Genetic Risk Assessment of Nonsyndromic Cleft Lip with or without Cleft Palate by Linking Genetic Networks and Deep Learning Models.

Recent deep learning algorithms have further improved risk classification capabilities. However, an appropriate feature selection method is required to overcome dimensionality issues in population-based genetic studies. In this Korean case-control study of nonsyndromic cleft lip with or without cleft palate (NSCL/P), we compared the predictive performance of models that were developed by using the genetic-algorithm-optimized neural networks ensemble (GANNE) technique with those models that were generated by eight conventional risk classification methods, including polygenic risk score (PRS), random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and deep-learning-based artificial neural network (ANN). GANNE, which is capable of automatic input SNP selection, exhibited the highest predictive power, especially in the 10-SNP model (AUC of 88.2%), thus improving the AUC by 23% and 17% compared to PRS and ANN, respectively. Genes mapped with input SNPs that were selected by using a genetic algorithm (GA) were functionally validated for risks of developing NSCL/P in gene ontology and protein-protein interaction (PPI) network analyses. The IRF6 gene, which is most frequently selected via GA, was also a major hub gene in the PPI network. Genes such as RUNX2, MTHFR, PVRL1, TGFB3, and TBX22 significantly contributed to predicting NSCL/P risk. GANNE is an efficient disease risk classification method using a minimum optimal set of SNPs; however, further validation studies are needed to ensure the clinical utility of the model for predicting NSCL/P risk.

A deep learning-based framework for retinal fundus image enhancement.

PROBLEM: Low-quality fundus images with complex degredation can cause costly re-examinations of patients or inaccurate clinical diagnosis. AIM: This study aims to create an automatic fundus macular image enhancement framework to improve low-quality fundus images and remove complex image degradation. METHOD: We propose a new deep learning-based model that automatically enhances low-quality retinal fundus images that suffer from complex degradation. We collected a dataset, comprising 1068 pairs of high-quality (HQ) and low-quality (LQ) fundus images from the Kangbuk Samsung Hospital's health screening program and ophthalmology department from 2017 to 2019. Then, we used these dataset to develop data augmentation methods to simulate major aspects of retinal image degradation and to propose a customized convolutional neural network (CNN) architecture to enhance LQ images, depending on the nature of the degradation. Peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), r-value (linear index of fuzziness), and proportion of ungradable fundus photographs before and after the enhancement process are calculated to assess the performance of proposed model. A comparative evaluation is conducted on an external database and four different open-source databases. RESULTS: The results of the evaluation on the external test dataset showed an significant increase in PSNR and SSIM compared with the original LQ images. Moreover, PSNR and SSIM increased by over 4 dB and 0.04, respectively compared with the previous state-of-the-art methods (P < 0.05). The proportion of ungradable fundus photographs decreased from 42.6% to 26.4% (P = 0.012). CONCLUSION: Our enhancement process improves LQ fundus images that suffer from complex degradation significantly. Moreover our customized CNN achieved improved performance over the existing state-of-the-art methods. Overall, our framework can have a clinical impact on reducing re-examinations and improving the accuracy of diagnosis.

Characteristics of Gait Event and Muscle Activation Parameters of the Lower Limb on the Affected Side in Patients With Hemiplegia After Stroke: A Pilot Study.

Objectives: To confirm the characteristics of gait events and muscle activity in the lower limbs of the affected and unaffected sides in patients with hemiplegia. Design: Cross-sectional study. Setting: Motion analysis laboratory of the Wonkwang University Gwangju Hospital. Participants: Outpatients, diagnosed with ischemic stroke more than 3 months and less than 9 months before participating in the study (N=29; 11 men, 18 women). Interventions: Not applicable. Main Outcome Measures: The gait event parameters and time- and frequency-domain electromyogram (EMG) parameters of the lower limbs of the affected and unaffected sides was determined using BTS motion capture with the Delsys Trigno Avanti EMG wireless system. Results: The swing time, stance phase, swing phase, single support phase, and median power frequency of the gastrocnemius muscle showed a significant difference between the affected and unaffected sides. Using a logistic regression model, the swing phase, single support phase, and median frequency of the gastrocnemius muscle were selected to classify the affected side. Conclusion: The single support phase of the affected side is shortened to reduce load bearing, which causes a reduction in the stance phase ratio. Unlike gait-event parameters, EMG data of hemiplegic stroke patients are difficult to generalize. Among them, the logistic regression model with some affected side parameters expected to be set as the severity and improvement baseline of the affected side. Additional data collection and generalization of muscle activity is required to improve the classification model.

