Effects of Dexamethasone on Postoperative Glycemic Control in Patients After Primary Total Joint Arthroplasty: A Randomized Double-Blind Controlled Trial.

BACKGROUND: In patients undergoing total joint arthroplasty, the use of dexamethasone (DEX) may cause perioperative blood glucose (BG) disorders, leading to complications even in patients who do not have diabetes. We aimed to evaluate the effects of different DEX doses on perioperative BG levels. METHODS: A total of 135 patients who do not have diabetes were randomized into three groups: preoperative intravenous (IV) injection of normal saline (Group A, the placebo group), preoperative IV injection of 10 mg DEX (Group B), and preoperative IV injection of 20 mg DEX (Group C). Postoperative fasting BG (FBG) levels were designated as the primary outcome, while postoperative postprandial BG (PBG) levels were assigned as the secondary outcome. The incidence of complications was recorded. We also investigated the risk factors for FBG ≥ 140 mg/dL and PBG ≥ 180 mg/dL. RESULTS: The FBG levels were higher in Groups B and C than in Group A on postoperative days (PODs) 0 and 1. The PBG levels were lower for Groups A and B compared to Group C on POD 1. No differences in FBG or PBG were detected beyond POD 1. Elevated preoperative glycosylated hemoglobin A1c levels increased the risk of FBG ≥ 140 mg/dL and PBG ≥ 180 mg/dL, respectively. However, preoperative IV injection of DEX was not associated with FBG ≥ 140 mg/dL or PBG ≥ 180 mg/dL. No differences were found in postoperative complications among the three groups. CONCLUSIONS: The preoperative IV administration of 10 or 20 mg DEX in patients who do not have diabetes showed transient effects on postoperative BG after total joint arthroplasty. The preoperative glycosylated hemoglobin A1c level threshold (regardless of the administration or dosage of DEX) that increased the risk for the occurrence of FBG ≥ 140 mg/dL and PBG ≥ 180 mg/dL was 5.75 and 5.85%, respectively.

The role of toll-like receptors in orchestrating osteogenic differentiation of mesenchymal stromal cells and osteoimmunology.

Osteoimmunology is a concept involving molecular and cellular crosstalk between the skeletal and immune systems. Toll-like receptors (TLRs) are widely expressed both on mesenchymal stromal cells (MSCs), the hematopoietic cells, and immune cells in the osteogenic microenvironment for bone development or repair. TLRs can sense both exogenous pathogen-associated molecular patterns (PAMPs) derived from microorganisms, and damage-associated molecular patterns (DAMPs) derived from normal cells subjected to injury, inflammation, or cell apoptosis under physiological or pathological conditions. Emerging studies reported that TLR signaling plays an important role in bone remodeling by directly impacting MSC osteogenic differentiation or osteoimmunology. However, how to regulate TLR signaling is critical and remains to be elucidated to promote the osteogenic differentiation of MSCs and new bone formation for bone tissue repair. This review outlines distinct TLR variants on MSCs from various tissues, detailing the impact of TLR pathway activation or inhibition on MSC osteogenic differentiation. It also elucidates TLR pathways' interplay with osteoclasts, immune cells, and extracellular vesicles (EVs) derived from MSCs. Furthermore, we explore biomaterial-based activation to guide MSCs' osteogenic differentiation. Therefore, understanding TLRs' role in this context has significant implications for advancing bone regeneration and repair strategies.

[Preliminary Study on the Effect of Whole-Process Case Management Based on Service Process Design on the Function and Satisfaction of Patients Undergoing Total Knee Arthroplasty].

Objective: To investigate the effect of whole-process case management based on service process design on patients undergoing total knee arthroplasty (TKA) in areas including pain, function, satisfaction, and complications. Methods: A total of 204 patients who underwent unilateral TKA between April 2021 and March 2022 at the Department of Orthopedics, West China Hospital, Sichuan University were enrolled. By using a random number table, the patients were randomly assigned to two groups, 102 in the general case management group (group G) and 102 in the whole-process case management group (group W). Patients in group G received traditional perioperative case management, while those in the whole-process case management group received integrated case management optimized on the basis of the service process design. The two groups of patients were studied through comparison of their general data, Visual Analogue Scale (VAS) pain score, knee flexion and range of motion, Hospital for Special Surgery (HSS) knee score, the 18-item Patient Satisfaction Questionnaire Short Form (PSQ-18), ability to climb stairs, and complications at 3 days and 3, 8, and 12 weeks after TKA. Results: There was no significant difference between the two groups in patient general information or baseline data collected at the time of enrollment ( P>0.05). There was no significant difference in HSS score, joint range of motion, and VAS pain score between the two groups before the surgery and 3 days after the surgery ( P>0.05). However, the HSS score, joint range of motion, and VAS pain scores of group W were significantly superior to those of group G at 3, 8 and 12 weeks after the surgery (all P<0.05). In addition, group W demonstrated significantly better ability to climb up and down stairs than that of group G at 12 weeks after the surgery ( P< 0.001). In terms of satisfaction, patients in group W were significantly more satisfied than those in group G at 3 days, and 3, 8, and 12 weeks after the surgery ( P<0.001). Conclusion: Whole-process case management based on service process design has a positive effect of relieving pain, increasing range of motion, improving function, increasing satisfaction, and reducing complications in patients undergoing TKA.

