N6-Methyladenosine in Cell-Fate Determination of BMSCs: From Mechanism to Applications.

The methylation of adenosine base at the nitrogen-6 position is referred to as "N6-methyladenosine (m6A)" and is one of the most prevalent epigenetic modifications in eukaryotic mRNA and noncoding RNA (ncRNA). Various m6A complex components known as "writers," "erasers," and "readers" are involved in the function of m6A. Numerous studies have demonstrated that m6A plays a crucial role in facilitating communication between different cell types, hence influencing the progression of diverse physiological and pathological phenomena. In recent years, a multitude of functions and molecular pathways linked to m6A have been identified in the osteogenic, adipogenic, and chondrogenic differentiation of bone mesenchymal stem cells (BMSCs). Nevertheless, a comprehensive summary of these findings has yet to be provided. In this review, we primarily examined the m6A alteration of transcripts associated with transcription factors (TFs), as well as other crucial genes and pathways that are involved in the differentiation of BMSCs. Meanwhile, the mutual interactive network between m6A modification, miRNAs, and lncRNAs was intensively elucidated. In the last section, given the beneficial effect of m6A modification in osteogenesis and chondrogenesis of BMSCs, we expounded upon the potential utility of m6A-related therapeutic interventions in the identification and management of human musculoskeletal disorders manifesting bone and cartilage destruction, such as osteoporosis, osteomyelitis, osteoarthritis, and bone defect.

Impact of spinal Anaesthesia versus general Anaesthesia on the incidence of surgical site infections after knee or hip arthroplasty: A meta-analysis.

Postoperative Surgical Site Infections (SSIs) pose significant challenges to recovery after joint arthroplasty. This systematic review and meta-analysis aim to compare the incidence of SSIs after knee or hip arthroplasty under Spinal Anaesthesia (SA) versus general anaesthesia (GA). We conducted the systematic review and meta-analysis following the PRISMA guidelines, analysing data from 15 studies selected from PubMed, Embase, Web of Science, and Cochrane Library up to May 16, 2023. The analysis included studies comparing SSIs incidence in patients aged 18 years and above who underwent knee or hip arthroplasty under SA or GA. Quality assessment was performed using the Cochrane Collaboration's risk of bias tool. The effect size was calculated using random or fixed-effects models based on the observed heterogeneity. We assessed the heterogeneity between studies and conducted a sensitivity analysis. Of 1651 initially identified studies, 15 articles encompassing 353 169 patients were included in the final analysis. A total of 156 405 patients were under SA, while 196 764 received GA. The studies demonstrated substantial heterogeneity (p = 0.007, I2 = 53.7%), resulting in a random-effects model being employed. Patients receiving SA showed a 23% lower likelihood of developing SSIs postoperatively compared to GA patients (OR: 0.77, 95% CI: 0.70-0.86, p < 0.001). Sub-group analysis further confirmed these findings regardless of the type of joint arthroplasty. This meta-analysis indicated a significantly lower incidence of SSIs following knee or hip arthroplasty under SA compared to GA. Despite observed heterogeneity, the results underscore the potential benefit of SA over GA in orthopaedic surgeries to reduce the risk of SSIs.

Diagnostic accuracy of dual-energy CT for bone marrow edema in patients with acute knee injury: a systematic review and meta-analysis.

