Faculty Profiles - OZAKI Toshifumi

Papers - OZAKI Toshifumi

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Methotrexate, Doxorubicin, and Cisplatin Versus Methotrexate, Doxorubicin, and Cisplatin + Ifosfamide in Poor Responders to Preoperative Chemotherapy for Newly Diagnosed High-Grade Osteosarcoma (JCOG0905): A Multicenter, Open-Label, Randomized Trial

Hiroaki Hiraga, Ryunosuke Machida, Akira Kawai, Toshiyuki Kunisada, Tsukasa Yonemoto, Makoto Endo, Yoshihiro Nishida, Akihito Nagano, Keisuke Ae, Shinichirou Yoshida, Kunihiro Asanuma, Junya Toguchida, Taisuke Furuta, Robert Nakayama, Toshihiro Akisue, Toru Hiruma, Takeshi Morii, Hideki Nishimura, Koji Hiraoka, Masanobu Takeyama, Makoto Emori, Satoshi Tsukushi, Hiroshi Hatano, Hiroyuki Kawashima, Kazuo Isu, Kazuhiro Tanaka, Tomoko Kataoka, Haruhiko Fukuda, Yukihide Iwamoto, Toshifumi Ozaki

Journal of Clinical Oncology 2025.3

Publishing type：Research paper (scientific journal) Publisher：American Society of Clinical Oncology (ASCO)

PURPOSE

Our previous NECO phase II studies on high-grade osteosarcoma suggested that administering ifosfamide (IF; 16 g/m ² [4g/m ² once on day 1, then 2g/m ² once on days 2-7] × six) to patients showing a poor response (PrRsp) to preoperative chemotherapy with methotrexate, doxorubicin, and cisplatin (MAP) improves their prognoses. In this Japan Clinical Oncology Group (JCOG) study, JCOG0905, we aimed to investigate the efficacy and safety of IF in patients with PrRsp.

METHODS

JCOG0905 is a multicenter, open-label, multi-institutional, randomized trial. Eligible patients (50 years and younger) had resectable, high-grade osteosarcoma (stage II or III, Union for International Cancer Control TNM) of the extremities, limb girdles, and thoracic wall. After two MAP cycles and tumor resection, patients with PrRsp were randomly assigned to either the MAP or MAP plus 15 g/m ² (3g/m ² once daily on days 1-5) × six IF (MAP + IF [MAPIF]) group. The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The planned sample size was 100 patients with a one-sided α of .1 and a power of 0.7, assuming a 3-year DFS of 50% and 65% for MAP and MAPIF, respectively. This trial is registered with the Japan Registry of Clinical Trials (jRCT; jRCTs031180126).

RESULTS

Of the 287 patients registered between February 2010 and August 2020, 51 and 52 patients with PrRsp were assigned to the MAP and MAPIF groups, respectively. As of March 2022, DFS did not differ between groups (hazard ratio [HR], 1.05 [95% CI, 0.55 to 1.98]) and OS was numerically inferior in the MAPIF group (HR, 1.48 [95% CI, 0.68 to 3.22]). Nine and zero patients in the MAPIF and MAP groups discontinued treatment because of adverse events, respectively.

CONCLUSION

Evidence from JCOG0905 does not support the addition of IF for patients with PrRsp.

DOI： 10.1200/jco-24-01281

Empowering pediatric, adolescent, and young adult patients with cancer utilizing generative AI chatbots to reduce psychological burden and enhance treatment engagement: a pilot study

Joe Hasei, Mana Hanzawa, Akihito Nagano, Naoko Maeda, Shinichirou Yoshida, Makoto Endo, Nobuhiko Yokoyama, Motoharu Ochi, Hisashi Ishida, Hideki Katayama, Tomohiro Fujiwara, Eiji Nakata, Ryuichi Nakahara, Toshiyuki Kunisada, Hirokazu Tsukahara, Toshifumi Ozaki

Frontiers in Digital Health 7 2025.2

Publishing type：Research paper (scientific journal) Publisher：Frontiers Media SA

Background

Pediatric and adolescent/young adult (AYA) cancer patients face profound psychological challenges, exacerbated by limited access to continuous mental health support. While conventional therapeutic interventions often follow structured protocols, the potential of generative artificial intelligence (AI) chatbots to provide continuous conversational support remains unexplored. This study evaluates the feasibility and impact of AI chatbots in alleviating psychological distress and enhancing treatment engagement in this vulnerable population.

Methods

Two age-appropriate AI chatbots, leveraging GPT-4, were developed to provide natural, empathetic conversations without structured therapeutic protocols. Five pediatric and AYA cancer patients participated in a two-week intervention, engaging with the chatbots via a messaging platform. Pre- and post-intervention anxiety and stress levels were self-reported, and usage patterns were analyzed to assess the chatbots’ effectiveness.

