Background Osteoarthritis (OA), a debilitating joint disorder lacking disease-modifying therapies, involves ferroptosis-an iron-dependent cell death. While ferroptosis contributes to OA progression, its autophagy-dependent mechanisms remain undefined. This study reveals DMT1 (divalent metal transporter 1) as a central regulator of autophagic ferroptosis in OA pathogenesis. Methods OA-related ferroptosis genes were screened by LASSO regression and random forest models. IL-1β/Erastin-stimulated chondrocytes and DMM-induced OA mice were used to investigate DMT1 function. Ferroptosis and autophagy were assessed by lipid peroxidation, autophagic flux, Western blot, and modulators. Micro-CT, OARSI scoring and behavioral tests evaluated joint damage. Regulatory mechanisms were examined by miR-17-5p mimic, luciferase assays and NEDD4-mediated ubiquitination. Results DMT1 was upregulated in OA cartilage and IL-1β-stimulated chondrocytes, correlating with ferroptosis activation. Genetic DMT1 suppression attenuated ferroptosis in vitro and in vivo, whereas overexpression exacerbated lipid peroxidation and impaired cartilage repair post-DMM surgery in mice. Mechanistically, DMT1 overexpression activated autophagy, linking it to ferroptosis execution – pharmacological autophagy inhibition reduced DMT1-driven ferroptosis, while autophagy inducers amplified its effects. Conclusions We identified a DMT1–autophagy–ferroptosis axis as a critical OA mechanism. Ferroptosis inhibitors and upstream regulators (miR-17-5p, NEDD4) show promise as disease-modifying strategies for OA. The translational potential of this article This study not only elucidates a novel DMT1-autophagy-ferroptosis axis but also identifies NEDD4 as upstream therapeutic targets. The demonstration that Lip-1 treatment alleviates DMT1-driven OA exacerbation in vivo highlights translational potential of ferroptosis inhibition as a disease-modifying strategy for OA. Moreover, NEDD4 overexpression represents promising gene-based interventions with potential for precision therapy in OA.
Osteoarthritis (OA) is a cartilage-degenerative joint disease. Mitophagy impacts articular cartilage damage. tRNA-derived small RNAs (tsRNAs) are one of the contents of adipose mesenchymal stem cell (AMSC)-derived exosomes (AMSC-exos) and are involved in disease progression. However, whether tsRNAs regulate mitophagy and whether tsRNA-modified AMSC-exos improve OA via mitophagy remain unclear. We performed small RNA sequencing to identify OA-related tsRNAs, which were then loaded into AMSC-exos, exploring the function and mechanisms related to mitophagy in vitro and in vivo. Overall, 53 differentially expressed tsRNAs (DEtsRNAs) were identified between OA and normal cartilage tissues, among which 42 DEtsRNAs, including tsRNA-12391, were downregulated in the OA group. Target genes of tsRNA-12391 mainly participated in mitophagy-related pathways such as Rap1 signaling pathway. Compared to the control group, tsRNA-12391 mimics significantly promoted mitophagy, as shown by the upregulated expression of PINK1 and LC3 and the co-localization of Mito-Tracker Green and PINK1. Furthermore, tsRNA-12391 mimics effectively enhanced chondrogenesis in chondrocytes, as demonstrated by the elevated expression of collagen II and ACAN. AMSC-exos with tsRNA-12391 overexpression also facilitated mitophagy and chondrogenesis in vitro and in vivo. Mechanistically, tsRNA-12391 bound to ATAD3A restricted ATAD31 from degrading PINK1, leading to PINK1 accumulation. ATAD31 overexpression reversed the effects of tsRNA-12391 mimics on mitophagy and chondrogenesis. AMSC-exos loaded with tsRNA-12391 promoted mitophagy and chondrogenesis by interacting with ATAD31; this may be a novel therapeutic strategy for OA.