BACKGROUND: Knee injuries are prevalent, and early diagnosis is crucial for guiding clinical therapy. MRI is the diagnostic gold standard for bone marrow edema (BME) in patients with acute knee injuries, yet there are still limitations. Dual-energy CT, a possible viable replacement, is being explored (DECT). METHODS: We systematically retrieved studies from EMBASE, Scopus, PUBMED, and the Cochrane Library and collected gray literatures. In accordance with the PRISMA-DTA standards, a systematic review was conducted between the study's initiation and July 31, 2021, utilizing an MRI reference standard and at least 10 adult patients with acute knee injuries to evaluate the diagnostic effectiveness of DECT for diagnosing BME. Two reviewers collected the study's details independently. For the meta-analysis, a bivariate mixed-effects regression model was utilized, and subgroup analysis was employed to determine the sources of variability. RESULTS: The research included nine studies that examined 290 individuals between the ages of 23 and 53 with acute knee injuries who had DECT and MRI. Overall, the sensitivity, specificity, and AUC of the BME were 85% (95% confidence interval [CI]: 77-90%), 96% (95% CI: 93-97%), and 0.97 (95% CI: 0.95-0.98), respectively. To account for the assumed diversity of research, there were no statistically significant differences between the comparison groups in terms of specificity and sensitivity. CONCLUSION: DECT is a viable alternative to MRI for individuals with acute knee injuries when MRI is inappropriate or unavailable.

Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability, thus adversely affecting locomotion ability and life quality. Consequently, good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA. Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging. Herein, we review the fluorescent probes developed for the detection and imaging of RA biomarkers, namely reactive oxygen/nitrogen species (hypochlorous acid, peroxynitrite, hydroxyl radical, nitroxyl), pH, and cysteine, and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

Morphometric characteristics of the knee are associated with the injury of the meniscus.

BACKGROUND: To assess the geometrical risk factors for meniscal injuries. We hypothesized that the narrowness of the intercondylar notch and the smaller tibial spine could increase the risk of meniscal injuries. METHODS: We retrospectively studied two hundred and seven patients examined for knee magnetic resonance images. Two experienced orthopedists evaluated the severity of meniscal injuries. The notch width, bicondylar notch width, notch width index, condyle width of the femur, tibial spine height, and intercondylar angle were measured in magnetic resonance image slides by two blinded orthopedists. RESULTS: A total of 112 patients with a meniscus injury and 95 patients were as healthy control in all two hundred and seven patients. The NWI (P = 0.027) in patients with meniscus injuries was significantly different from the control group. A 1 SD (0.04 mm) increase in NWI was associated with a 0.4-fold increase in the risk of meniscal injury. A 1 SD (0.04 mm) increase in NWI was associated with a 0.64-fold increase in the risk of grade 3 meniscal injury. Furthermore, NWI and medial spine height are decreased significantly in grade 2 (P < 0.05) meniscal injury than in other grades. The medial spine height was significantly decreased in the meniscal injury group (P = 0.025), and the decrease in medial spine height would increase the risk of meniscal injury (OR = 0.77) and grade 3 meniscal injury (OR = 0.8). CONCLUSIONS: The stenosis of the femoral intercondylar notch and small medial tibial spine is risk factors of meniscal injury. The decreased NWI and the medial tibial spine height were also associated with the severity of the meniscal injury.

[Focused extracorporeal shock wave therapy with centrifugal exercise for the treatment of greater trochanteric pain syndrome].

OBJECTIVE: To explore the clinical efficacy of focused extracorporeal shock wave therapy with centrifugal exercise in the treatment of greater trochanteric pain syndrome. METHODS: From September 2017 to June 2019, 53 eligible cases of greater trochanteric pain syndrome were randomly divided into observation group (29 cases) and control group (24 cases). In observation group, there were 8 males and 21 females, aged from 38 to 62 years old with an average of (49.96±6.39) years old; the course of disease ranged from 6 to 13 months with an average of (8.58±1.99) months;treated with focused extracorporeal shock wave therapy with centrifugal exercise. In control group, there were 5 males and 19 females, aged from 39 to 62 years old with an average of (52.79±5.86) years old;the course of disease ranged from 6 to 14 months with an average of (9.04±2.51) months;treated with centrifugal exercise alone. Visual analogue scale (VAS) and hip Harris score were measured before ESWT treatment and at 1, 2, and 6 months to evaluate relieve degree of pain and functional recovery of hip joint, respectively. RESULTS: At 1 month after treatment, there were no significant differences in VAS, hip Harris score and treatment success rate (all P>0.05). At 2 months after treatment, VAS score in observation group (3.20±0.81) was lower than that of control group (3.87±0.61, P=0.002), there were no significant differences in hip Harris score score between observation group (81.93±2.43) and control group (82.12±2.34, P=0.770), the treatment success rate in observation group (58.62%, 17 / 29) was higher than that of control group (29.16%, 7 / 24) (P=0.032). At 6 months after treatment, VAS score in observationgroup (2.24±0.68) was lower than that of control group (3.12±0.53, P<0.001), hip Harris score score in observation group(85.10±1.75) was higher than that of control group (83.66±1.78)(P=0.005), there were no significant differences in treatment success rate between observation group (82.75%, 24 / 29) and control group (62.50%, 15 / 24)(P=0.096). CONCLUSION: In treatment of greater trochanteric pain syndrome, focused extracorporeal shock wave therapy with centrifugal exercise could significantly relieve symptoms of lateral hip pain, improve functional recovery of hip joint with good safety. This treatment strategy is worthy of application and promotion in clinical practice.

