Xanthoma combining osteonecrosis in knee joint: a case report.

Xanthoma typically occurs in the subcutaneous tissues, with rare cases of xanthoma in the joints. However, the case of knee joint osteonecrosis combined with xanthoma is even more uncommon. In this article, we described a 50-year-old female patient who suffered xanthoma in the knee joint on the basis of osteonecrosis of the knee joint. The primary clinical symptoms were knee joint pain and limited mobility. The patient initially received conventional treatment for osteonecrosis. However, there was no significant improvement. Later, we found a synovial xanthoma in the patient's knee. Finally, she underwent arthroscopic excision of the knee joint synovial xanthoma. Following the procedure, her VAS score decreased from 7 to 2, and knee joint mobility increased from 10-103° to 10-140°. Through our follow-up, the patient did not exhibit symptom recurrence. This case is valuable as it provides a feasible therapeutic approach for future clinical applications.

Total Knee Arthroplasty in Patients Who Have Ankylosed Knees: A Ten-Year Retrospective.

INTRODUCTION: Knee ankylosis can result in major functional impairment, and surgical treatment of knee ankylosis is often regarded as a tremendous challenge due to technical difficulties such as difficult joint exposure and a high incidence of complications. The objective of this study was to review the results of preoperative and postoperative functional scores, range of motion (ROM), and complications of total knee arthroplasty (TKA) for the treatment of knee ankylosis. SURGICAL METHODS: Between January 2007 and January 2021, 19 patients (17 patients, 11 women, and 6 men) who had knee ankylosis underwent TKA. The mean age of the patients was 52 years (range, 31 to 71), and the mean follow-up period was 10.2 years (range, 3.1 to 13.9). The surgical procedure involved a total knee arthroplasty, performed via a medial parapatellar approach, a quadriceps snip, and a secondary osteotomy with soft-tissue release. The postoperative clinical outcomes and complications were evaluated using a range of methods, including ROM assessment, Hospital for Special Surgery Knee Score (HSS), and visual analogue scale (VAS) scores. RESULT: At final follow-up, the mean HSS score improved significantly from the preoperative score of (33.63 ± 8.69) to (88.05 ± 5.23) (P < 0.001), ROM improved from (0 ± 0°) to (100.90±14.07°) (P < 0.001), the VAS score improved from a preoperative score of 0 to (1.00 ± 0.94) (P< 0.001), and radiographs showed no aseptic loosening of the knee. There were eight knees (42.1%) that had postoperative complications. CONCLUSION: Total knee arthroplasty in patients who have ankylosing knees resulted in significant improvements in flexion and extension, mobility, and quality of life, despite a high incidence of complications such as skin necrosis.

The effects of ß-hydroxy-ß-methylbutyrate or HMB-rich nutritional supplements on sarcopenia patients: a systematic review and meta-analysis.

Background: Sarcopenia is a progressive, systemic skeletal muscle disorder. Resistance exercise and physical activity have been proven effective in its treatment, but consensus on pharmacological interventions has not yet been reached in clinical practice. ß-Hydroxy-ß-methylbutyrate (HMB) is a nutritional supplement that has demonstrated favorable effects on muscle protein turnover, potentially contributing to beneficial impacts on sarcopenia. Aim: To assess the potential positive effects of HMB or HMB-containing supplements on individuals with sarcopenia, a systematic review and meta-analysis was conducted. Methods: A systematic review and meta-analysis were conducted on randomized controlled trials (RCTs) examining the treatment of sarcopenia with HMB. Two assessors independently conducted screening, data extraction, and bias risk assessment. Outcome data were synthesized through a random-effects model in meta-analysis, using the mean difference (MD) as the effect measure. Results: A meta-analysis was conducted on six studies. HMB or HMB-rich nutritional supplements showed a statistically significant difference in Hand Grip Strength (HGS) for sarcopenia patients [MD = 1.26, 95%CI (0.41, 2.21), p = 0.004], while there was no statistically significant difference in Gait Speed (GS) [MD = 0.04, 95%CI (-0.01, 0.08), p = 0.09], Fat Mass (FM) [MD = -0.18, 95%CI (-0.38, 0.01), p = 0.07], Fat-Free Mass (FFM) [MD = 0.09, 95%CI (-0.23, 0.42), p = 0.58], and Skeletal Muscle Index (SMI) [MD = 0.01, 95%CI (-0.00, 0.01), p = 0.13]. Conclusion: HMB or HMB-rich nutritional supplements are beneficial for muscle strength in sarcopenia patients. However, there is limited evidence demonstrating significant effects on both muscle strength and physical performance in sarcopenia individuals. HMB may be considered as a treatment option for sarcopenia patients. Systematic review registration: CRD42024512119.

