Factors predicting lower limb alignment after Oxford medial unicompartmental knee arthroplasty.

This study aimed to identify the factors affecting hip-knee-ankle (HKA) angle following Oxford medial unicompartmental knee arthroplasty (MUKA). A retrospective analysis of 200 patients who underwent Oxford MUKA from June 2018 to October 2020 was conducted. Univariate and multivariate analyses were performed to investigate the impact of surgical and radiographic characteristics on the postoperative HKA angle. The mean HKA angle was 9.5 ± 4.3° before surgery and 3.6 ± 3.7° after surgery (p < 0.001). The postoperative HKA angle significantly correlated with the preoperative HKA angle, bearing size, tibial component alignment angle, and BMI (r = 0.71, p < 0.001; r = - 0.24, p = 0.001; r = 0.21, p = 0.004; r = - 0.18, p = 0.011). Multiple linear regression analysis revealed that the preoperative HKA angle (ß = 0.68, p < 0.001), bearing size (ß = - 0.31, p < 0.001), tibial component alignment angle (ß = 0.14, p = 0.003), and BMI (ß = - 0.09, p = 0.047) significantly affected the postoperative HKA angle. In conclusion, larger preoperative varus deformity, smaller bearing size, greater varus alignment of the tibial component, and lower BMI lead to greater postoperative varus alignment of the lower limb in Oxford MUKA. With this concept, surgeons can more accurately predict postoperative lower limb alignment and avoid malalignment in Oxford MUKA.

Isokinetic training of lower extremity during the early stage promote functional restoration in elder patients with disability after Total knee replacement (TKR) - a randomized control trial.

BACKGROUND: Transient progressive weakness and disability of lower limb during the early stage after TKR will increase the risk of fall, but the superior postoperative strength training mode have not been elucidated for functional restoration. This study aimed to compare whether the isokinetic lower limb training is superior to either isotonic or home isometric exercise during early stage after TKR in older people. METHODS: A total of 43 recruited old participants (mean age, 68.40 years old) receiving TKR were divided randomly based on the different four-week training modes into three groups including isokinetic, isotonic, and home isometric exercise (control group). The primary outcome was set as functional performance in terms of Timed Up and Go (TUG) test and the secondary outcomes include the peak torque of knee at 60 and 120 degree/ second, Short-Form 36 Health Survey (SF-36), and Western Ontario and McMaster Universities Arthritis index (WOMAC). RESULTS: All of the peak torque measurements of the knee improved significantly in both the isokinetic and the isotonic group, but not in the control group. Although isotonic training resulted in more strength gains, a significant enhancement in TUG test was observed in the isokinetic group only (p = 0.003). However, there were no significantly improvement of TUG test after training in other two groups. SF-36 and WOMAC improved after training in all three groups, with no significant difference in the degree of improvement between groups. CONCLUSION: Isokinetic training for 4 weeks following TKR effectively improved all the outcome parameters in this study, including the TUG test, lower limb strength, and functional scores. However, both isokinetic and isotonic training modes could be recommended after TKR because of no significant difference in the degree of improvement between these two groups. TRIAL REGISTRATION: Clinical trial registration number: NCT02938416. LEVEL OF EVIDENCE: I.

The compensatory hypertrophy of transferred flexor hallucis longus tendon for insertional Achilles tendinopathy: a retrospective MRI study.

Flexor hallucis longus (FHL) transfer is an effective surgery in treating insertional Achilles tendinopathy (IAT). However, limited data exist regarding the post-surgery changes in the transferred FHL. The study aimed to compare the sequential changes and hypertrophy of FHL after isolated FHL transfer (FHLT). We retrospectively enrolled patients who underwent isolated FHLT for insertional Achilles pathology from 2015 to 2020 and divided them into two groups based on whether reattachment of the residue Achilles stump to the FHL was performed or not. We recorded demographic characteristics, MRI parameters, and functional outcome. We also analyzed the correlation between the collected data and FHL hypertrophy. Results revealed no significant differences in most MRI parameters of FHL and functional outcomes between the groups. However, the fat distribution within the FHL showed significant reduction and notable 20.2% hypertrophy after FHLT. Interestingly, the hypertrophy of the FHL was significantly more pronounced in the non-reattached group. Furthermore, we observed a positive correlation between the follow-up period and FHL hypertrophy. In conclusion, the FHL demonstrated significant enlargement over time following FHLT. The compensatory hypertrophy of the transferred FHL was particularly evident and the cumulative incidences of FHL enlargement over time were higher in the non-reattached groupcompared to reattached group. However, both reattachment and non-reattachment of Achilles stump on FHL transfer for insertional Achilles tendinopathy carried similar postoperative functional outcomes.

