Massive Femoral Osteolysis Secondary to Loosening of a Cemented Roughened Long Stem: A Case Report

The surface finish of a femoral stem plays an important role in the longevity of cemented total hip arthroplasty. In efforts to decrease the rate of aseptic loosening, some prostheses have been designed to have a roughened surface that enhances bonding between the prosthesis and cement, but clinical outcomes remain controversial. We present a rare case of massive osteolysis with extreme femoral expansion that developed after cemented revision total hip arthroplasty. The destructive changes in the femur were attributable to abnormal motion of the stem and were aggravated by the roughened precoated surface of the long femoral component. Revision surgery using a total femur prosthesis was performed because there was insufficient remaining bone to fix the new prosthesis. The surgical technique involved wrapping polypropylene meshes around the prosthesis to create an insertion for the soft tissue, which proved useful for preventing muscular weakness and subsequent dislocation of the hip

Medial Patellofemoral Ligament Reconstruction for Patellar Dislocation due to Rupture of the Medial Structures after Total Knee Arthroplasty : A Case Report and Review of the Literature

Patellar dislocation is a well-recognized major complication after total knee arthroplasty (TKA). Treatment of this injury is determined according to the cause of the dislocation. In particular, proximal realignment, distal realignment, and lateral retinaculum release are options if patellar instability is not caused by prosthetic malposition. Here we report a case of patellar dislocation following TKA due to rupture of the medial structures that was treated by medial patellofemoral ligament reconstruction and lateral retinacular release. In addition, we provide a brief review of the related literature

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study) : A multicentre, open-label, dose-escalation phase 1 trial

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the loss of motor neurons, and development of effective medicines is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified the Src/c-Abl inhibitor bosutinib, which is approved for the treatment of chronic myelogenous leukemia (CML), as a candidate for the molecular targeted therapy of ALS. Methods: An open-label, multicentre, dose-escalation phase 1 study using a 3 + 3 design was conducted in 4 hospitals in Japan to evaluate the safety and tolerability of bosutinib in patients with ALS. Furthermore, the exploratory efficacy was evaluated using Revised ALS Functional Rating Scale (ALSFRS-R), predictive biomarkers including plasma neurofilament light chain (NFL) were explored, and single-cell RNA sequencing of iPSC-derived motor neurons was conducted. Patients, whose total ALSFRS-R scores decreased by 1–3 points during the 12 week, received escalating doses starting from 100 mg quaque die (QD) up to 400 mg QD based on dose-limiting toxicity (DLT) occurrence, and all participants who received one dose of the study drug were included in the primary analysis. This trial is registered with ClinicalTrials.gov, NCT04744532, as Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic Lateral Sclerosis Medicine (iDReAM) study. Findings: Between March 29, 2019 and May 7, 2021, 20 patients were enrolled, 13 of whom received bosutinib treatment and 12 were included in the safety and efficacy analyses. No DLTs were observed up to 300 mg QD, but DLTs were observed in 3/3 patients of the 400 mg QD cohort. In all patients receiving 100 mg–400 mg, the prevalent adverse events (AEs) were gastrointestinal AEs in 12 patients (92.3%), liver function related AEs in 7 patients (53.8%), and rash in 3 patients (23.1%). The safety profile was consistent with that known for CML treatment, and ALS-specific AEs were not observed. A subset of patients (5/9 patients) was found to respond well to bosutinib treatment over the 12-week treatment period. It was found that the treatment-responsive patients could be distinguished by their lower levels of plasma NFL. Furthermore, single-cell RNA sequencing of iPSC-derived motor neurons revealed the pathogenesis related molecular signature in patients with ALS showing responsiveness to bosutinib. Interpretation: This is the first trial of a Src/c-Abl inhibitor, bosutinib, for patients with ALS. The safety and tolerability of bosutinib up to 300 mg, not 400 mg, in ALS were described, and responsiveness of patients on motor function was observed. Since this was an open-label trial within a short period with a limited number of patients, further clinical trials will be required

