Glutathione determines chronic myeloid leukemia vulnerability to an inhibitor of CMPK and TMPK.

Bcr-Abl transformation leads to chronic myeloid leukemia (CML). The acquirement of T315I mutation causes tyrosine kinase inhibitors (TKI) resistance. This study develops a compound, JMF4073, inhibiting thymidylate (TMP) and cytidylate (CMP) kinases, aiming for a new therapy against TKI-resistant CML. In vitro and in vivo treatment of JMF4073 eliminates WT-Bcr-Abl-32D CML cells. However, T315I-Bcr-Abl-32D cells are less vulnerable to JMF4073. Evidence is presented that ATF4-mediated upregulation of GSH causes T315I-Bcr-Abl-32D cells to be less sensitive to JMF4073. Reducing GSH biosynthesis generates replication stress in T315I-Bcr-Abl-32D cells that require dTTP/dCTP synthesis for survival, thus enabling JMF4073 susceptibility. It further shows that the levels of ATF4 and GSH in several human CML blast-crisis cell lines are inversely correlated with JMF4073 sensitivity, and the combinatory treatment of JMF4073 with GSH reducing agent leads to synthetic lethality in these CML blast-crisis lines. Altogether, the investigation indicates an alternative option in CML therapy.

NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia.

NME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on the mitochondrial outer membrane (MOM). Here, we report a role of NME3 in hypoxia-induced mitophagy dependent on its active site phosphohistidine but not the NDPK function. Mice carrying a knock-in mutation in the Nme3 gene disrupting NME3 active site histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities in cerebellar function. Our mechanistic analysis reveals that hypoxia-induced phosphatidic acid (PA) on mitochondria is essential for mitophagy and the interaction of DRP1 with NME3. The PA binding function of MOM-localized NME3 is required for hypoxia-induced mitophagy. Further investigation demonstrates that the interaction with active NME3 prevents DRP1 susceptibility to MUL1-mediated ubiquitination, thereby allowing a sufficient amount of active DRP1 to mediate mitophagy. Furthermore, MUL1 overexpression suppresses hypoxia-induced mitophagy, which is reversed by co-expression of ubiquitin-resistant DRP1 mutant or histidine phosphorylatable NME3. Thus, the site-specific interaction with active NME3 provides DRP1 a microenvironment for stabilization to proceed the segregation process in mitophagy.

The Combination of Anti-CD47 Antibody with CTLA4 Blockade Enhances Anti-Tumor Immunity in Non-Small Cell Lung Cancer via Normalization of Tumor Vasculature and Reprogramming of the Immune Microenvironment.

In solid tumors, the formidable anti-tumor impact resulting from blocking the "don't eat me" signal, arising from CD47-SIRPα interaction, is constrained, especially compared to its efficacy in hematopoietic malignancies. Activating macrophage anti-tumor activity not only necessitates the inhibition of the "don't eat me" signal, but also the activation of the "eat me" (pre-phagocyte) signal. Intriguingly, the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody (Ab) has been identified to stimulate Fc receptor-mediated active phagocytes in the tumor microenvironment, thereby generating "eat me" signals. This study postulates that concurrently targeting CD47 and CTLA4 could intensify the anti-tumor effects by simultaneously blocking the "don't eat me" signal while triggering the "eat me" signal. The experimental data from this investigation confirm that the combined targeting of CD47 and CTLA4 enhances immunity against solid tumors in LLC cell-transplanted tumor-bearing mice. This effect is achieved by reducing myeloid-derived suppressor cell infiltration while increasing the presence of effector memory CD8+ T cells, NK1.1+ CD8+ T cells, and activated natural killer T cells. Meanwhile, combination therapy also alleviated anemia. Mechanistically, the anti-CD47 Ab is shown to upregulate CTLA4 levels in NSCLC cells by regulating Foxp1. Furthermore, targeting CD47 is demonstrated to promote tumor vascular normalization through the heightened infiltration of CD4+ T cells. These findings suggest that the dual targeting of CD47 and CTLA4 exerts anti-tumor effects by orchestrating the "eat me" and "don't eat me" signals, reshaping the immune microenvironment, and fostering tumor vascular normalization. This combined therapeutic approach emerges as a potent strategy for effectively treating solid tumors.

