Abstract : The Fourth Industrial Revolution (4IR) generated considerable interests among scholars, informaticists and educational leaders around the globe. This industry shift brings with it exciting opportunities and inevitable challengesto various industries and professional practices including the health sciences. The purpose of the article is to illuminate the influences of the Fourth Industrial Revolution on the research,education and technology on Nursing and the Health Sciences. This article is organized as follows : the historical developments in the evolution of nursing images, industries and technologies in healthcare praxis, juxtaposing of current and impending trends and their impact on education, research and scholarship, and education in the healthcare sector. This article concludes with shared insights on several creative and proactive solutions in preparing for, creating new technologies, and mitigating the effects of the upcoming revolution. J. Med. Invest. 66 : 3-7, February, 2019

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Abstract : Theory development in nursing has been contentious so that issues about theory as knowledge base and counterpart of practice, and theory as the foundation of nursing as a discipline of knowledge and practice profession have facilitated the seeming ambiguity hindering theoretical contributions integral to human health and well-being. Nursing science continues to generate discussions about its development particularly grounding its practice as a legitimate component of human health care. The aims of this paper are (a) to describe three contemporary issues regarding theory construction and development in nursing, and (b) to advance a theory of nursing that can reconcile these issues. Content analysis following a review of literature revealed ontological,epistemological, and contextual issues on nursing theory development and theory-based practice perspective. The middle-range theory of Technological Competency as Caring in Nursing is advanced as integral to pursuing the reconciliation of theory development and practice engagements within the Universal Technological Domain in nursing and the health sciences. J. Med. Invest. 66 : 8-11, February, 2019

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Abstract : The dominant issue of high-tech and high-touch has popularized the supposed dichotomy between technology and caring in health care. In today's highly technological world, the notion of the “lost touch” in human connectedness is clearly within the realm of human caring. Fostered by different technologies facilitating health care work, the process of caring in the human health experience creates unique individual identities as professional practitioners of human care. The argument is centered on technologies as essential in shaping professionalization by redefining practice boundaries and expanding societal roles and contributions. Consequently, the concept of caring is shared as the hallmark of health care professions. An assertion is made that although technology facilitates caring and competency in the human experience, the idea of human-connectedness can seem “lost” - missing in the discourse and practice within the technological world. Human-connectedness is presented as a concept, positioning its role and relevance in the continued dialogical engagement of technology and caring. A contemporary appreciation of reconciling human connectedness as integral to the process of knowing in a technological world bridging the seemingly paradoxical nature of technology and caring is proposed. J. Med. Invest. 66 : 12-14, February, 2019

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Abstract : This case study focuses on caring for a patient living with schizophrenia who has been isolated from the community caused by long-term hospitalization in Japan. Using the philosophical perspective of caring, which focuses on nurturing the wholeness and well-being of persons in caring relationship, the case study illuminates the caring, empathy, and courage among the interdisciplinary team. The purpose of this case study is to discuss the interdisciplinary caring process for patients living with schizophrenia using Carper's ways of knowing. Personal knowing is presented through the lens of patients and families and the stigma associated with mental illness. The expression of respect and caring for the patient and their families led by the interdisciplinary team aided in destigmatization of mental illness. Empirical and ethical knowing is demonstrated through the mental health care team's delivery of high quality and clinical excellence with competence, compassion and caring. Aesthetic knowing was offered by the interdisciplinary team focused on the patient's underlying hopes, dreams and aspirations. Through the support of the interdisciplinary team, patients are able to move toward their goals,hopes and dreams, externalizing tasks, as they grow together through mutual caring. J. Med. Invest. 66 : 15-18, February, 2019

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Japan's declining birth rate and increasing aging population prompted intercessory efforts towards robot technologies in nursing practice for theelderly. Today, technological companies are developing robots that meet universal health care technology demands. While human caring focus on human-to-human relationships,but between humans and nonhumans, e.g. Humanoid Nursing Robot (HNRs)-to-human relationships, caring practices have not been forthcoming. When HNRs can support patients independently, capabilities much like being human will be required, including intelligence and skill competencies. Currently, Tanioka's research group is conducting clinical trials of humanoid robots equipped with applications using Pepper (manufactured by SOFTBANK CORPORATION), towards elderly care and rehabilitation at the Mifune Hospital, Kagawa prefecture. Care Prevention Gymnastics Exercises (Pepper-CPGE) was madeby Xing Company, Japan. Therefore, this paper aims to describe the clinical trial outcomes based on the Transactive Relationship Theory of Nursing (TRETON) (Tanioka, 2017) emphasizing nursing engagement processes between HNRs and human persons. Observable effects include positive changes in relationships of patients, humanoid robots and healthcare providers. Emphasizing ethical concerns and human person safety as critical factors of care, and fears for divergent robot use are observed. Cooperative undertakings with various interdisciplinary activities mark the visioning of Japanese human caring ideas for an aging society. J. Med. Invest. 66 : 19-23, February, 2019

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Telenursing is one type of telehealth service delivery proposed to resolve the predicted gap between healthcare workforce demand and supply globally. The aim of this article is to explore the ‘Nurse Chatbot' for chronic care on the benefits of increasing patient/client access to healthcare information and maximizing the potential of artificial intelligence/AI to bridge the ‘demand-supply gap' of human healthcare providers. Moreover,closing this gap through the establishment of a ‘Nurse Chatbot' will be innovative, favorably scalable and customizable within a decentralized health network, and potentially sustainable in the new digital economy. Following are the assumptions : 1) “caring” communicated textually is highly ‘transactive' in chronic disease selfmanagement support/CDSMS for goal agreements between agents and for overcoming the system noise in the form of cross-entropy, perplexity, and information wastage ; 2) ‘Nurse Chatbot' is the interlocutor in nursing care and the nursing agency by superpositioning and entanglement ; and 3) possible effects of chatbot-user transactions are information flows, management of health, and patient satisfaction. This article also looks into ‘Nurse Chatbot' development for CDSMS, simulation of its diffusion capacity egocentrically, technology acceptance model/TAM to inquire the engagement of users, and possible approaches to ethical and safety issues. J. Med. Invest. 66 : 24-30, February, 2019

