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Selpercatinib is the first targeted therapy for rearranged during transfection (RET) fusion-positive unresectable non-small-cell lung cancer (NSCLC). The main adverse effects of selpercatinib include hypertension, liver dysfunction, diarrhea, and QT prolongation on electrocardiograms. However, instances of drug-induced interstitial lung disease (DI-ILD) are infrequently reported. We describe the first case of a patient with RET fusion-positive NSCLC treated with selpercatinib who developed DI-ILD, confirmed pathologically. The patient, a 72-year-old woman, initiated selpercatinib treatment following the postoperative recurrence of lung adenocarcinoma. After 15 months of treatment, computed tomography scans revealed multiple infiltrates and ground-glass opacities in both lungs. A thoracoscopic lung biopsy identified organizing pneumonia, attributed to DI-ILD caused by selpercatinib. Although she was asymptomatic, the patient's selpercatinib treatment was discontinued, leading to a gradual improvement in the lung infiltrates. Despite the lack of detailed reports, DI-ILD with selpercatinib represents a potentially serious adverse event and should be approached with caution., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: Despite experiencing pain relief and improved activities of daily living after total hip arthroplasty (THA) for osteoarthritis of the hip, a Trendelenburg gait may be observed in some patients. The concentric and eccentric contraction patterns of hip muscles in a Trendelenburg gait are not well understood., Methods: This study included 89 patients (28 males and 61 females, mean age 66.5 ± 8.4 years, mean postoperative period 1.3 ± 0.4 years) after unilateral THA without functional impairment on the contralateral side. Gait analysis utilized a three-dimensional motion capture system to assess pelvis and hip angles, hip moment, and hip power. A Trendelenburg gait was defined as positive when nonoperative pelvic descent occurred at 30 % of the gait cycle, equivalent to mid-stance. Patients were classified into Trendelenburg gait-positive and -negative groups for statistical analysis. Unpaired t -test and chi-square test were used to compare the two groups. Multiple regression analysis was conducted to identify factors associated with the presence of a Trendelenburg gait., Results: A Trendelenburg gait was observed in 24 patients (27 %). Multiple regression analysis indicated that abduction (p < 0.01) and extension (p = 0.03) of hip joint power were significant determining of a Trendelenburg gait. Patients with a Trendelenburg gait exhibited reduced eccentric contraction of the hip abductor muscles and decreased concentric contraction of hip extensor muscles during early to mid-stance of their gait., Conclusion: Centrifugal contraction of hip abductor muscles and diminished eccentric contractility of hip extensor muscles appear crucial for hip stabilization mechanisms during gait after THA., Competing Interests: None., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