TRPV1+ neurons alter Staphylococcus aureus skin infection outcomes by affecting macrophage polarization and neutrophil recruitment.

BACKGROUND: The interaction between the nervous system and the immune system can affect the outcome of a bacterial infection. Staphylococcus aureus skin infection is a common infectious disease, and elucidating the relationship between the nervous system and immune system may help to improve treatment strategies. RESULTS: In this study, we found that the local release of calcitonin gene-related peptide (CGRP) increased during S. aureus skin infection, and S. aureus could promote the release of CGRP from transient receptor potential cation channel subfamily V member 1 (TRPV1+) neurons in vitro. The existence of TRPV1+ neurons inhibited the recruitment of neutrophils to the infected region and regulated the polarization of macrophages toward M2 while inhibiting polarization toward M1. This reduces the level of inflammation in the infected area, which aggravates the local infection. Furthermore, this study demonstrates that TRPV1 may be a target for the treatment of S. aureus skin infections and that botulinum neurotoxin A (BoNT/A) and BIBN4096 may reverse the inhibited inflammatory effect of CGRP, making them potential therapeutics for the treatment of skin infection in S. aureus. CONCLUSIONS: In S. aureus skin infection, TRPV1+ neurons inhibit neutrophil recruitment and regulate macrophage polarization by releasing CGRP. BoNT/A and BIBN4096 may be potential therapeutic agents for S. aureus skin infection.

The Outcome of under 10 mm Single-Incision Surgery Using a Non-Specialized Volar Plate in Distal Radius Fractures: A Retrospective Comparative Study.

BACKGROUND: The distal radius fracture is a common orthopedic injury. We aimed to share the surgical steps and investigate the outcomes of treating distal radius fractures with wounds ≤10 mm using a globally accessible locking plate. METHODS: We collected 46 patients who underwent surgery via a <10 mm wound, with a control group consisting of 40 patients who underwent conventional procedures. Both groups were treated using the same volar plate. We compared the radiographic reduction quality, including volar tilt angle, radial inclination angle, and ulna variance. Additionally, clinical outcomes, such as pain assessed using VAS, Q-Dash score, and PRWE, were evaluated. Patient satisfaction with the wound was also analyzed. The follow-up time for the clinical outcomes was 24.2 ± 13.47 months. RESULTS: There were no differences in the quality of reduction in parameters such as the volar tilt angle (p = 0.762), radial inclination angle (p = 0.986), and ulna variance (p = 0.166). Both groups exhibited comparable results in pain VAS (p = 0.684), Q-Dash score (p = 0.08), and PRWE (p = 0.134). The ≤10 mm incision group displayed an increase in satisfaction with the wound (p < 0.001). CONCLUSIONS: Treating distal radius fractures with a <10 mm wound using a non-specialized locking plate is a feasible approach. It does not compromise the quality of fracture reduction or functional scores and improves wound satisfaction.

Prevalence of osteoporosis in patients awaiting unicompartmental knee arthroplasty: a cross-sectional study.

Objectives: Osteoporosis may contribute to failure of unicompartmental knee arthroplasty (UKA), yet the prevalence of osteoporosis in the population awaiting UKA has not been adequately studied. The objectives of this study were to report the prevalence of osteoporosis in people awaiting UKA and the rate of anti-osteoporosis treatment, and to explore factors associated with osteoporosis prevalence in people awaiting UKA. Methods: Participants awaiting UKA from January 2019 to May 2023 were consecutively enrolled. Participants ' age, gender, BMI, knee K-L score, VAS score, history of previous DXA testing, history of anti-osteoporosis treatment, and possible underlying risk factors were recorded. All participants were given a dual-energy x-ray absorptiometry (DXA) test after the visit. The diagnosis of osteoporosis was made according to the World Health Organization criteria. Compare the prevalence of osteoporosis between people waiting for UKA and the general population. Risk factors associated with osteoporosis were analyzed using multiple linear regression and binary logistic regression models. Results: A total of 340 participants were included in the study, 259 in female and 81 in male, with a mean age of 63.53 years (range: 41-84 years), and all participants completed UKA and had DXA prior to UKA. The prevalence of osteoporosis was 40.88% (44.79% in female and 28.40% in male). The prevalence of osteoporosis was higher in female than in male (p<0.001). The prevalence of osteoporosis in the population waiting for UKA was significantly higher than that in the general population (p < 0.001). DXA testing was performed in 12.06% within 1 year prior to the visit. The percentage of those who had received anti-osteoporosis treatment was 20.59% (20.86% in osteoporosis, 22.39% in Osteopenia and 16.42% in normal bone mass). The correlation between age, gender, body mass index, visual analogue scale score and osteoporosis was statistically significant. Conclusion: Osteoporosis is common in people waiting for UKA, but screening and treatment rates are low. Female patients of advanced age and low weight combined with significant pain should be considered for osteoporosis screening and appropriate treatment before UKA.