Diagnostic accuracy of synovial fluid D-lactate for periprosthetic joint infection: a systematic review and meta-analysis.

BACKGROUND: Periprosthetic joint infection is a grievous complication after arthroplasty that greatly affects the quality of life of patients. Rapid establishment of infection diagnosis is essential, but great challenges still exist. METHODS: We conducted research in the PubMed, Embase, and Cochrane databases to evaluate the diagnostic accuracy of D-lactate for PJI. Data extraction and quality assessment were completed independently by two reviewers. The pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), summarized receiver operating characteristic curve (sROC), and area under the sROC curve (AUC) were constructed using the bivariate meta-analysis framework. RESULTS: Five eligible studies were included in the quantitative analysis. The pooled sensitivity and specificity of D-lactate for the diagnosis of PJI were 0.82 (95% CI 0.70-0.89) and 0.76 (95% CI 0.69-0.82), respectively. The value of the pooled diagnostic odds ratio (DOR) of D-lactate for PJI was 14.18 (95% CI 6.17-32.58), and the area under the curve (AUC) was 0.84 (95% CI 0.80-0.87). CONCLUSIONS: According to the results of our meta-analysis, D-lactate is a valuable synovial fluid marker for recognizing PJI, with high sensitivity and specificity.

FDG-PET/CT versus bone marrow biopsy in bone marrow involvement in newly diagnosed paediatric lymphoma: a systematic review and meta-analysis.

BACKGROUND: Bone marrow infiltration (BMI) is a devastating stage of paediatric lymphoma. Prompt diagnosis of BMI in newly diagnosed paediatric lymphoma patients is critical but can be very challenging at present. METHODS: We systematically retrieved studies from PubMed, EMBASE, and the Cochrane Library. Data extraction and quality assessment were performed by two reviewers independently. A total of nine eligible studies were included in the quantitative analysis. RESULTS: The pooled sensitivity and specificity of FDG-PET/CT for diagnosing BMI in newly diagnosed paediatric lymphoma patients were 0.97 (95% confidence interval [CI], 0.93 to 0.99) and 0.99 (95% CI, 0.98 to 0.99), respectively. The pooled PLR, NLR, and DOR were 79.9 (95% CI, 42.7 to 149.6), 0.03 (95% CI, 0.01 to 0.17), and 2414.6 (95% CI, 989.6 to 5891.4), respectively. The AUC of FDG-PET/CT for BMI was 1.00 (95% CI, 0.99 to 1.00). Compared with FDG-PET/CT, BMB had a lower pooled sensitivity (0.44, 95% CI, 0.34 to 0.55) and comparable pooled specificity (1.00, 95% CI, 0.92 to 1.00). CONCLUSION: Compared with BMB, FDG-PET/CT was a more valuable diagnostic method for evaluating BMI in paediatric Hodgkin and non-Hodgkin lymphoma patients with extremely high diagnostic accuracy.