Hydroxygenkwanin Improves the Efficacy of Cytotoxic Drugs in ABCG2-Overexpressing Multidrug-Resistant Cancer Cells.

Hydroxygenkwanin, a flavonoid isolated from the leaves of the Daphne genkwa plant, is known to have pharmacological properties; however, its modulatory effect on multidrug resistance, which is (MDR) mediated by ATP-binding cassette (ABC) drug transporters, has not been investigated. In this study, we examine the interaction between hydroxygenkwanin, ABCB1, and ABCG2, which are two of the most well-characterized ABC transporters known to contribute to clinical MDR in cancer patients. Hydroxygenkwanin is not an efflux substrate of either ABCB1 or ABCG2. We discovered that, in a concentration-dependent manner, hydroxygenkwanin significantly reverses ABCG2-mediated resistance to multiple cytotoxic anticancer drugs in ABCG2-overexpressing multidrug-resistant cancer cells. Although it inhibited the drug transport function of ABCG2, it had no significant effect on the protein expression of this transporter in cancer cells. Experimental data showing that hydroxygenkwanin stimulates the ATPase activity of ABCG2, and in silico docking analysis of hydroxygenkwanin binding to the inward-open conformation of human ABCG2, further indicate that hydroxygenkwanin sensitizes ABCG2-overexpressing cancer cells by binding to the substrate-binding pocket of ABCG2 and attenuating the transport function of ABCG2. This study demonstrates the potential use of hydroxygenkwanin as an effective inhibitor of ABCG2 in drug combination therapy trials for patients with tumors expressing higher levels of ABCG2.

The WD repeat-containing protein 5 (WDR5) antagonist WDR5-0103 restores the efficacy of cytotoxic drugs in multidrug-resistant cancer cells overexpressing ABCB1 or ABCG2.

The development of multidrug resistance (MDR) is one of the major challenges in the treatment of cancer which is caused by the overexpression of the ATP-binding cassette (ABC) transporters ABCB1 (P-glycoprotein) and/or ABCG2 (BCRP/MXR/ABCP) in cancer cells. These transporters are capable of reducing the efficacy of cytotoxic drugs by actively effluxing them out of cancer cells. Since there is currently no approved treatment for patients with multidrug-resistant tumors, the drug repurposing approach provides an alternative route to identify agents to reverse MDR mediated by ABCB1 and/or ABCG2 in multidrug-resistant cancer cells. WDR5-0103 is a histone H3 lysine 4 (H3K4) methyltransferase inhibitor that disrupts the interaction between the WD repeat-containing protein 5 (WDR5) and mixed-lineage leukemia (MLL) protein. In this study, the effect of WDR5-0103 on MDR mediated by ABCB1 and ABCG2 was determined. We found that in a concentration-dependent manner, WDR5-0103 could sensitize ABCB1- and ABCG2-overexpressing multidrug-resistant cancer cells to conventional cytotoxic drugs. Our results showed that WDR5-0103 reverses MDR and improves drug-induced apoptosis in multidrug-resistant cancer cells by inhibiting the drug-efflux function of ABCB1 and ABCG2, without altering the protein expression of ABCB1 or ABCG2. The potential sites of interactions of WDR5-0103 with the drug-binding pockets of ABCB1 and ABCG2 were predicted by molecular docking. In conclusion, the MDR reversal activity of WDR5-0103 demonstrated here indicates that it could be used in combination therapy to provide benefits to a subset of patients with tumor expressing high levels of ABCB1 or ABCG2.

Comparison of the Therapeutic Effects Between Isokinetic and Isotonic Strength Training in Patients After Total Knee Replacement: A Prospective, Randomized Controlled Trial.