Comparing the Efficacy of Antiosteoporotic Drugs in Preventing Periprosthetic Bone Loss Following Total Hip Arthroplasty: A Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: Periprosthetic bone loss is a well-known phenomenon following total hip arthroplasty (THA). However, the choice of drugs for prevention remains controversial. Therefore, the aim of this study was to determine the best drug to treat periprosthetic bone loss by comparing changes in bone mineral density (BMD) at different times after THA. METHODS: A comprehensive search of five databases and two clinical trial registration platforms was undertaken from their inception through to August 31, 2023 to identify eligible randomized controlled trials. A Bayesian network meta-analysis (NMA) was carried out for calculating the standardized mean difference (SMD) and the surface under cumulative ranking curve (SUCRA) of the BMD in calcar (Gruen zone 7) at 6 months, 12 months, and 24 months and over. RESULTS: Twenty-nine trials involving 1427 patients and 10 different interventions were included. The results demonstrated that at 6 months, denosumab had the highest ranking (SUCRA = 0.90), followed by alendronate (SUCRA = 0.76), and zoledronate (SUCRA = 0.73). At 12 months, clodronate ranked highest (SUCRA = 0.96), followed by denosumab (SUCRA = 0.84) and teriparatide (SUCRA = 0.82). For interventions with a duration of 24 months and over, denosumab had the highest SUCRA value (SUCRA = 0.96), followed by raloxifene (SUCRA = 0.90) and zoledronate (SUCRA = 0.75). CONCLUSION: Investigating the existing body of evidence revealed that denosumab demonstrates potential as an intervention of superior efficacy at the three specifically examined time points. However, it remains crucial to conduct further research to confirm these findings and determine the most effective treatment strategy.

Etiology, pathology, and treatment of osteonecrosis of the femoral head in adolescents: A comprehensive review.

Femoral head necrosis is a common refractory disease in orthopedics, and shows a trend of getting younger. The occurrence of femoral head necrosis in adolescents is related to the use of glucocorticoids, autoimmune diseases, trauma, and other factors. Because adolescent patients are in the period of physical development, high activity requirements, and have fertility needs in the future, treatment is relatively difficult. Early artificial joint replacement may have problems such as wear and loosening, so total hip replacement is not the preferred treatment for adolescent patients with femoral head necrosis. This article will elaborate the research progress of femoral head necrosis in adolescents from 3 aspects, and summarize the benefits and side effects of core decompression combined with autologous stem cell transplantation in the treatment of early femoral head necrosis, so as to provide clinical ideas for the treatment of femoral head necrosis in adolescents.

Epimedium-Curculigo herb pair enhances bone repair with infected bone defects and regulates osteoblasts through LncRNA MALAT1/miR-34a-5p/SMAD2 axis.