Comparison of Metabolites and Gut Microbes between Patients with Ulcerative Colitis and Healthy Individuals for an Integrative Medicine Approach to Ulcerative Colitis-A Pilot Observational Clinical Study (STROBE Compliant).

Ulcerative colitis (UC) is an intractable disease associated with high morbidity and healthcare costs. Metabolites and gut microbes are areas of interest for mainstream and complementary and alternative medicine. We, therefore, aimed to contribute to the discovery of an integrative medicine for UC by comparing and analyzing gut microbes and metabolites in patients with UC and in healthy individuals. This was an observational case-control study. Blood and stool samples were collected from the participants, and metabolite and gut microbial studies were performed. Among metabolites, formate, glycolate, trimethylamine, valine, and pyruvate levels were significantly different between the two groups. Among gut microbes, the abundance of Bacteroidetes at the phylum level; Bacteroidia at the class level; Bacteroidales and Actinomycetales at the order level; Prevotellaceae, Acidaminococcaceae, and Leptotrichiaceae at the family level; and Prevotella, Roseburia, Paraprevotella, Phascolarctobacterium, Ruminococcus, Coprococcus, Clostridium_XIVB, Atopobium, and Leptotrichia at the genus level was also significantly different. Most of the metabolites and gut microbes significantly different between the two groups were involved in energy metabolism and inflammatory processes, respectively. The results of this study could be helpful for the identification of targets for integrative medicine approaches for UC.

Heritability of maxillary dental cephalometric variables among monozygotic twins, dizygotic twins and their siblings.

OBJECTIVES: The purpose of this study was to investigate the heritability of dental cephalometric variables by analyzing vertical linear measurements and angular measurements of the upper incisor, canine, and first molar. MATERIALS AND METHODS: Among the 553 Korean patients who participated in twin studies conducted at Samsung Medical Center, 150 patients had their lateral cephalometric radiograph data included in this study. The group was comprised of 36 monozygotic (MZ) twins (males, 16 pairs; females, 20 pairs), 13 dizygotic (DZ) twins (males, 7 pairs; females, 6 pairs), and 26 same-sex sibling pairs (males, 11 pairs; females, 15 pairs). All patients were over 20 years old with a mean age of 39.75 years. Lateral cephalometric diagrams and linear measurements (6 vertical factors, 6 horizontal factors) were taken. Three axial planes were measured for each tooth; intraclass correlation coefficients (ICCs) were obtained for each group and heritability was calculated using Falconer's method. RESULTS: ICCs of vertical linear measurements (average 0.837, P < 0.01) and the tooth axis of the central incisor and canine (average 0.679, P < 0.001) were higher in the MZ group compared to the DZ and sibling groups; thus, these variables showed high heritability. CONCLUSIONS: Orthodontic treatment aiming to alter the tooth axis of the maxillary central incisor or canine or other vertical factors with greater heritability can be difficult, requiring strategic treatment planning to achieve desired treatment outcome and stability. CLINICAL RELEVANCE: The active early treatment to gain tooth eruption space can lead to normal tooth position.

COVID-19 outbreak response at a nursing hospital in South Korea in the post-vaccination era, including an estimation of the effectiveness of the first shot of the Oxford-AstraZeneca COVID-19 vaccine (ChAdOx1-S).