Introduction:Osteoarthritis is the most prevalent progressive musculoskeletal disease. It leads to functional impairment and decreased quality of life. However, the current treatments remain unsatisfactory. Recent studies have revealed that exosomes derived from mesenchymal stem cells offer a promising approach to improve the pathological changes in osteoarthritis, cartilage tissue, and chondrocyte homeostasis. Material and methods:In this in vitro and in vivo study, we studied the effects and mechanisms of dental pulp stem cell-derived exosomes (DPSC-exosomes) on osteoarthritis in a mouse model. Results:The study findings showed that a dental pulp stem cell could generate typical characteristic exosomes. The injection of DPSC-exosomes ameliorated destruction of cartilage, promoted matrix synthesis, inhibited cell apoptosis, and decreased the expression of catabolic factors. However, this effect was shown to be almost eliminated when miR-31 antagomir was injected. Conclusions:Furthermore, DPSC-exosomes show an ability to promote autophagy in chondrocytes through mTOR inhibition, in addition to reducing the mTOR luciferase activity. The ability of DPSC-exosomes to partially regulate autophagy was blocked upon inhibition of miR-31. In brief, DPSC-exosomes have a chondroprotective role in a mouse osteoarthritis model. The underlying mechanism is possibly related to miR-31-mediated suppression of the mTOR-autophagy pathway.
Systemic lupus erythematosus (SLE) can adversely affect surgical outcomes, and the impact on revision total knee arthroplasty (TKA) outcomes is unclear. This study aimed to explore the impact of SLE on in-patient outcomes of revision TKA. The Nationwide Inpatient Sample (NIS) database from 2005 to 2018 was searched for patients aged ≥ 18 years old who received revision TKA. Patients with and without SLE were propensity score matched (PSM) at a 1:4 ratio. Associations between SLE and in-hospital outcomes were examined using regression analyses. The study included 133,054 patients, with 794 having SLE. After 1:4 PSM, data of 3,970 patients were analyzed (SLE, 794; non-SLE, 3,176). Multivariate-adjusted analyses revealed that SLE patients had a significantly higher risk of postoperative complications (adjusted odds ratio [aOR] = 1.23, 95
Objectives: Whether the application of MBP plus cannulated screws works for old femoral neck fractures(OFNF) is unknown.The purpose of this study is to present a case series of OFNF in young adults using calcar buttress plate and three cannulated screws with autologous iliac bone grafts.Methods: We conducted a retrospective study of eleven young patients (6 males and 5 females) with femoral neck fractures who were treated with open reduction and internal fixation at a single center between 2013 and 2021. The subjects had trauma-to-surgery intervals longer than 3 weeks and all were fixed with a calcar buttress plate combined with three cannulated screws, which were supplemented by autologous iliac bone grafts.Results: All eleven cases achieved radiological union under the surgery technique, which occurred on average at 4.46±1.29 months after surgery. Complications included femoral neck shortening in all cases, heterotopic ossification in three cases, and osteonecrosis of the femoral head in two cases. One patient with osteonecrosis of the femoral head received total hip arthroplasty. In follow-ups of 24-52 months, the median Harris hip score was 81.64±15.39.Conclusions: The medial buttress plate in combination with three cannulated screws and iliac autograft may be a good choice for treating old femoral neck fractures in young adults.Level of evidence IV, case series.
Osteoarthritis (OA) progression is highly associated with chondrocyte mitochondrial dysfunction and disorders of catabolism and anabolism of the extracellular matrix (ECM) in the articular cartilage. The mitochondrial unfolded protein response (UPRmt), which is an integral component of the mitochondrial quality control (MQC) system, is essential for maintaining chondrocyte homeostasis. We successfully validated the pivotal role of activating transcription factor 5 (ATF5) in upregulating the UPRmt, mitigating IL-1β-induced inflammation and mitochondrial dysfunction, and promoting balanced metabolism in articular cartilage ECM, proving its potential as a promising therapeutic target for OA. Modified mRNAs (modRNAs) have emerged as novel and efficient gene delivery vectors for nucleic acid therapeutic approaches. In this study, we combined Atf5-modRNA (modAtf5) with engineered exosomes derived from bone mesenchymal stem cells (ExmodAtf5) to exert cytoprotective effects on chondrocytes in articular cartilage via Atf5. However, the rapid localized metabolization of ExmodAtf5 limits its application. PLGA-PEG-PLGA (Gel), an injectable thermosensitive hydrogel, was used as a carrier of ExmodAtf5 (Gel@ExmodAtf5) to achieve a sustained release of ExmodAtf5. In vitro and in vivo, the use of Gel@ExmodAtf5 was shown to be a highly effective strategy for OA treatment. The in vivo therapeutic effect of Gel@ExmodAtf5 was evidenced by the preservation of the intact cartilage surface, low OARSI scores, fewer osteophytes, and mild subchondral bone sclerosis and cystic degeneration. Consequently, the combination of ExmodAtf5 and PLGA-PEG-PLGA could significantly enhance the therapeutic efficacy and prolong the exosome release. In addition, the mitochondrial protease ClpP enhanced chondrocyte autophagy by modulating the mTOR/Ulk1 pathway. As a result of our research, Gel@ExmodAtf5 can be considered to be effective at alleviating the progression of OA.