There is no approved drug treatment for autoimmune pulmonary alveolar proteinosis (APAP), although traditionally requires complex treatments such as whole lung lavage (WLL). We herein report on a 67-year-old man diagnosed with APAP. Treatment with atorvastatin (5 mg daily) resulted in significant improvement in symptoms, lung function, and computed tomography findings, with enhanced oxygenation, although serum anti-GM-CSF antibody levels remained elevated. This case suggests that the remission observed in this case could potentially be attributed to a direct effect of atorvastatin within the pulmonary alveoli. Statins may be considered as one of the treatment options for APAP., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: The efficacy and safety of sarilumab (SARI) were investigated in real-world clinical practice in Japan., Method: Subjects were 121 rheumatoid arthritis (RA) patients in 23 medical institutions in Fukuoka Prefecture, Japan, who started treatment with SARI between May 2018 and November 2021. Data on the SARI starting dose, patients' baseline characteristics, disease activity, and blood test data at the start of treatment, as well as follow-up data on the SARI dose, disease activity, and adverse events until Week 52. Safety and the continuation rate calculated by the Kaplan-Meier method were evaluated, and the effectiveness of treatment at 1 year was assessed using the clinical disease activity index (CDAI). Patients' baseline characteristics for which significant differences were evident were adjusted with a propensity score by using the inverse probability of treatment-weighting (IPTW) method., Results: The continuation rate at Week 52 was 66.1%. The CDAI showed significant improvement from Week 4 that was maintained until Week 52. Comparisons conducted after IPTW adjustment for patients' baseline characteristics for which significant differences were evident revealed no significant differences at Week 52 between the groups classified by higher or lower body mass index (BMI) (p = 0.231), serious comorbidities (p = 0.973), MTX use (p = 0.321), or prior treatment with ≤ 1 or ≥ 2 biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) (p = 0.765)., Conclusions: The results showed that the efficacy of SARI is not affected by BMI, comorbidities, MTX use, or the number of prior b/tsDMARDs, and no new safety concerns were apparent. Key Points • This is the first real-world clinical study to report on the efficacy and safety of SARI in Japan. The results of this study indicate that the efficacy of SARI was not affected by BMI, comorbidities, MTX use, or number of previous b/tsDMARDs. • It was shown that SARI can be used in a Japanese population without any new side effects., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: This study assessed the hip survival rate and patient-reported outcome measures (PROMs) of transtrochanteric curved varus osteotomy (CVO) for osteonecrosis of the femoral head (ONFH) compared with those of conservative management., Methods: The CVO group comprised 32 consecutive patients (39 hips) who underwent CVO for ONFH between 2000 and 2011. The conservative group consisted of 36 consecutive patients (37 hips) who were managed conservatively for at least 1 year after collapse and who had ONFH classified by the Japanese Investigation Committee of Health and Welfare as type B or C1, for which CVO is indicated. Kaplan-Meier analysis of hip survival used any ONFH-related therapeutic surgery as the endpoint. PROMs were evaluated for all patients with surviving hips and radiographs available at the latest follow-up., Result: The 10-year hip survival rate in the CVO group was 86.7%, which was significantly higher than the 51.0% 5-year survival rate in the conservative group (p < 0.0001). The Oxford Hip Score and UCLA Activity Score were significantly better in the CVO group without joint space narrowing than in the conservative group, with no significant differences between the CVO group with joint space narrowing and the conservative group., Conclusion: CVO could preserve hip joints more effectively than conservative follow-up after collapse, although the presence of joint space narrowing could reduce satisfaction levels even in patients with long-term hip survival., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objectives: The treatments for rheumatoid arthritis (RA) have been greatly improved, and the tight control of disease activity yields superior clinical outcomes. This study aimed to elucidate the accompanying changes in hip destruction following the implementation of a treat-to-target strategy for patients with RA., Methods: We extracted 190 hips over two periods, i.e. the early period (1998-2003) and the late period (2013-19), with 103 and 87 hips, respectively. The observed rheumatic changes, such as inward migration, upward migration, and femoral head collapse, were quantitatively evaluated, while osteoarthritic changes, such as the formation of a capital drop, were investigated from radiographs before primary total hip arthroplasty., Results: A comparison of the two periods' data showed that the degree of inward migration (-3.44 vs. -7.45 mm; P < .001) and upward migration (+4.3 vs. +0.95 mm; P < .001) significantly decreased in the late-period group. The collapse of the femoral head was not significantly different. The incidence of capital drops was significantly higher in the late-period group (7.8% vs. 27.5%; P < .001)., Conclusions: The degree of inward and upward migration representative of rheumatic changes reduced, whereas the frequency of capital drops as osteoarthritic changes increased during the late period., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Companion diagnostic tests play a crucial role in guiding treatment decisions for patients with non-small cell lung cancer (NSCLC). The Oncomine Dx Target Test (ODxTT) Multi-CDx System has emerged as a prominent companion diagnostic method. However, its efficacy in detecting driver gene mutations, particularly rare mutations, warrants investigation., Aims: This study aimed to assess the performance of the ODxTT in detecting driver gene mutations in NSCLC patients. Specifically, we aimed to evaluate its sensitivity in detecting epidermal growth factor receptor (EGFR) mutations, a key determinant of treatment selection in NSCLC., Materials and Methods: We conducted a retrospective analysis of NSCLC patients who underwent testing with the ODxTT at Keio University Hospital between May 2020 and March 2022. Patient samples were subjected to both DNA and RNA tests. Driver gene mutation status was assessed, and instances of missed mutations were meticulously examined., Results: Of the 90 patients, five had nucleic acid quality problems, while 85 underwent both DNA and RNA tests. Driver gene mutations were detected in 56/90 (62.2%) patients. Of the 34 patient specimens, driver mutations were not detected using the ODxTT; however, epidermal growth factor receptor (EGFR) mutations were detected using polymerase chain reaction-based testing in two patients, and a KRAS mutation was detected by careful examination of the sequence data obtained using the ODxTT in one patient. For the above three cases, carefully examining the gene sequence information obtained using the ODxTT could identify driver mutations that were not mentioned in the returned test results. Additionally, we confirmed comparable instances of overlook results for EGFR mutations in the dataset from South Korea, implying that this type of oversight could occur in other countries using the ODxTT. EGFR mutation was missed in ODxTT in Japan (6.3%, 2/32), South Korea (2.0%, 1/49), and overall (3.7%, 3/81)., Conclusion: Even if sufficient tumor samples are obtained, rare EGFR mutations (which are excluded from the ODxTT's genetic mutation list) might not be detected using the current ODxTT system due to the program used for sequence analysis. However, such rare EGFR mutations can still be accurately detected on ODxTT's sequence data using next-generation sequencing., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Immune checkpoint inhibitors (ICIs) have demonstrated efficacy over previous cytotoxic chemotherapies in clinical trials among various tumors. Despite their favorable outcomes, they are associated with a unique set of toxicities termed as immune-related adverse events (irAEs). Among the toxicities, ICI-related pneumonitis has poor outcomes with little understanding of its risk factors. This retrospective study aimed to investigate whether pre-existing interstitial lung abnormality (ILA) is a potential risk factor for ICI-related pneumonitis., Materials and Methods: Patients with non-small cell lung cancer, malignant melanoma, renal cell carcinoma, and gastric cancer, who was administered either nivolumab, pembrolizumab, or atezolizumab between September 2014 and January 2019 were retrospectively reviewed. Information on baseline characteristics, computed tomography findings before administration of ICIs, clinical outcomes, and irAEs were collected from their medical records. Pre-existing ILA was categorized based on previous studies., Results: Two-hundred-nine patients with a median age of 68 years were included and 23 (11.0%) developed ICI-related pneumonitis. While smoking history and ICI agents were associated with ICI-related pneumonitis (P = .005 and .044, respectively), the categories of ILA were not associated with ICI-related pneumonitis (P = .428). None of the features of lung abnormalities were also associated with ICI-related pneumonitis. Multivariate logistic analysis indicated that smoking history was the only significant predictor of ICI-related pneumonitis (P = .028)., Conclusion: This retrospective study did not demonstrate statistically significant association between pre-existing ILA and ICI-related pneumonitis, nor an association between radiologic features of ILA and ICI-related pneumonitis. Smoking history was independently associated with ICI-related pneumonitis. Further research is warranted for further understanding of the risk factors of ICI-related pneumonitis., (© The Author(s) 2023. Published by Oxford University Press.)