OBJECTIVES: We descriptively reviewed a coronavirus disease 2019 (COVID-19) outbreak at a nursing hospital in Gyeonggi Province (South Korea) and assessed the effectiveness of the first dose of the Oxford-AstraZeneca vaccine in a real-world population. METHODS: The general process of the epidemiological investigation included a public health intervention. The relative risk (RR) of vaccinated and unvaccinated groups was calculated and compared to confirm the risk of severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) infection, and vaccine effectiveness was evaluated based on the calculated RR. RESULTS: The population at risk was confined to ward E among 8 wards of Hospital X, where the outbreak occurred. This population comprised 55 people, including 39 patients, 12 nurses, and 4 caregivers, and 19 cases were identified. The RR between the vaccinated and unvaccinated groups was 0.04, resulting in a vaccine effectiveness of 95.3%. The vaccination rate of the nonpatients in ward E was the lowest in the entire hospital, whereas the overall vaccination rate of the combined patient and non-patient groups in ward E was the third lowest. CONCLUSION: The first dose of the Oxford-AstraZeneca vaccine (ChAdOx1-S) was effective in preventing SARS-CoV-2 infection. To prevent COVID-19 outbreaks in medical facilities, it is important to prioritize the vaccination of healthcare providers.

Comparison of Metabolites and Gut Microbes between Patients with Parkinson's Disease and Healthy Individuals-A Pilot Clinical Observational Study (STROBE Compliant).

INTRODUCTION: Even if levodopa, dopamine agonists, and others are used for patients with Parkinson's disease, the effect is not sustained, and side effects such as motor fluctuation and dyskinesia are more likely to appear as the dose increases. Thus, new approaches for managing Parkinson's disease are needed. This study aimed to compare the metabolites and gut microbes between patients with Parkinson's disease and healthy individuals. METHODS: This was an observational study with a case-control design. Metabolite and gut microbial analyses were performed using blood and stool samples collected from the subjects. RESULTS: Among the metabolites, the acetate, citrate, methionine, and trimethylamine levels were significantly different between the two groups. In the gut microbes, abundance of Bacteroidetes, Prevotella, Phascolarctobacterium, Pseudoflavonifractor, Eisenbergiella, and Gemella were also significantly different between the two groups. DISCUSSION: Metabolites are the products of gut microbes. Therefore, when the gut microbes change, the metabolites change accordingly. Metabolites and gut microbes that were significantly different between the two groups were mostly those involved in lipid and glucose metabolism. Our data may be helpful for the development of new drugs targeting metabolites and gut microbes through large-scale studies in the future.

Comparison of gait recovery patterns according to the paralyzed side in stroke patients: An observational study based on a retrospective chart review (STROBE compliant).

ABSTRACT: Gait rehabilitations have been abundantly performed for post-stroke patients, because gait is the most important factor for the return of post-stroke patients to daily life. However, conventional uniform gait rehabilitations tend to be tedious and reduce motivation. The aim of this study was to contribute to the development of personalized rehabilitation of gait by identifying differences in gait recovery pattern according to the paralyzed side of post-stroke patients.The gait analysis was performed on stroke patients who are right-handed and can walk independently. We retrospectively analyzed the results of pelvic movements and displacement of center of pressure (COP) during gait using corresponding equipments. To show the difference of gait recovery pattern according to the paralyzed side, we divided subjects into two groups, right (n = 19) and left (n = 20) hemiparesis group. The measured variables were as follows: tilt, obliquity, and rotation symmetries of pelvis; area, velocity, and lateral symmetry of COP.First, in the left hemiparesis group, obliquity (P < .01) and rotation (P < .01) symmetries of the movement of the pelvis were significantly improved in the follow-up compared to the initial gait analysis. In the right hemiparesis group, tilt (P < .001), obliquity (P < .001), and rotation (P < .05) symmetries were significantly improved in the follow-up compared to the initial gait analysis. Second, COP area and COP velocity values in the follow-up were significantly smaller than those in the initial gait analysis in the left (P < .001, P < .05) and right (P < .001, P < .01) hemiparesis groups. The positive value of lateral symmetry increased, although not a significant difference statistically, as walking ability improved in both groups. In the correlation analysis among variables obtained using Treadmill, there were significant positive linear relationships between the lateral symmetry and the COP area (P < .05), and between the COP velocity and the lateral symmetry (P < .001) of the follow-up gait analysis in the right hemiparesis group.It was confirmed that the gait recovery pattern differs according to the paralyzed side of post-stroke patients and the role of the intact side, such as moving the COP to the intact side, is important for the improvement of gait function in both groups.This study was registered with the Clinical Research Information Service (CRIS) of the Korea National Institute of Health (NIH), Republic of Korea (KCT0002984) and was approved by the Institutional Review Board (IRB) of the WKUGH (WKIRB [2018-25], November 28, 2018).