Adductor canal block combined with local infiltration analgesia with morphine and betamethasone show superior analgesic effect than local infiltration analgesia alone for total knee arthroplasty: a prospective randomized controlled trial.

BACKGROUND: Local infiltration analgesia (LIA) and adductor canal block (ACB) provide postoperative analgesia for total knee arthroplasty (TKA). ACB blocks the saphenous nerve and has smaller impacts on quadriceps muscle weakness. ACB theoretically does not have enough analgesic effects on posterior sensory nerves. LIA may increase its analgesic effects on the posterolateral knee. The purpose of this study was to evaluate whether ACB combined with a LIA cocktail of ropivacaine, morphine, and betamethasone has superior analgesic effect than LIA for TKA. METHODS: A total of 86 patients were assessed for eligibility from February 2019 to May 2019. 26 of those were excluded, and 60 patients were divided into 2 groups by computer-generated random number. Group A (LIA group) received LIA cocktail of ropivacaine, morphine and betamethasone. Group B (LIA+ ACB group) received ultrasound-guided ACB and LIA cocktail of ropivacaine, morphine and betamethasone. Postoperative visual analogue scale (VAS) resting or active pain scores, opioid consumption, range of motion (ROM), functional tests, complications and satisfaction rates were measured. The longest follow-up was 2 years. RESULTS: Two groups have no differences in terms of characteristics, preoperative pain or function (P > 0.05). ACB combined with LIA had significantly lower resting and active VAS pain scores, better ROM, better sleeping quality and higher satisfaction rates than LIA alone within 72 h postoperatively (P < 0.05). Complications, or adverse events and HSS score, SF-12 score were observed no significant differences within 2 years postoperatively. CONCLUSIONS: Adductor canal block combined with Local infiltration analgesia provide better early pain control. Although the small statistical benefit may not result in minimal clinically important difference, Adductor canal block combined with Local infiltration analgesia also reduce opioid requirements, improve sleeping quality, and do not increase the complication rate. Therefore, Adductor canal block combined with Local infiltration analgesia still have good application prospects as an effective pain management for total knee arthroplasty. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900021385 , 18/02/2019.

Near-Infrared Light-Controllable Multifunction Mesoporous Polydopamine Nanocomposites for Promoting Infected Wound Healing.

The successful treatment of infected wounds requires strategies with effective antimicrobial, anti-inflammatory, and healing-promoting properties. Accordingly, the use of Cu2+ and tetracycline (TC), which can promote angiogenesis, re-epithelialization, and collagen deposition, also antibacterial activity, at the wound site, has shown application prospects in promoting infected wound repair. However, realizing controllable release to prolong action time and avoid potential toxicities is critical. Moreover, near-infrared light (NIR)-activated mesoporous polydopamine nanoparticles (MPDA NPs) reportedly exert anti-inflammatory effects by eliminating the reactive oxygen species generated during inflammatory responses. In this study, we assess whether Cu2+ and TC loaded in MPDA NPs can accelerate infected wound healing in mice. In particular, Cu2+ is chelated and immobilized on the surface of MPDA NPs, while a thermosensitive phase-change material (PCM; melting point: 39-40 °C), combined with antibiotics, was loaded into the MPDA NPs as a gatekeeper (PPMD@Cu/TC). Results show that PPMD@Cu/TC exhibits significant great photothermal properties with NIR irradiation, which induces the release of Cu2+, while inducing PCM melting and, subsequent, TC release. In combination with anti-inflammatory therapy, NIR-triggered Cu2+ and TC release enables the nanocomposite to eradicate bacterial wound infections and accelerate healing. Importantly, negligible damage to primary organs and satisfactory biocompatibility were observed in the murine model. Collectively, these findings highlight the therapeutic potential of this MPDA-based platform for controlling bacterial infection and accelerating wound healing.