Background: In the natural course of osteonecrosis of the femoral head, sclerotic changes at the boundary of necrotic lesion gradually occur until femoral head collapse. This study aims to examine the effects of bone mineral density at the lateral boundary of necrotic lesion on a subsequent femoral head collapse., Methods: We developed patient-specific finite element models of 9 hips with subsequent collapse and 10 hips without subsequent collapse. Cubic regions of interest were selected at both subchondral areas of the lateral boundary and the adjacent necrotic lesion. Bone mineral density values of the regions of interest were quantitatively measured, and a ratio of bone mineral density values (lateral boundary/necrotic lesion) was calculated. Stress values at the lateral boundary were also evaluated., Findings: The ratio of bone mineral density values was significantly higher in hips with subsequent collapse than that without subsequent collapse (p = 0.0016). The median equivalent stress and shear stress were significantly higher in hips with subsequent collapse than that without subsequent collapse (p = 0.0071, and p = 0.0143, respectively). The ratio of bone mineral density values showed a promising value in predicting the occurrence of subsequent femoral head collapse (AUC = 0.97)., Interpretation: Our results indicated that bone mineral density value at the lateral boundary of necrotic lesion may be associated with the occurrence of subsequent femoral head collapse in pre-collapse stage osteonecrosis of the femoral head., Competing Interests: Declaration of Competing Interest Each author certifies that he or she has no commercial associations that might pose a conflict of interest in connection with the submitted article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly since 2019, and the number of reports regarding long COVID has increased. Although the distribution of long COVID depends on patient characteristics, epidemiological data on Japanese patients are limited. Hence, this study aimed to investigate the distribution of long COVID in Japanese patients. This study is the first nationwide Japanese prospective cohort study on long COVID., Methods: This multicenter, prospective cohort study enrolled hospitalized COVID-19 patients aged ≥18 years at 26 Japanese medical institutions. In total, 1200 patients were enrolled. Clinical information and patient-reported outcomes were collected from medical records, paper questionnaires, and smartphone applications., Results: We collected data from 1066 cases with both medical records and patient-reported outcomes. The proportion of patients with at least one symptom decreased chronologically from 93.9% (947/1009) during hospitalization to 46.3% (433/935), 40.5% (350/865), and 33.0% (239/724) at 3, 6, and 12 months, respectively. Patients with at least one long COVID symptom showed lower quality of life and scored higher on assessments for depression, anxiety, and fear of COVID-19. Female sex, middle age (41-64 years), oxygen requirement, and critical condition during hospitalization were risk factors for long COVID., Conclusions: This study elucidated the symptom distribution and risks of long COVID in the Japanese population. This study provides reference data for future studies of long COVID in Japan., Competing Interests: Conflict of Interest Norihiro Harada reports personal fees from AstraZeneca K.K., GlaxoSmithKline, Kyorin, Novartis Japan, Sanofi and grants from AstraZeneca, Daikin, Kyorin, SRL Medisearch, outside the submitted work. Other authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: This study aimed to clarify the relationship between vitamin D status and complications after periacetabular osteotomy., Methods: A total of 46 hips of 39 patients (3 men and 36 women; mean age at surgery, 41.0 years; mean postoperative follow-up duration, 63 months) were reviewed to obtain the following information: patients' serum 25-hydroxyvitamin D [25(OH)D] status, prevalence of postoperative delayed union of osteotomy sites in the greater trochanter (DUGT) and ischiopubic stress fractures (IPSFs), and risk factors., Results: The mean serum 25(OH)D level was 11.9 ng/ml. DUGT and IPSF were found in four (10.3%) and three (7.7%) patients, respectively. Serum 25(OH)D levels ≤ 11 ng/ml were significantly associated with DUGT in female patients (p = .02). Serum 25(OH)D levels ≤ 9 ng/ml and smoking were significantly associated with IPSF (p = 0.01 and 0.02, respectively). Overall, 21.7% of patients with serum 25(OH)D levels ≤ 11 ng/ml developed at least one complication; no complications occurred when serum 25(OH)D levels were >11 ng/ml., Conclusion: Severe vitamin D deficiency was highly prevalent in relatively young patients. Vitamin D deficiency and smoking were independent risk factors for postoperative complications. Proactive supplementation is advisable to reduce postoperative complications, especially in patients with serum 25(OH)D levels ≤ 11 ng/ml., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Articular surface irregularities are often observed in collapsed femoral heads with osteonecrosis, while the effects of the degree of collapse on the articular surface are poorly understood. We first macroscopically assessed the articular surface irregularities on 2-mm coronal slices obtained using high-resolution microcomputed tomography of 76 surgically resected femoral heads with osteonecrosis. These irregularities were observed in 68/76 femoral heads, mainly at the lateral boundary of the necrotic region. The mean degree of collapse was significantly larger for femoral heads with articular surface irregularities than for those without (p < 0.0001). Receiver operating characteristic analysis showed that the cutoff value for the degree of collapse in femoral heads with articular surface irregularities at the lateral boundary was 1.1 mm. Next, for femoral heads with <3-mm collapse (n = 28), articular surface irregularities were quantitatively assessed based on the number of automatically counted negative curvature points. Quantitative evaluation showed that the degree of collapse was positively correlated with the presence of articular surface irregularities (r = 0.95, p < 0.0001). Histological examination of articular cartilage above the necrotic region (n = 8) revealed cell necrosis in the calcified layer and abnormal cellular arrangement in the deep and middle layers. In conclusion, articular surface irregularities of the necrotic femoral head depended on the degree of collapse, and articular cartilage was already altered even in the absence of macroscopically determined gross irregularities., (© 2023 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Neutropenia, a rare immune-related adverse event, affects patients receiving treatment with immune checkpoint inhibitors (ICIs). We herein report a case of pembrolizumab-induced agranulocytosis. An 83-year-old man was diagnosed with advanced-stage lung carcinoma concomitant with splenomegaly complicated by hypersplenism, causing pancytopenia. To avoid the risk of bone marrow suppression due to cytotoxic chemotherapy, pembrolizumab monotherapy was chosen. However, the patient developed agranulocytosis despite the resolution of pancytopenia through splenectomy performed after the fourth pembrolizumab cycle. Neutrophil counts improved after steroid treatment but not after granulocyte colony-stimulating factor treatment. This case demonstrated that neutropenia can sometimes develop abruptly after several ICI therapy cycles.

Background: The exosome-focused translational research for afatinib (EXTRA) study is the first trial to identify novel predictive biomarkers for longer treatment efficacy of afatinib in patients with epidermal growth factor receptor ( EGFR ) mutation-positive nonsmall cell lung cancer (NSCLC) via a comprehensive association study using genomic, proteomic, epigenomic, and metabolomic analyses., Objectives: We report details of the clinical portion prior to omics analyses., Design: A prospective, single-arm, observational study was conducted using afatinib 40 mg/day as an initial dose in untreated patients with EGFR mutation-positive NSCLC. Dose reduction to 20 mg every other day was allowed., Methods: Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated., Results: A total of 103 patients (median age 70 years, range 42-88 years) were enrolled from 21 institutions in Japan between February 2017 and March 2018. After a median follow-up of 35.0 months, 21% remained on afatinib treatment, whereas 9% had discontinued treatment because of AEs. The median PFS was 18.4 months, with a 3-year PFS rate of 23.3%. The median afatinib treatment duration in patients with final doses of 40 ( n  = 27), 30 ( n  = 23), and 20 mg/day ( n  = 35), and 20 mg every other day ( n  = 18) were 13.4, 15.4, 18.8, and 18.3 months, respectively. The median OS was not reached, with a 3-year OS rate of 58.5%. The median OS in patients who did ( n  = 25) and did not ( n  = 78) receive osimertinib during the entire course of treatment were 42.4 months and not reached, respectively ( p  = 0.654)., Conclusions: As the largest prospective study in Japan, this study confirmed favorable OS following first-line afatinib in patients with EGFR mutation-positive NSCLC in a real-world setting. Further analysis of the EXTRA study is expected to identify novel predictive biomarkers for afatinib., Trial Registration: UMIN-CTR identifier (UMIN000024935, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;his&#95;list.cgi?recptno=R000028688., Competing Interests: Hisashi Tanaka: personal fees as honoraria from Ono Pharmaceutical, Bristol Myers Squibb, AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, and Pfizer; Yoshitaka Seki: personal fees as honoraria from AstraZeneca, Eli Lilly, MSD, Ono Pharmaceutical, Novartis, Taiho Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, Shionogi, Sanofi, Kyowa Kirin, Kyorin Pharmaceutical, and GSK; Kazuma Kishi: research funding and personal fees as honoraria from Boehringer Ingelheim; Yusuke Okuma: research funding and personal fees as honoraria from AstraZeneca and Chugai Pharmaceutical; research funding from AbbVie; and personal fees as honoraria from Eisai, Eli Lilly, MSD, Novartis, Ono Pharmaceutical, Takeda Pharmaceutical, and Taiho Pharmaceutical; Akira Togashi: employee of Boehringer Ingelheim; Nobuhiko Seki: research funding and personal fees as honoraria from Eli Lilly, Ono Pharmaceutical, Boehringer Ingelheim, Taiho Pharmaceutical, Chugai Pharmaceutical, Takeda Pharmaceutical, Nippon Kayaku, Pfizer, and Daiichi Sankyo; research funding from Eisai and Shionogi; and personal fees as honoraria from AstraZeneca, MSD, Bristol Myers Squibb, Novartis, and Kyowa Kirin. No potential conflicts of interest were disclosed by the other authors., (© The Author(s), 2023.)

