Involvement of interleukin-1ß in high glucose-activated proliferation of cholangiocarcinoma.

Background: Diabetes mellitus (DM) is associated with the increased risk of development and the advancement of cholangiocarcinoma (CCA). High glucose levels were previously shown for upregulating interleukin-1ß (IL-1ß) in CCA cells with unclear functions. The present study, thus, aimed to investigate molecular mechanisms linking DM to CCA progression, with IL-1ß hypothesized as a communicating cytokine. Methods: CCA cells were cultured in media with normal (5.6 mM) or high (25 mM) glucose, resembling euglycemia and hyperglycemia, respectively. Expressions of IL-1ß and IL-1 receptor (IL-1R) in CCA tissues from patients with and without DM were examined using immunohistochemistry. Functional analyses of IL-1ß were performed using siRNA and recombinant human IL-1R antagonist (rhIL-1RA), in which Western blots investigated the knockdown efficacy. BALB/c Rag-2-/- Jak3-/- (BRJ) mice were implanted with CCA xenografts to investigate hyperglycemia's effects on CCA growth and the anti-tumor effects of IL-1RA. Results: CCA tumors from patients with hyperglycemia showed significantly higher IL-1ß expression than those from non-DM patients, while IL-1ß was positively correlated with fasting blood glucose (FBG) levels. CCA cells cultured in high glucose showed increased IL-1ß expression, resulting in increased proliferation rates. Suppressing IL-1ß signaling by si-IL-1ß or rhIL-1RA significantly reduced CCA cell proliferation in vitro. Anakinra, a synthetic IL-1RA, also exerted significant anti-tumor effects in vivo and significantly reversed the effects of hyperglycemia-induced growth in CCA xenografts. Conclusions: IL-1ß plays a crucial role in CCA progression in a high-glucose environment. Targeting IL-1ß might, then, help improve therapeutic outcomes of CCA in patients with DM and hyperglycemia.

Flatfoot Surgery for Flexible Progressive Collapsing Foot Deformity With Inflammatory Joint Diseases: A Report of 3 Cases.

CASE: Three cases of inflammatory joint diseases (systemic lupus erythematosus and ongoing juvenile idiopathic arthritis) with painful flexible progressive collapsing foot deformity (PCFD) underwent flatfoot surgery. All cases maintained sufficient radiological correction and achieved good clinical condition at final follow-up. CONCLUSION: Although the prospect for recurrence of the deformity is not clear, even in inflammatory joint diseases, flat foot surgery such as flexor digitorum longs transfer, spring ligament reconstruction, and lateral column lengthening could have a possibility to be indicated against PCFD, as long as disease activity could be well suppressed by drug therapy, subsequently subtalar and talonavicular joints could be preserved.

Arthroscopic treatment of septic arthritis of the ankle joint caused by streptococcus in patients with chronic inflammatory diseases: two case reports.

This report describes the arthroscopic treatment of septic arthritis of the ankle joint in two patients with inflammatory diseases, including rheumatoid arthritis (RA) and nail psoriasis. We treated both the ankle joints with antibiotic administration and urgent arthroscopic synovectomy and irrigation, although the procedure was performed several days (4 and 6 days) after the time at which the infection would have occurred. Fortunately, no recurrence has been seen for more than 18 and 20 months, respectively, after surgery, without antibiotic administration. Although septic arthritis of the ankle joint accounts for a small proportion of joint arthritis cases, diagnosis as early as possible is important. Our experience suggests that arthroscopic synovectomy and irrigation are effective for septic ankle arthritis even in chronic inflammatory disease cases.

Intra-Articular Corrective Osteotomy for Distal Radial Intra-Articular Malunion Using Patient-Matched Instruments: A Prospective, Multicenter, Open-Label, Single-Arm Trial.