Osteoarthritis (OA) is the most common degenerative disease of the joint with irreversible cartilage damage as the main pathological feature. With the development of regenerative medicine, mesenchymal stem cells (MSCs) have been found to have strong therapeutic potential. However, intraarticular MSCs injection therapy is limited by economic costs and ethics. Exosomes derived from MSC (MSC-Exos), as the important intercellular communication mode of MSCs, contain nucleic acid, proteins, lipids, microRNAs, and other biologically active substances. With excellent editability and specificity, MSC-Exos function as a targeted delivery system for OA treatment, modulating immunity, inhibiting apoptosis, and promoting regeneration. This article reviews the mechanism of action of MSC-Exos in the treatment of osteoarthritis, the current research status of the preparation of MSC-Exos and its application of drug delivery in OA therapy.
Abstract Background The purpose of this study is to investigate the microbial patterns of periprosthetic joint infection (PJI) and fracture-related infection (FRI), and guide for the formulation of more accurate empirical antimicrobial regimens based on the differences in pathogen distribution. Methods A comparative analysis of pathogen distribution was conducted between 153 patients (76 with PJI and 77 with FRI). Predicted analyses against isolated pathogens from two cohorts were conducted to evaluate the best expected efficacy of empirical antimicrobial regimens (imipenem + vancomycin, ciprofloxacin + vancomycin, and piperacillin/tazobactam + vancomycin). Results Our study found significant differences in pathogen distribution between the PJI and FRI cohorts. Staphylococci (61.3% vs. 31.9%, p = 0.001) and Gram-negative bacilli (GNB, 26.7% vs. 56.4%, p < 0.001) were responsible for the majority of infections both in the PJI and FRI cohorts, and their distribution in the two cohorts showed a significant difference (p < 0.001). Multi-drug resistant organisms (MDRO) were more frequently detected in the FRI cohort (29.3% vs. 44.7%, p = 0.041), while methicillin-resistant coagulase-negative Staphylococci (MRCoNS, 26.7% vs. 8.5%, p = 0.002) and Canidia albicans (8.0% vs. 1.1%, p = 0.045) were more frequently detected in the PJI cohort. Enterobacter spp. and Acinetobacter baumannii were detected only in the FRI cohort (11.7% and 8.5%, respectively). Conclusions Staphylococci and GNB were responsible for the majority of infections in both PJI and FRI. Empirical antimicrobial therapy should focus on the coverage of Staphylococci in PJI and GNB in FRI, and infections caused by MDROs should be more vigilant in FRI, while the high incidence of MRCoNS in PJI should be noted, which could guide for the formulation of more accurate empirical antimicrobial regimens. Targeted therapy for FRI caused by A. baumannii and PJI caused by C. albicans needs to be further investigated. Our study reports significant differences in pathogen distribution between the two infections and provides clinical evidence for studies on the mechanism of implant-associated infection.
BACKGROUND:Osteosarcoma (OS) immune environment is complexed and the immune factors-related to OS progression need to be explored. Tumor-associated macrophages (TAMs) are regarded as immune suppressive and tumor-promoting cells. However, the underlying mechanisms through which TAMs function are still fragmentary. Here, we aim to explore the underlying mechanisms by which TAMs regulate OS progression.METHODS:TAMs from OS tissues were isolated by flow cytometry. Exosomes derived from TAMs were separated using ultracentrifugation and western blotting. Transmission electron microscopy (TEM), and flow cytometry were constructed to characterize TAMs-derived exosomes. Additionally, the differential MicroRNAs (miRNAs) and genes were detected through RNA sequencing, and further validated using real-time PCR (RT-PCR). OS cell metastasis ability was assessed using transwell invasion and scratch wound healing assays. MiRNAs mimic and lentiviral vectors were utilized to explore the effects on OS progression.RESULTS:Exosome secreted by TAMs accelerated the OS metastasis. Let-7a level was upregulated in TAMs derived exosomes, which downregulated C15orf41 by targeting 3'-untranslated region (UTR). Furthermore, overexpressing let-7a enhanced invasion and migration by blocking the transcription of C15orf41. In consistent, up-regulating let-7a promoted OS progression and made the prognosis to be worse, which can be reversed by C15orf41 overexpression.CONCLUSION:This study highlighted the critical role of TAMs-derived exosomes in OS progression and explored the potential value of the let-7a/C15orf41 axis as an indicator or target for OS.