Adductor Canal Block Combined With IPACK Block for Postoperative Analgesia and Function Recovery Following Total Knee Arthroplasty: A Prospective, Double-Blind, Randomized Controlled Study.

BACKGROUND: This study aimed to explore the analgesic effect among adductor canal block (ACB) combined with infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) block, ACB, and IPACK block following total knee arthroplasty (TKA). METHODS: One hundred twenty patients were randomly allocated into 3 groups including group A (ACB + IPACK block), group B (ACB), and group C (IPACK block). The primary outcome was postoperative pain score. The secondary outcome was opioid consumption. Other outcomes included functional evaluation and postoperative complications. RESULTS: Group A showed the lowest pain scores within 8 hours at rest and with knee maximum flexion (P < .001). From 12 to 24 hours, group C showed the highest pain scores, while no significant difference was found between group A and group B. No significant difference was found among the 3 groups 24 hours postoperatively. Group C showed the most opioid consumption within the first 24 hours and during the hospitalization, while no significant difference was found between group A and group B. No significant difference was found among the 3 groups including function evaluation and postoperative complications. CONCLUSION: ACB + IPACK block can improve early analgesia when compared with ACB. However, the small statistical benefit to the addition of IPACK block to ACB may be unlikely to be clinically significant. Further studies may focus on patient selection and how to prolong the effect of IPACK block.

A Comparison Between Unstemmed and Stemmed Constrained Condylar Knee Prostheses in Primary Total Knee Arthroplasty: A Propensity Score-Matched Analysis.

OBJECTIVE: To compare and analyze the clinical outcomes between unstemmed and stemmed constrained condylar knees (CCK) in complex primary total knee arthroplasty (TKA) in terms of implant survivorship, change in outcome evaluations, and complications. METHODS: We reviewed 156 consecutive patients who received primary TKA using PFC®SIGMA®TC3 (TC3) of constrained condylar design between January 2009 and January 2017 at our institution. After removing patients who met exclusion criteria, 25 patients were identified as unstemmed TC3 cases and 81 as stemmed TC3 cases. Propensity score matching was used to select 25 stemmed cases as a control group for the unstemmed group with comparable preoperative conditions including preoperative demographics, preoperative diagnosis, preoperative range of motion, main reason to use TC3, ASA score (American Society of Anesthesiologists), and follow-up duration. Preoperative and postoperative clinical evaluations including Knee Society Score (KSS), Hospital for Special Surgery (HSS) score, the 12-Item Short-Form Health Survey (SF-12), and the range of motion (ROM) were obtained and compared. The instability, periprosthetic fracture, radiolucent lines, polyethylene wear, and heterotrophic ossification were assessed according to the anteroposterior and lateral radiographs of the knee. The complications and implant survivorship between the two groups were also recorded and compared. RESULTS: 3After the index surgery, both groups showed substantial improvement in KSS (knee and function), HSS score, SF-12, and ROM compared with baseline. There was no significant difference in the mean KSS scores (knee and function), HSS score, SF-12, and ROM between the unstemmed and stemmed group postoperatively. No statistically significant difference was found in the overall complication rate between the two groups. The overall Kaplan-Meier survivorship was 98.0% (95% confidence interval 94.1%-100.0%) at 7 years. No significant difference was found in the survival rate between the unstemmed group (100.0%) and the stemmed group (96.0%) at 7 years (log rank, P = 0.317). The mean duration of follow-up was 7.0 years for unstemmed group and 7.7 years for stemmed group. CONCLUSIONS: In patients with adequate bone stock receiving complex primary TKA, unstemmed CCK could achieve similar clinical outcomes at mid-term follow-up as stemmed CCK.

Long-Term Clinical Outcomes and Survivorship of Total Hip Arthroplasty for Pyogenic Arthritis: A Retrospective Cohort Study of 168 Hips.