Multiplex PCR-based next generation sequencing as a novel, targeted and accurate molecular approach for periprosthetic joint infection diagnosis.

Objectives: Periprosthetic joint infection (PJI) diagnosis remains challenging, and the identification of the causative microorganism is, by far, the most important aspect. Here, we use multiple PCR-based targeted next-generation sequencing (tNGS) to detect pathogens in PJI. To explore 1. the ability of targeted next-generation sequencing (tNGS) to detect pathogens in PJI; 2. the consistency of tNGS, metagenomic NGS (mNGS), and culture results; and 3. the ability of tNGS to detect drug resistance genes in PJI. Methods: PJI was diagnosed according to the Musculoskeletal Infection Society (MSIS) criteria. The microorganisms were detected by culture, mNGS and tNGS to compare the diagnostic effectiveness of the three methods for PJI and to compare their consistency in detecting microorganisms. Drug resistance genes were detected using tNGS. The costs and turnaround times of mNGS and tNGS were compared. Results: Forty-three patients with PJI, 21 patients without PJI and 10 negative control cases were included. The culture, tNGS, and mNGS sensitivities for PJI diagnosis were 74.41%, 88.37%, and 93.02%, respectively, with no significant differences. The specificities were 90.48%, 95.24%, and 95.24%, respectively, with no significant differences. tNGS detected drug resistance genes in 37.5% of culture-positive PJIs. tNGS was superior to mNGS for turnaround time (14.5 h vs. 28 h) and cost ($150 vs. $260). Conclusions: tNGS can effectively identify PJI pathogens and may provide drug resistance information, while tNGS is superior to mNGS regarding cost and turnaround time. A multidisciplinary, multi-technology based algorithm to diagnose PJI is appropriate. Highlights: 298 microorganisms and 86 drug resistance genes were included in the tNGS panel.Diagnostic efficacy of tNGS is not inferior to that of commonly used indicators.tNGS is superior to mNGS in cost and turnaround time.

Indocyanine green angiography for lower incidence of anastomotic leakage after transanal total mesorectal excision: a propensity score-matched cohort study.

Background: Anastomotic leakage (AL) is the most serious complication that can arise during colorectal surgery. Indocyanine green (ICG) angiography offers an intraoperative assessment of colonic vascular perfusion in real time. We aimed to assess ICG's effects on the AL rate in patients who have undergone transanal total mesorectal excision (TaTME) for rectal cancer. Methods: This retrospective cohort study was conducted at our center from October 2018 to March 2022 to analyze the clinical data of patients with rectal cancer who have undergone TaTME after propensity score matching (PSM). The primary outcome was the proximal colonic transection line modification and clinical AL rate. Results: A total of 143 patients in the non-ICG group and 143 patients in the ICG group were included after PSM. The proximal colonic transection line of seven patients in the non-ICG group was modified, while 18 were in the ICG group (4.9% vs. 12.5%, p = 0.023). Twenty-three patients (16.1%) in the non-ICG group and five patients (3.5%) in the ICG group were diagnosed with AL (p < 0.001). The ICG group had a less hospital readmission rate than the non-ICG group (0.7% vs. 7.7%, p = 0.003). The between-group differences in basic line and other outcomes were not significant. Conclusions: ICG angiography is a safe and feasible method to help surgeons identify potentially poor colonic vascular perfusion and modify the proximal colonic transection line, resulting in a significant reduction in AL and hospital readmission rates.

Alteration of m6A-Tagged RNA Profiles in Bone Originated from Periprosthetic Joint Infection.