Expert-level segmentation using deep learning for volumetry of polycystic kidney and liver.

PURPOSE: Volumetry is used in polycystic kidney and liver diseases (PKLDs), including autosomal dominant polycystic kidney disease (ADPKD), to assess disease progression and drug efficiency. However, since no rapid and accurate method for volumetry has been developed, volumetry has not yet been established in clinical practice, hindering the development of therapies for PKLD. This study presents an artificial intelligence (AI)-based volumetry method for PKLD. MATERIALS AND METHODS: The performance of AI was first evaluated in comparison with ground-truth (GT). We trained a V-net-based convolutional neural network on 175 ADPKD computed tomography (CT) segmentations, which served as the GT and were agreed upon by 3 experts using images from 214 patients analyzed with volumetry. The dice similarity coefficient (DSC), interobserver correlation coefficient (ICC), and Bland-Altman plots of 39 GT and AI segmentations in the validation set were compared. Next, the performance of AI on the segmentation of 50 random CT images was compared with that of 11 PKLD specialists based on the resulting DSC and ICC. RESULTS: The DSC and ICC of the AI were 0.961 and 0.999729, respectively. The error rate was within 3% for approximately 95% of the CT scans (error<1%, 46.2%; 1%≤error<3%, 48.7%). Compared with the specialists, AI showed moderate performance. Furthermore, an outlier in our results confirmed that even PKLD specialists can make mistakes in volumetry. CONCLUSIONS: PKLD volumetry using AI was fast and accurate. AI performed comparably to human specialists, suggesting its use may be practical in clinical settings.

Development of Integrative Medicine Therapy for Gastrointestinal Autoimmune Diseases: A study protocol for a registry study.

BACKGROUND: Although the incidence of AD, including gastrointestinal AD, increases every year, there is no effective therapy for it yet. This causes high medical costs to be spent on the management of autoimmune patients every year. The aim of this study is to identify the characteristics related to the causes and symptoms of gastrointestinal autoimmune disease (AD) by collecting patients' information and to further contribute to the development of an integrative medicine therapy for gastrointestinal AD. METHODS/DESIGN: This study is a registry study of patients diagnosed with gastrointestinal AD. Subjects who voluntarily sign a written consent form after receiving a sufficient explanation will be assessed for compliance with the inclusion and exclusion criteria through a screening process on their first visit. A total of 35 subjects will be recruited; 15 will be assigned to the patient group, 10 to the control group, 8 to the caregiver group, and 2 to the medical staff group. The clinical information of the subjects will be evaluated through statistical analyses. As this study is a registry study, it will not test specific hypotheses. DISCUSSION: If this study identifies the significant characteristics of gastrointestinal AD patients, the results will be useful for the development of integrative medicine methods for the treatment of gastrointestinal AD. STUDY REGISTRATION: This study was registered with the Clinical Research Information Service (CRIS) of the Korea National Institute of Health (NIH), Republic of Korea (KCT0003976, date of registration: May 23, 2019).

Difference in gait recovery rate of hemiparetic stroke patients according to paralyzed side: A cross-sectional study based on a retrospective chart review.