Background: Rebuilding the strength of the quadriceps as soon as possible after total knee replacement (TKR) is important so as to restore gait stability. To date, there are no standard postoperative strength training programs during the early recovery stage after TKR. Purpose: To compare the therapeutic effects between isokinetic and isotonic strengthening in patients after TKR. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: From April 2018 to August 2020, 37 patients met the inclusion criteria and were randomly assigned to perform either 4-week isokinetic or isotonic strength training programs. Other components of the rehabilitation program were kept the same between the 2 groups. All cases were evaluated by the Timed Up and Go (TUG) test, peak torque of knee extension and flexion (60 and 120 deg/s), 36-item Short Form Health Survey (SF-36), and Western Ontario and McMaster Universities Arthritis Index (WOMAC). Results: After undergoing a 4-week strength training regimen, significant improvements in the TUG test were noted in both groups; however, the time improvement in the isotonic group did not reach the minimal detectable change. All peak torque measurements improved in the isokinetic group but not in the isotonic group for knee flexion at 60 deg/s. The pain subdomain, physical domain, mental domain, total SF-36 score, and WOMAC index all improved significantly in both groups after training. Both training groups improved significantly in peak torque of knee strength, TUG test, and functional scores, but the differences between isokinetic and isotonic training were not statistically significant. Conclusion: The study findings showed that a 4-week strengthening exercise program in the early postoperative stage, involving either isokinetic or isotonic training, resulted in significant improvements in patients undergoing TKR. Registration: NCT02938416 (ClinicalTrials.gov identifier).

Validation and modification of the Coronal Plane Alignment of the Knee classification in the Asian population.

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.

Novel Radiographic Measurements for Operatively Treated Haglund's Deformity.

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.

Intermittent parathyroid hormone treatment affects the bone structural parameters and mechanical strength of the femoral neck after ovariectomy-induced osteoporosis in rats.

BACKGROUND: Menopause-induced decline in estrogen levels in women is a main factor leading to osteoporosis. The objective of this study was to investigate the effect of intermittent parathyroid hormone (PTH) on bone structural parameters of the femoral neck in ovariectomized rats, in addition to correlations of maximum fracture force. METHODS: Fifteen female Wister rats were divided into three groups: (1) control group; (2) ovariectomized (OVX) group; and (3) OVX + PTH group. All rats were then killed and the femurs extracted for microcomputed tomography scanning to measure volumetric bone mineral density (vBMD) and bone structural parameters of the femoral neck. Furthermore, the fracture forces of femoral neck were measured using a material testing system. RESULTS: Compared with the control and OVX + PTH groups, the OVX group had significantly lower aBMD, bone parameter, and mechanical strength values. A comparison between OVX and OVX + PTH groups indicated that PTH treatment increased several bone parameters. However, the OVX + PTH groups did not significantly differ with the control group with respect to the bone structural parameters, except for trabecular bone thickness of cancellous bone, which was greater. In addition, among the bone structural parameters, the CSA and BSI of cortical bone were significantly correlated with the maximum fracture force of the femoral neck, with correlations of, respectively, 0.682 (p = 0.005) and 0.700 (p = 0.004). CONCLUSION: Intermittent PTH helped treat ovariectomy-induced osteoporosis of cancellous bone and cortical bone in the femoral necks of rats. The ability of the femoral neck to resist fracture was highly correlated with the two parameters, namely cross-sectional area (CSA) and bone strength index (= vBMD × CSA), of cortical bone in the femoral neck and was less correlated with aBMD or other bone structural parameters.

Biomechanical comparisons of different diagonal screw designs in a novel embedded calcaneal slide plate.

BACKGROUND: Medial displacement calcaneal osteotomy (MDCO) is frequently used for the surgical correction of flatfoot. This study aims to investigate the biomechanical effect of the different diagonal screw design on a novel-designed embedded calcaneal plate for MDCO using finite element analysis (FEA), mechanical test and digital image correlation (DIC) measurement. METHODS: Four groups according to the varied implanted plate were set as control group (Group 1), non-diagonal screw (Group 2), one-diagonal screw (Group 3), and two-diagonal screws groups (Group 4). For FEA, A 450 N load was applied to on the anterior process of the calcaneus from top to bottom. Observational indices included the stress on the cortical and cancellous bone of the calcaneus surrounding the implant, the plate itself as well as screws, and the displacement of the overall structure. In addition, this study also used in vitro biomechanics test to investigate the stiffness of the structure after implantation, and used DIC to observe the displacement of the calcaneus structure after external force. RESULTS: Under a simulated load in FEA, there are significant overall instability and high stress concentration on the calcaneal surrounding host bone and the plate/screws system, respectively, in group 2 compared with other groups. Regard to the mechanical testing with DIC system, significant increased rotation stability, maximum force and stiffness with the addition of diagonal screws. In comparison to Group 2, the increase of 112% and 157% in maximum force as well as 104% and 176% in stiffness were found in Group 3 and 4, respectively. CONCLUSION: For reducing stress concentration and enhancing overall stability, more than one-diagonal screw design is recommended and two-diagonal screws design will be superior. This study provided biomechanical references for further calcaneal implants design to prevent clinical failure after MDCO.