Periprosthetic joint infection (PJI) is a devastating complication. This study aimed to unravel the veil of the N6-methyladenine (m6A) modification in PJI. Synovium, synovial fluid, sonication fluid and bone samples were collected intraoperatively from Staphylococcus aureus PJI and aseptic failure (AF) patients. The overall m6A level was detected by the m6A RNA methylation quantification kit, and the expression of m6A-related genes was quantified by real-time PCR and Western blot. Finally, an epitranscriptomic microarray and bioinformatics analysis were performed. We showed that there was a significant difference in overall m6A level between the PJI group and the AF group (PJI group had a higher overall m6A level). The expression level of METTL3 was higher in the PJI group than that in the AF group. There were 2802 differential m6A-modified mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differential m6A-modified mRNAs were significantly enriched in the NOD-like receptor signaling pathway, Th17 cell differentiation and the IL-17 signaling pathway, which indicates that the m6A modification might be involved in the processes of infection and immune response, bone metabolism and programmed cell death in PJI. In summary, the present work demonstrated that m6A modification plays a role in PJI and might be a therapeutic target for developing effective treatment strategies.

Optimization and standardization of mNGS-based procedures for the diagnosis of Mycoplasma periprosthetic joint infection: A novel diagnostic strategy for rare bacterial periprosthetic joint infection.

Introduction: The diagnosis of Mycoplasma periprosthetic joint infection (PJI) is rather difficult due to its rarity and difficult in isolation, there are not standardized diagnostic procedure for Mycoplasma PJI presently. This study aimed to reported a metagenomic next-generation sequencing (mNGS)-based diagnostic strategy for Mycoplasma PJI. Methods: In the present study, we have reported the largest number of Mycoplasma PJI that were precisely diagnosed by mNGS and verified by optimized microbial culture methods and (or) 16S PCR polymerase chain reaction (PCR). Results: The positive rate of optimized microbial culture methods and 16S PCR in the detection of Mycoplasma PJI was 57.14% and 71.43%, respectively. The infections were well controlled by targeted treatment in all cases. Conclusion: The standardized and optimized procedure based on mNGS presented in this study is useful for the diagnosis of Mycoplasma PJI, which might also be provided as a novel diagnostic strategy for rare bacterial PJI.

Diagnosis of Coxiella burnetii Prosthetic Joint Infection Using mNGS and ptNGS: A Case Report and Literature Review.

BACKGROUND: Coxiella burnetii (C. burnetii) is the causative agent of Q fever and is found worldwide; however, prosthetic joint infections caused by C. burnetii are rarely seen. Because of advances in molecular diagnostic techniques, prosthetic joint infection (PJI) caused by C. burnetii can now be diagnosed. CASE PRESENTATION: A 77-year-old male who had undergone total knee arthroplasty had a displaced prosthesis and periprosthetic osteolysis; he had no obvious signs of infection, and microbiological culture was negative. However, C. burnetii was detected by metagenomic next-generation sequencing (mNGS) and pathogen-targeted next-generation sequencing (ptNGS). Finally, polymerase chain reaction (PCR) confirmed the diagnosis of C. burnetii prosthetic joint infection (PJI). After revision surgery (one-stage revision) and oral antibiotics (doxycycline and moxifloxacin hydrochloride), the patient's symptoms disappeared, and he regained the ability to walk. During the 6-month follow-up, the patient's knee showed no signs of swelling, pain or the recurrence of infection, and he experienced no significant complications. We also present a review of the literature for other cases of C. burnetii PJI. CONCLUSIONS: The symptoms of C. burnetii PJI may be different from those of Q fever, which may lead to misdiagnosis. mNGS and ptNGS may be helpful for the identification of C. burnetii. Once the diagnosis of C. burnetii PJI is confirmed, doxycycline in combination with a fluoroquinolone can be effectively administered after revision surgery.

Conversion Hip Arthroplasty Using Standard and Long Stems after Failed Internal Fixation of Intertrochanteric Fractures.