Background: Corrective osteotomy for intra-articular malunion is a challenging procedure. However, recent advancements, including patient-matched instruments created on the basis of preoperative computer simulation, enable accurate intra-articular correction. We hypothesized that intra-articular corrective osteotomy using patient-matched instruments for the treatment of distal radial intra-articular malunion would reduce intra-articular deformity and restore wrist function at 12 months of follow-up. Methods: This prospective study included 12 patients with distal radial intra-articular malunion who underwent intra-articular corrective osteotomy external to the joint using patient-matched instruments. The primary end point was the maximum step-off on the articular surface of the distal radius, measured with use of computed tomography (CT), with an expected postoperative value of ≤1.5 mm. The secondary end points included the gap of the articular surface; range of motion; grip strength; pain evaluated using a visual analog scale (VAS); patient satisfaction; Disabilities of the Arm, Shoulder and Hand (DASH) score; and Patient-Rated Wrist Evaluation (PRWE) score. A mean postoperative step-off of ≤1.5 mm for the primary end point was assessed with use of the 1-sample t test. The secondary end points were assessed with use of the Dunnett multiple comparison test. Results: The average step-off significantly improved from 3.75 ± 1.04 mm preoperatively to 0.51 ± 0.40 mm at the 52-week postoperative follow-up and was maintained within 1.5 mm. The average wrist and forearm range of motion, VAS score, grip strength, DASH score, and PRWE score significantly improved. Eleven patients were either very satisfied or satisfied with their outcomes. Conclusions: The use of patient-matched instruments could contribute to improving postoperative outcomes of intra-articular corrective osteotomy procedures involving the distal radius. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

PAX5 functions as a tumor suppressor by RB-E2F-mediated cell cycle arrest in Kaposi sarcoma-associated herpesvirus-infected primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a malignant B-cell lymphoma attributable to Kaposi sarcoma-associated herpesvirus (KSHV) infection. PEL is characterized by invasive behavior, showing recurrent effusions in body cavities. The clinical outcome and typical prognosis in patients with PEL are poor and potentially lethal. Clarification of the pathogenesis in PEL is urgently needed in order to develop novel therapies. PEL cells generally lack B-cell surface markers, and we therefore hypothesized that the B-cell transcription factor, PAX5, would be down-regulated in PEL. The expression of PAX5 is detected from the pro-B to the mature B-cell stage and is indispensable for the differentiation of B-cells. PAX5 was silenced in PEL cells via its promoter methylation. Up-regulation of PAX5 induced several genes coding for B-cell surface marker mRNA, but not protein level. PAX5 inhibited cell growth via G1 cell cycle arrest. PAX5 bound to RB and increased its protein expression. RB/E2F-regulated genes were significantly down-regulated in microarray analysis and PCR experiments. To elucidate the in vivo role of PAX5, we examined the restoration of PAX5 in a PEL mouse model. The ascites volume and organ invasions were significantly suppressed by PAX5 restoration. Reduction of PAX5 has played a crucial role in the oncogenesis of PEL, and PAX5 is a tumor suppressor in PEL. Targeting PAX5 could represent a novel therapeutic strategy for patients with PEL.

Association of dorsal malunion in distal radius fractures with wrist osteoarthritis: alterations of bone density and stress-distribution patterns in relation to deformation angles.

OBJECTIVE: Distal radius fractures (DRFs) with dorsal malunion increase the risk of osteoarthritis (OA), although the cause of post-DRF OA is yet to be elucidated. To clarify the abnormal effects of a post-DRF dorsal radius deformity, we evaluated the bone density (BD) and stress-distribution patterns of the articular surface in dorsally malunited DRFs. DESIGN: In 36 cases of dorsally malunited DRFs following extra-articular fractures, we generated three-dimensional computerized models of the malunited distal radius from computed tomography data and extracted the subchondral bones of the radiocarpal joint (RCJ) and distal radioulnar joint (DRUJ). Both BD and stress distribution in the subchondral bones were quantitatively evaluated by comparing the affected and normal sides. Correlations of alterations in high-BD distribution and deformation angles were analyzed. RESULTS: The center of high-BD distribution from the center of the RCJ in the volar(-)-dorsal(+) direction was dorsal (0.56±0.72 mm) on the affected side compared with the normal side (-0.15±0.63 mm) [95% CI: 0.43, 1.00, P<0.0001]. The maximum stress distribution was also dorsal on the affected side (2.34±3.52 mm) compared with the normal side (-2.49±1.62 mm) [95% CI: 0.89, 1.79, P<0.0001]. The alterations in BD and stress distribution correlated with the dorsiflexion and radial deviation angles. In the DRUJ, there was no significant difference in BD between the affected and normal sides. CONCLUSIONS: In dorsally malunited DRFs, the alignment change of the RCJ resulted in high BD-concentration areas and stress distribution on the dorsal side of the radius, which may constitute a precursor for OA.