Induced pluripotent stem cell–based Drug Repurposing for Amyotrophic lateral sclerosis Medicine (iDReAM) study : protocol for a phase I dose escalation study of bosutinib for amyotrophic lateral sclerosis patients

Introduction Amyotrophic lateral sclerosis (ALS) is a progressive and severe neurodegenerative disease caused by motor neuron death. There have as yet been no fundamental curative medicines, and the development of a medicine for ALS is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified an Src/c-Abl inhibitor, bosutinib, as a candidate molecular targeted therapy for ALS. The objectives of this study are to evaluate the safety and tolerability of bosutinib for the treatment of patients with ALS and to explore the efficacy of bosutinib on ALS. This study is the first clinical trial of administered bosutinib for patients with ALS. Methods and analysis An open-label, multicentre phase I dose escalation study has been designed. The study consists of a 12-week observation period, a 1-week transitional period, a 12-week study treatment period and a 4-week follow-up period. After completion of the transitional period, subjects whose total ALS Functional Rating Scale-Revised (ALSFRS-R) score decreased by 1–3 points during the 12-week observation period receive bosutinib for 12 weeks. Three to six patients with ALS are enrolled in each of the four bosutinib dose levels (100, 200, 300 or 400 mg/day) to evaluate the safety and tolerability under a 3+3 dose escalation study design. Dose escalation and maximum tolerated dose are determined by the safety assessment committee comprising oncologists/haematologists and neurologists based on the incidence of dose-limiting toxicity in the first 4 weeks of the treatment at each dose level. A recommended phase II dose is determined by the safety assessment committee on completion of the 12-week study treatment in all subjects at all dose levels. The efficacy of bosutinib is also evaluated exploratorily using ALS clinical scores and biomarkers. Ethics and dissemination This study received full ethical approval from the institutional review board of each participating site. The findings of the study will be disseminated in peer-reviewed journals and at scientific conferences

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial

筋萎縮性側索硬化症（ALS）患者さんを対象とした ボスチニブ第1相試験；iDReAM試験の成果報告 （論文発表）. 京都大学プレスリリース. 2022-10-26.Phase I clinical trial of bosutinib for amyotrophic lateral sclerosis (ALS); iDReAM study. 京都大学プレスリリース. 2022-11-28.[Background] Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the loss of motor neurons, and development of effective medicines is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified the Src/c-Abl inhibitor bosutinib, which is approved for the treatment of chronic myelogenous leukemia (CML), as a candidate for the molecular targeted therapy of ALS. [Methods] An open-label, multicentre, dose-escalation phase 1 study using a 3 + 3 design was conducted in 4 hospitals in Japan to evaluate the safety and tolerability of bosutinib in patients with ALS. Furthermore, the exploratory efficacy was evaluated using Revised ALS Functional Rating Scale (ALSFRS-R), predictive biomarkers including plasma neurofilament light chain (NFL) were explored, and single-cell RNA sequencing of iPSC-derived motor neurons was conducted. Patients, whose total ALSFRS-R scores decreased by 1–3 points during the 12-week, received escalating doses starting from 100 mg quaque die (QD) up to 400 mg QD based on dose-limiting toxicity (DLT) occurrence, and all participants who received one dose of the study drug were included in the primary analysis. This trial is registered with ClinicalTrials.gov, NCT04744532, as Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic Lateral Sclerosis Medicine (iDReAM) study. [Findings] Between March 29, 2019 and May 7, 2021, 20 patients were enrolled, 13 of whom received bosutinib treatment and 12 were included in the safety and efficacy analyses. No DLTs were observed up to 300 mg QD, but DLTs were observed in 3/3 patients of the 400 mg QD cohort. In all patients receiving 100 mg–400 mg, the prevalent adverse events (AEs) were gastrointestinal AEs in 12 patients (92.3%), liver function related AEs in 7 patients (53.8%), and rash in 3 patients (23.1%). The safety profile was consistent with that known for CML treatment, and ALS-specific AEs were not observed. A subset of patients (5/9 patients) was found to respond well to bosutinib treatment over the 12-week treatment period. It was found that the treatment-responsive patients could be distinguished by their lower levels of plasma NFL. Furthermore, single-cell RNA sequencing of iPSC-derived motor neurons revealed the pathogenesis related molecular signature in patients with ALS showing responsiveness to bosutinib. [Interpretation] This is the first trial of a Src/c-Abl inhibitor, bosutinib, for patients with ALS. The safety and tolerability of bosutinib up to 300 mg, not 400 mg, in ALS were described, and responsiveness of patients on motor function was observed. Since this was an open-label trial within a short period with a limited number of patients, further clinical trials will be required