OBJECTIVE: Failed internal fixation of intertrochanteric fractures (FIF-ITF) is often treated by conversion hip arthroplasty (CHA). This study aimed to evaluate the results and complications of using standard and long femoral stems in this operation. METHODS: This retrospective, multi-center study enrolled 31 total hip arthroplasty (THA) and 23 hemiarthroplasties (HA) cases (30 women, 24 men; mean age 76 years) after FIF-ITF between 2012 and 2019, divided into two groups: standard stem group (n = 20) and long stem group (n = 34). The initial internal fixation includes 38 cases of proximal femoral nail anti-rotation (PFNA), eight cases of the dynamic hip screw (DHS), and eight cases of locking proximal femoral plate (LPFP). The indications for CHA included 38 cases of failure of fixation, seven cases of nonunion, and nine cases of avascular necrosis or posttraumatic osteoarthritis. Perioperative data and complications related to fracture and operation were collected, and preoperative and postoperative clinical and radiological data were analyzed. Clinical outcomes were assessed using Harris hip score (HHS) and 36-item Short Form survey (SF-36: including physical function (PF) score and body pain (BP) score). Statistical analyses were performed using the chi-square or Fisher's exact test, and the 2-sample t-test or Wilcoxon rank sum test. RESULTS: At an average of 5.6 years with a minimum of 2 years follow-up. A significant overall surgeon-related complication rate was detected (27.8% [15/54]), five cases had an intraoperative femur fracture, one case had a late periprosthetic femoral fracture, two cases had a stem penetration, one case had a cement leakage, and two patients had an early postoperative dislocation, one infection and three cases of stem loosening or subsidence. Long stems had an increased risk of complication (13/34) compared to standard stems (2/20) (P = 0.031). The operation time and blood loss in the long stem group were higher than those in the standard stem group (P = 0.002; 0.017). HHS and SF-36 significantly improved in both groups from preoperative to the final follow-up and did not present significant differences at the final follow-up (P > 0.05). CONCLUSION: CHA following FIF-ITF showed a successful mid-term clinical result, long stem arthroplasty should be approached with caution for the risks of higher complication rate, especially intraoperative femoral fractures.

Motor neurons transplantation alleviates neurofibrogenesis during chronic degeneration by reversibly regulating Schwann cells epithelial-mesenchymal transition.

A novel understanding of peripheral nerve injury is epithelial-mesenchymal transition (EMT), which characterizes the process of dedifferentiation and transformation of Schwann cells after nerve injury. Despite being regarded as an important mechanism for healing nerve injuries, long-term EMT is the primary cause of fibrosis in other tissue organs. The potential mechanism promoting neurofibrosis in the process of chronic degeneration of nerve injury and the effects of motor neurons (MNs) transplantation on neurofibrosis and repair of nerve injury were studied by transcriptome sequencing and bioinformatics analysis, which were confirmed by in vivo and in vitro experiments. Even 3 months after nerve injury, the distal nerve maintained high levels of transforming growth factor ß-1 (TGFß-1) and Snail family transcriptional repressor 2 (Snai2). The microenvironment TGFß-1, Snai2 and endogenous TGFß-1 formed a positive feedback loop in vivo and in vitro, which may contribute to the sustained EMT state and neurofibrogenesis in the distal injured nerve. Inhibiting TGFß-1 and Snai2 expression and reversing EMT can be achieved by transferring MNs to distal nerves, and the removal of transplanted MNs is capable of reactivating EMT and promoting the growth of proximal axons. In conclusion, EMT persisting can be an explanation for distal neurofibrosis and a potential therapeutic target. By reversibly regulating EMT, MNs transplantation can alleviate neurofibrogenesis of distal nerve in chronic degeneration.

The role of Staphylococcus aureus small colony variants in intraosseous invasion and colonization in periprosthetic joint infection.