Promising immunotherapeutic approaches for primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a large B-cell neoplasm usually presenting as a serious effusion in body cavities without detectable tumor masses. It is an AIDS-related non-Hodgkin's lymphoma (HL) with human herpes virus 8 (HHV8)/Kaposi sarcoma-associated herpes virus (KSHV) infection. A combination antiretroviral therapy (cART) prolongs the lifespan of AIDS and AIDS-related malignant lymphoma patients, but PEL continues to have a dismal prognosis. PEL showed disappointing outcomes with standard chemotherapy such as CHOP or CHOP-like regimens. A PEL status highlights the urgent need for new therapeutic approaches and treatment strategies and improve clinical outcomes. This review discusses the current knowledge and some recent clinical trials for PEL in the platform of immunotherapy as well as promising future immunotherapeutic approaches for PEL.

Appropriate pelvic obliquity measurement method in Lenke type 5C adolescent idiopathic scoliosis: a preliminary study.

Background: Although pelvic obliquity (PO) is a risk factor for postoperative coronal decompensation in corrective surgery in adolescent idiopathic scoliosis (AIS), especially Lenke 5C, methods of measuring PO are controversial. This study aimed to establish an appropriate measurement method using multiplanar reconstructed computed tomography (MPR-CT) images instead of standing posteroanterior (PA) whole-spine radiographs to evaluate PO in patients with Lenke 5C AIS. Methods: This study was a retrospective cross-sectional study. Twenty-five patients who underwent corrective surgery for AIS in Osaka University Hospital from August 2014 to February 2023 were included. Cobb angle, L5 tilt, C7 plumb line to center sacral vertebral line (C7PL-CSVL), and leg length discrepancy (LLD) were measured on standing PA whole-spine radiographs preoperatively. Sacral obliquity (SO), the slope of the upper endplate of S1, and iliac obliquity (IO), the tilt of the line connecting the iliac crests, were measured on standing PA whole-spine radiographs and MPR-CT (SO/IO-X-ray, SO/IO-CT, respectively). S1 angle and S2 angle were measured on CT. Results: The mean age of the patients was 18.7±3.9 years and all of them were females. SO-X-ray and SO-CT were larger than IO-X-ray and IO-CT, respectively. SO-X-ray was highly correlated with SO-CT (r=0.838, P<0.001). L5 tilt had higher correlation with SO-CT (r=0.884, P<0.001) than with SO-X-ray (r=0.726, P=0.001) and IO-CT (r=0.550, P=0.22). L5 tilt was correlated poorly with IO-X-ray (r=0.104, P=0.69). The S1 angle was 4.5±3.5° meanwhile the S2 angle was 1.2±2.1°, the sacral deformity was mainly due to the S1 vertebral wedging. Conclusions: Given the asymmetric sacral morphology, SO is more appropriate pelvic parameter than IO to represent the sacral tilt of Lenke 5C AIS, especially when measured using CT images to overcome the poor visibility on PA whole-spine radiographs.

Trastuzumab, a monoclonal anti-HER2 antibody modulates cytotoxicity against cholangiocarcinoma via multiple mechanisms.