There are no reports on hip kinetics including contact forces and muscle activities during the golf swing after total hip arthroplasty (THA). The aim of this study was to identify the characteristics of three-dimensional dynamics during the golf swing. Ten unilateral primary THA patients participated in motion capture test of their driver golf swing. The driver swing produced approximately 20-30° of rotation in both lead and trail replaced hips. The mean hip contact forces (HCFs) of lead and trail replaced hips were 5.1 and 6.6 × body weight, respectively. Left and right THAs showed similar HCFs of lead and trail hips. More than 60% of the Percent maximum voluntary isometric contraction was found in bilateral iliopsoas muscles in all unilateral THA. Three factors [female sex, lower modified Harris Hip Score, and higher HCF of surgical side] were associated with the golf-related replacement hip pain. Golf is an admissible sport after THA because driver swings do not contribute excessive rotation or contact forces to hip prostheses. HCF could be reduced through swing adjustments, which may allow patients with golf-related replacement hip pain to develop a comfortable golf game free from pain., (© 2023. The Author(s).)

This study aimed to (1) set a reference value for anterior center edge angle (ACEA) for preoperative planning of periacetabular osteotomy (PAO), (2) investigate the effects of pelvic rotation and inclination from false profile (FP) radiographs on the measured ACEA, and (3) determine the "appropriate range of positioning" for FP radiograph. This single-centered, retrospective study analyzed 61 patients (61 hips) who underwent PAO from April 2018 and May 2021. ACEA was measured in each digitally reconstructed radiography (DRR) image of the FP radiograph reconstructed in different degrees of pelvic rotation. Detailed simulations were performed to determine the "appropriate range of positioning" (0.67 < ratio of the distance between the femoral heads to the diameter of the femoral head < 1.0). The vertical-center-anterior (VCA) angle was measured on the CT sagittal plane considering the patient-specific standing positions, and its correlation with the ACEA was investigated. The reference value of ACEA was determined by receiver operating characteristic (ROC) curve analysis. The ACEA measurement increased by 0.35° for every 1° pelvic rotation approaching the true lateral view. The pelvic rotation with the "appropriate range of positioning" was found at 5.0° (63.3-68.3°). The ACEA on the FP radiographs showed a good correlation with the VCA angle. The ROC curve revealed that an ACEA < 13.6° was associated with inadequate anterior coverage (VCA < 32°). Our findings suggest that during preoperative PAO planning, an ACEA < 13.6° on FP radiographs indicates insufficient anterior acetabular coverage. Images with the "appropriate positioning" can also have a measurement error of 1.7° due to the pelvic rotation., (© 2023. The Author(s).)

Background: This study aims to evaluate the accuracy of the axis connecting both anterior superior iliac spines (ASIS axis) as the absolute pelvic axis. No study has ever verified the accuracy of ASIS axis particularly on the AP pelvic radiograph, which cannot be specified on it., Methods: Sixty patients who underwent total knee arthroplasty and fifty patients with femoral neck fracture were recruited as subjects without hip deformities and their CT scan data were collected. We defined the line through both center of femoral heads as absolute reference axis of pelvis three-dimensionally. On the coronal plane, the errors between the femoral head axis and the axes through six pelvic landmarks in total, including ASIS were analyzed. On the axial plane, the errors of the lines through four landmarks were analyzed in the same way. Finally, on the coronal images, the mediolateral diameter of the obturator foramen and the mediolateral distance between the midline of the sacrum and the pelvic cavity were measured to evaluate bilateral symmetry of the pelvis., Results: The errors tended to be smaller as the axes were closer to the femoral head axis (axes connecting bilateral superior aspects of the acetabulum and the teardrops) and the ASIS axis errors were moderate. The obturator foramen based on the ASIS axis was more asymmetrical than the femoral head axis., Conclusion: Adjusting the pelvic tilt and rotation, surgeons should not always rely on the ASIS and refer to appropriate, close to the hip joint references in each case., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Human lung cancer is a constellation of tumors with various histological and molecular properties. To build a preclinical platform that covers this broad disease spectrum, we obtained lung cancer specimens from multiple sources, including sputum and circulating tumor cells, and generated a living biobank consisting of 43 lines of patient-derived lung cancer organoids. The organoids recapitulated the histological and molecular hallmarks of the original tumors. Phenotypic screening of niche factor dependency revealed that EGFR mutations in lung adenocarcinoma are associated with the independence from Wnt ligands. Gene engineering of alveolar organoids reveals that constitutive activation of EGFR-RAS signaling provides Wnt independence. Loss of the alveolar identity gene NKX2-1 confers Wnt dependency, regardless of EGFR signal mutation. Sensitivity to Wnt-targeting therapy can be stratified by the expression status of NKX2-1. Our results highlight the potential of phenotype-driven organoid screening and engineering for the fabrication of therapeutic strategies to combat cancer., Competing Interests: Declaration of interests T.Sato is an inventor on several patents related to organoid culture., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Association between baseline medications plus neutrophil-to-lymphocyte ratio (NLR) and the effectiveness of immune checkpoint inhibitor (ICI) plus platinum doublet remains unknown, despite several reported prognostic models. We used real-world data to investigate whether baseline medications plus NLR predict survival outcomes in patients with advanced non-small-cell lung cancer (NSCLC) receiving ICI plus platinum doublet. Methods: This multicenter, retrospective, observational study conducted in Japan between December 2018 and March 2021 used real-world data of consecutive patients with advanced NSCLC who received ICI (pembrolizumab or atezolizumab) plus platinum doublet as first-line treatment. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The prognostic score for baseline medications plus NLR was weighted by regression β coefficients and used to categorize patients into good, intermediate, and poor prognoses groups. In addition, time-dependent receiver operating characteristic curve analyses and univariable and multivariable Cox proportional hazards models were constructed. Results: Overall, 241 patients were included. Poor prognosis was significantly associated with worse PFS (hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.08-2.94; P = 0.025) and OS (HR: 3.59; 95% CI: 2.05-6.28; P < 0.001) than good prognosis. Harrell's C-index for this prognostic model was 0.648. Conclusions: Baseline medication plus NLR could predict progressively worse survival outcomes in patients with advanced NSCLC receiving ICI plus platinum doublet and could be used as a prognostic index for poor outcomes., Competing Interests: Competing Interests: Ryuji Uozumi received consulting fees from Eisai, Sawai Pharmaceutical, and EPS. Tadanori Sasaki received research grants from Nippon Kayaku, Daiichi Sankyo, Ono Pharmaceutical, and Mochida Pharmaceutical. Ken Maeno received research grants from Boehringer Ingelheim and Eli Lilly and payment for lectures from AstraZeneca, Chugai Pharmaceutical, and Ono Pharmaceutical. Satoshi Oizumi received payment for lectures from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Ono Pharmaceutical, Takeda, Novartis, Eli Lilly, Merck, Merck Sharp & Dohme, Pfizer, Taiho Pharmaceutical, and Nippon Kayaku. Sojiro Kusumoto received payment for lectures from AstraZeneca, Taiho Pharmaceutical, Kracie Pharmaceutical, Chugai Pharmaceutical, and Novartis Pharma KK. Daiya Takai received payment for lectures from Bristol-Myers Squibb, MSD, and Ono Pharmaceutical. Hitoshi Kawazoe received research funding from Eli Lilly. Tomonori Nakamura received research funding from Astellas Pharma, Chugai, Daiichi Sankyo, Kyowa Kirin, Otsuka Pharmaceutical, Sanofi, Sato Pharmaceutical, and Shionogi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The author(s).)