The Disproportionate Increase of the Intraoperative Flexion and Extension Gap Space after Posterior Cruciate Ligament Resection in Total Knee Arthroplasty.

PURPOSE: Maintaining gap balance is critical for total knee arthroplasty (TKA). This study aimed to elucidate if the extension-flexion gaps would be changed with posterior cruciate ligament (PCL) intact (PI) and PCL resection (PR) during TKA. The flexion gaps were measured using two methods, open-(Fo) and closed-chain position (Fc), based on the definition of kinetic chain position, respectively. METHODS: This retrospective study enrolled a total of 33 patients who underwent posterior-stabilized (PS) TKA for symptomatic advanced osteoarthritis of knees. After bone cuts were completed, the extension-flexion gaps before and after PCL resection during TKA were measured using a calibrated tensioning device set at a 100 Nm distraction force. To further differentiate the effect of thigh weight on the 90° flexion gap, two varied methods of examination, either in closed chain (Fc) or open chain (Fo) were performed. RESULTS: The increases in the 90° knee flexion gap after PCL resection were measured by both methods, i.e., ΔFc (PR-Fc-PI-Fc): 2.04 ± 2.06 mm, p < 0.001; and mean ΔFo (PR-Fo-PI-Fo): 1.64 ± 1.36 mm, p < 0.001. However, there were no differences between ΔFc and ΔFo before and after PCL resection. A greater amount of flexion gap was identified in open chain than in closed chain after PCL resection, and the PR-Fo and PR-Fc were 14.36 ± 3.13 and 11.40 ± 3.47 (p < 0.001), respectively. CONCLUSIONS: The resection of PCL during TKA distinctly increased the flexion gap, but not the extension gap. This disproportionate increase of the gap will cause a gap balance mismatch. The tensioning maneuver in open-chain was more effective to detect the gap differences than in closed-chain before and after PCL resection during TKA.

Poor Correction Capacity of Preexisting Ankle Valgus Deformity after Total Knee Arthroplasty.

This study investigated the differences in ankle alignment changes after TKA in patients with varying preexisting ankle deformities. We retrospectively examined 90 knees with osteoarthritis and varus deformity in 78 patients who underwent TKA. Preoperative and postoperative radiographic parameters were analyzed. According to their preexisting ankle deformity, patients were assigned to the valgus or varus group. Overall, 14 (15.6%) cases were of preoperative valgus ankle deformity; the remainder were of preoperative varus ankle deformity. Hip-knee-ankle angle (HKA), tibial plafond-ground angle (PGA), and talus-ground angle (TGA) all exhibited significant correction in both groups; however, tibial plafond-talus angle (PTA) and superior space of ankle joint (SS) only changed in the varus group. The median PTA and SS significantly decreased from 1.2° to 0.3° (p < 0.001) and increased from 2.5 to 2.6 mm (p = 0.013), respectively. Notably, ∆PTA positively correlated with ∆HKA in the varus group (r = 0.247, p = 0.032) but not in the valgus group. Between-group differences in postoperative PTA (p < 0.001) and ∆PTA (p < 0.001) were significant. The degree of ankle alignment correction after TKA differed between patients with preexisting varus and valgus ankle deformities. TKA could not effectively correct the preexisting ankle valgus malalignment.

Association of osteoporosis and varus inclination of the tibial plateau in postmenopausal women with advanced osteoarthritis of the knee.

BACKGROUND: Although varus inclination of the tibial plateau has increasingly been recognized as a major risk factor in the progression of Osteoarthritis of the knee (OA knee), little attention has been placed on the development of the varus inclination of the tibial plateau. Osteoporosis is a disease characterized by low bone mass and may increase the risk of a stress fracture in the proximal tibia. To date, risk factors for varus inclination of the tibial plateau are rarely reported. In this study, we investigated Bone Mineral Density (BMD) as a risk factor of varus inclination of the tibial plateau in postmenopausal women with advanced OA knee. METHODS: A total of 90 postmenopausal women with varus OA knee who had received a total knee arthroplasty in our department between January 2016 and December 2019 were reviewed. Certain factors may correlate to inclination of the tibial plateau (Medial Tibial Plateau Angle, MTPA), including age, operation side, Kellgren-Lawrence grade of OA knee, BMD, Body Mass Index (BMI), Lateral Distal Femur Angle (LDFA), lower extremity alignment (Hip-Knee-Ankle angle, HKAA), and history of both spinal compression fracture and hip fracture were collected and analyzed. RESULTS: Osteoporosis, lower extremity varus malalignment and age were significantly associated with varus inclination of the tibial plateau (MTPA) (P = 0.15, 0.013 and 0.033 respectively). For patients with a lower extremity varus malalignment (HKAA < 175°), osteoporosis (T-score ≤ -2.5) was significantly associated with inclination of the tibial plateau. For patients with a normal lower extremity alignment (HKAA ≥ 175°), no significant association was found between osteoporosis (T-score ≤ -2.5) and varus inclination of the tibial plateau. CONCLUSIONS: Osteoporosis, lower extremity varus malalignment and age are major risk factors for inclination of the tibial plateau in postmenopausal women with OA knee. More attention needs to be given to the progression of varus OA knee in postmenopausal women who simultaneously has osteoporosis and lower extremity varus malalignment.