Infected bone defects (IBDs) are the common condition in the clinical practice of orthopaedics. Although surgery and anti-infective medicine are the firstly chosen treatments, in many cases, patients experience a prolonged bone union process after anti-infective treatment. Epimedium-Curculigo herb pair (ECP) has been proved to be effective for bone repair. However, the mechanisms of ECP in IBDs are insufficiency. In this study, Effect of ECP in IBDs was verified by micro-CT and histological examination. Qualitative and quantitative analysis of the main components in ECP containing medicated serum (ECP-CS) were performed. The network pharmacological approaches were then applied to predict potential pathways for ECP associated with bone repair. In addition, the mechanism of ECP regulating LncRNA MALAT1/miRNA-34a-5p/SMAD2 signalling axis was evaluated by molecular biology experiments. In vivo experiments indicated that ECP could significantly promote bone repair. The results of the chemical components analysis and the pathway identification revealed that TGF-ß signalling pathway was related to ECP. The results of in vitro experiments indicated that ECP-CS could reverse the damage caused by LPS through inhibiting the expressions of LncRNA MALAT1 and SMAD2, and improving the expressions of miR-34a-5p, ALP, RUNX2 and Collagen type І in osteoblasts significantly. This research showed that ECP could regulate the TGF-ß/SMADs signalling pathway to promote bone repair. Meanwhile, ECP could alleviate LPS-induced bone loss by modulating the signalling axis of LncRNA MALAT1/miRNA-34a-5p/ SMAD2 in IBDs.

Clinical Efficacy of Intra-articular Tranexamic Acid Injection in the Management of Hemophilia with Total Hip Arthroplasty: A 24-month Retrospective Cohort Study.

OBJECTIVE: Total hip arthroplasty (THA) effectively treats end-stage hemophilic hip arthropathy. Given hemophilia's unique characteristics, perioperative bleeding remains a significant risk for patients undergoing THA. Tranexamic acid (TXA), an efficient antifibrinolytic agent, may benefit the outcomes of THA for patients with hemophilia (PWH). This study aims to explore the clinical efficacy of intra-articular injection of TXA in treating perioperative bleeding in PWH and assess its additional clinical benefits. METHODS: The retrospective study comprised data of PWH who received THA from January 2015 to December 2021 in the research center. A total of 59 individuals were included in the study, divided into a TXA group (n = 31) and a non-TXA group (n = 28). We compared various parameters, including total blood loss (TBL), visible blood loss (VBL), occult blood loss (OBL), intraoperative coagulation factor VIII (FVIII) consumption, perioperative total FVIII consumption, hemoglobin (HB), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), length of hospital stay, hospitalization costs, length of surgery, total protein, activated partial thromboplastin time (APTT), D-dimer, rate of joint swelling, hip joint range of motion (ROM), visual analogue scale (VAS), and Harris hip joint function scale (HHS) between the two groups. Follow-up assessments were conducted for up to 24 months. A Student's t test was utilized for the statistical analysis. RESULTS: This study demonstrated that intra-articular TXA effectively reduced TBL (1248.19 ± 439.88 mL, p < 0.001), VBL (490.32 ± 344.34 mL, p = 0.003), and OBL (757.87 ± 381.48 mL, p = 0.004) in PWH who underwent THA. TXA demonstrated effectiveness in reducing VAS scores on POD1, POD7, and POD14 and joint swelling rates on POD1, POD7, POD14, and at discharge (p < 0.05). Additionally, the TXA group achieved higher HHS ratings at all follow-up time points (p < 0.05), showing superior hip joint mobility, lower postoperative inflammation levels, reduced factor VIII consumption during surgery, and less postoperative nutritional loss. No statistically significant differences were observed between the two groups in terms of hospital stay, hospitalization costs, surgery duration, and coagulation indicators. CONCLUSION: Intra-articular injection of TXA reduces perioperative bleeding in PWH undergoing THA while also improving joint mobility, post-operative rehabilitation, and quality of life. This may provide value for the future application of TXA in PWH.

Corrigendum: Nanofat lysate ameliorates pain and cartilage degradation of osteoarthritis through activation of TGF-ß-Smad2/3 signaling of chondrocytes.

[This corrects the article DOI: 10.3389/fphar.2023.900205.].

miRNA-seq analysis of high glucose induced osteoblasts provides insight into the mechanism underlying diabetic osteoporosis.