The short-term effectiveness and safety of second-generation patellofemoral arthroplasty and total knee arthroplasty on isolated patellofemoral osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: We aimed to compare second-generation patellofemoral arthroplasty (2G PFA) with total knee arthroplasty (TKA) in treating isolated patellofemoral osteoarthritis (PFOA) by assessing the percentages of revisions, complications, and patient-reported outcome measures (PROMs). METHODS: Studies that compared the outcomes of 2G PFA and TKA in the treatment of isolated PFOA were searched in electronic databases, including MEDLINE, Embase, and Web of Science. Two researchers independently identified eligible studies, extracted the data, and evaluated the quality of the literature. Pooled risk ratios (RRs) or weighted mean differences with 95% confidence intervals were calculated using either fixed or random effects models. Descriptive analysis was used when data could not be pooled. RESULTS: A total of six studies were included in the review. For the revision percentage and complications, there were no significant differences between 2G PFA and TKA (RR = 2.29, 95% CI 0.69-7.58, P = 0.17; RR = 0.56, 95% CI 0.23-1.40, P = 0.22, respectively). Second, the results demonstrated that the differences in the Oxford Knee Score (OKS) and the University of California, Los Angeles (UCLA) activity score between 2G PFA and TKA were not significant (WMD -4.68, 95% CI -16.32 to 6.97, p = 0.43; WMD 0.16, 95% CI -1.21 to 1.53, P = 0.82). The Knee Injury and Osteoarthritis Outcome Score (KOOS), the American Knee Society Score (AKSS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were presented in a narrative form due to methodological heterogeneity. CONCLUSION: For isolated PFOA, 2G PFA demonstrated similar results to TKA with respect to the percentages of revisions, complications, and PROMs.

Deep learning for diagnosing osteonecrosis of the femoral head based on magnetic resonance imaging.

BACKGROUND AND OBJECTIVE: Early-stage osteonecrosis of the femoral head (ONFH) can be difficult to detect because of a lack of symptoms. Magnetic resonance imaging (MRI) is sufficiently sensitive to detect ONFH; however, the diagnosis of ONFH requires experience and is time consuming. We developed a fully automatic deep learning model for detecting early-stage ONFH lesions on MRI. METHODS: This was a single-center retrospective study. Between January 2016 and December 2019, 298 patients underwent MRI and were diagnosed with ONFH. Of these patients, 110 with early-stage ONFH were included. Using a 7:3 ratio, we randomly divided them into training and testing datasets. All 3640 segments were delineated as the ground truth definition. The diagnostic performance of our model was analyzed using the receiver operating characteristic curve with the area under the receiver operating characteristic curve (AUC) and Hausdorff distance (HD). Differences in the area between the prediction and ground truth definition were assessed using the Pearson correlation and Bland-Altman plot. RESULTS: Our model's AUC was 0.97 with a mean sensitivity of 0.95 (0.95, 0.96) and specificity of 0.97 (0.96, 0.97). Our model's prediction had similar results with the ground truth definition with an average HD of 1.491 and correlation coefficient (r) of 0.84. The bias of the Bland-Altman analyses was 1.4 px (-117.7-120.5 px). CONCLUSIONS: Our model could detect early-stage ONFH lesions in less time than the experts. However, future multicenter studies with larger data are required to further verify and improve our model.

How much improvement can satisfy patients? Exploring patients' satisfaction 3 years after total knee arthroplasty.