AIMS: This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI). METHODS: A PJI diagnosis was made according to the MusculoSkeletal Infection Society (MSIS) for PJI. Bone and tissue samples were collected intraoperatively and the intracellular invasion and intraosseous colonization were detected. Transcriptomics of PJI samples were analyzed and verified by polymerase chain reaction (PCR). RESULTS: SCVs can be isolated from samples collected from chronic PJIs intraoperatively. Transmission electron microscopy (TEM) and immunofluorescence (IF) showed that there was more S. aureus in bone samples collected from chronic PJIs, but much less in bone samples from acute PJIs, providing a potential mechanism of PJI. Immunofluorescence results showed that SCVs of S. aureus were more likely to invade osteoblasts in vitro. Furthermore, TEM and IF also demonstrated that SCVs of S. aureus were more likely to invade and colonize in vivo. Cluster analysis and principal component analysis (PCA) showed that there were substantial differences in gene expression profiles between chronic and acute PJI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these differentially expressed genes were enriched to chemokine-related signal pathways. PCR also verified these results. CONCLUSION: Our study has shown that the S. aureus SCVs have a greater ability to invade and colonize in bone, resulting in S. aureus remaining in bone tissues long-term, thus explaining the pathogenesis of chronic PJI.Cite this article: Bone Joint Res 2022;11(12):843-853.

Metagenomic next-generation sequencing assists the diagnosis treatment of fungal osteoarticular infections.

Background: Fungal osteoarticular infection (FOI) is not commonly seen in clinical practice but proposes a great challenge to orthopedic surgeons. In this study, we aimed to investigate the risk factors, the clinical features, and surgical outcomes of FOI in our institution. Specifically, we aimed to explore the role of metagenomic next-generation sequencing (mNGS) in the diagnosis and treatment of FOI. Methods: All the patients who were diagnosed and managed with FOI in our institution from January 2007 to December 2020 were retrospectively reviewed, including primary fungal implant-related infection, primary fungal osteomyelitis or arthritis, and fungal infections secondary to bacterial osteomyelitis or implant-related bacterial infections. The potential risk factors and the clinical and surgical features were analyzed. The pathogen data were compared between culture and the mNGS test. Results: A total of 25 patients were included, namely, 12 primary implant-related infections, 7 primary fungal osteomyelitis or arthritis, and 6 fungal infections secondary to bacterial osteomyelitis or implant-related bacterial infections. Most cases had undergone multiple surgeries or long-term antibiotic treatment. Diagnosis was mainly based on microbial culture and the mNGS test. Optimization of culture methods and the use of mNGS assisted the diagnosis. Specifically, mNGS was performed in 12 patients, 5 of whom were culture-negative. In the remaining seven cases, mNGS demonstrated the same results as culture. Management of FOI was complicated as most patients required multiple surgeries followed by long-term antifungal treatment. In selected cases, antifungal-impregnated cement spacer retention can be an optional choice. The overall success rate was 100% (25/25) for our cohort. Conclusion: We concluded that patients with comorbidities and a history of multiple surgeries or long-term antibiotics are under higher risk for FOI. Use of mNGS assists the diagnosis and treatment of FOI. Surgery combined with long-term antifungal treatment achieved satisfactory outcomes. In selected cases, antifungal-impregnated cement spacer retention can be an optional treatment choice.

New quantum physics, solving puzzles of Wheeler's delayed choice and a particle's passing N slits simultaneously and quantum oscillator in experiments.

This paper discovers new quantum physics, and gives solutions to puzzles of Wheeler's delayed choice and a particle's passing many slits simultaneously by exact quantum physics expressions. We further show new quantum control, new quantum oscillation, new quantum control experiments and new quantum oscillator being able to be installed in quantum communication network etc. We discover that the ability of a photon to hit electrons out in photoelectric effect is complementarily equivalent to the ability of wave of a photon to simultaneously pass through many slits in wave-particle duality. Objective criterion for distinguishing classical and quantum particles is found, and this paper gives applicable realm of quantum theories and new quantum physics expressions of wave-particle duality. All these studies above should be classified as classical and quantum particles, then classical particle and quantum particle wave cannot and can pass many slits, respectively. This paper discovers wave-particle duality's origin of displaying both wave property from plane wave part of the general Fourier expansion and particle property from the general Fourier expansion coefficients with the particle's global property and spins etc. We give the superposition state representation of wave-particle duality, further find the collapse of the duality superposition state to wave or particle state. The collapsed wave or particle state is related to the measure of wave or particle property. Then, we explain why sometimes it's a wave or a particle. Our achieved results are truly tested, and we discover new measured attractive state and quantum wave collapse velocity expression.

Metal Artifact Reduction Sequences MRI: A Useful Reference for Preoperative Diagnosis and Debridement Planning of Periprosthetic Joint Infection.