Cholangiocarcinoma (CCA) is an aggressive and fatal cancer. The prognosis is very poor and no optimal chemotherapy has been established. Human epidermal growth factor receptor 2 (HER2, neu, and erbB2) is highly-expressed in breast cancer and is expressed in many other tumors but poorly expressed in CCA. The anti-HER2 antibody, trastuzumab, has been used for the treatment of HER2-positive breast and gastric cancer. In this study, we examined the surface expression of HER2 on seven Thai liver-fluke-associated CCA cell lines by flow cytometry, and found all of these CCA cells were weakly positive for HER2. MTT assay revealed that trastuzumab directly suppressed the growth of CCA. By using FcR-bearing recombinant Jurkat T-cell-expressing firefly luciferase gene under the control of NFAT response elements, we defined the activities of antibody-dependent cytotoxicity (ADCC) and antibody-dependent cell phagocytosis (ADCP). ADCC was confirmed by using expanded NK cells. ADCP was confirmed by using mouse peritoneal macrophages and human monocyte-derived macrophages as effector cells. Rabbit serum was administered to test the complement-dependent cytotoxicity (CDC) activity of trastuzumab. Finally, we evaluated the efficacy of trastuzumab in in vivo patient-derived cell xenograft and patient-derived xenograft (PDX) models. Our results showed that a distinct population of CCA (liver-fluke-associated CCA) expressed HER2. Trastuzumab demonstrated a potent inhibitory effect on even HER2 weakly positive CCA both in vitro and in vivo via multiple mechanisms. Thus, HER2 is a promising target in anti-CCA therapy, and trastuzumab can be considered a promising antibody immunotherapy agent for the treatment of CCA.

Clinical effects of teriparatide, abaloparatide, and romosozumab in postmenopausal osteoporosis.

In the management of osteoporosis, anti-resorptive agents serve as a primary therapeutic approach. However, in cases where individuals exhibit an increased susceptibility to fractures, such as those characterized by severe low bone mass or a history of vertebral or hip fractures that markedly diminish life expectancy, the immediate reduction of fracture risk through the administration of osteoanabolic agents could be beneficial. Teriparatide, available in daily, once-weekly, or twice-weekly dosages, along with abaloparatide and romosozumab, constitutes a trio of such agents. Each of these medications is defined by unique characteristics, distinct efficacy profiles, and specific adverse effects. There is growing evidence to suggest that these agents have a superior effect on enhancing bone mineral density and reducing fracture incidence when compared to traditional bisphosphonate therapies. Nonetheless, their employment demands thorough consideration of clinical indications, which includes evaluating economic factors, the frequency of injections required, and the potential for adverse effects. The objective of this review is to consolidate the current evidence focusing primarily on the efficacy of these agents, with the goal of enhancing understanding and aiding in making more informed treatment decisions, particularly for those individuals who are at an elevated risk of fractures.

Cyclic compressive loading induces a mature meniscal cell phenotype in mesenchymal stem cells with an atelocollagen-based scaffold.

Introduction: Biomechanical stimulation is reportedly pivotal in meniscal regeneration, although its effect on mesenchymal stem cell (MSC) meniscal differentiation remains elusive. In this study, we investigated how cyclic compressive loading (CCL) could impact MSCs using three-dimensional cultures in atelocollagen-based meniscal substitute (ACMS). Methods: We extracted MSCs from the meniscus, synovium, and articular cartilage, cultured them in three-dimensional cultures, and exposed them to CCL for 7 days. We then compared the transcriptomes of MSCs treated with and without CCL. Results: Our RNA-seq analysis revealed that CCL induced significant transcriptome changes, significantly affecting chondrocyte-related genes, including SOX9, TGFB1, and PRG4 upregulation. CCL induced transcriptional differentiation of meniscus progenitors toward mature meniscal cells. Conclusion: This study unveils the potential of mechanical stress in promoting MSC meniscal differentiation within ACMS. Our investigations provide new insights for mechanisms underlying meniscal regeneration with ACMS.

Liraglutide exhibits potential anti-tumor effects on the progression of intrahepatic cholangiocarcinoma, in vitro and in vivo.