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Clinical imaging examinations and the diagnosis of their findings play an important role in patientcentered interdisciplinary care. Clinical imaging tests, such as X-ray, computed tomography (CT), magnetic resonance imaging (MRI) and nuclear medicine scans, are performed both in the initial diagnosis to identify the disease and at follow-up with the radiology team. Imaging technology is advancing day by day, both the hardware and software. CT and MRI are useful for confirming the size and location of lesions, providing what is known as morphologic images. CT can perform whole-body imaging very quickly, and the huge data are reconstructed in many ways with advanced computer systems. Three-dimensional CT, such as virtual colonography and bronchography, isuseful for planning the approach before surgery or endoscopic study. MRI isuseful for detecting acute cerebral infarction and evaluating brain perfusion or brain metabolites using MR spectroscopy. Fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT is a molecular imaging modality mainly used in oncology for the initial diagnosis, staging and detection of recurrence or metastasis after treatment as well as the evaluation of the treatment response. The focus of this paper was to elucidate the typesand use of clinical imaging technologies, with a focus on CT, MRI and FDG-PET. J. Med.I nvest. 66:31-34, February, 2019

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Radiomics has the potential to provide tumor characteristics with noninvasive and repeatable way. The purpose of this paper is to evaluate the standardization effect of imaging features for radiomics analysis. For this purpose, we prepared two CT databases ; one includes 40 non-small cell lung cancer (NSCLC) patients for whom tumor biopsies was performed before stereotactic body radiation therapy in The University of Tokyo Hospital, and the other includes 29 early-stage NSCLC datasets from the Cancer Imaging Archive. The former was used as the training data, whereas the later was used as the test data in the evaluation of the prediction model. In total, 476 imaging features were extracted from each data. Then, both training and test data were standardized as the min-max normalization, the z-score normalization, and the whitening from the principle component analysis. All of standardization strategies improved the accuracy for the histology prediction. The area under the receiver observed characteristics curve was 0.725, 0.789, and 0.785 in above standardizations, respectively. Radiomics analysis has shown that robust features have a high prognostic power in predicting early-stage NSCLC histology subtypes. The performance was able to be improved by standardizing the data in the feature space. J. Med. Invest. 66 : 35-37, February, 2019

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Clinical practicum is a major component in nursing education. Students are able to apply their classroom learning to the actual care setting. The clinical practicum setting must provide an authentic environment where students can maximize learning opportunities and demonstrate knowledge, skills, and attitude in caring for patients. Herein lies the challenge. The real world setting and timing may not be enough for students to learn the many complex tasks demanded as course outcomes and expected competencies. The purpose of this study was to describe the usefulness of using multimedia case study courseware in facilitating learning among students. The Virtual Clinical Environment multimedia courseware was structured around five case studies featuring major health concerns among adults, namely : chronic heart failure, stroke, breast cancer, chronic obstructive pulmonary disease, and dementia. Students were asked to use case studies in developing nursing care plans which facilitated authentic learning and encouraged active and reflective learning. Students were also encouraged to critically think and effectively solve problems. The case studies in the courseware helped in demonstrating the scope and processes of the clinical practicum, illustrating the setting, and stimulating critical thinking and decision-making in doing patient assessment and care. J. Med. Invest. 66 : 38-41, February, 2019

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The Perceived Inventory of Technological Competency as Caring in Nursing (PITCCN) based on Locsin's theory of Technological Competency as Caring in Nursing (TCCN, 2005) was developed (Kato et al. 2016) and revised by Miyamoto et al. (2017). The purpose of this study was to verify criterion-related validity of PITCCN using the Practice of Caring Behavior Questionnaire (PCBQ, Shigehisa, 2007). The study was approved by the Ethical Review Board of Tokushima University Hospital. Data were collected from September 2017 to October 2017. Of the 402 questionnaire copies distributed, only 299 copies were returned and analyzed to determine correlations between total score value and Mean Factor Point of each factor for PITCCN and PCBQ. These were analyzed using Pearson correlation coefficients. Statistical significance was at .01 levels. Strong positive correlation coefficient was obtained between total score values (r=.76, p?.01) and factors of PITCCN and PCBQ (r=.19 to .68, p?.01) , except the PITCCN's factor 3 : “Utilization of information obtained from technology and continuous knowing” and PCBQ's factor 6 : “Enriched relationships between patient and nurse”, (r=.13, not significant). From these results, the criterion-related validity of PITCCN as the inventory of TCCN could be confirmed. J. Med. Invest. 66 : 42-45, February, 2019

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Healthcare for older adults is a significant problem in Japan and in other developed countries. To address this problem, healthcare robots, now realized, can assist and meet healthcare and welfare practice demands. The aim of this study was to clarify characteristics of Transactive Relationships (TR) in older adults, in care workers as intermediaries, and Pepper (Softbank Robotics Corporation) a robot equipped with the application program of Care Prevention Gymnastics Exercises for Pepper (Pepper-CPGE) made by Xing Company, Japan. Data were collected by observing TRs between Pepper and older patients in Kagawa Prefecture,Japan between from May 8 to August 1 2018. The Transactive Relationship Theory of Nursing (TRETON) was used to explain how Pepper-CPGE led the exercises with older adults as physical exercises. The role of PepperCPGE was to provide instructions for the older adults in performing gymnastic exercises. During the exercising activity, care workers were present to prevent falls of the older adults, and to operate and observe the video presentations by supporting and caring for the participants. In using Pepper-CPGE, it was possible to change the role of the healthcare providers, originally thought to contribute to increasing the quality of older adult care and their rehabilitation. J. Med. Invest. 66 : 46-49, February, 2019