Results

Four out of five participants reported significant reductions in anxiety and stress levels post-intervention. Participants engaged with the chatbot every 2–3 days, with sessions lasting approximately 10 min. All participants noted improved treatment motivation, with 80% disclosing personal concerns to the chatbot they had not shared with healthcare providers. The 24/7 availability particularly benefited patients experiencing nighttime anxiety.

Conclusions

This pilot study demonstrates the potential of generative AI chatbots to complement traditional mental health services by addressing unmet psychological needs in pediatric and AYA cancer patients. The findings suggest these tools can serve as accessible, continuous support systems. Further large-scale studies are warranted to validate these promising results.

DOI： 10.3389/fdgth.2025.1543543

Radiographic and Clinical Assessment of Unidirectional Porous Beta-Tricalcium Phosphate to Treat Benign Bone Tumors. International journal

Toshiyuki Kunisada, Eiji Nakata, Tomohiro Fujiwara, Haruyoshi Katayama, Takuto Itano, Takanao Kurozumi, Teruhiko Ando, Toshifumi Ozaki

Biomimetics (Basel, Switzerland) 10 ( 2 ) 2025.2

Language：English Publishing type：Research paper (scientific journal)

The purpose of this study was to evaluate radiographic changes, clinical outcomes, and complications following unidirectional porous beta-tricalcium phosphate (UDPTCP) implantation for the treatment of benign bone tumors. We retrospectively analyzed 46 patients who underwent intralesional resection. The patients were divided into two cohorts: Cohort 1 (n = 32), which included all bones except the phalanges and metacarpal/tarsal bones, and Cohort 2 (n = 14), which included the phalanges and metacarpal/tarsal bones. Radiographic changes were assessed at each reading based on resorption of the implanted UDPTCP and bone trabeculation through the defect. UDPTCP resorption and bone trabeculation were observed on radiographs within 3 months of surgery in all patients. Bone remodeling in the cavity progressed steadily for up to 3 years postoperatively. In Cohort 1, resorption and trabeculation progressed significantly in young patients, and trabeculation developed significantly in small lesions. The rates of resorption and trabeculation at 3 months postoperatively correlated statistically with their increased rates at one year. There was no statistical difference in resorption and trabeculation rates between Cohort 1 and Cohort 2. There were no cases of postoperative deep infections or allergic reactions related to the implant. UDPTCP is a useful bone-filling substitute for the treatment of benign bone tumors and has a low complication rate.

DOI： 10.3390/biomimetics10020101

Clinicopathological background of local recurrence in high grade sarcoma of the extremity with preoperative chemotherapy: a supplementary analysis of JCOG0304. International journal

Satoshi Tsukushi, Kazuhiro Tanaka, Toshiyuki Kunisada, Ryunosuke Machida, Satoshi Takenaka, Akira Kawai, Hirohisa Katagiri, Masanobu Takeyama, Makoto Endo, Katsuhiro Hayashi, Robert Nakayama, Hiroshi Hatano, Makoto Emori, Shinichirou Yoshida, Toshio Kojima, Akio Sakamoto, Jungo Imanishi, Ryosuke Kita, Toshifumi Ozaki, Yukihide Iwamoto

Japanese journal of clinical oncology 2025.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The mainstay of treatment for soft-tissue sarcomas is complete resection with negative surgical margins. However, treatment strategies for local control including the frequency of adjuvant radiotherapy (RT) and surgical margin differ greatly between Japan and other countries, and the optimal strategy of local control remains controversial. METHODS: A total of 70 patients with high-grade sarcoma who underwent surgery of the 72 patients enrolled in JCOG0304, were included. The primary endpoint was the proportion of local recurrence, and we investigated the clinicopathological background of local recurrence cases, including the surgical margins according to the Japanese Orthopedic Association (JOA) margin classification or histological margin, and use of adjuvant RT. RESULTS: Local recurrence occurred in five patients, with a 5-year local recurrence proportion of 7.1% (95% confidence interval, 2.6%-14.8%) in 70 patients. The histological subtype were four cases of undifferentiated pleomorphic sarcoma (UPS) and 1 case of liposarcoma. The 5-year local recurrence proportions for UPS and non-UPS were 19.0% and 2.0%, respectively. Two of the five recurrent cases (40%) had adjuvant RT. The recurrent cases were four males and one female, median age 54 years (range: 33-66), JOA margin classification showed wide resection in four cases and marginal resection in one case, and histological margin showed negative in all five cases. CONCLUSION: Despite the low proportion of adjuvant RT, local control of high-grade soft tissue sarcoma with preoperative chemotherapy in JCOG0304 was good. However, more detailed surgical margin evaluation and the use of adjuvant RT should be further investigated in the future for UPS.

