Horizon Scanning in Tissue Engineering Using Citation Network Analysis.

BACKGROUND: Establishing a horizon scanning method is critical for identifying technologies that require new guidelines or regulations. We studied the application of bibliographic citation network analysis to horizon scanning. OBJECTIVE: The possibility of applying the proposed method to interdisciplinary fields was investigated with the emphasis on tissue engineering and its example, three-dimensional bio-printing. METHODOLOGY AND RESULTS: In all, 233,968 articles on tissue engineering, regenerative medicine, biofabrication, and additive manufacturing published between January 1, 1900 and November 3, 2021 were obtained from the Web of Science Core Collection. The citation network of the articles was analyzed for confirmation that the evolution of 3D bio-printing is reflected by tracking the key articles in the field. However, the results revealed that the major articles on the clinical application of 3D bio-printed products are located in clusters other than that of 3D bio-printers. We investigated the research trends in this field by analyzing the articles published between 2019 and 2021 and detected various basic technologies constituting tissue engineering, including microfluidics and scaffolds such as electrospinning and conductive polymers. The results suggested that the research trend of technologies required for product development and future clinical applications of the product are sometimes detected independently by bibliographic citation network analysis, particularly for interdisciplinary fields. CONCLUSION: This method can be applied to the horizon scanning of an interdisciplinary field. However, identifying basic technologies of the targeted field and following the progress of research and the integration process of each component of technology are critical.

Risk factors for contralateral total knee arthroplasty after unilateral total knee arthroplasty.

BACKGROUND: Little attention has been focused on risk factors for undergoing bilateral total knee arthroplasty (TKA) after primary unilateral TKA among patients with knee osteoarthritis (OA). This study investigated the differences in characteristics between groups with and without additional TKA for the contralateral knee among patients with knee OA who underwent primary unilateral TKA. METHODS: Seventy-six patients who underwent primary unilateral TKA were included in this study. We defined patients who underwent additional TKA for the contralateral knee within one year of the primary TKA as a bilateral TKA group, and patients who did not undergo bilateral TKA as a unilateral TKA group. Femorotibial angle (FTA), percentage of mechanical axis (%MA), Kellgren-Lawrence (KL) grade, range of motion, Japan Orthopaedic Association (JOA) score, 10 m-walking time, C-reactive protein, estimated glomerular filtration rate, and serum albumin levels were selected as independent variables including covariates of age, sex, and body mass index for predicting bilateral TKA. We compared differences in variables between the two groups using the t-test or Mann-Whitney U-test and general linear models. A multivariate stepwise logistic regression model was also used to determine which variables correlated with bailateral TKA. RESULTS: In pairwise comparisons, the KL grade, FTA, %MA, JOA score, and knee flexion angle in the contralateral knee were significantly worse in the bilateral TKA group than in the unilateral TKA group after controlling for covariates (P < 0.01, respectively). A stepwise logistic regression revealed that significant contributors to undergoing the contralateral TKA were FTA (OR = 1.47, P < 0.001) and knee flexion angle (OR = 0.96, P = 0.022) of the contralateral knee. CONCLUSIONS: Severe varus deformity and limitations of flexion in the contralateral knee were found to be risk factors for undergoing additional TKA within one year of primary unilateral TKA among patients with knee OA.

Application of Internet of Medical/Health Things to Decentralized Clinical Trials: Development Status and Regulatory Considerations.

Background: The need for a new style of clinical trials, called decentralized clinical trials (DCTs), has been increasing as they do not depend on physical visits to clinical sites. DCTs are expected to provide a new opportunity to patients who cannot participate in a clinical trial due to geographical and time limitations. For the adoption of DCTs, it is essential that medical devices with Internet of Medical Things (IoMT) and Internet of Health Things (IoHT) based technologies are developed and commercially adopted. In this study, we aimed to identify the regulatory considerations when IoMT/IoHT-based technologies are used in DCTs or products developed using DCTs. Method: To understand the study and development field of IoMT/IoHT comprehensively and panoramically, relevant papers published in Web of Science were searched online. Subsequently, a citation network was obtained and characterized as a cluster using a text mining method to identify IoMT/IoHT-based technologies expected to be utilized in DCTs or products developed using DCTs. Result and Discussion: Upon analysis of the top 15 clusters and subsequent 51 sub-clusters, we identified the therapeutic areas (psychology, neurology) and IoMT/IoHT-based technologies (telemedicine, remote monitoring, and virtual reality) that are expected to be used in DCTs. We also identified several considerations based on the current regulatory guidance. Conclusion: IoMT/IoHT-based technologies that are expected to be used or products developed using DCTs and key considerations made when they are used in DCTs were identified. The considerations could encourage conducting DCTs using IoMT/IoHT-based technologies.

Study on Horizon Scanning by Citation Network Analysis and Text Mining: A Focus on Drug Development Related to T Cell Immune Response.