Objectives: The purpose of this study is to present a case series of old femoral neck fractures in young adults using calcar buttress plate and three cannulated screws with autologous iliac bone grafts.Methods: We conducted a retrospective study of eleven young patients (6 males and 5 females) with femoral neck fractures who were treated with open reduction and internal fixation at a single center between 2013 and 2021. The subjects had trauma-to-surgery intervals longer than 3 weeks and all were fixed with a calcar buttress plate combined with three cannulated screws, which were supplemented by autologous iliac bone grafts. Results: Our study included eleven patients (6 males and 5 females) with femoral neck fractures who underwent surgery at a median age of 44.27±9.13 years (range 27-55 years). The median time from injury to surgery was 37.64±13.04 days (range 24-62 days). All eleven cases achieved radiological union, which occurred on average at 4.46±1.29 months (range 3-7 months) after surgery. Complications included femoral neck shortening in all cases (0.63±0.35 cm, range 0.3-1.5 cm), heterotopic ossification in three cases, and osteonecrosis of the femoral head in two cases. One patient with osteonecrosis of the femoral head received total hip arthroplasty. In follow-ups of 24-52 months (median, 33.82±7.833 months), the median Harris hip score was 81.64±15.39 (range 48-93).Conclusions: The medial buttress plate in combination with three cannulated screws and iliac autograft offers an optimal way to treat old femoral neck fractures in young adults.
Abstract Background This study was aimed to investigate whether the application of platelet-rich plasma (PRP) combined with β-tri-calcium phosphate (β-TCP) grafts after core decompression (CD) could improve the clinical outcomes of early stage of avascular necrosis of femoral head. Methods Forty-five (54 hips) patients with Ficat-Arlet classification stage I-II treated by CD with β-TCP grafts with or without the application of PRP from July 2015 to October 2020 were reviewed. Group A (CD + β-TCP grafts) included 24 patients (29 hips), while group B (CD + β-TCP grafts + PRP) included 21 patients (25 hips). Visual analogue scale (VAS) score, Harris hip score (HHS), change in modified Kerboul angle and the hip joint survival were evaluated and compared between the groups. Patients had a mean follow-up period of 62.1 ± 17.2 months and 59.3 ± 14.8 months in group A and group B, respectively. Results The mean VAS scores in group A was significantly higher than group B at the 6 months (2.9 ± 0.7 vs 1.9 ± 0.6, p < 0.01) and final follow up postoperative (2.8 ± 1.2 vs 2.2 ± 0.7, p = 0.04). The mean HHS in group A was significantly lower than group B at the 6 months (80.5 ± 13.8 vs 89.8 ± 12.8, p = 0.02). However, at the final follow up, there is no significant difference between the groups (77.0 ± 12.4 vs 83.1 ± 9.3, p = 0.07). The mean change in modified Kerboul angle was -7.4 ± 10.6 in group A and -19.9 ± 13.9 in group B which is statistically significant (p < 0.01). Survivorship from total hip arthroplasty were 86.2%/84% (p = 0.86) at the final follow up, which was not statistically significant. No serious complications were found in both groups. Conclusions A single dose of PRP combined with CD and β-TCP grafts provided significant pain relief, better functional outcomes, and delayed progression in the short term compared to CD combined with β-TCP grafts. However, the prognosis of the femoral head did not improve significantly in the long term. In the future, designing new implants to achieve multiple PRP injections may improve the hip preservation rate.