DOI： 10.1093/jjco/hyaf027

Could the Trabecular Bone Score Be a Complementary Tool for Evaluating Degenerative Lumbar Vertebrae?

Shinichiro Takao, Koji Uotani, Haruo Misawa, Tomoko Tetsunaga, Kensuke Shinohara, Kentaro Yamane, Yoshiaki Oda, Hironori Tsuji, Yuya Kajiki, Toshifumi Ozaki

Acta medica Okayama 79 ( 1 ) 39 - 45 2025.2

Language：English Publishing type：Research paper (scientific journal)

Evaluating vertebral bone mass and quality in the elderly poses challenges due to degenerative changes. This study aims to elucidate the usefulness of the trabecular bone score (TBS) by examining the relationship between bone mineral density (BMD), TBS, and Hounsfield unit (HU) values. A retrospective analysis of 599 vertebrae from 152 patients (mean age 69.0 years; range 44-89; 74 males and 78 females) undergoing dual-energy X-ray absorptiometry (DXA) and CT scans was conducted. Vertebrae were categorized into three grades based on the degree of degeneration. The TBS was calculated from DXA images, and the HU value was measured by placing a region of interest on an axial image of the vertebral mid-body. One-way analysis of variance and Pearson's correlation tests were employed to investigate the relationship between BMD and TBS or HU values. While lumbar BMD significantly increased (p<0.01) with degenerative changes, TBS and HU values showed no significant differences. The correlations between lumbar BMD and TBS values, and between BMD and HU values, were stronger without degenerative changes than with degenerative changes. Significantly different HU values were observed between the right and left sides of severely degenerated vertebrae. Severe degenerative changes, particularly those associated with sclerosis, may impact HU values. TBS exhibits greater potential than HU values as a complementary tool.

DOI： 10.18926/AMO/68360

LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in β-Catenin Signaling in Human Articular Chondrocytes. International journal

Shuichi Naniwa, Keiichiro Nishida, Aki Yoshida, Yoshihisa Nasu, Ryuichi Nakahara, Takashi Ohtsuki, Yoshifumi Hotta, Noriyuki Shimizu, Chinatsu Ichikawa, Deting Lin, Noriaki Otsuka, Toshifumi Ozaki

International journal of molecular sciences 26 ( 3 ) 2025.1

Language：English Publishing type：Research paper (scientific journal)

We investigated the roles of low-density lipoprotein receptor-related protein (LRP) 4 and its ligand Agrin in the pathophysiology of cartilage degeneration. Immunohistochemical analysis of human normal articular cartilage and cartilage tissues from patients with osteoarthritis (OA) obtained during surgery of the knee joint showed marked LRP4 expression in the early stages of OA, which then decreased with cartilage degeneration, whereas Agrin was consistently increased with cartilage degeneration. In normal human articular chondrocytes (NHACs), mild cyclic tensile strain (CTS) (0.5 Hz, 5% elongation, 2 h) increased the expression of LRP4 and aggrecan (ACAN), while intense CTS (0.5 Hz, 10% elongation, 6 h) increased the expression of Agrin without affecting LRP4 expression. Treatment with recombinant human (rh) Agrin downregulated the mRNA expression of LRP4 and ACAN, but upregulated the expression of LRP5/6, SRY-box transcription factor 9 (SOX9), Runt-related transcription factor 2 (RUNX2), and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4). Immunocytochemistry and Western blot analysis showed that rhAgrin treatment upregulated the expression of β-catenin and SOX9. Agrin knockdown by siAGRN transfection partially reduced the nuclear protein expression of β-catenin, which was increased with intense CTS. LRP4 knockdown by siLRP4 transfection increased the expression of LRP5/6, SOX9, RUNX2, ADAMTS-4, and Agrin. These results suggested that intense CTS increases the expression of Agrin, which might interfere with the role of LRP4 in the inhibition of LRP5/6 and their downstream β-catenin signaling, leading to cartilage degeneration.