Background: Potential novel strategies for adverse event (AE) management of osimertinib therapy, including therapeutic drug monitoring and the use of biomarkers, have not yet been fully investigated. This study aimed to evaluate (1) the relationship between exposure to osimertinib, especially its active metabolites (AZ5104 and AZ7550), and AEs, and (2) the relationship between germline polymorphisms and AEs., Methods: We conducted a prospective, longitudinal observational study of 53 patients with advanced non-small cell lung cancer receiving osimertinib therapy from February 2019 to April 2022. A population pharmacokinetic model was developed to estimate the area under the serum concentration-time curve from 0 to 24 h (AUC 0-24 ) of osimertinib and its metabolites. Germline polymorphisms were analyzed using TaqMan® SNP genotyping and CycleavePCR® assays., Results: There was a significant association between the AUC 0-24 of AZ7550 and grade ≥ 2 paronychia (p = 0.043) or anorexia (p = 0.011) and between that of osimertinib or AZ5104 and grade ≥ 2 diarrhea (p = 0.026 and p = 0.049, respectively). Furthermore, the AUC 0-24 of AZ5104 was significantly associated with any grade ≥ 2 AEs (p = 0.046). EGFR rs2293348 and rs4947492 were associated with severe AEs (p = 0.019 and p = 0.050, respectively), and ABCG2 rs2231137 and ABCB1 rs1128503 were associated with grade ≥ 2 AEs (p = 0.008 and p = 0.038, respectively)., Conclusion: Higher exposures to osimertinib, AZ5104, and AZ7550 and polymorphisms in EGFR, ABCG2, and ABCB1 were related to higher severity of AEs; therefore, monitoring these may be beneficial for osimertinib AE management., (© 2023. The Author(s).)