Objective We sought to correlate various spinopelvic and lower limb alignments, and to examine the current spinopelvic theories on a Chinese cohort. Methods We retrospectively reviewed 166 patients undergoing THA. Among them, 138 patients with unilateral THA met the inclusion criteria. Sagittal alignments and cup orientations were measured on standing and sitting lateral EOS images. Patients were categorized into two groups with a scoring system for lumbar spine degeneration. Patients’ demographics including age, sex, lumbar spine degeneration and radiographic measurements were studied. Results PT, SS, LL and TK differed significantly between standing and sitting within each group except for TK in degenerative group (32.8 ± 13.9 vs. 32.9 ± 14.2, p = 0.905). Compared with degenerative spine group, non-degenerative spine patients have great pelvic mobility (ΔPT, -24.4 ± 12.5° vs. -17.6 ± 10.7, p = 0.0008), greater lumbar mobility (ΔLL, -34.8 ± 15.2 vs. -21.7 ± 12.2, p = < 0.0001) and compensatory cup orientation changes (ΔRA, -15.5 ± 11.1 vs. -12.0 ± 8.4, p = 0.00920; ΔRI, -10.8 ± 11.5 vs. -5.6 ± 7.5, p = 0.0055). Standing PT and ankle dorsiflexion angle correlated positively (R 2 = 0.236, p = 0.005). Conclusion THA patients in this cohort showed a spinopelvic motion paradigm similar to that from previous studies on Caucasians. Ankle dorsiflexion indicate greater posterior pelvic tilt on standing. Surgeons should beware of risks of instability in patients with lower limb compensations. Advances in knowledge This study provides new insights into the clinical relevance of lower limb alignments to spinopelvic motion after THA in a relatively young Chinese population.
Abstract Background Osteoarthritis (OA) is a common chronic arthritis disease characterized by cartilage degeneration, sub-cartilage bone hyperplasia, osteophyte formation and joint space stenosis. Traditionally, OA treatment consists of pain management with joint replacement for end-stage disease. Patients diagnosed with OA have developed irreversible organic changes, so the focus should be shifted to prevention, early diagnosis and intervention of OA.Methods The differentially expressed genes (DEGs) were identified from the gene expression profile GSE48556 from the GEO database, and functional enrichment analyses were performed. Boruta algorithm and the least absolute shrinkage and selection operator (LASSO) analysis were used to select hub genes, then we used the LightGBM to evaluate the accuracy of hub genes prediction for OA. The CIBERSORT algorithm was used to analyze the immune infiltration of peripheral blood mononuclear cells (PBMCs) between OA and normal controls.Results A total of 35 DEGs including 29 downregulated genes and 6 upregulated genes were mainly involved in response to tumor necrosis factor (TNF) and TNF-mediated signaling pathway through GO analysis and were mainly enriched in cAMP signaling pathway, NF-κB signaling pathway through KEGG. The LightGBM prediction of the hub gene model showed that area under curve (AUC) of ROC curve and PR curve reached 0.988 and 0.996 respectively in verification set, indicating that hub genes have a high diagnostic accuracy for OA. Gene ADRB2 was the only up-regulated gene in OA group. H3F3B showed the largest AUC which means a high diagnostic power of OA. From the immune infiltration analysis, the content of CD8+ T cells and resting mast cells showed significant differences between the two groups and hub genes were closely related to immune cells.Conclusion The hub genes in PBMCs between OA and normal controls may potentially serve as biomarkers in both prevention and diagnosis of OA and indicate for the exploration of the mechanism of OA.