Glucagon-like peptide 1 receptor (GLP-1R) agonist is an emerging anti-diabetic medication whose effects on the risk and progression of cholangiocarcinoma (CCA) are controversial. This study aimed to elucidate the roles of GLP-1R and its agonists on intrahepatic CCA (iCCA) progression. Expressions of GLP-1R in iCCA tissues investigated by immunohistochemistry showed that GLP-1R expressions were significantly associated with poor histological grading (P = 0.027). iCCA cell lines, KKU-055 and KKU-213A, were treated with exendin-4 and liraglutide, GLP-1R agonists, and their effects on proliferation and migration were assessed. Exendin-4 and liraglutide did not affect CCA cell proliferation in vitro, but liraglutide significantly suppressed the migration of CCA cells, partly by inhibiting epithelial-mesenchymal transition. In contrast, liraglutide significantly reduced CCA tumor volumes and weights in xenografted mice (P = 0.046). GLP-1R appeared downregulated when CCA cells were treated with liraglutide in vitro and in vivo. In addition, liraglutide treatment significantly suppressed Akt and STAT3 signaling in CCA cells, by reducing their phosphorylation levels. These results suggested that liraglutide potentially slows down CCA progression, and further clinical investigation would benefit the treatment of CCA with diabetes mellitus.

Tri-specific killer engager: unleashing multi-synergic power against cancer.

Cancer continues to be a global health concern, necessitating innovative solutions for treatment. Tri-specific killer engagers (TriKEs) have emerged as a promising class of immunotherapeutic agents, offering a multifaceted approach to cancer treatment. TriKEs simultaneously engage and activate natural killer (NK) cells while specifically targeting cancer cells, representing an outstanding advancement in immunotherapy. This review explores the generation and mechanisms of TriKEs, highlighting their advantages over other immunotherapies and discussing their potential impact on clinical trials and cancer treatment. TriKEs are composed of three distinct domains, primarily antibody-derived building blocks, linked together by short amino acid sequences. They incorporate critical elements, anti-cluster of differentiation 16 (CD16) and interleukin-15 (IL-15), which activate and enhance NK cell function, together with specific antibody to target each cancer. TriKEs exhibit remarkable potential in preclinical and early clinical studies across various cancer types, making them a versatile tool in cancer immunotherapy. Comparative analyses with other immunotherapies, such as chimeric antigen receptor-T (CAR-T) cell therapy, immune checkpoint inhibitors (ICIs), cytokine therapies, and monoclonal antibodies (mAbs), reveal the unique advantages of TriKEs. They offer a safer pathway for immunotherapy by targeting cancer cells without hyperactivating T cells, reducing off-target effects and complications. The future of TriKEs involves addressing challenges related to dosing, tumor-associated antigen (TAA) expression, and NK cell suppression. Researchers are exploring innovative dosing strategies, enhancing specificity through tumor-specific antigens (TSAs), and combining TriKEs with other therapies for increased efficacy.

Identification of unapproved orthopedic regenerative medicine: Usefulness of the Act on Safety of Regenerative Medicine.

In Japan, the Act on Safety of Regenerative Medicine regulates unapproved regenerative medicine. Other nations market regenerative medicine products, bypassing regulatory approval. To identify unapproved orthopedic regenerative medicine, we have used data based on the Act. Platelet-rich plasma was often used. The common target was the knee. Prices averaged $2,490.

Nonunion after medial malleolar osteotomy in total ankle arthroplasties for severe varus deformity: a report of 3 cases.

Of the three ankles after total ankle arthroplasty (TAA) with medial malleolar osteotomy for severe varus deformity (talar varus tilt >10°), two failed in varus migration of the tibial component. In these two cases, tibial osteotomy was performed with varus alignment of 5°and 2°, and with medially shifted placement of tibial component, while one ankle showed no migratoin of prostheses after 5 years, even with nonunion. In this case, tibial osteotomy was performed with a valgus alignment of 4°. Internal fixation after medial malleolar osteotomy should be done for severe varus cases. Medially shifted placement of tibial component should be avoided. Fortunately, the failure did not occur in a case of valgus of the distal tibia. Valgus tibial osteotomy might help to reduce the collision of the talus against the medial malleolus.

Assessing the utility of osteoporosis self-assessment tool for Asians in patients undergoing hip surgery.

