly related to cerebral WMH, and among the clinical variables, age and hypertension were independent risk factors. In conclusion, CAC showed a significant association with cerebral WMH in a healthy population, which might provide evidence for referring to the CAC score to identify individuals with risk of cerebral WMH.

Abstract Raman spectroscopic-based biosensing strategies are often complicated by low signal and the presence of multiple chemical species. While surface-enhanced Raman spectroscopy (SERS) nanostructured platforms are able to deliver high quality signals by focusing the electromagnetic field into a tight plasmonic hot-spot, it is not a generally applicable strategy as it often depends on the specific adsorption of the analyte of interest onto the SERS platform. This paper describes a strategy to address this challenge by using surface potential as a physical binding agent in the context of microneedle sensors. We show that the potential-dependent adsorption of different chemical species allows scrutinization of the contributions of different chemical species to the final spectrum, and that the ability to cyclically adsorb and desorb molecules from the surface enables efficient application of multivariate analysis methods. We demonstrate how the strategy can be used to mitigate potentially confounding phenomena, such as surface reactions, competitive adsorption and the presence of molecules with similar structures. In addition, this decomposition helps evaluate criteria to maximize the signal of one molecule with respect to others, offering new opportunities to enhance the measurement of analytes in the presence of interferants.

We investigated the safety and efficacy of pemetrexed monotherapy in patients with lung adenocarcinoma and various renal conditions, including chronic kidney disease. We also analyzed whether baseline renal function affected progression-free survival (PFS). We retrospectively analyzed 71 patients who received maintenance-and second-line pemetrexed monotherapy. Patients were divided into two groups according to estimated glomerular filtration rate (eGFR): fair eGFR (>60 mL/min/1.73 m2) and lower eGFR (59 mL/min/1.73 m2 or less). The safety and efficacy were evaluated for each group. Median ages were 73.2 years in the lower eGFR group (n=28) and 64.5 years in the fair eGFR group (n=43). Patients with a lower eGFR achieved a median PFS of 4.7 months, while the median PFS for patients with a fair eGFR was 2.7 months. The difference between the two groups was not statistically significant (p=0.075). Both groups showed treatment-related low-grade hematological and non-hematological adverse events. Pemetrexed monotherapy is safe and effective in patients with lung adenocarcinoma with a lower eGFR.

Background/Aims Pleural fluid adenosine deaminase (ADA) levels are useful in discriminating tuberculous pleural effusions (TPEs) from malignant pleural effusions (MPEs). However, some patients with MPE exhibit high-ADA levels, which may mimic TPEs. There is limited data regarding the differential diagnosis between high-ADA MPE and high-ADA TPE. This study aimed to identify the predictors for distinguishing high-ADA MPEs from high-ADA TPEs. Methods Patients with TPE and MPE with pleural fluid ADA levels ≥ 40 IU/L were included in this study. Clinical, laboratory, and radiological data were compared between the two groups. Independent predictors and their diagnostic performance for high-ADA MPEs were evaluated using multivariate logistic regression analysis and receiver operating characteristic curve. Results A total of 200 patients (high-ADA MPE, n = 30, and high-ADA TPE, n = 170) were retrospectively included. In the multivariate analysis, pleural fluid ADA, pleural fluid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40 to 56 IU/L (3 points), pleural CEA level ≥ 6 ng/mL (6 points), and presence of pleural nodularity (3 points) for predicting high-ADA MPEs, a sum score ≥ 6 points yielded a sensitivity of 90%, specificity of 96%, positive predictive value of 82%, negative predictive value of 98%, and area under the receiver operating characteristic curve of 0.965. Conclusions A scoring system using three parameters may be helpful in guiding the differential diagnosis between high-ADA MPEs and high-ADA TPEs.

Abstract Even a tiny functioning pituitary adenoma could cause symptoms; hence, accurate diagnosis and treatment are crucial for management. However, it is difficult to diagnose a small pituitary adenoma using conventional MR sequence. Deep learning-based reconstruction (DLR) using magnetic resonance imaging (MRI) enables high-resolution thin-section imaging with noise reduction. In the present single-institution retrospective study of 201 patients, conducted between August 2019 and October 2020, we compared the performance of 1 mm DLR MRI with that of 3 mm routine MRI, using a combined imaging protocol to detect and delineate pituitary adenoma. Four readers assessed the adenomas in a pairwise fashion, and diagnostic performance and image preferences were compared between inexperienced and experienced readers. The signal-to-noise ratio (SNR) was quantitatively assessed. New detection of adenoma, achieved using 1 mm DLR MRI, was not visualised using 3 mm routine MRI (overall: 6.5% [13/201]). There was no significant difference depending on the experience of the readers in new detections. Readers preferred 1 mm DLR MRI over 3 mm routine MRI (overall superiority 56%) to delineate normal pituitary stalk and gland, with inexperienced readers more preferred 1 mm DLR MRI than experienced readers. The SNR of 1 mm DLR MRI was 1.25-fold higher than that of the 3 mm routine MRI. In conclusion, the 1 mm DLR MRI achieved higher sensitivity in the detection of pituitary adenoma and provided better delineation of normal pituitary gland than 3 mm routine MRI.