The Prevention of Periprosthetic Joint Infection in Primary Total Hip Arthroplasty Using Pre-Operative Chlorhexidine Bathing.

Periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is a devastating complication. The aim of this study was to investigate whether preoperative bathing using chlorhexidine gluconate (CHG) before THA can effectively reduce the postoperative PJI rate. A total of 933 primary THA patients, with the majority being female (54.4%) were included in the study. Primary THA patients who performed preoperative chlorhexidine bathing were assigned to the CHG group (190 subjects), and those who did not have preoperative chlorhexidine bathing were in the control group (743 subjects). The effects of chlorhexidine bathing on the prevention of PJI incidence rates were investigated. Differences in age, sex, and the operated side between the two groups were not statistically significant. Postoperative PJI occurred in four subjects, indicating an infection rate of 0.43% (4/933). All four infected subjects belonged to the control group. Although the PJI cases were significantly more in the control group than in the CHG group, statistical analysis revealed no statistical significance in the risk of PJI occurrence between the two groups (p = 0.588). Preoperative skin preparation by bathing with a 2% chlorhexidine gluconate cleanser did not produce significant effects on the prevention of postoperative PJI in primary THA.

Handgrip strength: a reliable predictor of postoperative early ambulation capacity for the elderly with hip fracture.

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.

Antipsychotic Medication in Schizophrenic Patients is Associated with Higher Risks of Developing Bone Fractures and Refractures.

OBJECTIVE: : The relationship of antipsychotics and the risk of refracture in treated patients is unclear. The aim of this study is to evaluate the association between prolonged antipsychotic and the incidences of bone fractures and refractures in schizophrenia. METHODS: This is a retrospective nested case-control study using Taiwan National Health Insurance Research Database recorded from 2000 to 2005, with cases followed up to end of 2011. Total of 7,842 schizophrenic patients, 3,955 had developed bone fractures were compared with 3,887 control subjects matched in age, sex, and index date. Antipsychotic drug exposure was classified based on the drug type and medication duration. Conditional logistic regression analyses were performed. Odds ratio (OR) and confidence interval (CI) were calculated. RESULTS: We found (after adjustments) higher risks of developing fractures under continued use of typical (OR = 1.70; 95% CI, 1.51-1.91) or atypical antipsychotics (OR = 1.43; 95% CI, 1.28-1.60) were found. Additionally, continued use typical (OR = 1.84; 95% CI, 1.35-2.50) or atypical antipsychotics (OR = 1.44; 95% CI, 1.06-1.95) was positively associated with refracture risks. Moreover, refractures were associated with continuous use of chlorpromazine (one typical antipsychotics, OR = 2.45; 95% CI, 1.14-5.25), and risperidone (OR = 1.48; 95% CI, 1.01-2.16) or zotepine (OR = 2.15; 95% CI, 1.06-4.36) (two atypical antipsychotics). CONCLUSION: Higher risks of bone fracture and refracture were found in schizophrenia under prolonged medication with typical or atypical antipsychotics. We therefore recommend that clinicians should pay more attention on bone density monitoring for patients using long-term antipsychotics.

Erdafitinib Resensitizes ABCB1-Overexpressing Multidrug-Resistant Cancer Cells to Cytotoxic Anticancer Drugs.

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.

Posterior cruciate ligament reconstruction implemented by the Ligament Advanced Reinforcement System over a minimum follow-up of 10 years.