DOI： 10.3390/ijms26031007

The use of lateral wedge insoles delays osteoarthritis progression and improves clinical outcomes in medial meniscus posterior root repair. International journal

Koki Kawada, Yusuke Yokoyama, Yuki Okazaki, Masanori Tamura, Toshifumi Ozaki, Takayuki Furumatsu

Journal of experimental orthopaedics 12 ( 1 ) e70141 2025.1

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The purpose of this retrospective study was to evaluate the efficacy of using a lateral wedge insole (LWI) during the first 3 months after medial meniscus posterior root (MMPR) repair. METHODS: Overall, 179 patients were categorized into LWI use (LWI group, 90 patients) and nonuse (control group, 89 patients) groups. Patients in the LWI group were instructed to wear an LWI from the initiation of load bearing up to 3 months postoperatively. Medial meniscus extrusion (MME) was evaluated preoperatively and 1 year postoperatively, Kellgren-Lawrence (KL) grade and clinical scores were evaluated preoperatively and 2 years postoperatively, and second-look arthroscopic meniscal healing scores were evaluated at 1 year postoperatively. RESULTS: The proportion of patients with KL grade progression at 2 years postoperatively was significantly lower in the LWI group than in the control group (23.3% vs. 39.3%; p = 0.024). Change in the MME at 1 year postoperatively was significantly smaller in the LWI group than in the control group (1.1 ± 1.2 vs. 1.6 ± 1.4 mm; p = 0.042). The Lysholm score (p = 0.003) and Knee Injury and Osteoarthritis Outcome Scores-sport and recreation function (p = 0.027) at 2 years postoperatively were significantly superior in the LWI group than in the control group. The arthroscopic meniscal healing score after 1 year was not significantly different between the LWI and control groups (total score, 7.6 ± 1.1 vs. 7.4 ± 1.3 points; p = 0.732). The anteroposterior width of the repaired posterior root at 1 year second-look evaluation was significantly broader in the LWI group than in the control group (7.7 ± 1.6 vs. 6.9 ± 1.6 mm; p = 0.001). CONCLUSIONS: The use of LWI is an effective way to delay postoperative osteoarthritis progression and improve clinical outcomes after MMPR repair. LEVEL OF EVIDENCE: Level III.

DOI： 10.1002/jeo2.70141

The Three-Class Annotation Method Improves the AI Detection of Early-Stage Osteosarcoma on Plain Radiographs: A Novel Approach for Rare Cancer Diagnosis. International journal

Joe Hasei, Ryuichi Nakahara, Yujiro Otsuka, Yusuke Nakamura, Kunihiro Ikuta, Shuhei Osaki, Tamiya Hironari, Shinji Miwa, Shusa Ohshika, Shunji Nishimura, Naoaki Kahara, Aki Yoshida, Tomohiro Fujiwara, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki

Cancers 17 ( 1 ) 2024.12

Language：English Publishing type：Research paper (scientific journal)

Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases is challenging owing to limited data availability. This study aimed to evaluate whether a novel three-class annotation method for preparing training data could enhance AI model performance in detecting osteosarcoma on plain radiographs compared to conventional single-class annotation. Methods: We developed two annotation methods for the same dataset of 468 osteosarcoma X-rays and 378 normal radiographs: a conventional single-class annotation (1C model) and a novel three-class annotation method (3C model) that separately labeled intramedullary, cortical, and extramedullary tumor components. Both models used identical U-Net-based architectures, differing only in their annotation approaches. Performance was evaluated using an independent validation dataset. Results: Although both models achieved high diagnostic accuracy (AUC: 0.99 vs. 0.98), the 3C model demonstrated superior operational characteristics. At a standardized cutoff value of 0.2, the 3C model maintained balanced performance (sensitivity: 93.28%, specificity: 92.21%), whereas the 1C model showed compromised specificity (83.58%) despite high sensitivity (98.88%). Notably, at the 25th percentile threshold, both models showed identical false-negative rates despite significantly different cutoff values (3C: 0.661 vs. 1C: 0.985), indicating the ability of the 3C model to maintain diagnostic accuracy at substantially lower thresholds. Conclusions: This study demonstrated that anatomically informed three-class annotation can enhance AI model performance for rare disease detection without requiring additional training data. The improved stability at lower thresholds suggests that thoughtful annotation strategies can optimize the AI model training, particularly in contexts where training data are limited.

DOI： 10.3390/cancers17010029

Medial meniscus posterior root tears with advanced osteoarthritis or subchondral insufficiency fracture are good indications for unicompartmental knee arthroplasty at a minimum 2-year follow-up. International journal

Koki Kawada, Yusuke Yokoyama, Yuki Okazaki, Masanori Tamura, Toshifumi Ozaki, Takayuki Furumatsu