Abstract To evaluate the association between thyroid echogenicity and heterogeneity seen on ultrasonography (US) and thyroid function in pediatric and adolescent populations with autoimmune diffuse thyroid diseases (AITD). From 2000 to 2020, we reviewed thyroid ultrasound (US) images and thyroid function statuses in 133 children and adolescent AITD patients. Our review of the images focused on decreased echogenicity and heterogeneity, which were classified into four grades. Among patients with overt hypothyroidism or overt hyperthyroidism, 94.2% (65/69) showed a US grade of 3 or 4. In patients with subclinical hyper/hypothyroidism or euthyroidism, 45.3% (29/64) showed grades 1 or 2. There were no overt hyper/hypothyroidism patients with US grade 1. When we compared US grades according to thyroid status, more severe thyroid dysfunction was significantly associated with higher US grade (p = 0.047). Thyroid stimulating hormone (TSH) level differed significantly according to US grades when we evaluated hyperthyroid (p = 0.035) and hypothyroid (p = 0.027) states independently. 11 patients showed both US grade and thyroid function status changes on follow-up US. In children and adolescent AITD patients, there was an association between decreased echogenicity and heterogeneity on US and thyroid dysfunction.

Abstract From May 2015 to June 2016, data on 296 patients undergoing 1.5-Tesla MRI for symptoms of acute ischemic stroke were retrospectively collected. Conventional, echo-planar imaging (EPI) and echo train length (ETL)-T2-FLAIR were simultaneously obtained in 118 patients (first group), and conventional, ETL-, and repetition time (TR)-T2-FLAIR were simultaneously obtained in 178 patients (second group). A total of 595 radiomics features were extracted from one region-of-interest (ROI) reflecting the acute and chronic ischemic hyperintensity, and concordance correlation coefficients (CCC) of the radiomics features were calculated between the fast scanned and conventional T2-FLAIR for paired patients (1st group and 2nd group). Stabilities of the radiomics features were compared with the proportions of features with a CCC higher than 0.85, which were considered to be stable in the fast scanned T2-FLAIR. EPI-T2-FLAIR showed higher proportions of stable features than ETL-T2-FLAIR, and TR-T2-FLAIR also showed higher proportions of stable features than ETL-T2-FLAIR, both in acute and chronic ischemic hyperintensities of whole- and intersection masks (p

Background Hypereosinophilic syndrome is a rare disease that increases the number of circulating eosinophils in the body. It has many complications, including peripheral polyneuropathy. Peripheral polyneuropathy often does not respond well to conventional therapies. Transcutaneous neurostimulatory treatment, also known as scrambler therapy, is an alternative modality for the treatment of chronic retractable pain. Case A 47-year-old female presented with complaints of bilateral calf pain. She had been under treatment for peripheral polyneuropathy induced by hypereosinophilic syndrome for 7 years. Pharmacologic treatment did not affect the patient’s symptoms. Conclusions Transcutaneous neurostimulatory treatment was administered to the patient. It was effective on her symptoms, and the effect of pain alleviation continued for 3 months.

Abstract Generative adversarial network (GAN) creates synthetic images to increase data quantity, but whether GAN ensures meaningful morphologic variations is still unknown. We investigated whether GAN-based synthetic images provide sufficient morphologic variations to improve molecular-based prediction, as a rare disease of isocitrate dehydrogenase (IDH)-mutant glioblastomas. GAN was initially trained on 500 normal brains and 110 IDH-mutant high-grade astocytomas, and paired contrast-enhanced T1-weighted and FLAIR MRI data were generated. Diagnostic models were developed from real IDH-wild type (n = 80) with real IDH-mutant glioblastomas (n = 38), or with synthetic IDH-mutant glioblastomas, or augmented by adding both real and synthetic IDH-mutant glioblastomas. Turing tests showed synthetic data showed reality (classification rate of 55%). Both the real and synthetic data showed that a more frontal or insular location (odds ratio [OR] 1.34 vs. 1.52; P = 0.04) and distinct non-enhancing tumor margins (OR 2.68 vs. 3.88; P

Abstract Imaging biomarkers support the diagnosis of Alzheimer’s disease (AD). We aimed to determine whether combining automated brain volumetry on MRI and quantitative measurement of tau deposition on [18F] THK-5351 PET can aid discrimination of AD spectrum. From a prospective database in an IRB-approved multicenter study (NCT02656498), 113 subjects (32 healthy control, 55 mild cognitive impairment, and 26 Alzheimer disease) with baseline structural MRI and [18F] THK-5351 PET were included. Cortical volumes were quantified from FDA-approved software for automated volumetric MRI analysis (NeuroQuant). Standardized uptake value ratio (SUVR) was calculated from tau PET images for 6 composite FreeSurfer-derived regions-of-interests approximating in vivo Braak stage (Braak ROIs). On volumetric MRI analysis, stepwise logistic regression analyses identified the cingulate isthmus and inferior parietal lobule as significant regions in discriminating AD from HC and MCI. The combined model incorporating automated volumes of selected brain regions on MRI (cingulate isthmus, inferior parietal lobule, hippocampus) and SUVRs of Braak ROIs on [18F] THK-5351 PET showed higher performance than SUVRs of Braak ROIs on [18F] THK-5351 PET in discriminating AD from HC (0.98 vs 0.88, P = 0.033) but not in discriminating AD from MCI (0.85 vs 0.79, P = 0.178). The combined model showed comparable performance to automated volumes of selected brain regions on MRI in discriminating AD from HC (0.98 vs 0.94, P = 0.094) and MCI (0.85 vs 0.78; P = 0.065).

Background Joubert syndrome and mitochondrial disease are rare congenital diseases in which a wide range of symptoms affects multiple organs. Patients with these diseases present characteristic symptoms related to the musculoskeletal, respiratory, and neurological systems, which make it difficult for anesthesiologists to manage the patient’s airway and choose appropriate anesthetic drugs. Case A 13-year-old male patient with Joubert syndrome and mitochondrial disease underwent elective surgery to insert a continuous ambulatory peritoneal dialysis catheter. Anesthesia was induced and maintained with propofol, remifentanil, and rocuronium. An I-gel was inserted to secure the airway; however, the fitting did not work properly, so the patient was intubated. The operation was completed without any major problems, and the intubated patient was transferred to the intensive care unit. Conclusions Anesthesiologists should determine the method of anesthesia and prepare for unintended complications based on a full understanding of these congenital diseases.