OBJECTIVE: The aim of the present study was to evaluate the 10-year outcomes of cementless total hip arthroplasty (THA) in adult patients with the late sequelae of septic arthritis of the hip. METHODS: We followed 166 consecutive patients (168 hips) who underwent cementless THA between March 2001 and December 2011. There were 79 men and 87 women, with a mean age of 50.4 years (range 21-76 years) at the time of index THA, all of whom had hip osteoarthritis secondary to hip pyogenic infection. The average duration of follow up was 10.6 years (range 6.9-17.2 years). Preoperative and postoperative clinical ratings were evaluated, including the hip dysfunction and osteoarthritis outcome score (HOOS), the Harris hip score (HHS), range of motion, a 100-point visual analog scale for hip pain, and the severity of limp and limb length discrepancy (LLD). The anteroposterior and lateral radiographs of the hip and full-length view of the lower extremities were obtained to assess the position of the components, radiolucent lines, osteolysis, loosening of components, and heterotopic ossification. The intraoperative and postoperative complications were also recorded. RESULTS: The mean HSS and hip pain score were 44.2 points (range 29-66 points) and 42.5 points (range 32-64 points), respectively, before the index surgery and significantly improved to 88.1 points (range 78-96 points) and 15.1 points (range 10-26 points), respectively, at final follow-up examination. The HOOS and range of motion also improved significantly. The mean limb length discrepancy was reduced from 2.6 to 0.8 cm. The limp at last follow-up examination was moderate in 3 cases because of hip osteoarthritis in the other limb, slight in 26, and absent in 137. A radiolucent line was observed in 12 hips (7.1%) around the acetabular or femoral components. A progressive radiolucent line around the undersized femoral stem in all zones was seen in 1 hip, resulting in aseptic loosening and breakage of the femoral component. There were 8 cases of intraoperative fracture, 7 cases of dislocation, and 7 cases of transient nerve palsy. Recurrence of infection occurred in 2 hips. Revision surgery was conducted in 2 hips because of isolated loosening of the acetabular cup and the femoral stem, respectively. Kaplan-Meier survival was 97% at 10 years, with revision for any reason with any component as an end-point. CONCLUSION: Improved surgical techniques and development of components with various sizes provided favorable results for cementless THA conducted for late sequelae of sepsis in these young and active patients. Although the incidence of complications was relatively high, the complications were treated successfully.

Nomogram to predict collapse-free survival after core decompression of nontraumatic osteonecrosis of the femoral head.

BACKGROUND: Nontraumatic osteonecrosis of the femoral head (NONFH) is a devastating disease, and the risk factors associated with progression into collapse after core decompression (CD) remain poorly defined. Therefore, we aim to define risk factors associated with collapse-free survival (CFS) after CD of precollapse NONFH and to propose a nomogram for individual risk prediction. METHODS: According to the baseline characteristics, clinical information, radiographic evaluations, and laboratory examination, a nomogram was developed using a single institutional cohort of patients who received multiple drilling for precollapse NONFH between January 2007 and December 2019 to predict CFS after CD of precollapse NONFH. Furthermore, we used C statistics, calibration plot, and Kaplan-Meier curve to test the discriminative ability and calibration of the nomogram to predict CFS. RESULTS: One hundred and seventy-three patients who underwent CD for precollapse NONFH were retrospectively screened and included in the present study. Using a multiple Cox regression to identify relevant risk factors, the following risk factors were incorporated in the prediction of CFS: acute onset of symptom (HR, 2.78; 95% CI, 1.03-7.48; P = 0.043), necrotic location of Japanese Investigation Committee (JIC) C1 and C2 (HR, 3.67; 95% CI, 1.20-11.27; P = 0.023), necrotic angle in the range of 250-299°(HR, 5.08; 95% CI, 1.73-14.93; P = 0.003) and > 299° (HR, 9.96; 95% CI, 3.23-30.70; P < 0.001), and bone marrow edema (BME) before CD (HR, 2.03; 95% CI, 1.02-4.02; P = 0.042). The C statistics was 0.82 for CFS which revealed good discriminative ability and calibration of the nomogram. CONCLUSIONS: Independent predictors of progression into collapse after CD for precollapse NONFH were identified to develop a nomogram predicting CFS. In addition, the nomogram could divide precollapse NONFH patients into prognosis groups and performed well in internal validation.

Intra-articular Injection of Kartogenin-Enhanced Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Knee Osteoarthritis in a Rat Model.

