The Long-term Efficacy of Total Knee Arthroplasty on End-stage Kashin-Beck Disease of the Knee in Highland Tibetan Areas Patients: A Retrospective Study with 10-Year Follow-up.

OBJECTIVE: Despite the established success of total knee arthroplasty (TKA) with end-stage osteoarthritis, there is a notable scarcity of research on its long-term outcomes in individuals suffering from end-stage Kashin-Beck disease (KBD). This retrospective study aimed to assess the long-term outcomes and effectiveness of clinical function, quality of life, and complications of TKA and end-stage KBD patients in Tibetan highland areas. METHODS: The retrospective cohort included 43 KBD patients, comprising a total of 59 knees, who had undergone TKA at West China Hospital, Sichuan University between 2008 and 2021. Patients were subsequently followed up for a minimum of 3 years, and received rigorous radiological and clinical assessments at 3, 6, and 12 months post surgery, followed by annual examinations thereafter. The evaluation included various efficacy indices, including visual analogue scale (VAS) scores, hospital for special surgery (HSS) scores, functional score for adult Tibetans with Kashin-Beck disease (FSAT-KBD), and radiographic findings. Comparison of indicators within the same group was conducted using one-way repeated-measures analysis of variance or paired sample t-tests, whereas between-group differences were compared using an independent t-test. RESULTS: Throughout the average follow-up duration of 10.8 years, patients experienced a substantial reduction in knee pain and noteworthy functional improvement. The VAS scores decreased significantly from 77.47 ± 4.12 mm before surgery to 10.91 ± 1.97 mm after surgery, indicating considerable alleviation of knee pain. The HSS scores improved markedly, increasing from 44.26 ± 4.95 preoperatively to 91.26 ± 4.37, indicating enhanced joint function. Similarly, the FSAT-KBD exhibited positive progression, increasing from 25.90 ± 3.12 to 36.95 ± 3.54. Importantly, at the last follow-up, none of the patients presented with periprosthetic infection, prosthesis loosening, or periprosthetic fracture. CONCLUSION: At long-term follow-up, compared with patients in the preoperative period, patients in Tibetan highland areas with KBD of the knee who underwent TKA benefited from a significant reduction in pain, improvement in joint function, and satisfactory improvement in quality of life.

M2 macrophage-derived exosome-functionalized topological scaffolds regulate the foreign body response and the coupling of angio/osteoclasto/osteogenesis.

Designing scaffolds that can regulate the innate immune response and promote vascularized bone regeneration holds promise for bone tissue engineering. Herein, electrospun scaffolds that combined physical and biological cues were fabricated by anchoring reparative M2 macrophage-derived exosomes onto topological pore structured nanofibrous scaffolds. The topological pore structure of the fiber and the immobilization of exosomes increased the nanoscale roughness and hydrophilicity of the fibrous scaffold. In vitro cell experiments showed that exosomes could be internalized by target cells to promote cell migration, tube formation, osteogenic differentiation, and anti-inflammatory macrophage polarization. The activation of fibrosis, angiogenesis, and macrophage was elucidated during the exosome-functionalized fibrous scaffold-mediated foreign body response (FBR) in subcutaneous implantation in mice. The exosome-functionalized nanofibrous scaffolds also enhanced vascularized bone formation in a critical-sized rat cranial bone defect model. Importantly, histological analysis revealed that the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation. This study elaborated on the complex processes within the cell microenvironment niche during fibrous scaffold-mediated FBR and vascularized bone regeneration to guide the design of implants or devices used in orthopedics and maxillofacial surgery. STATEMENT OF SIGNIFICANCE: How to design scaffold materials that can regulate the local immune niche and truly achieve functional vascularized bone regeneration still remain an open question. Here, combining physical and biological cues, we proposed new insight to cell-free and growth factor-free therapy, anchoring reparative M2 macrophage-derived exosomes onto topological pore structured nanofibrous scaffolds. The exosomes functionalized-scaffold system mitigated foreign body response, including excessive fibrosis, tumor-like vascularization, and macrophage activation. Importantly, the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation.