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In Japan, humanoid robots has been introduced in the medical and elderly care environment. The application program of Care Prevention Gymnastics Exercises for Pepper (Pepper-CPGE) made by Xing Company, Japan is a body-brain gymnastics recreation program for 40 minutes tailored to the elderly's functional level. It consists of moving, watching/healing, and playing. “Move the body” exercise and other active range of motion activities are done according to the music. Pepper-CPGE was introduced as a clinical trial at the Mifune hospital, beginning in May 2018. At the units where clinical trials are done, 80% of the patients are with mental illness diagnosis with decreased physical functions often moving by wheelchair only. When Pepper-CPGE was introduced, the following changes were observed : (1) communication between patients and nurses during rehabilitation care using Pepper-CPGE was increased ; (2) patients wereinteractive, engaged, and actively participated in the Care Prevention Gymnastic Exercises using Pepper-CPGE ; (3) patients had fun and enjoyed talking to Pepper-CPGE. Interventions using Pepper-CPGE appear to be an effective rehabilitation strategy to increase engagement and participation of elderly patients who require long-term care and rehabilitation. J. Med. Invest. 66 : 50-53, February, 2019

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The Second International Seminar and Workshop (ISW) on Technological Competency as Caring in the Health Sciences was offered by the Rozzano Locsin Institute for Advancing the Theory of Technological Competency as Caring in Nursing, and held from August 17- 19, 2018 at Tokushima University in Tokushima,Japan. The ISW was envisioned to provide a platform for sharing research and scholarly works into innovative design and developments on studying and applying the theory of Technological Competency as Caring in the Health Sciences. This ISW was founded on the theory of Technological Competency as Caring in Nursing (TCCN) (Locsin, 2005). The ISW, as aimed broadened the influence of theory, research, and practice through the advancements in technology, caring, and nursing, as espoused in the theory of Technological Competency as Caring particularly within the Health Sciences. This report illuminates the contents of the ISW and its outcomes, and reveals the direction of the theory, its development, and future implications through formalized activities. J. Med. Invest. 66 : 54-57, February, 2019

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Not much is known about the self-perceptions of persons using prosthetic devices. The purpose of the literature review was to explore the self-perceptions of persons living with visible artificial devices from published articles between 2010 and 2017. Using key words to search for published literature in the PubMed,CINAHL, IEEE Proceedings, and Scopus indices showed 680 articles. Braun and Clarke's six phases of qualitative thematic analysis were used on 25 articles meeting the inclusion criteria, revealing 29 data extracts (themes) as data summaries. Three key thematic categories were revealed : Body image and ownership, integration of prosthetic device into the self-body, and suspended enjoyment or delight, reflecting the longings for completeness affecting persons' use of prosthetic devices. Consistent with self-perceptions understood through social biases and customs, completeness is achieved through the happy paradox of a person made whole through artificial devices. This experience informs nursing practice in helping people find meaning in their life. Further research into selfperceptions with prosthetic devices is essential, particularly those reflecting the cultural influences of artificial devices on quality of life. J.Med.Invest. 66:58-64, February, 2019

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Background: One of the major cause of anastomotic leakage (AL) in anterior resection of the rectum is insufficient blood flow of the remnant colon. The indocyanine green fluorescence system (ICG-FS) can visualize the blood flow of organs intra-operatively. The aim of this study is to investigate the usefulness of ICG-FS for evaluating the blood flow of the remnant colon in laparoscopic anterior resection. Materials and Methods: Rectal cancer patients (n=24) who underwent laparoscopic anterior resection were included in this study. After resection of the rectum, 7.5mg of ICG was administered intravenously, and the blood flow of the oral stump was evaluated by the ICG-FS. The relationship between the fluorescence time (FT) of the oral stump and AL was investigated retrospectively. Result: Two of twenty-four patients (8.3%) suffered AL. The FT of these two cases were over 60 seconds. In the case with the FT was over 80 seconds, we performed additional resection of the late fluorescence portion of the remnant colon and could avoid AL. In patients whose FT was under 60 seconds, no patients suffered AL. Conclusion: ICG-FS may be useful for evaluating the blood flow of the remnant colon to avoid AL in laparoscopic anterior resection. J. Med. Invest. 66 : 65-69, February, 2019

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Purpose : The aims of this study were to clarify the effects of lipopolysaccharide (LPS) on the early development of endometriosis and on the production of cytokines and chemokines in the murine peritoneal cavity. Methods : Endometriotic lesions were induced in C57BL/6J adult female mice by intraperitoneal injection of endometrial fragments plus blood or endometrial fragments plus blood with LPS. On day 7, endometriotic lesions were assessed by gross and microscopic evaluations. Time-dependent changes in the secretion of TNF-α,IL-6,and CXCL2/MIP-2 in peritoneal lavage fluid after the intraperitoneal injection of LPS (50 µg/body) were measured by their respective enzyme-linked immunosorbent assays. Results : The areas of endometriotic lesions in the LPS group (10.8 8.6 mm²) were significantly larger than those in the control group (3.1 3.7 mm²).The levels of TNF-α and IL-6 peaked within 2 hours and the level of MIP-2 reached a maximum on day 1 after the injection of LPS. Conclusions : LPS promotes development of the early stages of murine endometriotic lesions. J. Med. Invest. 66 : 70-74, February, 2019

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Few reports have focused on hemodynamics around delivery in pregnant women because of the difficulty of continuous and noninvasive measurement. Electrical cardiometry allows noninvasive continuous monitoring of hemodynamics and has recently been used in non-pregnant subjects. We compared the use of electrical cardiometry versus transthoracic echocardiography in healthy pregnant women and evaluated hemodynamics immediately after vaginal delivery. In Study 1, electrical cardiometry and transthoracic echocardiography were used to measure cardiac output in 20 pregnant women with threatened premature delivery. A significant correlation was found between the two methods, with electrical cardiometry showing the higher cardiac output. In Study 2, heart rate, stroke volume, and cardiac output were continuously measured in 15 women during vaginal delivery up to 2 h postpartum. Cardiac output increased markedly because of an increased heart rate and stroke volume at the time of newborn delivery. The heart rate then immediately returned to baseline, while cardiac output remained elevated for at least 2 h after delivery because of a sustained high stroke volume. Electrical cardiometry was as readily available as transthoracic echocardiography for evaluating hemodynamics and allowed for continuous measurement during labor. High intrapartum cardiac output was sustained for at least 2 h after vaginal delivery. J. Med. Invest. 66 : 75-80, February, 2019