The present study aims to explore the etiology of Diabetic osteoporosis (DOP), a chronic complication associated with diabetes mellitus. Specifically, the research seeks to identify potential miRNA biomarkers of DOP and investigated role in regulating osteoblasts. To achieve this, an animal model of DOP was established through the administration of a high-sugar and high-fat diet, and then injection of streptozotocin. Bone microarchitecture and histopathology analysis were analyzed. Rat calvarial osteoblasts (ROBs) were stimulated with high glucose (HG). MiRNA profiles of the stimulated osteoblasts were compared to control osteoblasts using sequencing. Proliferation and mineralization abilities were assessed using MTT assay, alkaline phosphatase, and alizarin red staining. Expression levels of OGN, Runx2, and ALP were determined through qRT-PCR and Western blot. MiRNA-sequencing results revealed increased miRNA-702-5p levels. Luciferase reporter gene was utilized to study the correlation between miR-702-5p and OGN. High glucose impaired cell proliferation and mineralization in vitro by inhibiting OGN, Runx2, and ALP expressions. Interference with miR-702-5p decreased OGN, Runx2, and ALP levels, which were restored by OGN overexpression. Additionally, downregulation of OGN and Runx2 in DOP rat femurs was confirmed. Therefore, the miRNA-702-5p/OGN/Runx2 signaling axis may play a role in DOP, and could be diagnostic biomarker and therapeutic target for not only DOP but also other forms of osteoporosis.

Crohn's disease in hemophilic arthropathy patient: a case report.

Crohn's disease (CD) is an inflammatory bowel disease affecting the digestive tract, the incidence of which is on the rise worldwide. The most common clinical manifestation of hemophilia is arthropathy secondary to recurrent joint effusions and chronic synovitis. This article reports on a rare 25-year-old male patient with both hemophilic arthropathy and Crohn's disease who was at risk for pathogenic gastrointestinal bleeding. After undergoing endoscopic pathologic testing and genetic testing, a multidisciplinary expert work-up of a treatment and nutritional plan was performed. The patient improved clinically and adhered to conservative treatment. This case report is the first report of this rare co-morbidity, demonstrating the highly pathogenic mutation locus and summarizing the clinical experience of early diagnosis and treatment.

Aberrant methylation and expression of TNXB promote chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling.

Recurrent joint bleeding in hemophilia patients frequently causes hemophilic arthropathy (HA). Drastic degradation of cartilage is a major characteristic of HA, but its pathological mechanisms has not yet been clarified. In HA cartilages, we found server matrix degradation and increased expression of DNA methyltransferase proteins. We thus performed genome-wide DNA methylation analysis on human HA (N=5) and osteoarthritis (OA) (N=5) articular cartilages, and identified 1228 differentially methylated regions (DMRs) associated with HA. Functional enrichment analyses revealed the association between DMR genes (DMGs) and extracellular matrix (ECM) organization. Among these DMGs, Tenascin XB (TNXB) expression was down-regulated in human and mouse HA cartilages. The loss of Tnxb in F8-/- mouse cartilage provided a disease-promoting role in HA by augmenting cartilage degeneration and subchondral bone loss. Tnxb knockdown also promoted chondrocyte apoptosis and inhibited phosphorylation of AKT. Importantly, AKT agonist showed chondroprotective effects following Tnxb knockdown. Together, our findings indicate that exposure of cartilage to blood leads to alterations in DNA methylation, which is functionally related to ECM homeostasis, and further demonstrate a critical role of TNXB in HA cartilage degeneration by activating AKT signaling. These mechanistic insights allow development of potentially new strategies for HA cartilage protection.