Background: Missing responses are common when Asian patients complete the Forgotten Joint Score-12 (FJS-12), which is widely used to evaluate total hip arthroplasty (THA). We aimed to provide orthopaedic researchers with a solution for handling missing values in such patient-reported outcome measures (PROMs)., Methods: Patients who had undergone primary THA between 1998 and 2016 (n = 1,021) were investigated in 2020. The FJS-12 and 9 other PROMs, including questions related to Asian lifestyle activities, were administered. Risk factors for missing FJS-12 items were investigated. Partial respondents were matched with complete respondents; then, in each pair, the items not completed by the partial respondent were deleted from the responses of the complete respondent. Predictive mean matching (PMM) was performed in an attempt to recover the deleted items, using 65 sets of imputation models. After the missing values had been imputed, we explored patient characteristics that affected the FJS-12, using data from all complete and partial respondents., Results: A total of 652 patients responded to the survey (393 complete and 193 partial respondents). Partial respondents were older, more often female, and less active. Older respondents were more likely to skip items involving the bed, while those who reported a better ability to sit in the seiza style (traditional Japanese floor sitting) were more likely to skip items about chair sitting. The imputed FJS-12 value exhibited excellent reliability (intraclass correlation coefficient for agreement with the true scores, 0.985). FJS-12 values of complete respondents were significantly higher than those of respondents with 4 to 11 missing items (51.6 versus 32.8, p < 0.001). Older age was associated with higher FJS-12 values, which was revealed only via analysis of the multiply imputed data sets (p < 0.001)., Conclusions: Analysis of only complete FJS-12 responses after THA resulted in a nonresponse bias, preferentially excluding older, female, and less active individuals and those with a traditional floor living style. Multiple imputation could provide a solution to scoring and analyzing PROMs with missing responses by permitting the inclusion of partial respondents., Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H287 )., (Copyright © 2022 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Objective: Excessive pelvic tilt has been reported to impair the biomechanical loading of the hip joint. However, the influence of pelvic tilt in osteonecrosis of the femoral head (ONFH) remains unclear. This study aims to assess whether sagittal pelvic posture in the standing position correlates with progression of femoral head collapse in post-collapse stage ONFH., Methods: This is a single-center retrospective study. We investigated 107 patients (107 hips; 73 males and 34 females; mean age, 48 years) diagnosed with Association of Research Circulation Osseous (ARCO) stage III ONFH at the first visit and who subsequently underwent surgical treatment in our institution from July 2016 to December 2020. The sagittal pelvic posture in the standing position before surgery was quantified as the angle formed by the anterior pelvic plane and the vertical z-axis in the sagittal view (APP angle). An APP angle <0° indicated posterior pelvic tilt. Progression of femoral head collapse was calculated as collapse speed. The following factors potentially associated with collapse speed were evaluated by exploratory data analysis followed with multiple linear regression analysis: sex, age, BMI, etiology, pelvic incidence, contralateral hip condition, time interval between the first visit and surgery, size of necrotic lesion, location of necrotic lesion, and APP angle., Results: As ONFH progressed from ARCO stage IIIA to stage IV, APP angle decreased significantly and continuously (stage IIIA, -0.2° ± 5.5°; stage IIIB, -3.7° ± 5.8°; stage IV, -7.1° ± 6.4°). The factors significantly associated with collapse speed were size of necrotic lesion (p = 0.0079), location of necrotic lesion (p = 0.0190), and APP angle (p < 0.0001). APP angle showed a negative correlation with collapse speed (r = -0.40, p < 0.0001). After stratifying by size of necrotic lesion (<50% and ≥50% involvement) and location of necrotic lesion (JIC type C1 and C2), a significant negative correlation was observed between APP angle and collapse speed in each group (JIC type C1 with <50% involvement, r = -0.69, p < 0.0001; JIC type C1 with ≥50% involvement, r = -0.58, p = 0.0475; JIC type C2 with <50% involvement, r = -0.51, p = 0.0124; JIC type C2 with ≥50% involvement, r = -0.39, p = 0.0286)., Conclusions: Our results suggest that posterior pelvic tilt in the standing position occurred as ONFH progressed from ARCO stage IIIA to stage IV, which might be associated with progression of femoral head collapse in ONFH., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Purpose: Patients' values and priorities in their lives should be appreciated from an early phase of incurable diseases such as advanced cancer. However, studies examining these characteristics have been lacking. This study attempted to determine what patients with advanced lung cancer valued most, once they had been diagnosed, and any associated factors., Methods: Patients with newly diagnosed advanced lung cancer (N = 248) were enrolled in a questionnaire survey conducted at 16 hospitals in Japan. Their priorities were assessed using a free-text response to the question what is the most important thing to you now? at the time of diagnosis and 3 months after diagnosis. The free-text responses were classified into 10 categories for quantification. The clinical characteristics associated with the category describing daily life were further examined., Results: Free-text comments were obtained from 103 (44.0%) and 66 (42.6%) patients at the time of diagnosis and at 3 months, respectively. The most frequent categories were family (at diagnosis: 50.5%; at 3 months: 50.0%) and daily life (at diagnosis: 33.0%; at 3 months: 36.4%), followed by health (at diagnosis: 32.0%; at 3 months: 27.3%) at both time points. The patients mentioning daily life, the issues related to how to spend daily life, showed significantly higher total scores and functional well-being subscale scores on the Functional Assessment of Cancer Therapy-Lung scale at both time points and lower depression scores at diagnosis and lower anxiety scores at 3 months on the Hospital Anxiety and Depression Scale., Conclusion: Family and daily life were highly valued by patients with advanced lung cancer at diagnosis. A better quality of life and better mood were associated with mentioning daily life, which should be taken into account in care planning to maintain patients' involvement in daily life even with incurable diseases.

This study aimed to investigate the influence of bone marrow edema (BME) for the assessment of the boundaries of necrotic lesions using unenhanced and contrast-enhanced (CE) magnetic resonance (MR) images in patients with osteonecrosis of the femoral head (ONFH). We retrospectively reviewed 72 consecutive hips in 55 patients of ONFH that were Association Research Circulation Osseous (ARCO) stage III or higher and underwent both unenhanced and contrast-enhanced MR imaging between January 2005 and February 2016. The degree of extension of BMEs, and the boundaries of the necrotic lesions were compared using unenhanced and CE MR images on both mid coronal and mid oblique-axial slices. Forty-two percent of the coronal T1 images, 40% of the coronal fat-saturated T2 images, and 48% of the oblique-axial T1 images showed differences in the boundaries of necrotic lesion, by comparison with those of CET1-weighted MR images. The boundaries of necrotic lesions were clearly detected in all hips on CE coronal slices and 97% of all hips on CE oblique-axial slices. The BME grade in the difference group was significantly higher than in the non-difference group on the coronal plane (P = 0.0058). There were significant differences between the BME grade and duration from the onset of hip pain to MR imaging examination. Multivariate analyses revealed that the duration from the onset to MR imaging examination in both coronal (P = 0.0008) and oblique-axial slices (P = 0.0143) were independently associated with differences in the boundary of necrotic lesion between T1 and CET1-weighted MR images. Our findings suggest that unenhanced MR image may be insufficient for a precise assessment of the boundaries of the necrotic lesions for ONFH cases in the early phase of subchondral collapse due to the diffuse BME., (© 2022. The Author(s).)

Background: X-ray images are commonly used to assess the bone destruction of rheumatoid arthritis. The purpose of this study is to propose an automatic-bone-destruction-evaluation system fully utilizing deep neural networks (DNN). This system detects all target joints of the modified Sharp/van der Heijde score (SHS) from a hand X-ray image. It then classifies every target joint as intact (SHS = 0) or non-intact (SHS ≥ 1)., Methods: We used 226 hand X-ray images of 40 rheumatoid arthritis patients. As for detection, we used a DNN model called DeepLabCut. As for classification, we built four classification models that classify the detected joint as intact or non-intact. The first model classifies each joint independently, whereas the second model does it while comparing the same contralateral joint. The third model compares the same joint group (e.g., the proximal interphalangeal joints) of one hand and the fourth model compares the same joint group of both hands. We evaluated DeepLabCut's detection performance and classification models' performances. The classification models' performances were compared to three orthopedic surgeons., Results: Detection rates for all the target joints were 98.0% and 97.3% for erosion and joint space narrowing (JSN). Among the four classification models, the model that compares the same contralateral joint showed the best F-measure (0.70, 0.81) and area under the curve of the precision-recall curve (PR-AUC) (0.73, 0.85) regarding erosion and JSN. As for erosion, the F-measure and PR-AUC of this model were better than the best of the orthopedic surgeons., Conclusions: The proposed system was useful. All the target joints were detected with high accuracy. The classification model that compared the same contralateral joint showed better performance than the orthopedic surgeons regarding erosion., (© 2022. The Author(s).)