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Background : p-Cresol concentrations are high in the blood of hemodialysis (HD) patients. However, its organ distribution has not yet been investigated in detail. We herein report the distribution of p-cresolin HD patients from forensic autopsy cases. Methods : p-Cresol was measured in the blood, urine, lungs, liver, and kidneys from 4 HD and 4 non-HD cases. Samples were extracted with p-cresol-d8 (internal standard), derivatized,and injected on the GC-MS. Results and Discussion : The total urinary p-cresol/Cr was 79.73 ng/ml in HD cases,which was 16-fold higher than that in non-HD cases. p-Cresol in the blood and kidneys were 30-fold higher or more at 11.92 and 13.08 µg/mL(g), respectively. p-Cresol in the liver and lungs were approximately 20-fold higher at 4.82 and 9.99 µg/g, respectively. p-Cresol was markedly increased in not only the blood, but also the urine and organs of HD cases. The distribution of p-cresol in the blood, urine, and organs differed between HD and non-HD cases. In HD cases, the percentages of conjugated (C) and protein-bound conjugated (PC) urinary p-cresol were 57 and 41%, respectively. C and PC p-cresol was 66% and 25% in the kidneys, respectively, and similar results were obtained in the lungs. J. Med. Invest. 66 : 81-85, February, 2019

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This study aimed to accelerate the segmentation of organs in medical imaging with the revised radial basis function (RBF) network, using a graphics processing unit (GPU). We segmented the lung and liver regions from 250 chest x-ray computed tomography (CT) images and 160 abdominal CT images, respectively, using the revised RBF network. We compared the time taken to segment images and their accuracy between serial processing by a single-core central processing unit (CPU), parallel processing using four CPU cores, and GPU processing. Segmentation times for lung and liver organ regions shortened to 57.80 and 35.35 seconds for CPU parallel processing and 20.16 and 11.02 seconds for GPU processing, compared to 211.03 and 124.21 seconds for CPU serial processing, respectively. The concordance rate of the segmented region to the normal region in slices excluding the upper and lower ends (173 lung and 111 liver slices) was 98% for lung and 96% for liver. The use of CPU parallel processing and GPU shortened the organ segmentation time in the revised RBF network without compromising segmentation accuracy. In particular, segmentation time was shortened to less than 10%with GPU. This processing method will contribute to workload reduction in imaging analysis. J. Med. Invest. 66 : 86-92, February, 2019

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Ureteric bud branching and nephrogenesis are performed through large-scale proliferation and apoptosis events during renal development. Reactive oxygen species (ROS), produced by NADPH oxidase, may contribute to cell behaviors, including proliferation and apoptosis. We investigated the role of NADPH oxidase expression and ROS production in developing kidneys. Immunohistochemistry revealed that NADPH oxidase componentswere expressed on epithelial cells in ureteric bud branches, as well as on immature glomerular cells and epithelial cells in nephrogenic zones. ROS production, detected by dihydroethidium assay, was strongly observed in ureteric bud branches and nephrogenic zones, corresponding with NADPH oxidase localization. Organ culture of E14 kidneys revealed that the inhibition of NADPH oxidase significantly reduced the number of ureteric bud branches and tips, consistent with reduced ROS production. This was associated with reduced expression of phosphorylated ERK1/2 and increased expression of cleaved caspase-3. Organ culture of E18 kidneys showed that the inhibition of NADPH oxidase reduced nephrogenic zone size, accompanied by reduced ROS production, fewer proliferating cell nuclear antigen-positive cells, lower p-ERK1/2 expression, and increased expression of cleaved caspase-3. These results demonstrate that ROS produced by NADPH oxidase might play an important role in ureteric bud branching and nephrogenesis by regulating proliferation and apoptosis. J.Med. Invest. 66 :93-98, February, 2019

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Purpose To assess the treatment results of definitive radiotherapy for esophageal cancer at Tokushima University Hospital and clarify the prognostic factors. Methods Seventy consecutive patients with esophageal cancer who underwent definitive radiotherapy between May 2004 and March 2012 were included in the present study. Local control rate, overall survival rate, and radiation morbidity were examined and univariate and multivariate analyses were performed to investigate prognostic factors. Results The 5-yearoverall survival rates of stages I, II, III, and IVA were 81%, 71%, 0%, and 9%, respectively. Performance status, clinical stage, and neoadjuvant chemotherapy were significant prognostic factors. A past history of interstitial pneumonia was associated with severe radiation-induced lung injury. Conclusions Patients who underwent definitive chemoradiotherapy for esophageal cancer in stage I/II showed good prognosis. However, treatment results of the patients in stage III/IV were not satisfactory, and those who could not undergo surgery after neoadjuvant chemotherapy had the worst prognosis.J.Med.Invest.66:99-105, February, 2019

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Objective : To identify and differentiate patients with mediastinal cysts from those with cystic tumors requiring surgery. Methods : A total of 36 patients with mediastinal cystic lesions were enrolled. The patients were separated into two groups based on pathological findings : those with mediastinal cysts (n=23) and those with mediastinal tumors (n=13). The cystic components were measured using imaging parameters including mean computed tomography (CT) value, apparent diffusion coefficient (ADC), T1 signal intensity ratio (T1SIratio), and T2 signal intensity ratio (T2SI-ratio), acquired from magnetic resonance imaging (MRI) ; and standardized maximum uptake value (SUVmax) from¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT). Both groups were statistically compared. Results : Comparative parameters between the cysts and tumors revealed the following ratios : CT value, 40.9?21.2 versus (vs) 24.8?12.9 (p = 0.019) ;SUVmax, 1.18?0.50 vs 4.32?3.52 (p = 0.003) ; ADC, 3.46?0.96 vs 2.68?0.74 (p = 0.022) ; T1SI-ratio, 1.06?0.60 vs 1.35? 0.92 (p = 0.648) ; T2SI-ratio, 5.40?1.80 vs 4.33?1.58 (p = 0.194). However, there was no correlation between FDG uptake and ADC value. Conclusions : SUVmax from¹⁸F-FDG PET/CT and ADC derived from MRI were effective in facilitating preoperative diagnosis to differentiate mediastinal cysts from tumors. However, these examinations may be complementary to one another, not dominant. J. Med. Invest. 66 : 106-111, February, 2019