BACKGROUND: In this study, we investigated the in vitro and in vivo chondrogenic capacity of kartogenin (KGN)-enhanced bone marrow-derived mesenchymal stem cells (BMSCs) for cartilage regeneration. PURPOSE: To determine (1) whether functionalized nanographene oxide (NGO) can effectively deliver KGN into BMSCs and (2) whether KGN would enhance BMSCs during chondrogenesis in vitro and in vivo in an animal model. STUDY DESIGN: Controlled laboratory study. METHODS: Functionalized NGO with line chain amine-terminated polyethylene glycol (PEG) and branched polyethylenimine (BPEI) were used to synthesize biocompatible NGO-PEG-BPEI (PPG) and for loading hydrophobic KGN molecules noncovalently via π-π stacking and hydrophobic interactions (PPG-KGN). Then, PPG-KGN was used for the intracellular delivery of hydrophobic KGN by simple mixing and co-incubation with BMSCs to acquire KGN-enhanced BMSCs. The chondrogenic efficacy of KGN-enhanced BMSCs was evaluated in vitro. In vivo, osteoarthritis (OA) was induced by anterior cruciate ligament transection in rats. A total of 5 groups were established: normal (OA treated with nothing), phosphate-buffered saline (PBS; intra-articular injection of PBS), PPG-KGN (intra-articular injection of PPG-KGN), BMSCs (intra-articular injection of BMSCs), and BMSCs + PPG-KGN (intra-articular injection of PPG-KGN-preconditioned BMSCs). At 6 and 9 weeks after the surgical induction of OA, the rats received intra-articular injections of PPG-KGN, BMSCs, or KGN-enhanced BMSCs. At 14 weeks after the surgical induction of OA, radiographic and behavioral evaluations as well as histological analysis of the knee joints were performed. RESULTS: The in vitro study showed that PPG could be rapidly uptaken in the first 4 hours after incubation, reaching saturation at 12 hours and accumulating in the lysosome and cytoplasm of BMSCs. Thus, PPG-KGN could enhance the efficiency of the intracellular delivery of KGN, which showed a remarkably high chondrogenic differentiation capacity of BMSCs. When applied to an OA model of cartilage injuries in rats, PPG-KGN-preconditioned BMSCs contributed to protection from joint space narrowing, pathological mineralization, OA development, and OA-induced pain, as well as improved tissue regeneration, as evidenced by radiographic, weightbearing, and histological findings. CONCLUSION: Our results demonstrate that KGN-enhanced BMSCs showed markedly improved capacities for chondrogenesis and articular cartilage repair. We believe that this work demonstrates that a multifunctional nanoparticle-based drug delivery system could be beneficial for stem cell therapy. Our results present an opportunity to reverse the symptoms and pathophysiology of OA. CLINICAL RELEVANCE: The intracellular delivery of KGN to produce BMSCs with enhanced chondrogenic potential may offer a new approach for the treatment of OA.

Mid-long-term results of total knee arthroplasty followed by ipsilateral total hip arthroplasty versus total hip arthroplasty subsequent to ipsilateral total knee arthroplasty: a case-control analysis.

BACKGROUND: The aim of the present study was to compare the outcomes of patients who underwent different sequences of ipsilateral total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: We retrospectively identified 47 patients who underwent TKA followed by ipsilateral THA (THA-TKA) and 36 patients who received THA subsequent to ipsilateral TKA (TKA-THA) for rheumatoid arthritis or osteoarthritis between January 2008 and April 2014. Twenty-eight patients were selected for each group after case-control matching with preoperative demographics and protheses of THA. Clinical scores, radiographic results, complication rates, and survivorship were compared. The median duration of follow-up was 110 (range 80-149) months. RESULTS: Both groups showed significant improvement in Harris Hip Scores, Knee Society Score, and Short Form-12 at the last follow-up compared to baseline (p < .001). At the last follow-up, all clinical scores were actually lower in the THA-TKA group, but those differences were not statistically significant. Otherwise, there was no significant difference in radiological alignment or complication rates. The survivorship of THA and TKA in the THA-TKA group was 94.7 and 95.7%, respectively, compared with 92.4 and 100.0% in the TKA-THA group at 8 years (log rank, p = .939 and .187). CONCLUSIONS: Patients who underwent ipsilateral THA and TKA with different sequences achieved similar favorable outcomes. Total joint arthroplasty can be performed safely with excellent outcomes in patients with a history of prior ipsilateral THA or TKA. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR2000035147 ) dated 2 August 2020.

Multiple drilling is not effective in reducing the rate of conversion to Total hip Arthroplasty in early-stage nontraumatic osteonecrosis of the femoral head: a case-control comparative study with a natural course.

BACKGROUND: To determine whether multiple drilling is effective in postponing the need for total hip arthroplasty (THA) in early-stage nontraumatic osteonecrosis of the femoral head (ONFH). METHODS: We identified 514 patients who were diagnosed with early-stage ONFH between January 2008 and December 2018. One hundred ninety-six patients underwent multiple drilling, and 318 patients had a natural course of progression. One hundred fifty-nine patients were selected for each group after case-control matching for preoperative demographics and modified Ficat and Arlet stage. The rates of THA conversion were compared. We also performed Cox regression to identify risk factors associated with THA conversion in patients who underwent multiple drilling. RESULTS: Kaplan-Meier survivorship with an endpoint of THA for nontraumatic reasons were not significantly different between the multiple drilling group (75.6, 95% confidence interval 67.8-83.4%) and the natural course group (72.2, 95% confidence interval 64.8-79.6%) at 5 years (log-rank, P = .191). In the Cox regression model, a larger extent of necrotic lesion, bone marrow edema (BME), and higher postoperative work intensity significantly increased the risk of THA conversion (P < .05). Among patients treated with autogenous bone grafting, there was a lower risk of failure in patients with necrotic lesion less than 15% (P < .05). CONCLUSIONS: Multiple drilling is not effective in reducing the rate of THA conversion in early-stage nontraumatic ONFH. The risk of conversion to THA after multiple drilling is increased by a larger extent of necrotic lesion, presence of BME, and higher postoperative work intensity in patients with early-stage ONFH. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR2000035180 ) dated 2 August 2020.