Purpose The study is aimed at investigating the association between different reduction classifications (anatomic reduction, positive buttress position reduction, and negative buttress position reduction) and two end points (complications and reoperations). Methods The study retrospectively analyzed 110 patients undergoing internal fixation with three parallel cannulated screws from January 2012 to January 2019 in Huashan Hospital. Based on the principles of the “Gotfried reduction,” all enrolled patients were divided into three groups: anatomic reduction, positive buttress position reduction, and negative buttress position reduction intraoperatively or immediately after surgery. Clinical characteristics including age, sex, side, Garden classification, Pauwels classification, fracture level, reduction classification, Garden alignment index angles, cortical thickness index (CTI), tip-caput distance (TCD), angle of the inferior screw, and the two ending points (complications and reoperations) were included in the statistical analysis. The Mann-Whitney U-test, the chi-square test, Fisher's exact test, and multiple logistic regression analysis were used in the study. Results Of the 110 patients included in our study, the mean ± standard deviation (SD) of age was 51.4 ± 10.4 years; 41 patients showed anatomic reduction, 35 patients showed positive buttress position reduction, and 34 patients showed negative buttress position reduction. For the outcomes, 24 patients (anatomic reduction: 6 [14.6%]; positive buttress position reduction: 5 [14.3%]; negative buttress position reduction: 13 [38.2%]) had complications, while 18 patients (anatomic reduction: 5 [12.2%]; positive buttress position reduction: 3 [8.6%]; negative buttress position reduction: 10 [29.4%]) underwent reoperations after surgery. In the multivariate logistic regression analysis of complications, negative buttress position reduction (negative buttress position reduction vs. anatomic reduction, OR = 4.309, 95%CI = 1.137 to 16.322, and p = 0.032) was found to be correlated with higher risk of complications. The same variable (negative buttress position reduction vs. anatomic reduction, OR = 5.744, 95%CI = 1.177 to 28.042, and p = 0.031) was also identified as risk factor in the multivariate logistic regression analysis of reoperations. However, no significant difference between positive reduction and anatomical reduction was investigated in the analysis of risk factors for complications, not reoperations. Conclusion Positive buttress position reduction of femoral neck fractures in young patients showed a similar incidence of complications and reoperations compared with those of anatomic reduction. For irreversible femoral neck fractures, if positive buttress position reduction has been achieved intraoperatively, it is not necessary to pursue anatomical reduction; however, negative reduction needs to be avoided.
Purpose The aim of this study is to investigate the prognostic value of tibial component coverage (over-hang and under-hang) and the alignment of total knee arthroplasty (TKA) components 1 week after surgery. We select patient-reported outcome measures (PROMS) (the Knee Society score (KSS score) and the Western Ontario and McMaster Universities Osteoarthritis Index-pain score (WOMAC pain score)) and tibial bone resorption (TBR) 2 years after surgery as the end points. Methods The study retrospectively analyzed 109 patients undergoing TKA (fixed-bearing prosthesis with asymmetrical tibial tray) from January 2014 to December 2017 in Huashan Hospital. By using standard long-leg X-rays, anteroposterior (AP) and lateral X-rays of the knee, tibial component coverage (under-hang or over-hang), AP tibial-femoral anatomical angle (AP-TFA), AP femoral angle (AP-FA), AP tibial angle (AP-TA), and lateral tibial angle (L-TA) were measured at 1 week after surgery, while TBR was measured through postoperative 1-week and 2-year AP and lateral radiographs of the knee on three sides (medial side, lateral side on AP radiograph, and anterior side on lateral radiograph). The Pearson correlation analysis, simple linear regression, multiple linear regression, the Student’s t test, and one-way ANOVA together with Tukey’s post hoc test (or Games-Howell post hoc test) were used in the analyses. Results Tibial under-hang was more likely to appear in our patients following TKA (42%, medially, 39%, laterally, and 25%, anteriorly). In multivariate linear regression analysis of TBR, tibial under-hang (negative value) 1 week after surgery was positively correlated with TBR 2 years later on the medial ( p = 0.003) and lateral ( p = 0.026) side. Tibial over-hang (positive value) 1 week after surgery on the medial side was found negatively related with KSS score ( p = 0.004) and positively related with WOMAC pain score ( p = 0.036) 2 years later in multivariate linear regression analysis of PROMS. Both scores were better in the anatomically sized group than in the mild over-hang group (or severe over-hang) ( p < 0.001). However, no significant relationship was found between the alignment of TKA components at 1 week after surgery and the end points (TBR and PROMS) 2 years later. Conclusion Under-hang of the tibial component on both the medial and lateral sides can increase the risk of TBR 2 years later. Over-hang of tibial component on the medial side decreases the PROMS (KSS score and WOMAC pain score) 2 years later. An appropriate size of tibial component during TKA is extremely important for patient’s prognosis, while the alignment of components might not be as important.