Decoding the "Fingerprint" of Implant Materials: Insights into the Foreign Body Reaction.

Foreign body reaction (FBR) is a prevalent yet often overlooked pathological phenomenon, particularly within the field of biomedical implantation. The presence of FBR poses a heavy burden on both the medical and socioeconomic systems. This review seeks to elucidate the protein "fingerprint" of implant materials, which is generated by the physiochemical properties of the implant materials themselves. In this review, the activity of macrophages, the formation of foreign body giant cells (FBGCs), and the development of fibrosis capsules in the context of FBR are introduced. Additionally, the relationship between various implant materials and FBR is elucidated in detail, as is an overview of the existing approaches and technologies employed to alleviate FBR. Finally, the significance of implant components (metallic materials and non-metallic materials), surface CHEMISTRY (charge and wettability), and physical characteristics (topography, roughness, and stiffness) in establishing the protein "fingerprint" of implant materials is also well documented. In conclusion, this review aims to emphasize the importance of FBR on implant materials and provides the current perspectives and approaches in developing implant materials with anti-FBR properties.

Pharmacological use of gamma-aminobutyric acid derivatives in osteoarthritis pain management: a systematic review.

BACKGROUND: Pain is the major complication of osteoarthritis (OA) patients and is a decisive symptom for medical intervention. Gamma-aminobutyric acid (GABA) derivatives are optional painkillers but not widely used in pain management of OA patients. We synthesized the efficacy and safety of GABA derivatives for OA pain management. METHODS: We searched Medline, Cochrane CENTRAL, Embase, and ClinicalTrals.gov from inception to 13 October 2021 and included randomized controlled trials (RCTs) comparing the efficacy and safety of GABA derivatives with placebo or standard control in OA pain management. Two independent reviewers extracted data and assessed these studies for risk of bias using Cochrane Collaboration's tool for RCT. RESULTS: In total, three eligible RCTs (n = 3) meeting the eligibility criteria were included. Among these RCTs, one focused on hand OA pain management, while two RCTs focused on knee OA. In hand OA, pregabalin reduced numerical rating scale (NRS) score and the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain score significantly compared with placebo, and caused 55 AEs. In knee OA, pregabalin reduced visual analogue scale (VAS) score and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score significantly with no recorded adverse event (AE). Meanwhile, in knee OA, gabapentin reduced both VAS score and WOMAC pain score compared with acetaminophen and caused 9 AEs. CONCLUSIONS: GABA derivatives seem to be effective and safe in OA pain management. However, future researches with large sample size are needed to further prove the efficacy of GABA derivatives in OA pain control. TRIAL REGISTRATION: CRD42021240225.

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.

Does systemic lupus erythematosus increase the risk of complications from total hip arthroplasty?

BACKGROUND: Patients with systemic lupus erythematosus are more likely to receive THA than the general population. However, it is controversial whether SLE increases the risk of complications from THA. The purpose of this retrospective study was to reassess the risks from THA in patients with SLE under the management model of enhanced recovery after surgery. METHODS: Patients with systemic lupus erythematosus diagnosed from December 2011 to December 2017 and treated with THA were compared with THA patients with osteoarthritis. The data were extracted from the medical record system of our department. The chi-square test and t-test were used for comparison. RESULTS: The postoperative blood loss in patients with SLE was significantly higher than that in the control group, and the postoperative hemoglobin (Hb) and hematocrit (Hct) in the control group were lower than those in the control group (P < 0.05). There was no significant difference in the rate of blood transfusion (9.733 vs 8.133 P = 0.3148) or other complications between the two groups (P > 0.05). CONCLUSION: Well-controlled and well-managed SLE will not increase the risk of complications in THA, but can increase the amount of perioperative blood loss. Therefore, perioperative blood management is still essential in SLE patients.