Background: Identifying factors associated with poor hip contact mechanics after periacetabular osteotomy (PAO) may help surgeons optimize acetabular corrections in individual patients. We performed individual-specific finite-element analyses to identify preoperative morphological and surgical correction factors for abnormal contact pressure (CP) after PAO., Methods: We performed finite-element analyses before and after PAO with reference to the standing pelvic position on individual-specific 3-dimensional hip models created from computed tomography images of 51 dysplastic hips. Nonlinear contact analyses were performed to calculate the joint CP of the acetabular cartilage during a single-leg stance., Results: The maximum CP decreased in 50 hips (98.0%) after PAO compared to preoperative values, and the resulting maximum CP was within the normal range (<4.1 MPa) in 33 hips (64.7%). Multivariate analysis identified the roundness index of the femoral head (P = .002), postoperative anterior center-edge angle (CEA; P = .004), and surgical correction of lateral CEA (Δlateral CEA; P = .003) as independent predictors for abnormal CP after PAO. A preoperative roundness index >54.3°, a postoperative anterior CEA <36.3°, and a Δlateral CEA >27.0° in the standing pelvic position predicted abnormal CP after PAO., Conclusion: PAO normalized joint CP in 64.7% of the patients but was less likely to normalize joint CP in patients with aspheric femoral heads. Successful surgical treatment depends on obtaining adequate anterior coverage and avoiding excessive lateral correction, while considering the physiological pelvic tilt in a weight-bearing position., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: In modern society, car usage is one of the most important activities of daily living. However, the three-dimensional (3D) mechanics of getting into and out of a car in total hip arthroplasty (THA) patients have not been studied., Research Question: This study aimed to elucidate the hip kinematics and kinetics of unilateral THA patients while getting into and out of a car., Methods: 3D motion and ground reaction force data were collected for 40 unilateral primary THA and 30 control participants using motion capture of getting into and out of a car. Normalized joint power was used to determine the individual joint contribution and was calculated by dividing the power of each joint by the total lower-extremity power. These kinematic and kinetic data were compared between unilateral THA and control participants., Results: When getting into the car using the surgical side as the pivot limb, the peak flexion, abduction angle, and normalized power of the pivot hip were significantly lower, and the normalized power of the contralateral ankle was significantly higher. The peak flexion and abduction angle of the pivot hip were significantly lower, and normalized contralateral hip power was significantly higher when getting out of the car. In getting into and out of the car using the contralateral side as the pivot limb, there was no significant difference in the range of motion (RoM) and normalized joint power., Significance: The restoration of RoM and muscle strength in the surgical hip joint and adopting the normal side as the pivot limb may allow for a more appropriate balance in motion of getting into and out of a car, which will lead to safe mobility, assist in social participation, and improved quality of life., Level of Evidence: Level III, therapeutic study., Competing Interests: Conflict of interest statement The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The optimal treatment for advanced non-small cell lung cancer (NSCLC) in very elderly patients is unclear. We aimed to evaluate their treatment in real-world clinical practice and identify suitable therapy that can improve their prognosis., Materials and Methods: The medical records of 132 Japanese patients aged 80 years and older with advanced NSCLCs who were enrolled at a university hospital and its 9 affiliates were retrospectively analyzed. Clinical characteristics and overall survival (OS) were compared based on the Eastern Cooperative Oncology Group Performance Status (ECOG PS) and biomarker statuses. Patients were defined as biomarker-positive if programmed death-ligand 1 tumor proportion score (PD-L1 TPS) was ≥ 50% or activating mutations were present in epidermal growth factor receptor, anaplastic lymphoma kinase, or c-ros oncogene 1. Finally, the factors contributing to better prognosis were explored in both PS 0 - 2 and PS 3 - 4 patient groups., Results: The PS 0 - 2 patients showed a longer median OS than the PS 3 - 4 patients (5.5 vs. 1.6 months). PS 0 - 2 patients with positive biomarkers who received chemotherapy showed a significantly longer median OS than those without (18.1 vs. 3.7 months). Among the biomarker-negative/unknown PS 0 - 2 patients, the median OS showed no significant difference between those who received chemotherapy and those who did not (4.5 vs. 3.1 months). The multivariate analysis showed that treatment with tyrosine kinase inhibitors or immune checkpoint inhibitors was related to better prognoses in the PS 0 - 2 group., Conclusion: Biomarker-matched therapy is effective even in very elderly patients. Meanwhile, the effectiveness of chemotherapy for biomarker-negative/unknown PS 0 - 2 patients is questionable., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

We report the synthesis of photoactive carbon monoxide-releasing coordination polymer particles through the assembly of Mn(I) carbonyl complexes with bis(imidazole) ligands. The use of Mn(I) carbonyl complexes as metallic nodes in the coordination network avoids the potential for aggregation-induced self-quenching, favouring their use in the solid state.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge 1-5 . Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection., (© 2022. The Author(s).)

Aims: Although periacetabular osteotomies are widely used for the treatment of symptomatic dysplastic hips, long-term surgical outcomes and patient-reported outcome measures (PROMs) are still unclear. Accordingly, we assessed hip survival and PROMs at 20 years after transpositional osteotomy of the acetabulum (TOA)., Methods: A total of 172 hips in 159 patients who underwent TOA were followed up at a mean of 21.02 years (16.6 to 24.6) postoperatively. Kaplan-Meier analysis was used to assess survivorship with an endpoint of total hip arthroplasty (THA). PROMs included the visual analogue scale (VAS) Satisfaction, VAS Pain, Oxford Hip Score (OHS), and Forgotten Joint Score-12 (FJS-12). Thresholds for favourable outcomes for OHS (≥ 42) and FJS-12 (≥ 51) were obtained using the receiver operating characteristic curve with VAS Satisfaction ≥ 50 and VAS Pain < 20 as anchors., Results: THA was performed on 37 hips (21.5%) by the latest follow-up. Kaplan-Meier analysis indicated that the hip survival rate at 20 years was 79.7% (95% confidence interval (CI) 73.7 to 86.3). Multivariate analysis showed that preoperative Tönnis grade significantly influenced hip survival. Tönnis grades 0, 1, and 2 were associated with 20-year survival rates of 93.3% (95% CI 84.8 to 100), 86.7% (95% CI 79.8 to 94.3), and 54.8% (95% CI 41.5 to 72.3), respectively. More than 60% of the patients exhibited favourable PROMs. An advanced Tönnis grade at the latest follow-up and a higher BMI were both significantly associated with unfavourable OHS, but not with other PROMs., Conclusion: This study demonstrated the durability of TOA for hips with Tönnis grades 0 to 1 at 20 years. While the presence of advanced osteoarthritis and higher BMI was associated with lower hip functions (OHS), it was not necessarily associated with worse patient satisfaction and joint awareness. Cite this article: Bone Joint J  2022;104-B(7):767-774.