Duloxetine reduces pain after Total hip arthroplasty: a prospective, randomized controlled study.

BACKGROUND: Previous studies have demonstrated the efficacy of duloxetine in reducing postoperative pain and opioid consumption. However, the effect of duloxetine on total hip arthroplasty (THA) remains unclear. The objective of this study was to assess the efficacy of oral duloxetine in THA. METHODS: We enrolled 96 patients in this randomized controlled trial. These patients were randomized (1,1) to either the duloxetine group or the placebo group and received daily doses of 60 mg duloxetine or placebo, respectively, from 2 d pre-operation to 14 d after surgery. The primary outcome was pain severity upon movement measured by a visual analogue scale (VAS). The secondary outcomes included VAS scores for resting pain, morphine consumption, Harris Hip Score, patient satisfaction at discharge, length of postoperative hospital stay, and adverse events. RESULTS: Patients in the duloxetine group had significantly lower pain severity scores upon movement within 3 postoperative weeks (p < 0.05) while none of the differences met the minimum clinically important difference (MCID). Moreover, patients in the duloxetine group performed better in terms of resting pain (in 3 weeks after surgery), morphine requirements, and satisfaction level at discharge (all p < 0.05). There was no difference between groups in the prevalence of adverse events. CONCLUSIONS: Although it did not result in a clinically meaning reduction in pain after total hip arthroplasty, perioperative administration of 60 mg of duloxetine daily significantly alleviated pain in the postoperative 3 weeks and morphine requirements during the postoperative 48 h. Therefore, duloxetine still shows promise in optimizing the multimodal pain-management protocols in total hip arthroplasty. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000033606 , 06/06/2020.

Synchronous or sequential cementless bilateral total hip arthroplasty for osseous ankylosed hips with ankylosing spondylitis.

BACKGROUND: Bilateral osseous ankylosed hips secondary to ankylosis spondylitis (AS) are relatively rare but impact the quality of life hugely. Cementless total hip arthroplasty (THA) for bilateral osseous ankylosed hips with AS is a challenging procedure. No previous literature compares the clinical outcomes of synchronous and sequential bilateral THA for these special patients. METHODS: 23 patients (46 hips) were retrospectively analyzed and divided into bilateral THA synchronously (group A) and sequentially (group B). The clinical measurement, radiological assessments, and complications were compared. Independent sample T test was used for data analysis. RESULTS: Harris Hip Scores (HHS) improved greatly for both groups (P = 0.58) as well as the range of motion (P = 0.64). But group B can realize shorter time (3.6 ± 1.2 days) to walk for the first time postoperatively (P = 0.02). Group A needed more blood transfusions (P = 0.028). For group A, no statistical difference was found in the bilateral inclination of cup (IC) (P = 0.48) and femoral offset (FO) (P = 0.07). For group B, no statistical difference was observed in bilateral IC (P = 0.37) but in bilateral FO (P = 0.04). Group A showed the fewer difference of bilateral IC (P = 0.02), while comparative measurements were found for two groups in the difference of bilateral FO (P = 0.78) and leg length discrepancy (P = 0.83). For both groups, the total hospital expense for each patient was similar and almost all patients were very satisfied with the outcomes. For group A, one patient encountered femoral fracture intraoperatively and another patient encountered hip dislocation and delay union of wound. 3 hips from group A and 3 hips from group B encountered heterotopic ossification. CONCLUSIONS: Our retrospective research demonstrated that cementless bilateral THA was a reliable treatment for osseous ankylosed hip due to AS. Synchronous and sequential bilateral THA can realize similarly satisfactory clinical outcomes and radiographic evaluation.