Certain innovative technologies applied to medical product development require novel evaluation approaches and/or regulations. Horizon scanning for such technologies will help regulators prepare, allowing earlier access to the product for patients and an improved benefit/risk ratio. This study investigates whether citation network analysis and text mining of scientific papers could be a tool for horizon scanning in the field of immunology, which has developed over a long period, and attempts to grasp the latest research trends. As the result of the analysis, the academic landscape of the immunology field was identified by classifying 90,450 papers (obtained from PubMED) containing the keyword "immune* and t lymph*" into 38 clusters. The clustering was indicative of the research landscape of the immunology field. To confirm this, immune checkpoint inhibitors were used as a retrospective test topic of therapeutics with new mechanisms of action. Retrospective clustering around immune checkpoint inhibitors was found, supporting this approach. The analysis of the research trends over the last 3 to 5 years in this field revealed several candidate topics, including ARID1A gene mutation, CD300e, and tissue resident memory T cells, which shows notable progress and should be monitored for future possible product development. Our results have demonstrated the possibility that citation network analysis and text mining of scientific papers can be a useful objective tool for horizon scanning of life science fields such as immunology.

Study on Horizon Scanning with a Focus on the Development of AI-Based Medical Products: Citation Network Analysis.

Horizon scanning for innovative technologies that might be applied to medical products and requires new assessment approaches to prepare regulators, allowing earlier access to the product for patients and an improved benefit/risk ratio. The purpose of this study is to confirm that citation network analysis and text mining for bibliographic information analysis can be used for horizon scanning of the rapidly developing field of AI-based medical technologies and extract the latest research trend information from the field. We classified 119,553 publications obtained from SCI constructed with the keywords "conventional," "machine-learning," or "deep-learning" and grouped them into 36 clusters, which demonstrated the academic landscape of AI applications. We also confirmed that one or two close clusters included the key articles on AI-based medical image analysis, suggesting that clusters specific to the technology were appropriately formed. Significant research progress could be detected as a quick increase in constituent papers and the number of citations of hub papers in the cluster. Then we tracked recent research trends by re-analyzing "young" clusters based on the average publication year of the constituent papers of each cluster. The latest topics in AI-based medical technologies include electrocardiograms and electroencephalograms (ECG/EEG), human activity recognition, natural language processing of clinical records, and drug discovery. We could detect rapid increase in research activity of AI-based ECG/EEG a few years prior to the issuance of the draft guidance by US-FDA. Our study showed that a citation network analysis and text mining of scientific papers can be a useful objective tool for horizon scanning of rapidly developing AI-based medical technologies.

Meniscal Repair Using Fibrin Clots Made From Bone Marrow Blood Wrapped in a Polyglycolic Acid Sheet.

Meniscal repair is one of the most common procedures for meniscal tears; however, a previous systematic review showed meniscal repairs have a greater reoperation rate compared with partial meniscectomies. Therefore, an improvement of existing meniscal repair techniques is warranted. Clinical results of polyglycolic acid (PGA) sheets have been reported for rotator cuff repairs. In recent years, we have performed meniscal repairs using wrapped fibrin clots in PGA sheet. We considered the use of wrapped fibrin clots with a PGA sheet to treat meniscus tears. The purpose of this paper is to introduce a step-by-step guide to our new delivery technique using fibrin clots.

The Cut-off Value of Physical Activity for Undergoing Total Knee Arthroplasty in Patients with Knee Osteoarthritis.

BACKGROUND: We aimed to determine a cut-off value for physical activity (PA), measured using an accelerometer, between patients with knee osteoarthritis (OA) who decided to undergo total knee arthroplasty (TKA) and those who continued conservative treatment. METHODS: Forty-two participants were assigned to either a TKA group or a non-TKA group (21 per group). They were instructed to wear an accelerometer throughout the day. Average daily steps (steps/day), average daily time of light PA (LPA) (min/day), and average daily time of moderate-to-vigorous PA (MVPA) (min/day) were measured for seven days. Variables between the two groups were compared using univariate analyses, and then a stepwise logistic regression was conducted to determine which variables best correlated with undergoing TKA. The PA cut-offs were analysed using the receiver operating characteristic curve. RESULTS: Pain severity (p = 0.002), KL grade (p = 0.001), and MVPA (p = 0.012) differed significantly between the groups. The most useful cut-off value was 5.84 (min/day) for MVPA (AUC = 0.773), although only pain severity and KL grade were found to be significant contributors to undergoing TKA. CONCLUSIONS: Our results revealed there was a significant decrease in PA levels (MVPA cut-off, 5-6 min/day) in the TKA group compared with the non-TKA group.

Suprapatellar plica classification and suprapatellar plica syndrome.