MINK1 deficiency stimulates nucleus pulposus cell pyroptosis and exacerbates intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration, induced by aging and irregular mechanical strain, is highly prevalent in the elderly population, serving as a leading cause of chronic low back pain and disability. Evolving evidence has revealed the involvement of nucleus pulposus (NP) pyroptosis in the pathogenesis of IVD degeneration, while the precise regulatory mechanisms of NP pyroptosis remain obscure. Misshapen/Nck-interacting kinase (NIK)-related kinase 1 (MINK1), a serine-threonine protein kinase, has the potential to modulate the activation of NLRP3 inflammasome, indicating its pivotal role in governing pyroptosis. In this study, to assess the significance of MINK1 in NP pyroptosis and IVD degeneration, NP tissues from patients with varying degrees of IVD degeneration, and IVD tissues from both aging-induced and lumbar spine instability (LSI) surgery-induced IVD degeneration mouse models, with or without MINK1 ablation, were meticulously evaluated. Our findings indicated a notable decline in MINK1 expression in NP tissues of patients with IVD degeneration and both mouse models as degeneration progresses, accompanied by heightened matrix degradation and increased NP pyroptosis. Moreover, MINK1 ablation led to substantial activation of NP pyroptosis in both mouse models, and accelerating ECM degradation and intensifying the degeneration phenotype in mechanically stress-induced mice. Mechanistically, MINK1 deficiency triggered NF-κB signaling in NP tissues. Overall, our data illustrate an inverse correlation between MINK1 expression and severity of IVD degeneration, and the absence of MINK1 stimulates NP pyroptosis, exacerbating IVD degeneration by activating NF-κB signaling, highlighting a potential innovative therapeutic target in treating IVD degeneration.

The association between weight-adjusted-waist index and sarcopenia in adults: a population-based study.

This study aims to investigate the relationship between weight-adjusted-waist index (WWI), a new body index, and sarcopenia, while also assessing the potential of WWI as a tool for screening sarcopenic patients. The cross-sectional study involved adults who possessed complete data on WWI and appendicular skeletal muscle mass from the 1999-2006 and 2011-2018 National Health and Nutrition Examination Surveys. Weighted multivariate regression and logistic regression analyses were employed to explore the independent relationship between WWI and sarcopenia. The study included 26,782 participants. The results showed that WWI demonstrated a positive correlation with sarcopenia risk. In the fully adjusted model, with each 1 unit increase in WWI, the risk of developing sarcopenia rose 14.55 times higher among males (OR: 14.55, 95% CI 12.33, 17.15) and 2.86 times higher among females (OR: 2.86, 95% CI 2.59, 3.15). The optimal cutoff values of WWI for sarcopenia were 11.26 cm/√kg for males and 11.39 cm/√kg for females. Individuals with a higher WWI have an increased risk of developing sarcopenia, and a high WWI functions as a risk factor for sarcopenia. Assessing WWI could assist in identifying individuals at risk of sarcopenia.

Factors influencing periprosthetic bone mineral density in total knee arthroplasty: a systematic review.

INTRODUCTION: Following total knee arthroplasty (TKA), there is a significant decline in periprosthetic bone mineral density (BMD), potentially resulting in complications such as prosthetic loosening, periprosthetic fracture, and influencing the postoperative recovery. The objective of this study was to summarize the factors influencing periprosthetic BMD in TKA from existing studies. METHODS: A comprehensive systematic search was performed in 4 databases: Pubmed, Embase, Web of Science, and Cochrane Library. The last search was carried out on October 12, 2023. We used the keywords ''total knee arthroplasty'', ''bone mineral density'' and each of them combined with ''tibia'' and ''femur'' to identify all relevant articles reporting about potential impact factors influencing the periprosthetic BMD in patients after TKA. RESULTS: Out of 1391 articles, 22 published from 2001 to 2023 were included in this systematic review. Following eligibility screening, six significant categories affecting periprosthetic BMD were recognized: prosthesis type, design of stem, coating, body weight, cement, and peg distance. CONCLUSION: Mobile-bearing prostheses, modular polyethylene design, short stems, cruciform stems, avoidance of bone cement, higher body mass index, titanium nitride coating, and a smaller medial peg distance could potentially benefit periprosthetic BMD. Comprehensive consideration of diverse factors influencing periprosthetic BMD before surgery and collaboration with post-operative drug therapy are essential. TRIAL REGISTRY: The PROSPERO registration number is CRD42023472030.

Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study.