Abstract Hydroxychloroquine has recently received attention as a treatment for COVID-19. However, it may prolong the QTc interval. Furthermore, when hydroxychloroquine is administered concomitantly with other drugs, it can exacerbate the risk of QT prolongation. Nevertheless, the risk of QT prolongation due to drug-drug interactions (DDIs) between hydroxychloroquine and concomitant medications has not yet been identified. To evaluate the risk of QT prolongation due to DDIs between hydroxychloroquine and 118 concurrent drugs frequently used in real-world practice, we analyzed the electrocardiogram results obtained for 447,632 patients and their relevant electronic health records in a tertiary teaching hospital in Korea from 1996 to 2018. We repeated the case–control analysis for each drug. In each analysis, we performed multiple logistic regression and calculated the odds ratio (OR) for each target drug, hydroxychloroquine, and the interaction terms between those two drugs. The DDIs were observed in 12 drugs (trimebutine, tacrolimus, tramadol, rosuvastatin, cyclosporin, sulfasalazine, rofecoxib, diltiazem, piperacillin/tazobactam, isoniazid, clarithromycin, and furosemide), all with a p value of

Abstract The purpose of this study was to establish a high-performing radiomics strategy with machine learning from conventional and diffusion MRI to differentiate recurrent glioblastoma (GBM) from radiation necrosis (RN) after concurrent chemoradiotherapy (CCRT) or radiotherapy. Eighty-six patients with GBM were enrolled in the training set after they underwent CCRT or radiotherapy and presented with new or enlarging contrast enhancement within the radiation field on follow-up MRI. A diagnosis was established either pathologically or clinicoradiologically (63 recurrent GBM and 23 RN). Another 41 patients (23 recurrent GBM and 18 RN) from a different institution were enrolled in the test set. Conventional MRI sequences (T2-weighted and postcontrast T1-weighted images) and ADC were analyzed to extract 263 radiomic features. After feature selection, various machine learning models with oversampling methods were trained with combinations of MRI sequences and subsequently validated in the test set. In the independent test set, the model using ADC sequence showed the best diagnostic performance, with an AUC, accuracy, sensitivity, specificity of 0.80, 78%, 66.7%, and 87%, respectively. In conclusion, the radiomics models models using other MRI sequences showed AUCs ranging from 0.65 to 0.66 in the test set. The diffusion radiomics may be helpful in differentiating recurrent GBM from RN. .

Abstract Current image processing methods for dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) do not capture complex dynamic information of time-signal intensity curves. We investigated whether an autoencoder-based pattern analysis of DSC MRI captured representative temporal features that improves tissue characterization and tumor diagnosis in a multicenter setting. The autoencoder was applied to the time-signal intensity curves to obtain representative temporal patterns, which were subsequently learned by a convolutional neural network. This network was trained with 216 preoperative DSC MRI acquisitions and validated using external data (n = 43) collected with different DSC acquisition protocols. The autoencoder applied to time-signal intensity curves and clustering obtained nine representative clusters of temporal patterns, which accurately identified tumor and non-tumoral tissues. The dominant clusters of temporal patterns distinguished primary central nervous system lymphoma (PCNSL) from glioblastoma (AUC 0.89) and metastasis from glioblastoma (AUC 0.95). The autoencoder captured DSC time-signal intensity patterns that improved identification of tumoral tissues and differentiation of tumor type and was generalizable across centers.

Background Postpartum hemorrhage is the leading cause of maternal mortality. Oxytocin being the most popular uterotonic agent, has been routinely administered after both vaginal delivery and cesarean section. Carbetocin is a newer uterotonic agent and provides the benefit of a longer duration of action without additional administration post-delivery. Methods We recruited 34 women undergoing elective cesarean section under spinal anesthesia. All patient was received spinal anesthesia using 0.5% hyperbaric Marcaine 8–10 mg in conjugation with fentanyl 20 μg in the left lateral decubitus position. Hartmann’s solution 10–15 ml/kg was administered before carbetocin. The operation started as soon as sensory block at level T4–T6 was confirmed. A non-invasive hemodynamic monitoring cuff (Finometer®) was attached to the patient’s finger soon after the induction of spinal anesthesia. Using the Finometer, we recorded the heart rate and mean arterial pressure at every 15 s, starting from 15 s before the administration of carbetocin to 5 min after. After the removal of the placenta, the bolus group was administered intravenous bolus injection of carbetocin 100 μg and the infusion group was administered carbetocin 100 μg diluted in 50 ml normal saline, over 5 min using an infusion pump. Results The demographic data showed no significant difference between the two groups. Furthermore, there were no significant hemodynamic differences between the two groups. Conclusions The method of administration of carbetocin does not influence its hemodynamic effects.