Objectives: Diagnosis and treatment of osteoporosis are instrumental in obtaining good outcomes of hip surgery. Measuring bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing osteoporosis. However, due to limited access to DXA, there is a need for a screening tool to identify patients at a higher risk of osteoporosis. We analyzed the potential utility of the Osteoporosis Self-assessment Tool for Asians (OSTA) as a screening tool for osteoporosis. Methods: A total of 1378 female patients who underwent hip surgery at 8 institutions were analyzed. For each patient, the BMD of the proximal femoral region was measured by DXA (DXA-BMD), and the correlation with OSTA score (as a continuous variable) was assessed. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of OSTA score to predict osteoporosis. Lastly, the OSTA score was truncated to yield an integer (OSTA index) to clarify the percentage of patients with osteoporosis for each index. Results: DXA-BMD showed a strong correlation with OSTA (r = 0.683; P < 0.001). On ROC curve analysis, the optimal OSTA score cut-off value of -5.4 was associated with 73.8% sensitivity and 80.9% specificity for diagnosis of osteoporosis (area under the curve: 0.842). A decrease in the OSTA index by 1 unit was associated with a 7.3% increase in the probability of osteoporosis. Conclusions: OSTA is a potentially useful tool for screening osteoporosis in patients undergoing hip surgery. Our findings may help identify high-risk patients who require further investigation using DXA.

Establishment and characterization of TK-ALCL1: a novel NPM-ALK-positive anaplastic large-cell lymphoma cell line.

TK-ALCL1, a novel anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALK+ ALCL) cell line, was established from the primary tumor site of a 59-year-old Japanese male patient. The immune profile of TK-ALCL1 corresponds to that seen typically in primary ALCL cells, i.e., positive for ALK, CD30, EMA, and CD4, but negative for CD2, CD3, CD5, CD8a, and EBV-related antigens. The rearrangement of the T cell receptor-gamma locus shows that TK-ALCL1 is clonally derived from T-lineage lymphoid cells. FISH and RT-PCR analysis revealed that TK-ALCL1 has the nucleophosmin (NPM)-ALK fusion transcript, which is typical for ALK+ ALCL cell lines. When TK-ALCL1 was subcutaneously inoculated into 6-week-old BALB/c Rag2-/-/Jak3-/- (BRJ) mice, it formed tumor masses within 4-6 weeks. Morphological, immunohistochemical, and molecular genetic investigations confirmed that the xenograft and the original ALCL tumor were identical. The ALK inhibitors Alectinib and Lorlatinib suppressed proliferation in a dose-dependent manner. Thus, TK-ALCL1 provides a useful in vitro and in vivo model for investigation of the biology of ALK+ ALCL and of novel therapeutic approaches targeting ALK.

Cubitus varus deformity following paediatric supracondylar humeral fracture remodelling predominantly in the sagittal direction: A three-dimensional analysis of eighty-six cases.

PURPOSE: Three-dimensional (3D) capacity for remodelling in cubitus varus deformity (CVD) after paediatric supracondylar humeral fractures (PSHFs) remains unelucidated. This study investigated remodelling patterns after PSHFs by examining 3D deformity distribution over time after injury. METHODS: Computed tomography (CT) data of 86 patients with CVD after PSHFs were analysed. The 3D deformity angles in the sagittal, coronal, and axial directions were assessed and correlated with the duration between the age at injury and CT evaluation. For the subgroup analysis, we performed the same correlation analysis in a younger (< 8 years old) and an older group (≥ 8 years old); we categorized the duration into early (< 2 years), middle (≥ 2 to < 5 years), and late periods (≥ 5 years) and compared the deformity angles of each direction among the three groups. RESULTS: Sagittal deformity showed a moderate correlation with the duration of deformity (r = -0.54; P < 0.001), while coronal and axial deformities showed a negligible correlation. Sagittal deformity showed moderate correlations with the duration in the younger group (r = -0.62; P < 0.001) and weak correlations in the older group (r = -0.37; P = 0.091). In the sagittal direction, the deformity angle in the early period was significantly larger than those in the mid and late periods (P < 0.001). However, there were no significant differences among the three groups in the coronal and axial directions. CONCLUSION: Sagittal deformities in CVDs are capable of remodelling, especially in the early period and at a younger age, whereas coronal and axial deformities are less likely to undergo remodelling.