Outcome of an elbow check-up system for child and adolescent baseball players

Purpose : Our aim was to examine the outcome of an elbow check-up system for youth baseball players. In particular, we investigated the nature of elbow injuries in youth baseball players with elbow pain and ultrasonographic findings of the capitellum. Materials and Methods : A total of 1605 players participating in the regional summer championship in July 2013 underwent a questionnaire survey, physical examination, ultrasound imaging, and radiographic examination. Results : A total of 499 (31.1%) players reported episodes of elbow pain, of whom 320 (64.1%) had abnormal findings on physical examination, and 115 (35.9%) agreed to undergo radiography. Among them, 98 (85.2%) exhibited radiographic abnormalities. On the initial ultrasonography screening, 60 (3.7%) players had an abnormal finding and 55 (91.7%) agreed to undergo radiography. Among them, 26 (47.3%) were found to have osteochondritis dissecans (OCD) of the capitellum on radiographs. Conclusions : About 30% of youth baseball players had episodes of elbow pain, and 64.1% of players with elbow pain had abnormal findings on physical examination. Furthermore, 85.2% of subjects who underwent radiographic examination exhibited radiographic abnormalities. About 4% of young baseball players had an abnormal finding on initial ultrasonography screening, and nearly 50% of them had OCD of the capitellum on radiographs

State of the Art : Elbow Arthroscopy : Review of the Literature and Application for Osteochondritis Dissecans of the Capitellum

Elbow arthroscopy has become a safe and effective treatment option for a number of elbow disorders. The most rewarding and successful indication is the removal of loose bodies. Loose bodies are often a result of osteochondritis dissecans (OCD) of the　capitellum, and arthroscopy in this case is useful for performing debridement, thereby eliminating the need for a more extensive open procedure associated with complications. In this review, we describe our arthroscopic technique for OCD of the capitellum. We usually conduct arthroscopy in the supine position, and use 2.9-mm arthroscopes of 30°and 70°. The 70°arthroscope provides a greater operative field than the 30°arthroscope. Arthroscopic treatment for OCD may require 2 anterior and 2 posterior portals. Loose bodies are commonly found in the radial fossa, coronoid fossa, and in the olecranon fossa. Once the loose bodies are removed, all unstable cartilage of the capitellum lesion is removed to create a stable bed. If any sclerotic changes to the lesion bed are observed, we create microfractures in the lesion bed. The most significant complication in arthroplasty is neurovascular injury. However, we have never experienced this devastating complication, which can be avoided by paying careful attention to detail

The state of the art in arthroscopic hip surgery

Hip arthroscopy is among the most rapidly evolving arthroscopic techniques in the last decade and offers the benefits of being both a minimally invasive procedure and an excellent diagnostic tool. Improvements in instrumentation and surgical skills have advanced our ability to accurately diagnose and treat various conditions of the hip joint, and hip arthroscopy has elucidated several pathologies that cause disabling symptoms. Many of these conditions were previously unrecognized and left untreated. The indications for hip arthroscopy include the management of early osteoarthritis, synovial disorders (e.g., synovial osteochondromatosis), labral tears, chondral lesions, and femoroacetabular impingement (FAI), which is increasingly recognized as a disorder that can lead to the development of early cartilage and labral injury. A better understanding of hip arthroscopy, including the anatomy, improved surgical techniques, indications, and complications of the procedure, is essential for its success. This review article discusses the state of the art of arthroscopic hip surgery