INTRODUCTION: Endometrial cancer is the most common type of cancer in the female genital tract. Most patients are diagnosed during postmenopausal periods. To investigate the demographic characteristics as well as cutoff value of endometrial thickness and ultrasound characteristics of endometrial cancer in postmenopausal patients. METHODS: we retrospectively analyzed 244 postmenopausal women who underwent endometrial sampling from February 2016 to December 2019. Information of patients was obtained through medical records. The patients were divided into two groups according to histopathological results. Group A included patients with endometrial cancer and group B included patients with non-malignant lesions. Data were summarized based on demographic and ultrasound characteristics. RESULTS: hypertension and history of endometrial hyperplasia were associated with the incidence of endometrial cancer in this study. Endometrial cancer was diagnosed in all ranges when the endometrial thickness was great than 5 mm. Endometrial fluid collection, with increased endometrial thickness, was a risk factor associated with endometrial cancer. CONCLUSION: regardless of symptoms and risk factors, endometrial histological confirmation in postmenopausal women should be conducted immediately if endometrial abnormalities such as an endometrial thickness greater than 5 mm or endometrial fluid collection are detected by transvaginal ultrasound.

Background Melanoma-associated antigen H1 (MAGEH1) is a protein that belongs to melanoma-associated antigen (MAGE) superfamily. Growth arrest and DNA damage 45G (GADD45G) is a member of the DNA damage-inducible gene family which responds to environmental stresses. We have previously shown that GADD45G is a protein that promotes apoptosis of renal tubular cells in response to a nephrotoxic injury. In this study, we show evidence that MAGEH1 interacts with GADD45G and is involved in the induction of nephrotoxin-induced apoptosis of renal tubular cells. Methods Primary human renal tubular epithelial (HRE) cells and human kidney 2 (HK-2) cells were used in this study. To produce stable cell lines in which MAGEH1 expression was silenced, HRE cells were transduced with a lentiviral vector encoding a single guide RNA construct targeting the MAGEH1 gene. To knockdown GADD45G expression in HRE cells, a vector containing short hairpin RNA (shRNA) was used. We used short interfering RNAs (siRNA) to achieve transient silencing of genes in HK-2 cells. Recombinant adenoviruses were synthesized to overexpress MAGEH1 and GADD45G proteins. Human protein microarray was used to identify proteins that binds to GADD45G. Co-immunoprecipitation assays were then performed to confirm microarray results. Cell death was induced by cyclosporine A (CsA). Real-time quantitative PCR assay was used to evaluate gene expression levels. The degree of apoptosis and necrosis of cultured cells was evaluated by flow cytometry. Expression levels of caspases were examined using western blot analysis. Results We found that GADD45G bound to one protein spotted in the protein microarray, which was subsequently identified as MAGEH1. We confirmed the interaction between GADD45G and MAGEH1 protein using the co-immunoprecipitation assay. MAGEH1 gene expression was not altered by CsA-induced cytotoxic injury, whereas GADD45G gene expression was increased significantly upon CsA treatment. MAGEH1 expression was significantly downregulated in GADD45G knockdown HRE stable cells suggesting that MAGEH1 expression may be dependent on GADD45G expression. CsA-induced apoptosis was significantly reduced in MAGEH1 knockdown HRE stable cells which led to an increased survival of these cells. Similar results were observed in GADD45G knockdown HRE stable cells. Accordingly, CsA-induced apoptosis was significantly decreased in MAGEH1 siRNA and GADD45G siRNA transfected HK-2 cells. CsA-induced activation of caspase-7 and caspase-9 was inhibited in MAGEH1 knockdown HRE stable cells, and similarly in GADD45G knockdown HRE stable cells. Conclusions To the best of our knowledge, this is the first study to show that MAGEH1 interacts with GADD45G and that MAGEH1 is involved in caspase-dependent apoptosis of renal tubular cells induced by nephrotoxic drugs.

IntroductionPsychological factors such as anxiety and confidence that students have in the patient care situation are important in that this affects the actual clinical performance. Students who are just starting clinical practice have a lack of clinical knowledge, skill proficiency, and patient communication skills, so they experience anxiety and lack of confidence in clinical setting. Practice in a safe environment, such as simulation education, can help students perform more settled and competently in patient care. The purpose of this study was to analyze the effect of high-fidelity simulation experience on anxiety and confidence in medical students.Materials and methodsThis study enrolled 37 5th-year students at Ajou University School of Medicine in 2020. Two simulation trainings were implemented, and a survey was conducted to measure students' level of anxiety and confidence before and after each simulation. Based on the research data, a paired t-test was conducted to compare these variables before and after the simulation, and whether this was their first or second simulation experience.ResultsStudents had a significantly lower level of anxiety and a significantly higher level of confidence after the simulation than before. In addition, after one simulation experience, students had less anxiety and more confidence before the second simulation compared to those without simulation experience.ConclusionsWe confirmed that medical students need to be repeatedly exposed to simulation education experiences in order to have a sense of psychological stability and to competently deliver medical treatment in a clinical setting. There is a practical limitation in that medical students do not have enough opportunities to meet the patients during clinical practice in hospitals. Therefore, in order to produce excellent doctors, students should have the expanded opportunities to experience simulation education so they can experience real-world medical conditions.

It can be difficult for anesthesiologists to determine the optimal dose of propofol for end-stage kidney disease (ESKD) patients due to changes in drug disposition. The purpose of this study was to evaluate the potency of propofol for inducing loss of consciousness in ESKD patients. Patients with normal kidney function (Control group, n = 15), those with ESKD (ESKD group, n = 15), and those with ESKD undergoing cervical epidural anesthesia (ESKD-CEB group, n = 15) were administered propofol by target-controlled infusion (TCI) using the Schneider model. The effect-site concentration (Ce) of propofol started at 0.5 μg/ml and increased in increments of 0.5 μg/ml until the patient did not respond to verbal commands. The relationship between the probability (P) of loss of consciousness and the Ce of propofol was analyzed in each group using logistic regression. The Ce values of propofol at the time of loss of consciousness were 4.3 ± 0.9, 3.7 ± 0.9, and 3.3 ± 1.0 μg/ml for the Control, ESKD, and ESKD-CEB* groups, respectively (*significant difference vs. control, P < 0.05). The estimated Ce50 values for lost ability to respond to verbal command were 4.56, 3.75, and 3.21 μg/ml for the Control, ESKD, and ESKD-CEB groups, respectively. In conclusion, when inducing anesthesia in ESKD patients, we recommend using an initial dose similar to that of patients with normal kidney function, or rather starting with a lower dose.