In Donguibogam, a representative encyclopedic source of knowledge on traditional Korean medicine, left-sided hemiparesis due to stroke is called "Tan" as a sort of "Heyol-Byeong," while right-sided hemiparesis due to stroke is called "Tan" as a sort of "Gi-Byeong." According to the theory of Donguibogam, diseases on the left or right side of the human body must be treated differently. Clinically, the symptoms caused by left and right hemisphere lesions in stroke patients differ, as the functions of the left and right hemispheres differ. Considering these facts, when treating patients in clinical practice, it may be useful to distinguish between diseases on the left or right side according to Donguibogam. This study set out to confirm whether side-dependent gait rehabilitation could be used to treat hemiparetic stroke patients. Gait was selected for analysis, as it is the most important factor in returning stroke patients to daily life.This study conducted a retrospective chart review of stroke patients who satisfied the following criteria: outpatient or inpatient at the Wonkwang University Korean Medicine Hospital in Gwangju (WKUGH) with hemiparesis due to stroke; aged between 19 and 85 years old; with a stroke onset within the past 6 months; having undergone gait analysis (GAITRite) more than twice between September 1, 2017 and June 30, 2018 at the WKUGH, with a minimum 2-week interval between the first and next gait analysis; right-handed stroke patient; able to walk unaided. The spatio-temporal parameters for analysis included the FAP, walking velocity, step length, stance time, and swing time as obtained with GAITRite.In the initial gait analysis, there was no significant difference between the 2 groups in all spatio-temporal parameters. However, in the follow-up gait analysis, the left hemiparesis group showed a significantly higher FAP and faster walking velocity than the right hemiparesis group.This study found a difference in the recovery rate between the left and right hemiparesis groups. Based on this, we suggest that a different treatment strategy for gait rehabilitation can be used according to the paralyzed side.This study was approved by the Institutional Review Board (IRB) of the Wonkwang University Korean Medicine Hospital in Gwangju (WKUGH), Republic of Korea (WKIRB 2018 - 25, November 28, 2018). This trial was registered with the Clinical Research Information Service (CRIS) of the Korea National Institute of Health (NIH), Republic of Korea (KCT0002984).

Comparison of recovery patterns of gait patterns according to the paralyzed side in Korean stroke patients: Protocol for a retrospective chart review.

INTRODUCTION: In Traditional Korean Medicine (TKM), diseases on the left or right side of the human body have been treated differently according to the theory of Donguibogam, which is an encyclopedic source for TKM. In the Wind chapter of Donguibogam, left hemiparesis due to stroke is called Tan, a sort of Hyeol-Byeong, and right hemiparesis due to stroke is called Tan, a sort of Gi-Byeong. As neuroscience develops, it has been shown that the functions of the left and right hemispheres differ, as do the symptoms caused by differently located lesions in the brain. In light of these recent findings and the theory of Donguibogam, it may be useful when treating patients in clinical practice to consider the side of the human body on which symptoms appear. The aim here is to establish whether side-dependent treatments are more effective in treating patients with symptoms on different sides of the body. Specifically, this exploratory study investigates changes in gait pattern among stroke patients with hemiparesis or hemiplegia during gait recovery. METHODS: To develop this protocol, a retrospective review of charts will be used to assess differences in gait recovery patterns among stroke patients with left or right hemiparesis, using gait analysis systems that include GAITRite, G-walk, and Treadmill. The data will be selected from gait analysis performed more than twice in the period from September 1, 2017 to June 31, 2018 at Wonkwang University Gwangju Hospital (WKUGH). RESULTS: The primary outcomes include spatiotemporal parameters obtained using GAITRite (FAP, velocity, step length, swing time, and stance time); symmetric parameters obtained using G-walk (tilt, obliquity, and pelvis rotation symmetry); and center of pressure (COP) area and velocity as measured by Treadmill. DISCUSSION: This will be the first study to analyze the gait recovery pattern of stroke patients according to the paralyzed side by comparing spatiotemporal, symmetric, and COP parameters using gait analysis systems. Like all retrospective studies, the present research was subject to certain limitations related to bias (selection bias, recall bias, misclassification bias, confounding value bias), difficulty in assessing temporal relationships, and small sample size. However, these limitations were of less significance here because gait parameters and body side of symptoms of hemiplegia or hemiparesis are relatively clear. CONCLUSION: If the use of gait analysis systems (GAITRite, G-walk, and Treadmill) confirms differences in gait recovery pattern among stroke patients according to the paralyzed side, the findings will provide essential evidence for differential treatment of stroke patients on that basis.

Change of Safe Needling Depth at Acupoint GB21 according to Posture and Breathing.