Background Postoperative delirium (PD), as an acute brain failure, is widely reported as a very common postoperative complication, and it is closely associated with increased morbidity and mortality. Recently, malnutrition is reported as one of the risk factors for PD. The prognostic nutritional index (PNI) is a simple method for nutritional evaluation. However, few studies have discussed the effectiveness of PNI as a nutritional assessment in predicting PD after primary total joint arthroplasty (TJA). The aim of this study is to investigate potential risk factors including PNI for PD following primary TJA. Methods A retrospective analysis of 994 patients was performed to identify risk factors associated with PD after primary TJA by using univariate and multivariate analyses. A receiver operating characteristic curve and the area under the curve were applied to evaluate the significant results of the multivariate analysis and the optimal cutoff value (CV). Results Postoperatively, sixty-seven patients (67/994, 6.7 %) experienced PD. Univariate analysis demonstrated that operative time, duration of anesthesia, age, hypertension, serum albumin, and PNI differed between the PD and non-PD groups ( P < 0.05). Multivariate logistic regression analysis showed that the preoperative PNI (odds ratio [OR]: 0.908; 95 % confidence interval [CI]: 0.840–0.983; CV: 47.05), age of patients (OR: 1.055; 95 % CI: 1.024–1.087; CV: 73.5 years), and hypertension (OR: 1.798; 95 % CI: 1.047–3.086), were independently associated with PD ( P < 0.05). Conclusions A low preoperative PNI associated with malnutrition was demonstrated to be an independent risk factor for PD following primary TJA. Patients with preoperative low PNI should be cautioned and provided with adequate nutritional intervention to reduce postoperative PD.
Objective:To explore the clinical characteristics of artificial femoral head replacement with SuperPATH approach under the enhanced recovery after surgery (ERAS) concept for the treatment of femoral neck fractures in the elderly, and analyze the clinical benefits and medical risks of this model.Methods:A prospective data collection of 80 elderly patients with femoral neck fractures treated with artificial femoral head replacement via SuperPATH approach, including 40 cases of ERAS and 40 conventional rehabilitation cases were collected, and the gender, age, preoperative score, comorbidities, hemoglobin level, blood loss, blood transfusion rate, complication rate, length of hospital stay, Harris score, independent walking ability and EQ-5D score of the two groups were compared.Results:All the 80 patients were followed up completely, and the follow-up rate was 100%. The follow-up time ranged from 3 to 36 months, with an average of (15±7) months. The follow-up time of ERAS group ranged from 3 to 31 months, with an average of (14±7) months. The follow-up time of the conventional rehabilitation group was from 3 to 34 months, with an average of (16±7) months. The ages of the patients in the ERAS group and the conventional rehabilitation group were 81±5 years and 81±4 years, respectively. The patients in the two groups with medical complications were 95% and 97.5%, respectively. There were no significant differences between the two groups in indicators such as gender, age, comorbidities, ASA classification, preoperative walking ability and cognitive status (P>0.05). The intraoperative blood loss, total blood loss, allogeneic blood transfusion rate, postoperative complications and hospital stay in the ERAS group were significantly reduced compared with the conventional group (P<0.05). The incidence of postoperative complications in the ERAS group and the conventional rehabilitation group were 25.0% and 47.5, respectively, and the hospital stay in both groups was more than 10 days. There was no significant difference in Harris score, independent walking ability and 2-year overall survival rate (Kaplan-Meier curve) between the two groups at 12 months after surgery (P>0.05).Conclusion:Under the ERAS concept, SuperPATH artificial femoral head replacement can speed up recovery, but the perioperative complication rate is still high, and the hospital stay is longer. The treatment of elderly femoral neck fractures with more comorbidities needs to emphasize the patient-centered approach and focus on individualized treatment of all aspects of ERAS, so as to increase the speed and to ensure the quality.
Articular cartilage injuries are common orthopedic conditions that severely affect the quality of life of patients. Tissue engineering can facilitate cartilage repair and the key points involve scaffolding and seed cell selection. Pre-experiments found a range of microstructures of bioceramic scaffolds suitable for chondrocyte adhesion and proliferation, and maintaining chondrocyte phenotype. Three-dimensional cultures of bone marrow mesenchymal stem cell (BMSC) scaffolds were implanted into mice. According to the shape of the bioceramic scaffolds and the implantation time in vivo, RNA sequencing was performed on the removed scaffolds to explore the molecular mechanism. The in vitro bone plate culture can induce differentiation of chondrocytes, making culture different to that produced in vitro. Implantation of scaffolds in vivo increases the expression of bone-related genes. The ceramic rod-like material was found to be superior to the disc shape, and the bone repair effect was more marked with longer implantation times. Gene Ontology analysis revealed that 'cell chemotaxis', 'negative regulation of ossification' and 'bone development' pathways were involved in recovery. It was further confirmed that BMSCs were suitable as seed cells for cartilage tissue engineering, and that the beta -tricalcium phosphate scaffold maybe ideal as cartilage tissue engineering scaffold material. The present research provided new insights into the molecular mechanism of cartilage repair by BMSCs and bioceramic scaffolds. Bioinformatics analysis revealed that AMMECR1L-like protein, tumor necrosis factor-induced protein 2, inhibitor of nuclear factor-B kinase subunit and protein kinase C type and 'negative regulation of ossification' and 'bone development' pathways may be involved in osteoblast maturation and bone regeneration.