A Comparison Between GPT-3.5, GPT-4, and GPT-4V: Can the Large Language Model (ChatGPT) Pass the Japanese Board of Orthopaedic Surgery Examination?

Introduction Recently, large-scale language models, such as ChatGPT (OpenAI, San Francisco, CA), have evolved. These models are designed to think and act like humans and possess a broad range of specialized knowledge. GPT-3.5 was reported to be at a level of passing the United States Medical Licensing Examination. Its capabilities continue to evolve, and in October 2023, GPT-4V became available as a model capable of image recognition. Therefore, it is important to know the current performance of these models because they will be soon incorporated into medical practice. We aimed to evaluate the performance of ChatGPT in the field of orthopedic surgery. Methods We used three years' worth of Japanese Board of Orthopaedic Surgery Examinations (JBOSE) conducted in 2021, 2022, and 2023. Questions and their multiple-choice answers were used in their original Japanese form, as was the official examination rubric. We inputted these questions into three versions of ChatGPT: GPT-3.5, GPT-4, and GPT-4V. For image-based questions, we inputted only textual statements for GPT-3.5 and GPT-4, and both image and textual statements for GPT-4V. As the minimum scoring rate acquired to pass is not officially disclosed, it was calculated using publicly available data. Results The estimated minimum scoring rate acquired to pass was calculated as 50.1% (43.7-53.8%). For GPT-4, even when answering all questions, including the image-based ones, the percentage of correct answers was 59% (55-61%) and GPT-4 was able to achieve the passing line. When excluding image-based questions, the score reached 67% (63-73%). For GPT-3.5, the percentage was limited to 30% (28-32%), and this version could not pass the examination. There was a significant difference in the performance between GPT-4 and GPT-3.5 (p < 0.001). For image-based questions, the percentage of correct answers was 25% in GPT-3.5, 38% in GPT-4, and 38% in GPT-4V. There was no significant difference in the performance for image-based questions between GPT-4 and GPT-4V. Conclusions ChatGPT had enough performance to pass the orthopedic specialist examination. After adding further training data such as images, ChatGPT is expected to be applied to the orthopedics field.

Automatic hip osteoarthritis grading with uncertainty estimation from computed tomography using digitally-reconstructed radiographs.

PURPOSE: Progression of hip osteoarthritis (hip OA) leads to pain and disability, likely leading to surgical treatment such as hip arthroplasty at the terminal stage. The severity of hip OA is often classified using the Crowe and Kellgren-Lawrence (KL) classifications. However, as the classification is subjective, we aimed to develop an automated approach to classify the disease severity based on the two grades using digitally-reconstructed radiographs from CT images. METHODS: Automatic grading of the hip OA severity was performed using deep learning-based models. The models were trained to predict the disease grade using two grading schemes, i.e., predicting the Crowe and KL grades separately, and predicting a new ordinal label combining both grades and representing the disease progression of hip OA. The models were trained in classification and regression settings. In addition, the model uncertainty was estimated and validated as a predictor of classification accuracy. The models were trained and validated on a database of 197 hip OA patients, and externally validated on 52 patients. The model accuracy was evaluated using exact class accuracy (ECA), one-neighbor class accuracy (ONCA), and balanced accuracy. RESULTS: The deep learning models produced a comparable accuracy of approximately 0.65 (ECA) and 0.95 (ONCA) in the classification and regression settings. The model uncertainty was significantly larger in cases with large classification errors ( P < 6 e - 3 ). CONCLUSIONS: In this study, an automatic approach for grading hip OA severity from CT images was developed. The models have shown comparable performance with high ONCA, which facilitates automated grading in large-scale CT databases and indicates the potential for further disease progression analysis. Classification accuracy was correlated with the model uncertainty, which would allow for the prediction of classification errors. The code will be made publicly available at https://github.com/NAIST-ICB/HipOA-Grading .