Archives of orthopaedic and trauma surgery 145 ( 1 ) 64 - 64 2024.12

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: The outcomes of unicompartmental knee arthroplasty (UKA) in the presence and absence of medial meniscus posterior root tears (MMPRTs) have not been compared. This study compared the characteristics and clinical outcomes of patients undergoing UKA with and without MMPRTs. MATERIALS AND METHODS: This study analyzed 68 patients. The presence or absence of MMPRTs was evaluated using preoperative magnetic resonance imaging. Patient characteristics, clinical scores before surgery and at the final evaluation, and imaging findings were compared between patients with and without MMPRTs. Multiple regression analysis was conducted on postoperative visual analog scale (VAS)-pain scores. RESULTS: MMPRTs were present in 64.7% (44/68) of patients. Patients with MMPRTs were significantly younger (67.8 ± 8.2 vs. 75.0 ± 7.1 years, p < 0.001) and had a shorter duration from the development of symptoms to the time of surgery than those without (6.8 ± 8.4 vs. 36.1 ± 38.9 months, p < 0.001). Component placement or lower-limb alignment did not significantly differ between the groups. Preoperative clinical scores were not significantly different between the groups; however, patients with MMPRTs showed significantly better postoperative VAS-pain scores than those without (10.0 ± 9.0 vs. 28.2 ± 26.0 points, p = 0.026). Multiple regression analysis of postoperative VAS-pain scores revealed the significant effect of duration from the development of symptoms to the time of surgery (p = 0.038). CONCLUSIONS: Patients undergoing UKA with MMPRTs were younger with less radiographic osteoarthritic changes compared to those without MMPRTs, and their postoperative VAS-pain scores were significantly superior. The duration from the development of symptoms to the time of surgery significantly influenced postoperative pain in patients undergoing UKA.

DOI： 10.1007/s00402-024-05671-1

Association between lower limb muscle strength and musculoskeletal ambulation disability symptom complex in patients with medial meniscus posterior root tears. International journal

Mikao Fukuba, Koki Kawada, Yuki Okazaki, Yoshimi Katayama, Masanori Hamada, Toshifumi Ozaki, Takayuki Furumatsu

European journal of orthopaedic surgery & traumatology : orthopedie traumatologie 35 ( 1 ) 40 - 40 2024.12

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: In this study, we aimed to evaluate the changes in and the relationship between lower limb muscle strength and physical function before and after medial meniscus posterior root (MMPR) repair. METHODS: Thirty-three patients who underwent MMPR repair were evaluated. Pain was evaluated with the numerical rating scale (NRS), and knee flexor/extensor muscle strength was assessed using a handheld dynamometer. Physical function was evaluated using a timed up and go (TUG) test. The NRS, knee flexor/extensor muscle strength, and TUG were compared preoperatively and 1 year postoperatively using the Wilcoxon signed-rank test. The correlation of patient characteristics, NRS score, knee flexor/extensor muscle strength, and preoperative TUG with the postoperative TUG was analyzed using Spearman's correlation coefficient. RESULTS: NRS (3.5 ± 2.1 to 0.1 ± 0.5 points), knee flexor strength (111.9 ± 50.2 to 146.7 ± 51.5 Nm), knee extensor strength (181.9 ± 92.8 to 256.9 ± 107.1 Nm), and TUG (12.3 ± 5.7 to 9.2 ± 2.2 s) all improved significantly from preoperatively to 1 year postoperatively (p < 0.001). The postoperative TUG was negatively correlated with the preoperative TUG (r = 0.578, p < 0.001), preoperative knee flexor muscle strength (r = - 0.355, p = 0.042), preoperative knee extensor muscle strength (r = - 0.437, p = 0.010), and postoperative knee extensor muscle strength (r = - 0.478, p = 0.004). CONCLUSION: In patients undergoing MMPR repair, surgery and rehabilitation significantly improve lower limb muscle strength and physical function. There was a significant correlation between lower limb muscle strength and TUG, and further strengthening of the lower limb muscles from the preoperative level is desirable to improve patients' physical function further. LEVEL OF EVIDENCE: IV.

DOI： 10.1007/s00590-024-04158-4

関節リウマチ患者における内側半月板後根断裂に対する半月版修復術 ―関節温存をめざして

川田紘己, 古松毅之, 横山裕介, 岡﨑勇樹, 田村優典, 尾﨑敏文

臨床雑誌整形外科 75 ( 13 ) 1307 - 1311 2024.12

The role of C1orf50 in breast cancer progression and prognosis.