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Polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome are common inflammatory rheumatic diseases in the elderly. In this study, we investigate predictive factors which correspond to subsequent disease control of PMR and RS3PE syndrome. Twenty four patients, which contained 18 PMR and 6 RS3PE syndrome, were treated with initial dosages of 10-20 mg per day oral prednisolone, and the dosage of prednisolone was then tapered. Significantly higher initial CRP was observed in patients with poor disease control than in those with good disease control afterwards. The number of patients with negative CRP after 4 weeks was significantly more in patients with good disease control after 1 year than in those with poor disease control. Patients were shown to be in good disease control status after 1 year when CRP after 4 weeks became negative even if they had initial high CRP. Our study clarify that to make CRP negative after 4 weeks is associated with subsequent suppression of the disease activity and with decreased dosages of corticosteroids. J. Med. Invest. 66 : 112-118, February, 2019

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INTRODUCTION Titanium (Ti) coated polyether ether ketone (PEEK) interbody cages (IBCs) have been introduced to overcome any disadvantages. The purpose of this study was to investigate the radiological outcomes of lumbar interbody fusion (LIF) surgery using the Ti-coated PEEK IBC with a minimum of 1-year of follow-up. METHODS A total of 26 intervertebral spaces in consecutive 21 patients who underwent posterior/transforaminal LIF using the Ti-coated PEEK IBC were evaluated. Rates of bone union, screw loosening, cage subsidence and bone cyst formation around the endplate were evaluated on computed tomography scans acquired at least 1 year postoperatively. RESULTS AND DISCUSSION At the 1-year follow-up, bone fusion was achieved in 23 (88.4%) of 26 intervertebral spaces. Cagesubsidence was found in 5 intervertebral spaces ; however,bone fusion was achieved in all these spaces. Bone cysts formed in 4 intervertebral spaces and 4 of 94 screws were found to be loosened. Three of the loosened screws were found in vertebral bodies adjacent to intervertebral spaces with nonunion. However, there was no association between these events. Although more scientific evidence is required to determine the advantages of Ti-coated PEEK IBCs, we believe the clinical outcomes achieved were favorable at the 1 year minimum follow-up. J. Med. Invest. 66 : 119-122, February, 2019

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PURPOSE : This study aimed to investigate the effect of intraperitoneal administration of activin on the occurrence of endometriosis using a mouse model of endometriosis. METHODS : A mouse model of endometriosis was prepared by intraperitoneally administering endometrial tissue and blood collected from donor mice to C57BL/6J 7-8- week-old recipient mice. A total of 400 μg of activin A was intraperitoneally administered to model mice in the activin group for 5 days. Intraperitoneal endometriotic lesions were confirmed macroscopically and IL-6 and TNF-α levels in washed ascites were measured by ELISA. RESULTS : Endometriotic lesions were observed in all mice. In the activin group, the maximum diameter of endometriotic lesions was significantly larger than that in control group (4.7?1.3 vs 2.9?0.9 mm, p?0.01). The total area of the lesion was also significantly higher in the activin group than in the control group (21.1?9.9 vs 8.8?5.4 mm²,p?0.01). Furthermore, IL-6 and TNF-α levels in ascites were significantly higher in the activin group than in the control group (IL-6 : 85.8?15.3 vs 75.1?19.3 pg/ml, p?0.05 ; TNF-α : 629.8?15.4 vs 605.9?11.4 pg/ml, p?0.05). CONCLUSION : Activin promotes occurrence of endometriosis. Inflammatory cytokines are also elevated by activin administration,suggesting that they may contribute to progression of endometriosis J. Med. Invest. 66 : 123-127, February, 2019

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Abstract : We aimed to demonstrate that the serum 25-hydroxyvitamin D (25(OH)D) level in maternal and umbilical cord blood has a seasonal variation in Japanese women. The study cohort comprised 256 healthy Japanese women with a singleton pregnancy who delivered after 36 gestational weeks between 2012 and 2015. The season at delivery was categorized for 3 months and recorded as “spring”, “summer”, “autumn” and “winter”. Subjects were divided into four groups according to season. A sample of peripheral venous blood at 35-36 gestational weeks and blood from the umbilical vein at delivery were taken. The mean serum 25(OH)D concentra tion (ng/mL) in maternal blood for each season (spring, summer, autumn and winter) was 18.0 (?6.7), 17.1 (?5.1), 21.6 (?8.0) and 16.0 (?5.1), whereas that for umbilical cord blood was 8.8 (?3.6), 8.6 (?2.6), 10.7 (?3.5) and 8.6 (?2.1), respectively. The mean serum 25(OH)D concentration of maternal and umbilical cord blood in autumn was higher than that for the other three seasons. In pregnant Japanese women, the mean serum 25(OH)D concentration in maternal and umbilical cord blood was affected by the season of delivery, with both being highest in autumn. Regardless of the season, the maternal serum concentration of 25(OH)D was low in Japan. J. Med. Invest. 66 : 128-133, February, 2019