BACKGROUND: Despite the innovations in total knee arthroplasty (TKA), there is still a subset of patients who do not acquire significant relief or expected satisfaction after primary TKA. However, this subgroup of patients still gains improvements more or less in terms of objective or quantified assessments after the procedure. The purpose of our study is to explore the factors that correlate with patients' satisfaction and identify minimal clinically important difference (MCID) and minimum important change (MIC) in clinical parameters. METHODS: We conducted a retrospective study of 161 patients diagnosed with osteoarthritis who underwent unilateral total knee arthroplasty from January 2017 to December 2017. We collected the following parameters: body mass index (BMI), duration of disease, education level, depression state, preoperative flexion contracture angle of knee, HSS scores, 11-point NRS scores, and radiological parameters (preoperative minimal joint space width and varus angle of knee). The satisfaction was graded by self-reported scores in percentage (0-100). RESULTS: We revealed that 80.8% of patients were satisfied 3 years overall after primary TKA. HSS score change, NRS-Walking score change, age, and pre-mJSW showed significant difference between satisfied and dissatisfied group. The varus angle change revealed statistical significance according to the levels of satisfaction. Simple linear regression identified the MCID for HSS score to be 5.41 and for the NRS-Walking to be 1.24. The receiver operating characteristics (ROC) curve identified the MIC for HSS score to be 25.5 and for the NRS-Walking score to be 6.5. CONCLUSIONS: In summary, we identified several factors that correlated with patients' satisfaction independently after TKA in a long term. In addition, we revealed the minimal clinically important difference (MCID) and minimum important change (MIC) for HSS and NRS score in these patients.

The Role of Fibular Fixation in Distal Tibia-Fibula Fractures: A Meta-Analysis.

OBJECTIVES: The necessity of fibular fixation in distal tibia-fibula fractures remains controversial. This study aimed to assess its impact on radiographic outcomes as well as rates of nonunion and infection. METHODS: A systematic search of the electronic databases of PubMed, Embase, and Cochrane library was performed to identify studies comparing the outcomes of reduction and internal fixation of the tibia with or without fibular fixation. Radiographic outcomes included malalignment and malrotation of the tibial shaft. Data regarding varus/valgus angulation, anterior/posterior angulation, internal/external rotation deformity, and the rates of nonunion and infection were extracted and then polled. A meta-analysis was performed using the random-effects model for heterogeneity. RESULTS: Additional fibular fixation was statistically associated with a decreased rate of rotation deformity (OR = 0.13; 95% CI 0.02-0.82, p=0.03). However, there was no difference in the rate of malreduction between the trial group and the control group (OR = 0.86; 95% CI 0.27-2.74, p=0.80). There was also no difference in radiographic outcomes of varus-valgus deformity rate (OR = 0.17; 95% CI 0.03-1.00, p=0.05) or anterior-posterior deformity rate (OR = 0.76; 95% CI 0.02-36.91, p=0.89) between the two groups. Meanwhile, statistical analysis showed no significant difference in the nonunion rate (OR = 0.62; 95% CI 0.37-1.02, p=0.06) or the infection rate (OR = 0.81; 95% CI 0.18-3.67, p=0.78) between the two groups. CONCLUSIONS: Additional fibular fixation does not appear to reduce the rate of varus-valgus deformity, anterior-posterior deformity, or malreduction. Meanwhile, it does not appear to impair the union process or increase the odds of infection. However, additional fibular fixation was associated with decreased odds of rotation deformity compared to controls.

Irritant contact dermatitis following extracorporeal shockwave therapy: a case report.

Extracorporeal shockwave therapy (ESWT) has been widely used in the treatment of various musculoskeletal disorders with remarkable efficacy, with no relevant severe complications being reported. In this study, we report a rare case of acute irritant contact dermatitis following ESWT with serious skin damage, which has never been previously reported. A 42-year-old male patient with osteonecrosis of the femoral head (ONFH) was subjected to two sessions of ESWT. In the first session of low-energy ESWT (0.15 mJ/mm2, 3 Hz, and a total of 2,000 impulses), no local or systematic adverse reactions occurred. Three months later, he was subjected to a second session of high-energy ESWT (0.28 mJ/mm2, 4 Hz, and a total of 2,000 impulses). However, on the second day, the patient presented with itching and painful erythema and blisters on the local skin of the hip. Based on these manifestations and the results of patch testing, the patient was diagnosed with irritant contact dermatitis and treated by an oral antihistamine combined with external calamine lotions. The skin lesions began to develop exudate from erosion and scabs had gradually formed with treatment, and finally dry scabs fell off with no scar left. This is the first reported irritant contact dermatitis after ESWT. Although bone pathologies should be treated with high energy, patients should be informed of this potential rare complication.

