Aims: The Coronal Plane Alignment of the Knee (CPAK) classification is a simple and comprehensive system for predicting pre-arthritic knee alignment. However, when the CPAK classification is applied in the Asian population, which is characterized by more varus and wider distribution in lower limb alignment, modifications in the boundaries of arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) should be considered. The purposes of this study were as follows: first, to propose a modified CPAK classification based on the actual joint line obliquity (aJLO) and wider range of aHKA in the Asian population; second, to test this classification in a cohort of Asians with healthy knees; third, to propose individualized alignment targets for different CPAK types in kinematically aligned (KA) total knee arthroplasty (TKA). Methods: The CPAK classification was modified by changing the neutral boundaries of aHKA to 0° ± 3° and using aJLO as a new variable. Radiological analysis of 214 healthy knees in 214 Asian individuals was used to assess the distribution and mean value of alignment angles of each phenotype among different classifications based on the coronal plane. Individualized alignment targets were set according to the mean lateral distal femoral angle (LDFA) and medial proximal tibial angle (MPTA) of different knee types. Results: A very high concentration, 191 from 214 individuals (89.3%), were found in knee types with apex distal JLO when the CPAK classification was applied in the Asian population. By using aJLO as a new variable, the high distribution percentage in knee types with apex distal JLO decreased to 125 from 214 individuals (58.4%). The most common types in order were Type II (n = 70; 32.7%), Type V (n = 55; 25.7%), and Type I (n = 46; 21.5%) in the modified CPAK classification. Conclusion: The modified CPAK classification corrected the uneven distribution when applying the CPAK classification in the Asian population. Setting individualized TKA alignment targets according to CPAK type may be a practical method to recreate optimal LDFA and MPTA in KA-TKA. Cite this article: Bone Jt Open 2022;3(3):211–217.

The development of multidrug resistance (MDR) in cancer patients, which is often associated with the overexpression of ABCB1 (MDR1, P-glycoprotein) in cancer cells, remains a significant problem in cancer chemotherapy. ABCB1 is one of the major adenosine triphosphate (ATP)-binding cassette (ABC) transporters that can actively efflux a range of anticancer drugs out of cancer cells, causing MDR. Given the lack of Food and Drug Administration (FDA)-approved treatment for multidrug-resistant cancers, we explored the prospect of repurposing erdafitinib, the first fibroblast growth factor receptor (FGFR) kinase inhibitor approved by the FDA, to reverse MDR mediated by ABCB1. We discovered that by reducing the function of ABCB1, erdafitinib significantly resensitized ABCB1-overexpressing multidrug-resistant cancer cells to therapeutic drugs at sub-toxic concentrations. Results of erdafitinib-stimulated ABCB1 ATPase activity and in silico docking analysis of erdafitinib binding to the substrate-binding pocket of ABCB1 further support the interaction between erdafitinib and ABCB1. Moreover, our data suggest that ABCB1 is not a major mechanism of resistance to erdafitinib in cancer cells. In conclusion, we revealed an additional action of erdafitinib as a potential treatment option for multidrug-resistant cancers, which should be evaluated in future drug combination trials.

Previous studies have shown that the natural diterpene compound, sclareol, potentially inhibits inflammation, but it has not yet been determined whether sclareol can alleviate inflammation associated with rheumatoid arthritis (RA). Here, we utilized human synovial cell line, SW982, and an experimental murine model of rheumatoid arthritis, collagen-induced arthritis (CIA), to evaluate the therapeutic effects of sclareol in RA. Arthritic DBA/1J mice were dosed with 5 and 10 mg/kg sclareol intraperitoneally every other day over 21 days. Arthritic severity was evaluated by levels of anti-collagen II (anti-CII) antibody, inflammatory cytokines, and histopathologic examination of knee joint tissues. Our results reveal that the serum anti-CII antibody, cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-17, as well as Th17 and Th1 cell population in inguinal lymph nodes, were significantly lower in sclareol-treated mice compared to the control group. Also, the sclareol treatment groups showed reduced swelling in the paws and lower histological arthritic scores, indicating that sclareol potentially mitigates collagen-induced arthritis. Furthermore, IL-1β-stimulated SW982 cells secreted less inflammatory cytokines (TNF-α and IL-6), which is associated with the downregulation of p38-mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and NF-κB pathways. Overall, we demonstrate that sclareol could relieve arthritic severities by modulating excessive inflammation and our study merits the pharmaceutical development of sclareol as a therapeutic treatment for inflammation associated with RA.

Backgrounds: A common sequela of hip fracture is loss of ambulation capacity. Prediction of postoperative ambulation capacity is important for surgical and rehabilitation decision making. Handgrip strength is a quick and convenient tool for evaluating postoperative functional ability and outcome in variety of clinical conditions for the elderly and is associated with the use of walking aids. We propose that handgrip strength may be a good predictor for postoperative early ambulation. The purpose of our study was to investigate the contribution of handgrip strength in the prediction of postoperative early ambulation capacity in elderly hip fracture patients. Methods: Clinical data of patients with low-energy hip fractures who received surgery from Jan 2018 to Dec 2019 were prospectively collected. The correlations of ambulation time with complication rate, age, gender, injured side, fracture classifications, surgical procedure, body mass index (BMI), and handgrip strength were analyzed. Results: Sixty-three hip fracture patients were included in this study. Patients whose ambulation time was less than 3 days after the operation had significantly fewer postoperative complications (P = 0.006). Handgrip strength showed the strongest correlation with postoperative early ambulation capacity (P = 0.004). The handgrip strength threshold value for early ambulation was found to be 20.5 kg for male patients and 11.5 kg for female patients. Conclusion: Handgrip strength testis a quick and convenient tool for predicting postoperative early ambulation capacity. In elderly Asians, male patients with a handgrip strength above 20.5 kg and female patients with a handgrip strength above 11.5 kg suggest a high likelihood of early postoperative ambulation and a lower risk of complications after the hip surgery.

Background: Haglund’s deformity, which is characterized by a bony prominence of the posterosuperior aspect of the calcaneus, causes posterior heel pain. To date, there is no standard radiographic parameter to diagnose symptomatic Haglund’s deformity. Herein, we proposed novel radiographic measurements to distinguish between patients with and without symptomatic Haglund’s deformity. Methods: We retrospectively evaluated ankle radiographs of 43 patients who underwent surgery for symptomatic Haglund’s deformity (Haglund group) and 41 healthy individuals (control group) free of heel complaints. Fowler–Phillip angle (FPA), Heneghan–Pavlov parallel pitch lines (PPL), Haglund’s deformity height, bump height, and bump-calcaneus ratio were measured and compared between the groups. Furthermore, the reliability and cut-off value of each parameter were validated via ICC and ROC curve analysis, respectively. Results: The bump height (p < 0.001) and the bump-calcaneus ratio (p < 0.001) showed significant differences between the control and Haglund groups, unlike FPA, PPL, and Haglund’s deformity height. ROC curve analysis revealed that the AUC of bump-calcaneus ratio was larger than that of bump height. The optimal threshold was 4 mm or higher for bump height and 7.5% or higher for bump-calcaneus ratio. The intra- and inter- observer ICCs were, respectively, 0.965 and 0.898 for bump height and 0.930 and 0.889 for bump-calcaneus ratio. Conclusions: This study proposes two novel radiographic parameters to identify operatively treated Haglund’s deformity, namely bump height and bump-calcaneus ratio. They are easy to measure and intuitive. Both of them are effective diagnostic parameters for Haglund’s deformity. Furthermore, bump-calcaneus ratio is more reliable diagnostic parameter than bump height.