Yusuke Otani, Atsushi Tanaka, Masaki Maekawa, Tirso Peña, Anna Rogachevskaya, Teruhiko Ando, Takuto Itano, Haruyoshi Katayama, Eiji Nakata, Toshifumi Ozaki, Shinichi Toyooka, Hiroyoshi Doihara, Michael H Roehrl, Atsushi Fujimura

Breast cancer (Tokyo, Japan) 2024.11

Language：English Publishing type：Research paper (scientific journal)

Although the prognosis of breast cancer has significantly improved compared to other types of cancer, there are still some patients who expire due to recurrence or metastasis. Therefore, it is necessary to develop a method to identify patients with poor prognosis at the early stages of cancer. In the process of discovering new prognostic markers from genes of unknown function, we found that the expression of C1orf50 determines the prognosis of breast cancer patients, especially for those with Luminal A breast cancer. This study aims to elucidate the molecular role of C1orf50 in breast cancer progression. Bioinformatic analyses of the breast cancer dataset of TCGA, and in vitro analyses, reveal the molecular pathways influenced by C1orf50 expression. C1orf50 knockdown suppressed the cell cycle of breast cancer cells and weakened their ability to maintain the undifferentiated state and self-renewal capacity. Interestingly, upregulation of C1orf50 increased sensitivity to CDK4/6 inhibition. In addition, C1orf50 was found to be more abundant in breast cancer cells than in normal breast epithelium, suggesting C1orf50's involvement in breast cancer pathogenesis. Furthermore, the mRNA expression level of C1orf50 was positively correlated with the expression of PD-L1 and its related factors. These results suggest that C1orf50 promotes breast cancer progression through cell cycle upregulation, maintenance of cancer stemness, and immune evasion mechanisms. Our study uncovers the biological functions of C1orf50 in Luminal breast cancer progression, a finding not previously reported in any type of cancer.

DOI： 10.1007/s12282-024-01653-8

Transtibial pullout repair improved short-term clinical outcomes in patients with oblique medial meniscus posterior root tear comparable to radial root tear. International journal

Naohiro Higashihara, Takayuki Furumatsu, Yuki Okazaki, Yusuke Yokoyama, Masanori Tamura, Koki Kawada, Tsubasa Hasegawa, Toshiki Kohara, Toshifumi Ozaki

European journal of orthopaedic surgery & traumatology : orthopedie traumatologie 35 ( 1 ) 30 - 30 2024.11

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Medial meniscus (MM) posterior root tears (PRT) can lead to excessive knee loading and unsatisfactory clinical outcomes after non-operative treatment or meniscectomy. Although favourable clinical outcomes after MM posterior root (PR) repair have been reported, no study has specifically investigated the outcomes of different types of MMPRT. This study aimed to compare the clinical outcomes of patients with complete radial and oblique MMPRT following MMPR repair. METHODS: Forty patients who had undergone MMPR repair were retrospectively investigated. Patients with type 2 (20 knees) and 4 MMPRT (20 knees) were included in this study. The MMPRT type was classified according to the LaPrade classification. Plain radiographs, magnetic resonance images, arthroscopic findings, and pre- and postoperative clinical outcomes were evaluated. RESULTS: At 1 year postoperatively, clinical outcomes notably improved in patients with type 2 and 4 MMPRT. No significant differences were observed in any of the evaluations between these patients, both before and after the surgery. CONCLUSION: Patients with type 2 and type 4 MMPRT exhibited significantly improved clinical outcomes. MMPR repair is beneficial in treating type 2 and type 4 MMPRT. LEVEL OF EVIDENCE: IV.

DOI： 10.1007/s00590-024-04137-9

Genotypes and phenotypes of neurofibromatosis type 1 patients in Japan: A Hereditary Tumor Cohort Study. International journal

Mashu Futagawa, Tetsuya Okazaki, Eiji Nakata, Chika Fukano, Risa Osumi, Fumino Kato, Yusaku Urakawa, Hideki Yamamoto, Toshifumi Ozaki, Akira Hirasawa

Human genome variation 11 ( 1 ) 42 - 42 2024.11

Language：English Publishing type：Research paper (scientific journal)

Neurofibromatosis type 1 (NF1) presents with a broad spectrum of clinical manifestations, including an increased risk of tumor development and hypertension. Comprehensive data on genotype‒phenotype correlations in patients with NF1 are limited. Therefore, in this study, we aimed to elucidate the detailed genetic and clinical characteristics of NF1 in a hereditary tumor cohort. We performed sequencing and copy number assays in a clinical laboratory and analyzed the clinical data of 44 patients with suspected NF1. Germline pathogenic variants were detected in 36 patients (81.8%), and 20.7% of the variants were novel. Notably, 40.0% of adult patients presented with malignancies; female breast cancer occurred in 20.0% of patients, which was a higher rate than that previously reported. Hypertension was observed in 30.6% of the adult patients, with one patient experiencing sudden death and another developing pheochromocytoma. Three patients with large deletions in NF1 exhibited prominent cutaneous, skeletal, and neurological manifestations. These results highlight the importance of regular surveillance, particularly for patients with malignancies and hypertension. Our findings provide valuable insights for genetic counseling and clinical management, highlighting the multiple health risks associated with NF1 and the need for comprehensive and multidisciplinary care.