Small bowel obstruction due to congenital adhesion bands is a very rare occurrence during pregnancy, but is associated with significant fetal and maternal mortality. A 24-year-old primigravida woman, without previous abdominal surgeries, was referred to the emergency department at 35 weeks of gestation with the complaint of sudden abdominal pain. Abdominal magnetic resonance imaging revealed multiple loops of dilated small intestine and adhesion bands in the distal jejunum. The decision was made to proceed with a cesarean delivery and to explore the abdomen to determine the cause of the small bowel obstruction. A 2,680-gram male baby with a 7/9 Apgar score was delivered. A fibrotic band between the jejunal mesentery and distal jejunum caused the small bowel obstruction. After release of the adhesive band, the bowel regained its color and was viable. No adverse event developed in the mother or baby during a 1-year period. Although congenital bands are very rare in pregnant women, they can cause serious maternal and fetal mortality due to the delayed diagnosis and treatment, and physicians should be aware of this clinical condition.

There have been no studies on the characteristics of parenteral nutrition (PN) supply for adult inpatients in South Korea. The aim of this retrospective multicenter cross sectional study was to investigate the current practice and characteristics of PN support in hospitalized adult patients in South Korea for the first time. This study was conducted retrospectively for the adult patients who were hospitalized and received PN in nine hospitals on August 1st, 2017 to October 30th, 2017. We evaluated the type of PN formulation, PN administration period, administration route, calories supplied, amount of protein supplied, and laboratory results. Among the 11,580 inpatient admissions on that day, 1,439 patients received PN (12.4%). The majority of enrolled patients (96.5%) used the commercial PN, of which 86.2% were multi-chamber. 71.2% of them received PN peripherally. The average in hospital PN duration was 17.8 ± 52.6 days. Patients received only 65.4 ± 25.4% calories of their target calories. The in-hospital mortality of enrolled patients was 22%. In South Korea, commercial PN was usually administered to hospitalized adult patients and in-hospital mortality in adult patients using PN was higher in South Korea compared to other countries. This study provides the characteristics and the PN support status of hospitalized adult patients receiving PN in South Korea.

Background: This study aimed to reveal the clinicopathologic features and causes of bleeding in older patients with postmenopausal bleeding (PMB) and to investigate the correlation between the ultrasonographic findings and etiology of PMB. Methods: We retrospectively analyzed the causes and clinical characteristics of PMB in 498 patients who were diagnosed between January 2007 and December 2017. The population with PMB was divided into 2 groups according to age: Group A (n=204) included individuals more than 65 years of age and group B (n=294) included those less than 65 years of age. Clinical characteristics such as age, parity, underlying conditions, previous surgical history, and previous menopausal hormone therapy were compared between the groups. Cervical cytology testing and transvaginal ultrasonography were performed in all patients with PMB. Endometrial biopsy was performed in all cases of endometrial thickness ≥5 mm. Results: We examined 498 patients with PMB. In group A, atrophic endometrium (n=125, 61.27%) was the most common cause of PMB. Twenty-three patients had gynecological malignancy (cervical cancer: n=12, 5.88%; endometrial cancer: n=8, 3.42%; ovarian cancer: n=3, 1.46%), and 30 patients had benign gynecological disease (endometrial polyp: n=10, 4.90%; submucosal myoma: n=6, 2.94%; uterine prolapse: n=7, 3.42%; cervical dysplasia; n=5, 2.45%; cervical polyp: n=2, 0.98%). Forty patients had endometrial thickness ≥5 mm. Eight patients were diagnosed with endometrial cancer. All cases of endometrial cancer were diagnosed with endometrial thickness ＞10 mm. Conclusion: Atrophic endometrium was the most common cause of PMB in both groups, and approximately 12% of cases were associated with gynecological malignancy in older patients.

INTRODUCTION: We investigated the clinicopathologic features, method of treatment, and complications related to the conservative treatment and surgical treatment of patients with pelvic organ prolapse (POP).

Introduction We investigated the rate and longitudinal trends of gestational trophoblastic disease (GTD) incidence in the Republic of Korea between 2009 and 2015 using population-based data. Materials and Methods Data of patients diagnosed with GTD from 2009 to 2015 were obtained from the Health Insurance Review and Assessment Service/National Inpatient Sample (HIRA-NIS) in the Republic of Korea. The HIRA annually provides the HIRA-NIS, a collection of clinical data from over one million people. For each year, the HIRA-NIS extracted records of 13% of patients admitted at any one time during the year and 1% of all remaining patients using the weighted sample method. Results Medical records of 370,117 women with at least one pregnancy (GTD, ectopic pregnancy, abortion, or delivery) were extracted from a total of 4,476,495 records. Of these, 372 episodes of GTD were identified in women with a mean age of 35.4 ± 0.7 years. The incidence rate of GTD was 130 ± 10 cases per 100,000 pregnancies, which was classified as hydatidiform mole (HM), invasive mole, or malignant neoplasm of the placenta with incidence rates of 110 ± 10, 20 ± 0, or 10 ± 0 cases per 100,000 pregnancies, respectively. Incidence of GTD was lowest among women in their late 20 s and early 30 s. Occurrences of HM accounted for 80.3% all GTD cases. Weighted logistic analysis indicated that while age significantly affected the incidence of GTD (odds ratio (OR): 2.46; 95% confidence interval (CI) [1.79–3.37]; P < 0.001), socioeconomic status did not (OR: 1.94; 95% CI [1.0–3.79]; P = 0.05). Conclusions In the Republic of Korea, we observed overall incidence rates of GTD and HM of 1.3 and 1.1 per 1,000 pregnancies, respectively, which are similar to those reported in recent Western population-based studies. We also noted that annual incidence rates of GTD stabilized from 2009 to 2015.