The diagnosis and treatment of periprosthetic joint infection (PJI) is complex and the use of MRI in PJI is gaining attention from orthopedic surgeons as MR technology continues to advance. This study aimed to investigate whether metal artefact reduction sequence (MARS) MRI could be used as an adjunct in the preoperative diagnosis of PJI and to explore its role in PJI debridement planning. From January 2020 to November 2021, participants with metal joint prostheses that needed to be judged for infection were prospectively enrolled. According to Musculoskeletal Infection Society standards, 31 cases were classified as infection, and 20 as non-infection. The sensitivity and specificity of MARS MRI for the diagnosis of PJI were 80.65% and 75%, respectively. In MARS MRI, the incidence of bone destruction, lamellar synovitis, and extracapsular soft tissue oedema were significantly higher in PJI than in non-PJI. Fourteen suspicious occult lesions were found in the preoperative MARS MRI in 9 cases, and the location of 9 infection lesions was confirmed intraoperatively. In conclusion, MARS MRI is an effective diagnostic tool for PJIand can provide a visual reference for preoperative surgical planning.

The role of metagenomic next-generation sequencing in the pathogen detection of invasive osteoarticular infection.

OBJECTIVES: This study aimed to analyze the pathogenic bacteria spectrum in invasive and primary osteoarticular infection (IOI and POI) and compare the pathogen detection rate of metagenomic next-generation sequencing (mNGS) and microbial culture in IOI and POI. METHODS: The suspected POI and IOI cases from 2014-2021 were included. The diagnosis of POI or IOI was made by at least two orthopedic surgeons, two infectious diseases specialists, and one senior microbiologist. Demographic characteristics, microbial culture results, and so on were recorded. The pathogenic bacteria spectrum in IOI and POI were analyzed, and the ability of mNGS and microbial culture in pathogen detection in IOI and POI were compared. RESULTS: There were 52 POI cases and 92 IOI cases; the common pathogen in POI and IOI were both Staphylococcus aureus. There are more cases with negative microbial culture results and multiple infections in IOI, and many cases were caused by rare and fastidious bacteria. The introduction of the mNGS could significantly increase the pathogen detection rate to 92.39% in IOI, which was 8.69% higher than that of microbial culture (P = 0.007), whereas the improvement in POI was limited to about 2%. CONCLUSION: mNGS is an promising tool for IOI pathogen detection.

Clinical Outcomes of Culture-Negative and Culture-Positive Periprosthetic Joint Infection: Similar Success Rate, Different Incidence of Complications.

OBJECTIVE: To compare the clinical outcomes of culture-negative periprosthetic joint infection (CN PJI) with those of culture-positive periprosthetic joint infection (CP PJI). METHODS: This study retrospectively examined data from 77 patients who underwent revision surgery due to periprosthetic joint infection (PJI) after hip and knee arthroplasty at our center from January 2012 to June 2017. There were 37 males and 40 females, with an average age of 63.6 year. All patients were classified by Tsukayama type, according to the bacterial culture results of synovial fluid and pre- and intraoperative tissues, 24 cases were included in the CN PJI group, and 53 cases were included in the CP PJI group. All patients underwent routine blood tests, liver, renal function tests, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) measurements. The remission rates of CN PJI and CP PJI were compared. The effects of the culture results on the curative effect were further compared by survival analysis. RESULTS: The patients were followed regularly with an average of 29.2 months (range, 12-76 months). In total, there were 24 cases of CN PJI, with an incidence of 29.63%. The overall success rate of CN PJI group was 86.4% (19/22), and overall success rate of CP PJI group was 87.5% (42/48). The relative efficacy of various surgical options was: one-stage revision 100% (7/7), two-stage revision 96.3% (26/27), debridement and implant retention 64.3% (9/14), respectively. There was no significant difference in the success rate between the CN PJI group and the CP PJI group. The incidence of antibiotic-related complications for the CN PJI group was significantly higher than that of the CP PJI group, with 58.3% for CN PJI and 11.3% for CP PJI, respectively. CONCLUSION: When CN PJI was treated according to the strict standards for the diagnosis and treatment, the success rate of treatment for the CN PJI group was similar to that for the CP PJI group. The incidence of antibiotic-related complications from the CN PJI group was higher than that from the CP PJI group.