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Abstract : Hyperphosphatemia is associated with an increased risk of developing cardiovascular disease. Recently, it has been shown that high serum phosphorus levels are associated with increased cardiovascular events in healthy subjects, but the dietary factors determining serum phosphorus level have not been fully investigated. The study investigated the influence of habitual dietary factors on serum phosphorus levels in healthy young participants. This cross-sectional study conducted fasting blood sampling in 109 healthy young people and used a brief-type self-administered diet history questionnaire to evaluate the subject's habitual meals. Since the bioavailability of dietary phosphorus depends on the food sources, habitual phosphorus intakes from different food groups and intake frequency (times/month) of processed foods were calculated. The mean serum phosphorus level was 3.9 0.5 mg/dl ; 10.1% of the subjects had serum phosphorus levels that exceeded the reference levels of 4.5 mg/dl. Total phosphorus intake and phosphorus intake from animal-based food did not differ between serum phosphorus quartiles. Higher intake of confectionery was associated with increased serum phosphorus levels. This study showed that frequent consumption of confectionery was associated with elevated serum phosphorus levels. Additional studies are needed to determine whether this is a causal relationship. J. Med. Invest. 66 : 134-140, February, 2019

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The aim of this study was to clarify the associations of family members living together with healthrelated behaviors in Japanese young workers. The participants were 300 men and women aged 20-39 years in 2015 who had a job. A web-based self-administered questionnaire on status of partnering and parenting, number of family members living together, dietary habits, drinking habit, smoking habit, self-rated health, employment status, working time and commuting time was conducted through Internet. Multiple logistic regression analysis and general linear models were used to assess the association of family members living together with healthrelated behaviors. The multivariate-adjusted odds ratio (95% confidence interval, p-value) for current drinking in unmarried participants living with their parents compared to unmarried participants living alone was 0.35 (0.13-0.93, p=0.036). The adjusted means of frequency of breakfast skipping and frequency of eating out showed a trend for inverse associations with the presence of a partner and children. However, those associations disappeared after adjustment for age of youngest child. The findings suggest that the presence of parents might affect drinking behavior and that age of youngest child living together might affect the frequency of breakfast skipping in young Japanese workers. J. Med. Invest. 66 : 141-147, February, 2019

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Chronic care patients undergoing hemodialysis for treatment of end-stage renal failure experience higher rates of bloodstream-associated infection due to the patients' compromised immune system and management of the bloodstream through catheters. Staphylococcus species are acommon cause of hemodialysis catheterrelated bloodstream infections. We investigated environmental bacterial contamination of dialysis wards and contamination of hemodialysis devices to determine the source of bacteria for these infections. All bacterial samples were collected by the swab method and the agarose stamp method. And which bacterium were identified by BBL CRYSTAL Kit or 16s rRNA sequences. In our data, bacterial cell number of hemodialysis device was lower than environment of patient surrounds. But Staphylococcus spp. were found predominantly on the hemodialysis device (46.8%), especially on areas frequently touched by healthcare-workers (such as Touch screen). Among Staphylococcus spp., Staphylococcus epidermidis was most frequently observed (42.1% of Staphylococcus spp.), and more surprising, 48.2% of the Staphylococcus spp. indicated high resistance for methicillin. Our finding suggests that hemodialysis device highly contaminated with bloodstream infection associated bacteria. This study can be used as a source to assess the risk of contamination-related infection and to develop the cleaning system for the better prevention for bloodstream infections in patients with hemodialysis. J. Med. Invest. 66 : 148-152, February, 2019

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Objective : We aimed to demonstrate the effect of prolonged hospitalization on fetal growth in cases of threatened preterm labor (TPL). Methods : In this retrospective cohort study, we included women who received prenatal care for TPL but delivered their child after 36 weeks of gestation. These were compared with a control group of healthy pregnant women and fetuses delivered at term. Fetal growth was compared using biparietal diameter, abdominal circumference (AC), femur length, and estimated fetal weight (EFW) assessed using ultrasonography at 18, 26, 30, and 36 weeks of gestation. Neonatal parameters at birth were also compared. Results : In total, we enrolled 228 control women and 114 women with TPL who were treated with hospitalization,including bed rest. The AC at 30 and 36 weeks of gestation and EFW at 36 weeks of gestation were smaller in women treated with bed rest than for normal pregnant women. The mean duration of pregnancy was shorter in the hospitalization group than in the control group. Neonatal weight, length, head circumference, and chest circumference at birth were smaller after prolonged hospitalization for TPL than after normal pregnancy. Conclusion : Prolonged hospitalization for threatened preterm labor is associated with impaired fetal growth, particularly AC. J.Med.Invest.66:153-156, February, 2019

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Background Asthma-COPD overlap (ACO) is a disease that shares clinical features of both asthma and COPD. The purpose of this study is to investigate the prevalence and clinical features of ACO. Methods We retrospectively reviewed data for 170 patients with persistent airflow limitation and diagnosed them according to “The Japanese Respiratory Society Guidelines for the Management of ACO 2018”. Results Of the 170 patients, 111 were diagnosed as follows : COPD (74 patients, 66.6%), ACO (34 patients, 30.6%), and asthma (3 patients, 2.8%). There was no significant difference in clinical features between ACO and COPD patients. The following pulmonary function tests were significantly lower in ACO than in COPD patients : forced expiratory volume in 1 second/forced vital capacity, peak expiratory flow, maximal mid-expiratory flow, and the maximum expiratory flow at 50%and75%. The following respiratory impedance parameters were significantly higher in ACO than in COPD patients : respiratory resistance (Rrs) at 5 Hz (R5), Rrsat 20 Hz (R20), R5-R20, and low-frequency reactance area. Conclusions About 30% of patients with persistent airflow limitation were diagnosed with ACO. ACO patients had lower lung function and higher respiratory impedance compared with COPD patients. J. Med. Invest. 66 : 157-164, February, 2019