PURPOSE:To assess the in vivo whole-brain relationship between uptake of [18F]THK-5351 on PET and cortical atrophy on structural MRI according to the presence and severity of Alzheimer's disease (AD). MATERIALS AND METHODS:Sixty-five participants (21 normal controls, 32 mild cognitive impairment [MCI] subjects, and 12 AD patients) were enrolled from a prospective multicenter clinical trial (NCT02656498). Structural MRI and [18F]THK-5351 PET were performed within a 2-month interval. Cortical volume and standardized uptake value ratios (SUVR) were calculated from MRI and PET images, respectively, for 35 FreeSurfer-derived cortical regions. Pearson's correlation coefficients between SUVR and cortical volume were calculated for the same regions, and correlated regions were compared according to disease severity and β-amyloid PET positivity. RESULTS:No significantly correlated regions were found in the normal controls. Negative correlations between SUVR and cortical volume were found in the MCI and AD groups, mainly in limbic locations in MCI and isocortical locations in AD. The AD group exhibited stronger correlations (r = -0.576-0.781) than the MCI group (r = 0.368-0.571). Hippocampal atrophy did not show any correlation with SUVR in the β-amyloid PET-negative group, but negatively correlated with SUVR (r = -0.494, P = .012) in the β-amyloid PET-positive group. CONCLUSIONS:Regional THK-5351 uptake correlated more strongly with cortical atrophy in AD compared with MCI, thereby demonstrating a close relationship between the neuro-pathologic process and cortical atrophy. Hippocampal atrophy was associated with both β-amyloid and THK-5351 uptake, possibly reflecting an interaction between β-amyloid and tau deposition in the neurodegeneration process.

BackgroundGrowth Arrest and DNA Damage 45γ (GADD45γ) is a member of the DNA damage-inducible gene family which responds to environmental stresses. Apoptosis is a critical mode of renal tubular cell death in nephrotoxin-induced acute kidney injury. In this study, we investigated the role of GADD45γ in renal tubular cell apoptosis induced by nephrotoxic drugs.MethodsPrimary human renal tubular epithelial (HRE) cells were used in this study. To derive stable cell lines in which GADD45γ expression was silenced, HRE cells were transduced with a plasmid encoding GADD45γ-specific shRNA. The recombinant adenovirus containing the GADD45γ gene was synthesized to overexpress GADD45γ protein. Cell death was induced by cisplatin and cyclosporine A (CsA). To prevent apoptotic cell death, pan-caspase inhibitor ZVAD-FMK was used. To prevent non-apoptotic cell death, necrostatin-1 and ferrostatin-1 were used. The degree of apoptosis and necrosis of cultured cells were evaluated by flow cytometry.ResultsExpression of the GADD45γ gene was significantly upregulated in response to treatment with CsA and cisplatin. Apoptosis and necrosis induced by these drugs were significantly reduced by silencing of GADD45γ, and significantly augmented by the overexpression of GADD45γ. The activation of caspase-3 and caspase-7 as well as caspase-9 induced by cisplatin or CsA was reduced by silencing of GADD45γ, and was augmented by the overexpression of GADD45γ, indicating that caspase activation is dependent on the expression of GADD45γ. ZVAD-FMK significantly inhibited apoptosis induced by cisplatin or CsA, indicating a role of caspases in mediating apoptotic cell death. ZVAD-FMK was effective to prevent necrosis as well, indicating that the observed necrosis was a secondary event following apoptosis at least in part.ConclusionsTo our knowledge, this is the first study to show that GADD45γ is required for the caspase-dependent apoptosis of renal tubular cells induced by nephrotoxic drugs.

To evaluate the patients' morphologic factors affecting radiation dose in pediatric chest CT.From November 2013 to May 2015, 315 pediatric chest CT scans were obtained using a CT scanner, and classified into 5 groups according to the patients' age. For each age group, the chest CT scans were divided into two subgroups. A cut-off value used was the 75th percentile of size-specific dose estimates (SSDE), age-specific diagnostic reference level (DRL): less than the 75th percentile of SSDE (Group A, n = 238) and greater than the 75th percentile of SSDE (Group B, n = 77). All CT scans were performed with the same protocol using automatic tube voltage selection and current modulation techniques. The morphologic factors of the patients including body mass index (BMI), arm angles, presence of medical devices in the scan field, and degree of off-centering within the CT gantry were compared between groups A and B.Group B showed narrower arm angles on scout and coronal reformatted images, higher frequency of the presence of devices and higher BMI than group A (P < 0.001, P < 0.001; P = 0.018, and P < 0.001, respectively). In multivariate analysis, narrower arm angles, the presence of devices on the scout images and higher BMI were independently associated with higher SSDE (P = 0.001, P = 0.037, and P < 0.001, respectively).During acquisition of the scout images, arms-down position and the presence of medical devices were associated with a high radiation dose above age-specific DRLs in pediatric chest CT, regardless of repositioning before the actual scanning. In addition, off-centering had no clinical impact on radiation dose in the routine practice.