DOI： 10.1038/s41439-024-00299-4

Assessment of All-Inside Sutures to the Posteromedial Capsule in Medial Meniscus Posterior Root Repair: Findings From a Retrospective Three-Dimensional Magnetic Resonance Imaging Study

Yuki Okazaki, Takayuki Furumatsu, Keisuke Kintaka, Yusuke Yokoyama, Masanori Tamura, Koki Kawada, Tsubasa Hasegawa, Toshifumi Ozaki

Cureus 2024.11

Curve Progression After the Termination of Bracing for Adolescent Idiopathic Scoliosis: Usefulness of Combining the Proximal Femur Maturity Index (PFMI) and Risser Staging

Hisakazu Shitozawa, Haruo Misawa, Koji Uotani, Tomoko Tetsunaga, Kensuke Shinohara, Yoshiaki Oda, Masataka Ueda, Ryo Takatori, Kazutaka Yamashita, Toshifumi Ozaki

Cureus 2024.11

Study protocol: randomized phase III trial of neo-adjuvant and adjuvant chemotherapy vs. immediate surgery and adjuvant chemotherapy for localized soft tissue sarcoma: Japan Clinical Oncology Group study JCOG2102 (NACLESS). International journal

Yuki Funauchi, Satoshi Tsukushi, Hiroaki Hiraga, Akio Sakamoto, Toshiyuki Kunisada, Akihito Nagano, Koji Hiraoka, Kazutaka Kikuta, Tsukasa Yonemoto, Keisuke Ae, Akira Kawai, Makoto Endo, Yusuke Sano, Ryunosuke Machida, Tetsuya Sekita, Haruhiko Fukuda, Yoshinao Oda, Toshifumi Ozaki, Kazuhiro Tanaka

Japanese journal of clinical oncology 2024.11

Language：English Publishing type：Research paper (scientific journal)

The optimal timing of surgery and the number of courses of perioperative chemotherapy for high-risk soft tissue sarcoma patients are still controversial. Tumour growth during neoadjuvant chemotherapy led to limb amputation in some patients. This study aims to confirm the non-inferiority of surgery and three courses of adjuvant chemotherapy with adriamycin (30 mg/m2, days 1 and 2) plus ifosfamide (2 g/m2, days 1-5) compared with our standard treatment of three courses of neoadjuvant chemotherapy and surgery followed by two courses of adjuvant chemotherapy with adriamycin plus ifosfamide for localized high-risk soft tissue sarcoma patients. This is a multi-center, two-arm, open-label, randomized phase III trial. The primary aim is to confirm the non-inferiority in overall survival (margin: hazard ratio of 1.61). This is the first randomized controlled trial to compare neoadjuvant chemotherapy and immediate surgery for soft tissue sarcoma. This trial was initiated on 16 November 2022 and registered with the Japan Clinical Trials Registry (jRCTs031220446).

DOI： 10.1093/jjco/hyae160

Accuracy of Cup Alignment in Total Hip Arthroplasty: A Comparison Between Portable Navigation and Goniometer. International journal

Tomonori Tetsunaga, Tomoko Tetsunaga, Kazuki Yamada, Takashi Koura, Tomohiro Inoue, Ryuichiro Okuda, Yasutaka Masada, Sho Muguruma, Yuki Okazaki, Toshifumi Ozaki

Cureus 16 ( 11 ) e74176 2024.11

Language：English Publishing type：Research paper (scientific journal)

Background Navigation systems, including portable navigation systems, used for total hip arthroplasty (THA) are useful for achieving higher cup alignment accuracy. NAVBIT, a newly available portable navigation system, uses a unique registration method, the table tilt registration. However, its accuracy is unclear. This retrospective study aimed to investigate whether THA with a portable navigation system in the lateral position with the flip technique is more accurate than THA with a cup goniometer in the supine or lateral positions. Methodology This study included 96 consecutive patients (77 women, 19 men) who underwent primary cementless THA using either a portable navigation system in the lateral position with the flip technique or a cup goniometer in the supine or lateral positions. The average age of the patients was 66.8 years (range = 29-91) and the average body mass index was 24.6 kg/m2 (range = 17.5-39.9). The accuracy of cup orientation was compared among the three groups. Results The absolute values of the difference in cup inclination and anteversion with the NAVBIT (2.1 ± 1.7°, 2.0 ± 1.4°) were smaller than that with the cup goniometer in the supine (3.4 ± 2.4°, 3.4 ± 2.2°) and lateral decubitus positions (3.4 ± 2.5°, 5.0 ± 3.5°). Overall, 91%, 64.5%, and 56.3% were within 5° of the target angles in the navigation, supine goniometer, and lateral goniometer groups, respectively. Conclusions The accuracy of cup alignment with the portable navigation system using the flip technique was significantly higher than that with the cup goniometer in the supine and lateral decubitus positions.