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As the follicular environment transits from being activin dominant to inhibin dominant during folliculogenesis, it is assumed that activin plays an important role in the early stage of follicular growth. We examined the effects of activin on morphological, biochemical and molecular changes in isolated preantral follicles. Preantral follicles were mechanically isolated from 14-day old female C57BL/6 mice. Each follicle was cultured and observed for 14 days usingan in vitro follicle culture system containing FSH, FSH + activin A and FSH + inhibin in the culture medium. We subsequently examined FSH receptor (FSH-R) mRNA expression in isolated follicle cultures with or without activin on days 0 and 2. Activin was observed to significantly stimulate follicle enlargement on days 2, 4, 6 and 8, accelerate morphological changes and increase estradiollevels in culture medium on days 4, 12 and 14. In contrast, inhibin did not alter follicular growth. Additionally, activin stimulated the expression of FSH-R mRNA in isolated granulosa cells. It was demonstrated that activin stimulated the growth of preantral follicles, mainly during the early stage of folliculogenesis, by inducing FSH-R expression, in an isolated follicle culture system. J. Med. Invest. 66 : 165-171, February, 2019

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Background : IVC diameter on expiration (IVCdexp) is measured by echocardiography routinely. It is used to estimate volume status and designated as a definitive marker for determining dry weight (DW) in patients undergoing hemodialysis (HD). Methods : A cross-sectional study. Outpatients (n = 107), and inpatients (n = 35) undergoing HD were enrolled. IVCdexp was measured on non-dialysis days in outpatients and dialysis days before and after the dialysis session in inpatients. In outpatients, the relationship of IVCdexp with echocardiography findings and clinical characteristics was analyzed. IVCdexp was compared with the other DW markers as a predictive factor for intradialytic hypotension. In inpatients, IVCdexp was analyzed by dividing inpatients with or without fluid in extravascular space. Results : IVCdexp ranged from 5.4 to 16.9 mm in outpatients who had optimal DW. IVCdexp could reflect on volume status, but not predictive for intradialytic hypotension and not suggestive of fluid in extravascular space. Conclusions : IVCdexp was a rough marker to estimate volume status and only useful in suggesting apparent hypervolemia or hypovolemia. We should know that the IVCdexp value is affected by a lotof factors and not a definitive marker for estimating practical DW. J. Med. Invest. 66 : 172-177, February, 2019

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The purpose of this study was to clarify the impact of self-exercise for elderly patients in an acute hospital after hip fracture. This retrospective observational study used data from the Japan Rehabilitation Database spanning 2005−2015. This study identified in-hospital hip fracture patients admitted to an acute hospital. After applying exclusion criteria, 375 patients were eligible. The primary outcome was motor Functional Independence Measure (FIM) efficiency. Of the patients with hip fracture, 39% performed self-exercises. Patients who performed self-exercise had significantly higher motor FIM efficiency than those who did not (1.22 vs. 0.79 ; P ?0.01). Multivariable regression analysis showed that motor FIM efficiency was significantly and positively correlated with self-exercise (coefficient, 0.25 ; 95% confidence interval, 0.13 to 0.43 ; P ?0.01). The data suggest that self-exercise is associated with good rehabilitation outcomes in hip fracture patients. J. Med. Invest. 66 : 178-181, February, 2019

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Protein S (PS) deficiency is an inherited thrombophilia associated with an increased risk of venous thromboembolism (VTE). In Japan, unfractionated heparin followed by warfarin has been historically applied for the treatment of VTE. Recent evidence showed that direct oral anticoagulants (DOACs) were non-inferior to standard therapy with warfarin, with significantly less bleeding in patients with VTE. However, it is unknown whether DOACs are effective for the treatment of VTE in patients with thrombophilia, including protein S deficiency, due to lack of evidence. Here, we report a case of recurrent venous thrombosis during edoxaban therapy in a patient with protein S deficiency, which was successfully treated using high-dose apixaban therapy. J.Med. Invest. 66 : 182-184, February, 2019

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Abstract : The culprit lesion of acute myocardial infarction could be predicted by electrocardiogram findings. However, we experienced some cases with coronary angiographic finding in the area of ST-T elevation that was different from that predicted. The lambda-like J wave could be caused by ischemia although the mechanism has not been fully elucidated. We report a case of acute myocardial infarction that showed discrepancy between ST-T elevation with lambda-like ischemic J wave in a broad area and coronary angiographical finding of diagonal branch occlusion. J. Med. Invest. 66 : 185-187, February, 2019

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Background : Pseudoaneurysm of the internal carotid artery (ICA) is a very rare but potentially fatal complication of deep neck space infection. Methods : This paper describes a very rare case of an ICA pseudoaneurysm rupture in the sphenoid sinus caused by a deep neck abscess. Results : A 62-year-old male with a deep neck space infection underwent surgical drainage. On the postoperative 21st day, however, he suddenly had massive epistaxis. A transnasal endoscopic examination found massive bleeding out of the sphenoid sinus. Immediate intra-arterial angiography revealed two pseudoaneurysms of the left ICA at the cavernous segment (C4) and the clinoid segment (C5), which were embolized with coils. The patient made an uneventful recovery after the embolization. Conclusion : We found no reports in the literature that pseudoaneurysms associated with a deep neck infection rupture in the sphenoid sinus. Prompt treatment along with accurate diagnosis is essential for successful management of such cases. J. Med. Invest. 66 : 188-189, February, 2019

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Neoplasm of a colonic graft after esophageal reconstruction is rare. We treated a colon cancer patient who developed malignancy in a colonic graft after esophagectomy and reconstruction through a retrosternal route. A male had undergone esophagectomy in his 50s due to a benign esophago-bronchial fistula. His dysphagia became exacerbated 20 years later, and further examinations showed a circumferential tumor on the esophagocolonic anastomosis. He underwent resection of the colonic graft adenocarcinoma with median sternotomy after neoadjuvant chemotherapy. Gastric tube reconstruction was performed through a retrosternal route. This report should be informative in terms of making decisions from an initial reconstruction to follow-up and choosing a therapeutic strategy for colonic graft cancer in the future. J. Med. Invest. 66 : 190-193, February, 2019