PURPOSE: This study evaluated the long-term clinical follow-up results of patients who underwent double-bundle posterior cruciate ligament (PCL) reconstruction using the Ligament Advanced Reinforcement System (LARS). METHODS: Patients were assessed using clinical scores that included the Tegner activity level scale, the Lysholm score, and the International Knee Documentation Committee (IKDC) score. KT-1000 was adopted to assess stability. Radiographs and magnetic resonance imaging (MRI) were used to evaluate osteoarthritis and LARS condition. RESULTS: This study examined 38 patients, of which follow-up procedures were completed for 33 patients, resulting in a follow-up rate of 86.8%. The average follow-up period was 11.9 ±â€¯1.2 years (range: 10.3-14.2 years). The median scores of the clinical scales were as follows: Tegner activity score, 6 (range: five to seven); Lysholm score, 90 (range: 67-100); and IKDC score, 89.7 (range: 46-100). The median of the side-to-side difference (SSD) was four millimeters (range: 0-10 mm). In radiographs, the moderate OA rate was 6.9%. MRI results revealed that 26 patients exhibited ingrowth and 11 patients exhibited partial rupture of the LARS. With SSD ≤ 3 mm set as the standard for successful knee stabilization, the optimal cutoff point of LARS midsubstance thickness in the receiver operating characteristic (ROC) curve analysis was 14.3 mm. CONCLUSIONS: Long-term follow-up of the studied patients demonstrated the durability of LARS. However, clinical outcomes showed no enhancement using LARS, so it is not recommended for routine use in PCL reconstruction. LEVEL OF EVIDENCE: IV.

Isorhamnetin ameliorates inflammatory responses and articular cartilage damage in the rats of monosodium iodoacetate-induced osteoarthritis.

Context: Osteoarthritis (OA) is a degenerative joint disease with damage to the articular cartilage. Active production of inflammatory cytokine/chemokine and matrix metalloproteinases may be found during the progression of OA. Isorhamnetin had the effects of anti-inflammatory, antioxidant, anti-ischemia, anti-atherosclerotic hepatoprotective and anticancer activities. Objective: Our study was focused on the effects of isorhamnetin treatment in OA. Materials and methods: We used monosodium iodoacetate (MIA)-induced OA rats to evaluate the effects of isorhamnetin related anti-inflammatory process. The rats in all groups were sacrificed on four weeks post-MIA injection. The measurements of knee joint swelling, histological analysis, serum inflammatory biomarkers and western blot were evaluated. Results: We found that isorhamnetin may reduce MIA-induced knee swelling by significantly reduction of articular cartilage damage.in rats. Suppression of pro-inflammatory cytokines production was found after isohamnetin treatment. Isorhamnetin inhibited the production of NO and PGE2, and the expression of iNOS and COX-2. The production of COMP, CTX-II and osteopontin (OPN) were also inhibited in MIA-induced OA rats. Discussion and conclusions: Isorhamnetin may modulate the inflammatory progression of OA in MIA-induced OA rats. The prevention of cartilage damage was found in OA after adequate isorhamnetin treatment. Isorhamnetin may serve as a potential agent for the management of OA.

Extraction of gray-scale intensity distributions from micro computed tomography imaging for femoral cortical bone differentiation between low-magnesium and normal diets in a laboratory mouse model.

Previous studies have shown that the geometric development of femoral trabecular bone is affected by insufficient dietary intake of magnesium. However, it is not clear whether the development of femoral cortical bone can be quantitatively evaluated according to a diet with inadequate magnesium supplementation. Therefore, we used a micro computed tomography (CT) imaging approach with a laboratory mouse model to explore the potential application of texture analysis for the quantitative assessment of femoral cortical bones. C57BL/6J male mice were divided into two groups, where one group was fed a normal diet and the other group was fed a low-magnesium diet. We used a micro CT scanner for image acquisition, and the subsequent development of cortical bone was examined by texture analysis based on the statistical distribution of gray-scale intensities in which seven essential parameters were extracted from the micro CT images. Our calculations showed that the mean intensity increased by 7.20% (p = 0.000134), sigma decreased by 29.18% (p = 1.98E-12), skewness decreased by 19.52% (p = 0.0000205), kurtosis increased by 9.62% (p = 0.0877), energy increased by 24.19% (p = 3.32E-09), entropy decreased by 6.14% (p = 3.00E-10), and the Nakagami parameter increased by 104.32% (p = 4.13E-12) in the low-magnesium group when compared to the normal group. We found that the statistical parameters extracted from the gray-scale intensity distribution were able to differentiate between femoral cortical bone developments in the two different diet groups.