Although advanced magnetic resonance imaging (MRI) techniques provide useful information for the differential diagnosis of intra-axial mass-like lesions, the specific diagnostic role of multimodal MRI over conventional magnetic resonance imaging (CMRI) alone in the differential diagnosis of mass-like lesions from a large heterogeneous cohort has not been studied. In this study, we aimed to determine the added value of a joint approach of diffusion-weighted imaging (DWI) and dynamic-susceptibility-contrast perfusion imaging (DSC-PWI) for diagnosis of intra-axial mass-like lesions, comparing them with CMRI alone. Furthermore, we performed these evaluations in a manner simulating clinical practice. Our institutional review board approved this retrospective study and waived the requirement for informed consent. A total of 1038 patients with intra-axial mass-like lesions were retrospectively recruited according to their histological and clinico-radiological diagnoses made between January 2005 and December 2014. All patients underwent CMRI, DWI and DSC-PWI. The diagnostic accuracy and confidence in diagnosing each type of intra-axial mass-like lesions, and for differentiating the intra-axial brain tumors from non-neoplastic lesions, were compared according to the MRI protocols. The disease-specific sensitivity of joint approach differed according to specific disease entities in diagnosing each disease category. Joint approach provided the best diagnostic accuracy for discriminating intra-axial brain tumors from non-neoplastic lesions, with high diagnostic accuracy (95.3-96.7%), specificity (82-84.0%), positive-predictive-value (97.0-97.3%), and negative-predictive-value (84.8-92.7%), with the reader's confidence values being significantly improved over those on CMRI alone (all p-values < 0.001). In conclusion, joint approach of DWI, DSC-PWI to CMRI helps to differentiate non-neoplastic lesions from intra-axial brain tumors, and improves diagnostic confidence compared with CMRI alone. The benefit from the combined imaging differs for each disease category; thus joint approach needs to be customized according to clinical suspicion.

To determine if perfusion in surgical cavity wall enhancement (SCWE) obtained in early post-treatment MR imaging can stratify time-to-progression (TTP) in glioblastoma.This study enrolled 60 glioblastoma patients with more than 5-mm-thick SCWEs as detected on contrast-enhanced MR imaging after concurrent chemoradiation therapy. Two independent readers categorized the shape and perfusion state of SCWEs as nodular or non-nodular and as having positive or negative perfusion compared with the contralateral grey matter on arterial spin labeling (ASL). The perfusion fraction on ASL within the contrast-enhancing lesion was calculated. The independent predictability of TTP was analyzed using the Kaplan-Meier method and Cox proportional hazards modelling.The perfusion fraction was higher in the non-progression group, significantly for reader 2 (P = 0.03) and borderline significantly for reader 1 (P = 0.08). A positive perfusion state and (P = 0.02) a higher perfusion fraction of the SCWE were found to become an independent predictor of longer TTP (P = 0.001 for reader 1 and P < 0.001 for reader 2). The contrast enhancement pattern did not become a TTP predictor.Assessment of perfusion in early post-treatment MR imaging can stratify TTP in patients with glioblastoma for adjuvant temozolomide therapy. Positive perfusion in SCWEs can become a predictor of a longer TTP.

Distinguishing non-neoplastic pituitary stalk lesions (non-NPSLs) from neoplastic pituitary stalk lesions (NPSLs) is a major concern in guiding treatment for a thickened pituitary stalk. Our study aimed to aid provide preoperative diagnostic assistance by combining clinical and magnetic resonance imaging (MRI) findings to distinguish non-NPSLs from NPSLs.We recruited 158 patients with thickened pituitary stalk lesions visible on MRI. Laboratory findings included hypopituitarism, diabetes insipidus (DI), and hyperprolactinemia. MR images were assessed for anterior-posterior thickness (mm), diffuse pituitary stalk thickening, cystic changes, a high T1 signal, and glandular or extrasellar involvement. A diagnostic model was developed using a recursive partitioning logistic regression analysis. The model was validated in an independent dataset comprising 63 patients, and its diagnostic performance was compared with that of the original radiological reports.A univariate analysis found significant associations of DI (P = 0.006), absence of extrasellar involvement (P = 0.002), and lower stalk thickness (P = 0.031) with non-NPSLs. A diagnostic model was created using the following parameters (in order of priority): 1) lack of extrasellar involvement, 2) stalk thickness < 5.3 mm, and 3) presence of DI. The diagnostic performance (area under the curve; AUC) of this model in the independent set was 0.813, representing a significant improvement over the original radiological reports (AUC: 0.713, P = 0.029).The joint diagnostic approach based on clinical and imaging-based factors robustly distinguished non-NPSLs from NPSLs. This approach could guide treatment strategies and prevent unnecessary surgery in patients with non-NPSL.

To determine whether multiple repeated administrations of gadolinium-based macrocyclic ionic MR contrast agent (MICA) are associated with intracranial gadolinium deposition and identify the predisposing factors for deposition in various clinical situations.In this institutional review board-approved retrospective study, 385 consecutive patients who underwent MICA-enhanced MR imaging were enrolled. The dentate nucleus-to-pons (DN/P) and globus pallidus-to-thalamus (GP/Th) signal intensity (SI) ratios on unenhanced T1-weighted images were recorded by 2 independent readers and averaged. The mean DN/P and GP/Th SI ratio difference between the last and the first examinations were tested using the one-sample t-test. Student's t-test and stepwise regression analysis were used to identify the predisposing factors for deposition based on the number of administrations, time interval, hepatic and renal function, magnetic field strength, and chemo- or radiation therapy.The mean DN/P SI ratio difference was not different from zero (P = .697), even in patients with ≥20 administrations (n = 33). Only patients with abnormal renal function showed an increase in the mean DN/P SI ratio difference (P = .019). The mean DN/P SI ratio difference was not associated with any predisposing factors. However, the mean GP/Th SI ratio difference showed decrease (P < .001), which was associated with age (P = .007), number of administrations (P = .01) and number of radiation therapy sessions (P = .022) on multivariate analysis.Multiple repeated administrations of MICA were not associated with increased T1 signal intensity in deep brain nuclei suggestive of Gd deposition in patients with normal renal function.

Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro. Here, we prepared the CFZ-loaded PM, PEG-PCL-deoxycholic acid (CFZ-PM) and assessed its in vivo anticancer efficacy and pharmacokinetic profiles. Despite in vitro metabolic protection of CFZ, CFZ-PM did not display in vivo anticancer efficacy in mice bearing human lung cancer xenograft (H460) superior to that of the clinically used cyclodextrin-based CFZ (CFZ-CD) formulation. The plasma pharmacokinetic profiles of CFZ-PM were also comparable to those of CFZ-CD and the residual tumors that persisted in xenograft mice receiving CFZ-PM displayed an incomplete proteasome inhibition. In summary, our results showed that despite its favorable in vitro performances, the current CFZ-PM formulation did not improve in vivo anticancer efficacy and accessibility of active CFZ to solid cancer tissues over CFZ-CD. Careful consideration of the current results and potential confounding factors may provide valuable insights into the future efforts to validate the potential of CFZ-based therapy for solid cancer and to develop effective CFZ delivery strategies that can be used to treat solid cancers.

The purpose of this study was to evaluate the accuracy of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) perfusion MR imaging for distinguishing tumor recurrence from post-treatment effect as alternatives to dynamic-susceptibility contrast-enhanced (DSC) perfusion MR imaging when the DSC image is uninterpretable.This retrospective study was approved by our institutional review board. Seventy one post-treatment glioblastoma patients who showed enlarged contrast-enhancing lesions on follow-up MR images after concurrent chemoradiotherapy and uninterpretable DSC images for corresponding enhancing lesions, underwent additional DWI and DCE MR imaging. The primary outcome was the frequency of interpretable DWI and DCE MR cases in these 71 patients. The secondary outcome was the area under the receiver operating characteristic curve (AUC) of DWI and DCE imaging parameters for distinguishing tumor recurrence from post-treatment effect in selected patients with interpretable DWI and DCE images. The imaging parameters were quantified as 10% cumulative histogram cutoff of apparent diffusion coefficient (ADC10) and 90% cumulative histogram cutoff of initial area under the time signal intensity curve (IAUC90). The AUCs were cross-validated by using leave-one-out method.Of the 71 patients, the uninterpretable DSC images were associated with treatment-related hemorrhage within the corresponding enhancing lesions (n = 54, 76.1%) and a near skull base location (n = 17, 23.9%). The frequencies of interpretable DWI and DCE image were 51 (71.8%) and 59 (83.1%) of the 71 cases with uninterpretable DSC images, respectively. Of the 45 selected patients with interpretable DWI and DCE images, the combination of DWI with DCE imaging showed a superior diagnostic performance than DWI or DCE imaging alone for differentiating tumor recurrence from post-treatment effect (cross-validated AUC: 0.78 versus 0.55 and 0.73 for reader 1; cross-validated AUC: 0.78 versus 0.53 and 0.75 for reader 2, respectively). Cross-validated accuracy of the single and combined imaging parameters also showed the highest for the combination of DWI with DCE MR imaging (72.9% for reader 1; 72.5% for reader 2) and the lowest for DWI alone (54.0% for reader 1; 56.4% for reader 2). Inter-reader agreement for DCE imaging was higher than that for DWI (intraclass correlation coefficient: 0.95 versus 0.87).DCE MR imaging could be a superior and more reproducible imaging biomarker than DWI for differentiating tumor recurrence from post-treatment effect in patients with post-treatment glioblastoma when DSC MR images are not interpretable.

The proteasome is a key regulator of cellular protein homeostasis and is a clinically validated anticancer target. The immunoproteasome, a subtype of proteasome expressed mainly in hematopoietic cells, was initially recognized for its role in antigen presentation during the immune response. Recently, the immunoproteasome has been implicated in several disease conditions including cancer and autoimmune disorders, but many of the factors contributing to these pathological processes remain unknown. In particular, the codon 60 polymorphism of the PSMB9 gene encoding the β1i immunoproteasome catalytic subunit has been investigated in the context of a variety of diseases. Despite this, previous studies have so far reported inconsistent findings regarding the impact of this polymorphism on proteasome activity. Thus, we set out to investigate the impact of the PSMB9 codon 60 polymorphism on the expression and activity of the β1i immunoproteasome subunit in a panel of human cancer cell lines. The β1i-selective fluorogenic substrate Acetyl-Pro-Ala-Leu-7-amino-4-methylcoumarin was used to specifically measure β1i catalytic activity. Our results indicate that the codon 60 Arg/His polymorphism does not significantly alter the expression and activity of β1i among the cell lines tested. Additionally, we also examined the expression of β1i in clinical samples from colon and pancreatic cancer patients. Our immunohistochemical analyses showed that ≈ 70% of clinical colon cancer samples and ≈ 53% of pancreatic cancer samples have detectable β1i expression. Taken together, our results indicate that the β1i subunit of the immunoproteasome is frequently expressed in colon and pancreatic cancers but that the codon 60 genetic variants of β1i display similar catalytic activities and are unlikely to contribute to the significant inter-cell-line and inter-individual variabilities in the immunoproteasome activity.