Acupoint GB21 (Jianjing) is used for treating back and shoulder pain but is associated with a risk of pneumothorax. We aimed to determine the SND (safe needling depth) at GB21 according to posture and breathing in real time. Ultrasonographic images of GB21 during normal breathing, inspiration, and expiration in a SP (sitting position) were acquired for 52 healthy volunteers. Images were also acquired during normal respiration in the PP (prone position) with arms raised and lowered. The average SND was greater for men than for women (p < 0.05). Analysis of variance revealed that the SND was greater for the PP than for the SP (p = 0.01 and p < 0.05, resp.). Although the SND tended to change according to posture, the average depth tended to deviate widely in some subjects. During breathing, the differences between inspiration and expiration were less than 1 mm in most subjects, but some showed differences more than 4.5 mm. The SND at GB21 was greater in overweight subjects and significantly greater in the PP and during maximal expiration. However, intragroup differences were greater than the intergroup differences. Therefore, it is dangerous to simply apply needling depth on a gender or BMI basis. The practitioner would adjust the SND by examining the individual anatomical structures.

Hepatic Crtc2 controls whole body energy metabolism via a miR-34a-Fgf21 axis.

Liver plays a crucial role in controlling energy homeostasis in mammals, although the exact mechanism by which it influences other peripheral tissues has yet to be addressed. Here we show that Creb regulates transcriptional co-activator (Crtc) 2 is a major regulator of whole-body energy metabolism. Crtc2 liver-specific knockout lowers blood glucose levels with improved glucose and insulin tolerance. Liver-specific knockout mice display increased energy expenditure with smaller lipid droplets in adipose depots. Both plasma and hepatic Fgf21 levels are increased in Crtc2 liver-specific knockout mice, as a result of the reduced miR-34a expression regulated by Creb/Crtc2 and the induction of Sirt1 and Pparα. Ectopic expression of miR-34a reverses the metabolic changes in knockout liver. We suggest that Creb/Crtc2 negatively regulates the Sirt1/Pparα/Fgf21 axis via the induction of miR-34a under diet-induced obesity and insulin-resistant conditions.

NFIL3 is a negative regulator of hepatic gluconeogenesis.

OBJECTIVE: Nuclear factor interleukin-3 regulated (NFIL3) has been known as an important transcriptional regulator of the development and the differentiation of immune cells. Although expression of NFIL3 is regulated by nutritional cues in the liver, the role of NFIL3 in the glucose metabolism has not been extensively studied. Thus, we wanted to explore the potential role of NFIL3 in the control of hepatic glucose metabolism. MATERIALS/METHODS: Mouse primary hepatocytes were cultured to perform western blot analysis, Q-PCR and chromatin immunoprecipitation assay. 293T cells were cultured to perform luciferase assay. Male C57BL/6 mice (fed a normal chow diet or high fat diet for 27weeks) as well as ob/ob mice were used for experiments with adenoviral delivery. RESULTS: We observed that NFIL3 reduced glucose production in hepatocytes by reducing expression of gluconeogenic gene transcription. The repression by NFIL3 required its basic leucine zipper DNA binding domain, and it competed with CREB onto the binding of cAMP response element in the gluconeogenic promoters. The protein levels of hepatic NFIL3 were decreased in the mouse models of genetic- and diet-induced obesity and insulin resistance, and ectopic expression of NFIL3 in the livers of insulin resistant mice ameliorated hyperglycemia and glucose intolerance, with concomitant reduction in expression of hepatic gluconeogenic genes. Finally, we witnessed that knockdown of NFIL3 in the livers of normal chow-fed mice promoted elevations in the glucose levels and expression of hepatic gluconeogenic genes. CONCLUSIONS: In this study, we showed that NFIL3 functions as an important regulator of glucose homeostasis in the liver by limiting CREB-mediated hepatic gluconeogenesis. Thus, enhancement of hepatic NFIL3 activity in insulin resistant state could be potentially beneficial in relieving glycemic symptoms in the metabolic diseases.

Regulation of glucose metabolism from a liver-centric perspective.