DOI： 10.7759/cureus.74176

Quadriceps muscle strength of the affected limb in medial meniscus posterior root tears is negatively correlated with the progression of postoperative medial joint space narrowing. International journal

Koki Kawada, Mikao Fukuba, Yuki Okazaki, Masanori Tamura, Yusuke Yokoyama, Toshifumi Ozaki, Takayuki Furumatsu

Journal of experimental orthopaedics 11 ( 4 ) e70057 2024.10

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The effect of quadriceps muscle strength on medial joint space (MJS) narrowing after repair for medial meniscus (MM) posterior root tears (MMPRTs) has not yet been determined. This study aimed to evaluate the effect of preoperative and postoperative quadriceps muscle strength on the change in MJS (ΔMJS) in MMPRTs. METHODS: Thirty patients who underwent pullout repair for MMPRTs were retrospectively evaluated. The MJS width using fixed-flexion view radiographs, MM extrusion (MME) using magnetic resonance imaging, quadriceps muscle strength using the Locomo Scan-II and clinical scores were measured and compared preoperatively and 1 year postoperatively. Correlations between the ΔMJS, change in MME (ΔMME), and preoperative and postoperative quadriceps muscle strength were evaluated using Spearman's rank correlation coefficient. RESULTS: MJS narrowing and MME progressed significantly at 1 year postoperatively (p < 0.001). Quadriceps muscle strength in MMPRT knees and all clinical scores significantly improved at 1 year postoperatively (p < 0.001). ΔMJS and ΔMME showed a significant positive correlation (0.50 ± 0.70 and 1.22 ± 0.92 mm, respectively; r = 0.516, p = 0.004). Both preoperative and postoperative quadriceps muscle strength in MMPRT knees showed significant negative correlations with ΔMJS (preoperative: r = -0.529, p = 0.003; postoperative: r = -0.477, p = 0.008) and ΔMME (preoperative: r = -0.431, p = 0.018; postoperative: r = -0.443, p = 0.014). CONCLUSIONS: In pullout repair for MMPRTs, preoperative and postoperative quadriceps muscle strength in MMPRT knees was negatively correlated with the progression of MJS narrowing and MME. Rehabilitation with a focus on quadriceps muscle strengthening, including preoperative rehabilitation, may delay knee-osteoarthritis progression after pullout repair for MMPRTs. LEVEL OF EVIDENCE: Level IV.

DOI： 10.1002/jeo2.70057

Fast rehabilitation does not worsen clinical, radiological, and arthroscopic outcomes after medial meniscus posterior root repair: A retrospective comparative study. International journal

Masanori Tamura, Takayuki Furumatsu, Yusuke Yokoyama, Yuki Okazaki, Koki Kawada, Toshifumi Ozaki

Asia-Pacific journal of sports medicine, arthroscopy, rehabilitation and technology 38 29 - 35 2024.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/OBJECTIVE: The main surgical treatment for medial meniscus posterior root tear (MMPRT) has shifted from meniscectomy to meniscus repair; however, there is no clear consensus regarding the optimal postoperative management strategy after MMPRT repair. This study aimed to perform a comparative analysis of patients who received conventional rehabilitation or fast rehabilitation following MMPRT repair. METHODS: The current retrospective cohort study compared clinical, radiological, and arthroscopic outcomes after conventional rehabilitation (group A, January 2020 to April 2020, 24 patients) with those after fast rehabilitation (group B, May 2020 to August 2020, 24 patients) in patients who underwent pullout repair for MMPRT. Partial weight-bearing and range of motion exercises were allowed 2 weeks postoperatively in group A and 1 week postoperatively in group B. In patients with an average weight of approximately 60 kg, full weight bearing was allowed 4 weeks postoperatively in group A and 3 weeks postoperatively in group B. RESULTS: At 12 months postoperatively, the clinical scores, including International Knee Documentation Committee and Japanese Knee Injury and Osteoarthritis Outcome Score, significantly improved in both groups (p < 0.01). Although meniscus healing was achieved in both groups, medial meniscus extrusion significantly progressed by 0.9 mm in group A and 0.8 mm in group B (p < 0.01, compared with preoperative extrusion). There were no significant differences in clinical scores, arthroscopic meniscal healing status, or medial meniscus extrusion progression on magnetic resonance images between the groups. CONCLUSION: A fast rehabilitation protocol can be safely implemented without compromising patient outcomes after pullout repair for MMPRT.

DOI： 10.1016/j.asmart.2024.09.003

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