Mitochondria-targeting graphene oxide nanocomposites for fluorescence imaging-guided synergistic phototherapy of drug-resistant osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and young adults. Drug-resistant osteosarcoma often results in chemotherapy failure. Therefore, new treatments aimed at novel therapeutic targets are urgently needed for the treatment of drug-resistant osteosarcoma. Mitochondria-targeted phototherapy, i.e., synergistic photodynamic/photothermal therapy, has emerged as a highly promising strategy for treating drug-resistant tumors. This study proposed a new nano-drug delivery system based on near-infrared imaging and multifunctional graphene, which can target mitochondria and show synergistic phototherapy, with preferential accumulation in tumors. METHODS AND RESULTS: Based on our previous study, (4-carboxybutyl) triphenyl phosphonium bromide (TPP), a mitochondria-targeting ligand, was conjugated to indocyanine green (ICG)-loaded, polyethylenimine-modified PEGylated nanographene oxide sheets (TPP-PPG@ICG) to promote mitochondrial accumulation after cellular internalization. Thereafter, exposure to a single dose of near-infrared irradiation enabled synergistic photodynamic and photothermal therapy, which simultaneously inhibited adenosine triphosphate synthesis and mitochondrial function. Induction of intrinsic apoptosis assisted in surmounting drug resistance and caused tumor cell death. After fluorescence imaging-guided synergistic phototherapy, the mitochondria-targeting, multifunctional graphene-based, drug-delivery system showed highly selective anticancer efficiency in vitro and in vivo, resulting in marked inhibition of tumor progression without noticeable toxicity in mice bearing doxorubicin-resistant MG63 tumor cells. CONCLUSION: The mitochondria-targeting TPP-PPG@ICG nanocomposite constitutes a new class of nanomedicine for fluorescence imaging-guided synergistic phototherapy and shows promise for treating drug-resistant osteosarcoma.

Risk of Dislocation After Total Hip Arthroplasty in Patients with Crowe Type IV Developmental Dysplasia of the Hip.

OBJECTIVE: To investigate whether the risk of dislocation after total hip arthroplasty (THA) in patients with Crowe type IV developmental dysplasia of the hip (DDH) is high and to further identify the risk factors for postoperative dislocation in these patients. METHODS: This retrospective cohort study reviewed Crowe type IV DDH patients undergoing THA between January 2009 and December 2017 in our institution. Each Crowe type IV DDH patient was matched with three Crowe type I, II, or III DDH patients according to gender, side and date of operation. The primary outcome of this study was postoperative dislocation after THA. Occurrence, rate, classification, treatment and outcome of dislocation were documented in detail for all patients. The dislocation rates were compared between Crowe type IV DDH patients and Crowe type I, II, or III DDH patients. Demographic data, implant factors, and surgical factors were compared between the dislocation and no dislocation groups. Multiple logistic regression analysis was used to determine the independent risk factors for dislocation in Crowe type IV hips. RESULTS: A total of 131 Crowe type IV hips were followed up for a mean of 76.5 ± 28.1 months. Three hundred and ninety-three Crowe type I, II and III hips, including 261 type I hips, 94 type II hips, and 38 type III hips, were identified as controls and followed up for a mean of 76.4 ± 28.2 months. No significant difference was observed in follow-up time between two groups (P = 0.804). One or more dislocations occurred in 22 of the 524 dysplasia hips (4.20%). Of the 22 dislocated hips, 20 hips (90.9%) were successfully managed with non-operative treatment. Two patients (9.1%, one Crowe type I and one Crowe type IV) experienced recurrent dislocation and required revision surgery. Crowe type IV hips had a significantly higher postoperative dislocation rate than type I, II, and III hips (11.45% vs 1.78%, P < 0.001). The use of a 22-mm femoral head (odds ratio [OR] = 23.55, 95% confidence interval [CI] = 1.901-291.788, P = 0.014), older age (OR = 1.128, 95% CI = 1.037-1.275, P = 0.031), and absence of false acetabulum (OR = 12.425, 95% CI = 1.982-77.879, P = 0.007) were identified as independent risk factors for dislocation in Crowe type IV hips. CONCLUSIONS: Crowe type IV DDH patients were at a high risk of dislocation after THA, and using large femoral heads and improving abductor muscle strength may help decrease the rate of postoperative dislocation in such patients.

Do patients with diabetes have an increased risk of impaired fracture healing? A systematic review and meta-analysis.