目的 旨在开发预后列线图来预测四肢骨肉瘤患者的生存率.方法 回顾分析1995年至2014年,1910例四肢骨肉瘤患者(来自SEER数据库),通过单因素Log-rank分析和多因素COX分析找出存在统计学差异的预后因素,使用相应的预后因素构建列线图,进而对患者1、3、5年的总生存期(overall survival,OS)和癌症特异性生存期(cancer-specific survival,CSS)进行预测.然后对列线图进行内外部验证,并且通过使用C指数为量化指标来计算模型的准确性.结果 单因素和多因素分析显示肿瘤确诊年龄、分期、手术状态、大小和病理类型与患者的OS和CSS显著相关.基于这些预后指标,构建能够预测患者的1、3、5年OS和CSS的列线图.对该列线图进行内外部验证,发现该列线图均具有较好的C指数,其中在内部验证中,OS为0.721,CSS为0.712;外部验证中,OS为0.681,CSS为0.683.在内外部验证中,列线图的校准图显示了骨肉瘤患者的实际存活率和该列线图预测结果 之间有着良好的一致性.结论 骨肉瘤确诊年龄、分期、手术状态、大小和病理类型与患者的OS和CSS显著相关.四肢骨肿瘤患者OS和CSS的列线图,可较为准确地估计四肢骨肉瘤患者1、3、5年的OS和CSS,进而帮助临床医生更快、更可靠的做出临床预测.
Abstract Background Several studies have been conducted to report diagnostic values of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in the many diseases, such as oncological, inflammatory, and some infectious diseases. However, the predictive value of these laboratory parameters for early periprosthetic joint infections (PJIs) has not yet been reported. The aim of this study was to determine predictive values of the postoperative NLR, PLR, and LMR for the diagnosis of PJIs. Methods In this retrospective study, 104 patients (26 early PJI cases and 78 non-PJI cases) who underwent total joint arthroplasty were enrolled in this study. All the patients were then categorized into two groups: PJI group, patients with the diagnosis of PJI (26 patients; 14 males, 12 females; mean age = 65.47 ± 10.23 age range = 51–81 ) and non-PJI group, patients without PJI (78 patients; 40 males, 38 females; mean age = 62.15 ± 9.33, age range = 41–92). We defined “suspected time” as the time that any abnormal symptoms or signs occurred, including fever, local swelling, or redness around the surgical site between 2 and 4 weeks after surgery and before the diagnosis. Suspected time and laboratory parameters, including NLR, PLR, LMR, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), were compared between both groups. The trends of postoperative NLR, LMR, PLR, CRP, and ESR were also reviewed. The predictive ability of these parameters at the suspected time for early PJI was evaluated by multivariate analysis and receiver operating characteristic (ROC) curve analysis. Results NLR, PLR, and LMR returned to preoperative levels within 2 weeks after surgery in the two groups. In the PJI group, NLR and PLR were significantly increased during the incubation period of infection or infection, and LMR was significantly reduced, although 61.5% (16/26) of the patients had normal white blood cells. Interestingly, ESR and CRP were still relatively high 2 weeks after surgery and were not different between the two groups before infection started (p = 0.12 and 0.4, respectively). NLR and PLR were significantly correlated with early PJI (Odds ratios for NLR and PLR = 88.36 and 1.12, respectively; p values for NLR and PLR = 0.005 and 0.01, respectively). NLR had great predictive ability for the diagnosis of early PJI, with a cut-off value of 2.77 (sensitivity = 84.6%, specificity = 89.7%, 95% CI = 0.86–0.97). Conclusions ESR and CRP seem not to be sensitive for the diagnosis of early PJI due to their persistently high levels after arthroplasty. The postoperative NLR at the suspected time may have a great ability to predict early PJI.