Purpose: This prospective randomized controlled study examined whether accelerometer-based navigation resulted in more accurate or precise cup orientation than a conventional mechanical guide. We used a simulation to evaluate how cup orientation affected potential hip range of motion (RoM) and freedom from prosthetic impingement., Methods: Sixty hips were randomly allocated 1:1 to accelerometer-based portable navigation or conventional guidance. Procedures were performed through a standard posterolateral approach and combined anteversion technique. Cup inclination, cup anteversion, and stem anteversion were measured using computed tomography (CT). Using CT-based simulation, we evaluated impingement-free potential RoM and the proportion of hips with potential RoM required for daily activities., Results: Absolute cup inclination and anteversion error averaged 4.3° ± 3.2° and 4.4° ± 2.9° for the navigation cohort and 5.6° ± 3.7° and 5.7° ± 4.2° for the conventional cohort, with no significant differences. Navigation resulted in significantly less variation in anteversion error than the conventional guide (p = .0049). Flexion, internal rotation (IR) at 90° of flexion, extension, and external rotation (ER) averaged 123° ± 12°, 46° ± 13°, 50° ± 10°, and 73° ± 23°, respectively, in the navigation cohort and 127° ± 10°, 52° ± 14°, 45° ± 10°, and 63° ± 12°, respectively, in the conventional cohort (p = .15, .15, .03, and .03, respectively). Flexion > 110°, IR > 30° at 90° of flexion, extension > 30°, and ER > 30° were achieved by 93%, 90%, 100%, and 100% of hips, respectively, in the navigation cohort and 97%, 93%, 97%, and 100% of hips, respectively, in the conventional cohort, with no significant differences., Conclusions: Cup anteversion with the navigation system was more precise, but not more accurate, than with the conventional guide. The navigation cohort exhibited greater potential extension and ER than the conventional cohort, but no significant difference in impingement within the potential RoM required for daily activities., Trial Registration Number: 29036. Date of registration: November 14, 2017., (© 2022. CARS.)

The impact of sports on long-term wear of highly cross-linked polyethylene (XLPE) after total hip arthroplasty (THA) is not fully understood. We investigated (1) the wear performance of the first-generation XLPE, and (2) whether sports participation influences the steady wear rate of XLPE. The femoral head penetration into the cup was measured digitally on radiographs of hips undergoing THA with XLPE. We retrospectively reviewed data that included age, gender, body mass index, follow-up period, preoperative diagnosis, types of XLPE, ball diameter, head material, inclination of the cup, physical function score, and sports participation. Statistical analyses were applied to determine whether sports affect the wear of XLPE and which factors were associated with the steady wear rate. Creep and steady wear rate were found to be 0.18 mm and 0.005 mm/year, respectively. Sports participation, regardless of impact, provided no significant difference in the steady wear rate. Multiple regression analysis demonstrated that sports did not increase the steady wear rate. Our findings showed excellent wear performance of the first-generation XLPE at a minimum of ten years after THA, without significant effect of sports participation on the liner wear., (© 2021. The Japanese Society for Artificial Organs.)

Reports on the therapeutic drug monitoring (TDM) of second- and third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer patients are limited and are required to improve the safety of EGFR-TKI therapy. Some EGFR-TKIs have active metabolites with similar or higher potency compared with the parent compounds; thus, monitoring the parent compound as well as its active metabolites is essential for truly effective TDM. In this study, we developed and validated a method that simultaneously quantifies second- and third-generation EGFR-TKIs (afatinib, dacomitinib, and osimertinib) and the active metabolites of osimertinib, AZ5104 and AZ7550, in the human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The clinical application of the method was also evaluated. The analytes were extracted from a 100 μL serum sample using a simple protein precipitation method and analyzed using LC-MS/MS. Excellent linearity of calibration curves was observed at ranges of 2.5-125.0 ng/mL for afatinib, 2.5-125.0 ng/mL for dacomitinib, 4.0-800.0 ng/mL for osimertinib, 1.0-125.0 ng/mL for AZ5104, and 2.5-125.0 ng/mL for AZ7550. The precision and accuracy were below 14.9% and within ± 14.9% of the nominal concentrations, respectively. The mean recovery was higher than 94.7% and the coefficient of variation (CV) was lower than 8.3%. The mean internal-standard normalized matrix factors ranged from 94.6 to 111.9%, and the CVs were lower than 9.7%. This analytical method met the acceptance criteria of the U.S. Food and Drug Administration guidelines. The method was also successfully applied to the analysis of 45 clinical samples; it supports the efficient and valuable analysis for TDM investigations of EGFR-TKIs., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: To compare the degree of stem subsidence between two different femoral component designs and to determine the risk factors associated with stem subsidence after cementless total hip arthroplasty (THA) in Dorr type C femurs., Methods: We retrospectively reviewed 104 consecutive hips in 100 patients with Dorr type C proximal femoral morphology who underwent primary cementless THA using a fit-and-fill stem or a tapered wedge femoral stem at our institution between January 2012 and June 2021. A fit-and-fill stem was used in 55 hips and a tapered wedge stem was used in 49 hips. Radiologically, the distance between the apex of the major trochanter and the stem shoulder were measured at three different time points (immediately [0W], one week [1W], and six weeks [6W] after surgery) and the degrees of stem subsidence were assessed by comparing the distance between 0 and 1W, 1W and 6W, and 0W and 6W, respectively., Results: The mean degree of stem subsidence (0W vs. 1W) was 0.24 mm (standard deviation [SD] 0.36) in the fit-and-fill stem group, and 0.23 mm (SD 0.41) in the tapered wedge stem group. There was no significant difference between the two groups (P = 0.4862). However, the mean degrees of subsidence were significantly higher in the fit-and-fill stem group (1W vs. 6W, 0.38 mm [SD 0.68]; 0W vs. 6W, 0.65 mm [SD 0.87]) than in the tapered wedge stem group (1W vs. 6W, 0.16 mm [SD 0.32]; 0W vs. 6W, 0.24 mm [SD 0.38]) (P < 0.05 for both). In addition, the rates of > 3 mm subsidence (in which instability can be observed) were 18.2% (10 of 55 hips) and 2.0% (1 of 49 hips), respectively. There was also a significant difference between the two stems (P = 0.0091). Multivariate analysis demonstrated that fit-and-fill stem was a risk factor for > 3 mm subsidence after THA in Dorr type C femurs (P = 0.0050)., Conclusion: Our findings suggest that the tapered wedge stem is more suitable for Dorr type C femurs than the fit-and-fill stem to avoid early postoperative subsidence in cementless THA., (© 2022. The Author(s).)