Glucose homeostasis is tightly regulated to meet the energy requirements of the vital organs and maintain an individual's health. The liver has a major role in the control of glucose homeostasis by controlling various pathways of glucose metabolism, including glycogenesis, glycogenolysis, glycolysis and gluconeogenesis. Both the acute and chronic regulation of the enzymes involved in the pathways are required for the proper functioning of these complex interwoven systems. Allosteric control by various metabolic intermediates, as well as post-translational modifications of these metabolic enzymes constitute the acute control of these pathways, and the controlled expression of the genes encoding these enzymes is critical in mediating the longer-term regulation of these metabolic pathways. Notably, several key transcription factors are shown to be involved in the control of glucose metabolism including glycolysis and gluconeogenesis in the liver. In this review, we would like to illustrate the current understanding of glucose metabolism, with an emphasis on the transcription factors and their regulators that are involved in the chronic control of glucose homeostasis.

Medullary thyroid carcinoma with ectopic adrenocorticotropic hormone syndrome.

Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.

Arginine methylation of CRTC2 is critical in the transcriptional control of hepatic glucose metabolism.

Fasting glucose homeostasis is maintained in part through cAMP (adenosine 3',5'-monophosphate)-dependent transcriptional control of hepatic gluconeogenesis by the transcription factor CREB (cAMP response element-binding protein) and its coactivator CRTC2 (CREB-regulated transcriptional coactivator 2). We showed that PRMT6 (protein arginine methyltransferase 6) promotes fasting-induced transcriptional activation of the gluconeogenic program involving CRTC2. Mass spectrometric analysis indicated that PRMT6 associated with CRTC2. In cells, PRMT6 mediated asymmetric dimethylation of multiple arginine residues of CRTC2, which enhanced the association of CRTC2 with CREB on the promoters of gluconeogenic enzyme-encoding genes. In mice, ectopic expression of PRMT6 promoted higher blood glucose concentrations, which were associated with increased expression of genes encoding gluconeogenic factors, whereas knockdown of hepatic PRMT6 decreased fasting glycemia and improved pyruvate tolerance. The abundance of hepatic PRMT6 was increased in mouse models of obesity and insulin resistance, and adenovirus-mediated depletion of PRMT6 restored euglycemia in these mice. We propose that PRMT6 is involved in the regulation of hepatic glucose metabolism in a CRTC2-dependent manner.

A case of recurrent pulmonary inflammatory myofibroblastic tumor with aggressive metastasis after complete resection.

An inflammatory myofibroblastic tumor (IMT) is a rare disease entity reported to arise in various organs. It is thought to be a neoplastic or reactive inflammatory condition, controversially. The treatment of choice for myofibroblastic tumor is surgery, and recurrence is known to be rare. The optimal treatment method is not well-known for patients ineligible for surgery. We report a 47-year-old patient with aggressive recurrent IMT of the lungs. The patient had been admitted for an evaluation of back-pain two years after a complete resection of pulmonary IMT. Radiation therapy was performed for multiple bone recurrences, and the symptoms were improved. However the patient presented again with aggravated back-pain six months later. High-dose steroid and non-steroidal anti-inflammatory drugs were administered, but the disease progressed aggressively, resulting in spinal cord compression and metastasis to intra-abdominal organs. This is a very rare case of aggressively recurrent pulmonary IMT with multi-organ metastasis.

Radioimmunotherapy with (131)i-rituximab in a patient with diffuse large B-cell lymphoma relapsed after treatment with (90)y-ibritumomab tiuxetan.

We report a case that demonstrates the efficacy of radioimmunotherapy (RIT) with radioiodinated rituximab ((131)I-rituximab) for relapsed diffuse large B-cell lymphoma (DLBCL). A 79-year-old male patient with DLBCL initially achieved a complete response (CR) after six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. However, the lymphoma relapsed 20 months later. Although the patient had achieved a second and a third CR after two cycles of (90)Y-ibritumomab tiuxetan, he experienced a third relapse approximately 3 years later. Between March and June 2011, the patient received three cycles of (131)I-rituximab. Although he had achieved partial response after the second cycle, the disease progressed after the third cycle, and the total progression-free survival was thus 5 months. The patient suffered only relatively mild toxicity (grade 1 thrombocytopenia) during treatment. RIT with (131)I-rituximab is therefore potentially effective in patients with relapsed DLBCL, even after the failure of (90)Y-ibritumomab tiuxetan therapy.