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Transcatheter closure with an Amplatzer Septal Occluder (ASO) has become the standard treatment for secundum atrial septal defect (ASD). However, this procedure is associated with complications, such as device dislodgement. A 52-year-old woman was admitted with exertional dyspnea. Transesophageal echocardiography showed an ASD involving a 29 mm defect. Calculated Qp/Qs was 5.6 and all the rims were ?5 mm, with the exception of the posterior rim, which was 3 mm. Transcatheter ASD closure with an ASO was performed under general anesthesia. During emergence from anesthesia, tachycardia developed and the ASO device became dislodged. Hemodynamic changes associated with the end of anesthetic administration were believed to have led to device dislodgement. In a second transcatheter ASD closure, a low dose of propofol and remifentanil was maintained during emergence from anesthesia to reduce hemodynamic changes. However, device dislodgement occurred with nonsustained ventricular tachycardia. Finally, surgical ASD closure was performed. The large defect size, high Qp/Qs, and rim deficiency may have predisposed to device dislodgement after transcatheter ASD closure with ASO. The risk of device dislodgement should be considered in advance of surgery and, in high-risk cases, the patient's cardiovascular status should be closely monitored. J. Med. Invest. 66 : 194-198, February, 2019

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Introduction : Spina bifida occulta (SBO) is a common malformation of lamina of the spine, most commonly occurring in the sacrum or lower lumbar spine. Athletes with anatomical abnormalities such as SBO may be vulnerable to discoordination of muscles and/or skeletal structures. Case Report : We present a case of a 15- year-old male adolescent who presented with persistent low back pain (LBP) associated with SBO at T11-L1 that had been overlooked for several years. He participated in karate as a top-level competitor at the nationallevel, but the LBP interfered with his play. Dynamic X-ray films showed limited range of motion (ROM) in his lower lumbar spine (L3-S1). Instead, the thoracolumbar junction compensated for the lack of ROM in the lumbar spine,enabling trunk flexion and extension. To restore normal coordination, he was treated with a 2-week rehabilitation program including flexibility and core conditioning for the trunk to improve coordination of spinal movement. Two weeks later, his LBP resolved. Conclusion : These results suggest that evaluation of the coordination of the muscles and skeletal structures has an important role in the treatment of cases with an anatomical abnormality such as SBO. J.Med.Invest.66:199-200, February, 2019

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Eosinophilic gastrointestinal disorders are chronic inflammatory diseases in which eosinophils highly infiltrate into gastrointestinal tissue, resulting in gastrointestinal dysfunction. Here, we report a case of pediatric eosinophilic gastroenteritis (EGE). A 7-year-old boy with multiple food allergies (cow milk, hen's egg, fish,shellfish, and chicken) was admitted to our hospital because of continuous abdominal pain and vomiting. His soy allergy had been diagnosed to have oral tolerance based on an oral food challenge at the age of 6 years. He was diagnosed with EGE based on biopsy findings showing eosinophilic infiltration ( 20 eosinophils per high-power field) into the gastrointestinal mucosa. A diet eliminating soy, wheat, beef, pork, rice, and sesame in addition to the food that had already been eliminated and oral corticosteroids improved his symptoms and peripheral eosinophilia. A relapse of both abdominal pain and peripheral eosinophilia after the reintroduction of soy or pork identified them as foods causative of EGE. This report highlights the utility of elimination diets in improving EGE symptoms and the subsequent reintroduction of offending foods in identifying causative foods. Furthermore,EGE onset should be considered when introducing potentially allergic food in the management of food allergy. J. Med. Invest. 66 : 201-204, February, 2019

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We present a rare case of intimal sarcoma arising from the common iliac artery in an 82-year-old man who presented with intermittent claudication. He had undergone endovascular therapy with self-expanding stents to both iliac arteries that had occluded soon after placement. After salvage bypass grafting, a diagnosis of intimal sarcoma with angiosarcoma phenotype from the iliac artery was made. Further bypass graft surgery relieved symptoms temporarily. However, the tumor progressed and the left limb became ischemic. The chemotherapy of eribulin did not prevent tumor progression. The patient died of the disease 20 months after the first surgery. J. Med. Invest. 66 : 205-208, February, 2019

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Abstract : An arteriovenous fistula of the superficial temporal artery (STA) is a direct and abnormal communication between the STA, feeding artery, and superficial temporal vein, draining veins that bypass the capillary network. Several cases of trauma-induced or iatrogenic-induced arteriovenous fistula (AVF) of the STA have been reported ; however, spontaneous AVF of the STA not associated with trauma or medical treatment are extremely rare. Herein, we present a case of spontaneous AVF of the STA diagnosed in old age. J. Med. Invest. 66 : 209-210, February, 2019

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Pes anserinus pain syndrome is a common, clinically defined condition that is characterized by pain around the medial knee and tenderness over the upper medial tibia. The anserine bursa could be the site of proliferative and inflammatory conditions due to knee osteoarthritis, leading to pain and fluid retention. However, rupture of the pes anserinus is rare. Herein, we present a case of rupture of the pes anserine bursa in a patient with pes anserine pain syndrome and osteoarthritis. Physicians should consider rupture of the pes anserine bursa as a differential diagnosis of acute unilateral lower leg swelling. J. Med. Invest. 66 : 211-212, February, 2019

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Chondral and osteochondral injuries of the femoral condyle are rare, and relatively few cases have been reported. Therefore, the mechanism, treatment, and findings on follow-up of these injuries are not well described. Here, we report the case of an adolescent basketball player who sustained a sports-related traumatic osteochondral injury of the lateral femoral condyle. He was treated with open reduction and internal fixation with the pull-out suture technique. Two years later, he was able to resume sporting activities at his pre-injury level with no symptoms. Magnetic resonance imaging (MRI) confirmed survival of the fixed osteochondral fragment and restoration of the congruity of the articular cartilage with no sign of delamination. This report describes the clinical outcome of this osteochondral injury of the lateral femoral condyle as seen on MRI at the 2-year follow-up and discuss the mechanism and treatment of this injury. J. Med. Invest. 66 : 213-217, February, 2019

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