BACKGROUND: Plicae around the knee are anatomically normal structures that are remnants of embryonic membranes and are generally asymptomatic. Synovial plica syndrome is known to cause knee symptoms; however, its pathological contribution has been rarely reported. This study aimed to investigate the clinical significance of suprapatellar plicae as well as the morphological characteristics of suprapatellar plicae in patients with knee symptoms who required arthroscopic treatment. METHODS: Of 223 arthroscopic knee surgeries, 125 patients undergoing primary arthroscopy for various diseases were eligible for inclusion in this study. All affected knees were preoperatively examined by two skilled physicians in a routine manner. Each patient was diagnosed with one primary disease entity based on clinical examinations and arthroscopic findings. At least two skilled orthopedic physicians watched the surgical videos together and defined the type of plicae based on the Dandy classification (Dandy DJ. 1990) as follows: (A) absent, (B) the plica was up to one-quarter of the width of the suprapatellar pouch, (C) the plica was between one-quarter and one-third of the width of the suprapatellar pouch, (D) the plica was between one-third and two-thirds of the width of the suprapatellar pouch, (E) the plica was more than two-thirds of the width of the suprapatellar pouch, (F) the plica had a complete membrane, (G) the plica was perforated, (H) arch, (I) pillar, or (J) lateral. Suprapatellar plica syndrome was considered when (1) the patient complained of anterior knee pain and had localized tenderness above the suprapatellar pouch, (2) magnetic resonance imaging revealed suprapatellar plica structures, and (3) other suspicious pathologies accounting for knee symptoms were excluded. We investigated primary disease type, type of plica, and the relationships between them. RESULTS: The results revealed that meniscus injuries and anterior cruciate ligament injuries caused the majority of primary diseases (approximately 80%). Regarding plica forms, 23 knees were classified as having absent (type A) plicae, 14 knees as having a complete septum (type F), and 88 knees were classified as "other." There were no significant relationships between disease type and the morphological characteristics of the plicae (chi-squared test, p = 0.35). Suprapatellar pain was observed in five cases, of which two patients were diagnosed with intra-articular free body, one patient with synovitis combined osteoarthritis, and two patients with suprapatellar plica syndrome with a complete septum. The latter two cases experienced knee symptom resolution soon after arthroscopic resection of the plica. CONCLUSIONS: Although the results did not show any relationship between forms of plica remnants and primary disease type, all patients diagnosed with suprapatellar plica syndrome showed complete septum type suprapatellar plicae. A large population study is required in the future.

Bizarre parosteal osteochondromatous proliferation of the femur: A case report.

A 54-year-old man initially presented with left distal thigh pain during walking. Imaging analysis revealed a diffuse calcified or ossified mass adjacent to the medial cortex of the distal femur and absence of continuity with the medulla. We performed resection biopsy. Histological examination revealed a large amount of hypercellular cartilage showing transformation to trabecular bone and BPOP was diagnosed. Postoperative course was uneventful and he remained free of recurrence. The method of resection should depend on the stage of reactive proliferation and whether the lesion is pathologically immature or mature. We also provide a brief review of the literature.

Evaluation of a single-dose PIGRET assay for acetaminophen in rats compared with the RBC Pig-a assay.

As a part of a collaborative study of the Pig-a assay by the Mammalian Mutagenicity Study Group of the Japanese Environmental Mutagen Society, a genotoxicity study on acetaminophen (APAP) was performed using the red blood cell (RBC) Pig-a and PIGRET assays. The dose levels were set at 0 (vehicle, 0.5% methylcellulose solution), 500, 1000, and 2000mg/kg, and APAP was administered once by oral gavage to male Sprague Dawley rats. For the positive control group, N-nitroso-N-ethylurea (ENU, 40mg/kg) was administered in the same way. The RBC Pig-a and PIGRET assays were performed using peripheral blood collected at pre-dosing and 1, 2 and 4 weeks after dosing. In both the RBC Pig-a and PIGRET assays, there were no changes in the Pig-a gene mutant frequency (MF) by the APAP treatment at any time point. The Pig-a MFs as measured by the RBC Pig-a assay for the ENU-treated group increased in a time-dependent manner with the maximum value at week 4; however, those using the PIGRET assay reached comparable values at week 1. Based on the above results, APAP was determined to have no mutagenicity under the conditions of this study, and the PIGRET assay could detect mutagenicity of ENU much earlier than the RBC Pig-a assay.

Evaluation of a single-dose PIGRET assay for cisplatin in rats compared with the RBC Pig-a assay.

As a part of a collaborative study of the Pig-a assay by the Mammalian Mutagenicity Study Group of the Japanese Environmental Mutagen Society, a genotoxicity study on cisplatin was performed using red blood cell (RBC) Pig-a and PIGRET assays. The dose levels were set at 0 (vehicle, physiological saline), 0.5, 1, and 2 mg/kg, and cisplatin was administered intravenously once to male F344 rats. The RBC Pig-a and PIGRET assays were performed using peripheral blood collected at pre-dosing and 1, 2 and 4 weeks after dosing. In the RBC Pig-a assay, an increase in the Pig-a mutant frequency (MF) was observed at week 4 in the high dose group. Although a significant increase in the Pig-a MF was also observed at week 2 in all cisplatin-treated groups, it was considered that this change was caused by a low MF in the vehicle control group and not to be biologically relevant. In the PIGRET assay, the Pig-a MF was increased at weeks 1, 2 and 4 in the high dose group. In addition, the means of the vehicle control group's Pig-a MFs in the PIGRET assay were lower than those in the RBC Pig-a assay. Based on the above results, cisplatin was determined to have mutagenicity under the conditions of this study, and it was demonstrated that the PIGRET assay was an appropriate tool to evaluate the in vivo mutagenicity much earlier than the RBC Pig-a assay.