Purpose: To explore the effect of AFN on knee function and complications in patients after TKA. Methods: We evaluated 150 patients undergoing unilateral TKA, specifically including 102 patients with varying degrees of AFN after selection. They were divided into four groups based on AFN grade. About 48 patients did not produce AFN, 63 patients were grade I, 29 patients were grade II, and 10 patients were grade III. All patients were followed up for 24 months, and knee function, pain, complications, and other indicators were compared between the four groups. Correlation analysis and regression analysis were used to study the relationship between AFN and other indicators. Results: Two cases of periprosthetic fractures (PPF) occurred in our study, with an incidence of 1.35%, which did not show a significant association with AFN. The changes in knee social score (ΔKSS), Western Ontario and McMaster Universities Osteoarthritis Index (ΔWOMAC), and postoperative anterior knee pain visual analog scale (VAS) score were higher in patients with AFN than in those without. Particularly, grades II and III AFN demonstrated superior efficacy. Pearson's correlation analysis showed that AFN grade is positively correlated with both ΔKSS and ΔWOMAC (r = 0.44, P < 0.001), and AFN grade had a negative correlation with the anterior knee pain VAS (r = -0.250, P < 0.05). In linear regression analysis, AFN grade was positively correlated with both ΔKSS (ß = 5.974, 95% CI: 3.968-7.981, P < 0.001) and ΔWOMAC (ß = 6.356, 95% CI: 4.223-8.490, P < 0.001). Besides that, there was a negative correlation between AFN grade and anterior knee pain (ß = 5.974, 95% CI: 3.968-7.981, P < 0.05). Conclusion: Patients with grade II and III AFN who underwent TKA exhibited better knee function and lower levels of anterior knee pain post-surgery.

Expert consensus on Prospective Precision Diagnosis and Treatment Strategies for Osteoporotic Fractures.

Osteoporotic fractures are the most severe complications of osteoporosis, characterized by poor bone quality, difficult realignment and fixation, slow fracture healing, and a high risk of recurrence. Clinically managing these fractures is relatively challenging, and in the context of rapid aging, they pose significant social hazards. The rapid advancement of disciplines such as biophysics and biochemistry brings new opportunities for future medical diagnosis and treatment. However, there has been limited attention to precision diagnosis and treatment strategies for osteoporotic fractures both domestically and internationally. In response to this, the Chinese Medical Association Orthopaedic Branch Youth Osteoporosis Group, Chinese Geriatrics Society Geriatric Orthopaedics Committee, Chinese Medical Doctor Association Orthopaedic Physicians Branch Youth Committee Osteoporosis Group, and Shanghai Association of Integrated Traditional Chinese and Western Medicine Osteoporosis Professional Committee have collaborated to develop this consensus. It aims to elucidate emerging technologies that may play a pivotal role in both diagnosis and treatment, advocating for clinicians to embrace interdisciplinary approaches and incorporate these new technologies into their practice. Ultimately, the goal is to improve the prognosis and quality of life for elderly patients with osteoporotic fractures.

How Do Muscle Function and Quality Affect the Progression of KOA? A Narrative Review.

Knee osteoarthritis (KOA) is widely recognized as a chronic joint disease characterized by degeneration of knee cartilage and subsequent bone hyperplasia. However, it is important to acknowledge the significant role of muscles in the development and progression of KOA. Muscle function (MF) and muscle quality (MQ) are key factors in understanding the involvement of muscles in KOA. Quantitative indices such as muscle mass, muscle strength, muscle cross-sectional area, muscle thickness, and muscle fatigue are crucial in assessing MF and MQ. Despite the growing interest in KOA, there is a scarcity of studies investigating the relationship between muscles and this condition. This review aims to examine the commonly used indices and measurement methods for assessing MF and MQ in clinical settings, while also exploring the association between muscles and KOA. Furthermore, this article highlights the importance of restoring MF and MQ to enhance symptom management and improve the quality of life for patients with KOA.

An evidence-based guideline on treating lumbar disc herniation with traditional Chinese medicine.

BACKGROUND: Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. STUDY DESIGN: Evidence-based guideline. METHODS: We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. CONCLUSION: This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.