Effectiveness of Focused Shockwave Therapy versus Radial Shockwave Therapy for Noncalcific Rotator Cuff Tendinopathies: A Randomized Clinical Trial.

BACKGROUND: The superiority of focused shockwave therapy (F-SWT) versus radial shockwave therapy (R-SWT) for treating noncalcific rotator cuff tendinopathies remains controversial. This study is aimed at comparing the effectiveness of F-SWT versus R-SWT for the management of noncalcific rotator cuff tendinopathies. METHODS: A total of 46 patients affected by noncalcific rotator cuff tendinopathies were randomly divided into 2 groups of 23 individuals. Patients in group A received 4 sessions of F-SWT, while patients in group B were treated by 4 sessions of R-SWT. In each session, mean energy flux density (EFD) for F-SW 3000 shots was 0.09 ± 0.018 mJ/mm2 with 5.1 ± 0.5 Hz, while average pressure for R-SW 3000 shots was 4.0 ± 0.35 bar with 3.2 ± 0.0 Hz. Pain level and shoulder function were assessed with the numerical rating scale (NRS) and Constant-Murley Scale (CMS). The primary endpoint was the change in the mean NRS pain score from baseline to 24 weeks after the intervention. Secondary endpoints were changes in the mean NRS pain scores at all other follow-up points, changes in the mean CMS scores, and radiographic findings. RESULTS: There were no significant differences between the two groups regarding NRS pain score and CMS score within 24 weeks after intervention (all p > 0.05). However, F-SWT resulted in significantly lower NRS compared with R-SWT at 24 weeks and 48 weeks after treatment (2.7 ± 1.0 vs. 4.5 ± 1.2 and 1.4 ± 1.0 vs. 3.0 ± 0.8, respectively, all p < 0.001). Similar results were found in CMS changes and radiographic findings. CONCLUSIONS: Both F-SWT and R-SWT are effective in patients with noncalcific rotator cuff tendinopathy. F-SWT proved to be significantly superior to R-SWT at long-term follow-up (more than 24 weeks). This trial is registered with ChiCTR1900022932.

Alpha-Defensin versus Leukocyte Esterase in Periprosthetic Joint Infection: An Updated Meta-Analysis.

Periprosthetic joint infection (PJI) is a devastating complication after arthroplasty. Prompt establishment of an infection diagnosis is critical but can be very challenging at present. In order to evaluate the diagnostic accuracy of alpha-defensin or leukocyte esterase for PJI, we performed systematic research in PubMed, Embase, and Cochrane Library to retrieve relevant studies. Data extraction and quality assessment were performed by two reviewers independently. A total of thirty-one eligible studies were finally included in the quantitative analysis. The pooled sensitivity and specificity of alpha-defensin (21 studies) for the diagnosis of PJI were 0.89 (95% confidence interval (CI), 0.83 to 0.93) and 0.96 (95% CI, 0.95 to 0.97), respectively. The value of the pooled diagnostic odds ratios (DOR) of alpha-defensin for PJI was 209.14 (95% CI, 97.31 to 449.50), and the area under the curve (AUC) was 0.98 (95% CI, 0.96 to 0.99). The pooled sensitivity and specificity of leukocyte esterase (17 studies) for the diagnosis of PJI were 0.90 (95% CI, 0.84 to 0.95) and 0.96 (95% CI, 0.93 to 0.97), respectively. The value of the DOR of leukocyte esterase for PJI was 203.23 (95% CI, 96.14 to 429.61), and the AUC was 0.98 (95% CI, 0.96 to 0.99). Based on the results of our meta-analysis, we can conclude that alpha-defensin and leukocyte esterase are valuable synovial fluid markers for identifying PJI with comparable high diagnostic accuracy.