BACKGROUND: The majority of the existing evidence showing an association between diabetes and impaired fracture healing comes from basic scientific research. This systematic review and meta-analysis aimed to summarize the current clinical literature that investigates fracture healing in patients with diabetes. METHODS: The outcome of interest was impaired fracture healing including non-union, delayed union and malunion. Studies that compared fracture healing outcomes between patients with and without diabetes were included in this study. Subgroup analyses regarding different fracture sites, types of fracture and classifications of diabetes were performed. RESULTS: A total of 14 studies involving 695 patients with diabetes and 4937 controls fulfilled the inclusion criteria. Diabetes was associated with an increased risk of impaired fracture healing (odds ratio (OR): 2.11, 95% confidence interval (CI) 1.33-3.37, P = 0.002). Subgroup analyses showed that diabetes was associated with a significantly higher incidence of impaired fracture healing in lower extremity fractures (OR 2.63, 95% CI 1.30-5.30, P = 0.007), short bone fractures (OR 2.64, 95% CI 1.35-5.20, P = 0.005), long bone fractures (OR 2.13, 95% CI 1.23-3.70, P = 0.007) and osteoporosis-unrelated fractures (OR 2.39, 95% CI 1.19-4.80, P = 0.01). Both insulin-dependent diabetes (OR 4.04, 95% CI 1.05-15.56, P = 0.04) and non-insulin-dependent diabetes (OR 5.83, 95% CI 1.73-19.58, P = 0.004) were associated with significantly higher risks of impaired fracture healing. CONCLUSIONS: Patients with diabetes have an increased risk of impaired fracture healing when compared to patients without diabetes. Fracture healing in the lower extremities, short bones and osteoporosis-unrelated fractures is affected more severely by diabetes.

Long-Term Results of Cementless Total Hip Arthroplasty for Patients With High Hip Dislocation After Childhood Pyogenic Infection.

BACKGROUND: The purpose of this study is to analyze the 10-year outcomes of cementless, modular total hip arthroplasty (THA) in adult patients who had high dislocation secondary to childhood pyogenic arthritis. METHODS: We retrospectively followed 56 consecutive patients who underwent cementless, modular THA for the late sequelae of childhood septic arthritis of the hip from 2001 to 2011. There were 23 men and 33 women with a mean age of 47 years (24 to 68). Of the 56 hips, 25 were classified as Crowe type III and 31 as type IV. Mean follow-up was 10.7 years. RESULTS: One hip with a quiescent period of 23 years had recurrence of infection. Revision surgery was performed in 2 patients because of loosening and breakage of femoral stem and new infection with no correlation with childhood sepsis, respectively. The mean Harris hip scores improved from 44.2 points preoperatively to 87.5 points at final follow-up. Similarly, the Hip dysfunction and Osteoarthritis Outcome Score and hip pain also significantly improved at the latest follow-up. The mean acetabular cup abduction was 40.8° and the mean anteversion 27.8°, respectively. There were 5 cases of transient nerve palsy and 5 cases of intraoperative fracture. CONCLUSION: THA can reliably restore the abnormal anatomy and provide good results in these young and active patients who had high hip dislocation secondary to childhood pyogenic arthritis with a relatively high incidence of complications. However, these complications can be treated.

miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis.

Osteoarthritis (OA) is the most common disabling joint disease throughout the world and its therapeutic effect is still not satisfactory in clinic nowadays. Recent studies showed that the exosomes derived from several types of mesenchymal stem cells (MSCs) could maintain chondrocyte homeostasis and ameliorate the pathological severity of OA in animal models, indicating that MSCs-derived exosomes could be a novel promising strategy for treating OA. In this study, we investigated the role and underlying mechanisms of infrapatellar fat pad (IPFP) MSCs-derived exosomes (MSCIPFP-Exos) on OA in vitro and in vivo. Our data revealed that MSCIPFP could produce amounts of MSCIPFP-Exos, which exhibited the typical morphological features of exosomes. The MSCIPFP-Exos ameliorated the OA severity in vivo and inhibited cell apoptosis, enhanced matrix synthesis and reduced the expression of catabolic factor in vitro. Moreover, MSCIPFP-Exos could significantly enhance autophagy level in chondrocytes partially via mTOR inhibition. Exosomal RNA-seq showed that the level of miR-100-5p that could bind to the 3'-untranslated region (3'UTR) of mTOR was the highest among microRNAs. MSCIPFP-Exos decreased the luciferase activity of mTOR 3'UTR, while inhibition of miR-100-5p could reverse the MSCIPFP-Exos-decreased mTOR signaling pathway. Intra-articular injection of antagomir-miR-100-5p dramatically attenuated MSCIPFP-Exos-mediated protective effect on articular cartilage in vivo. In brief, MSCIPFP-derived exosomes protect articular cartilage from damage and ameliorate gait abnormality in OA mice by maintaining cartilage homeostasis, the mechanism of which may be related to miR100-5p-regulated inhibition of mTOR-autophagy pathway. As it is relatively feasible to obtain human IPFP from OA patients by arthroscopic operation in clinic, MSCIPFP-derived exosomes may be a potential therapy for OA in the future.