Impact of intraosseous regional administration of tranexamic acid in total knee arthroplasty on perioperative blood loss: a protocol for a randomised controlled trial.

INTRODUCTION: Total knee arthroplasty (TKA) is a common surgical intervention to treat joint diseases. However, TKA is associated with significant blood loss. Tranexamic acid (TXA) has been used to reduce perioperative bleeding and postoperative blood transfusion. This study aims to explore the effectiveness and safety of intraosseous regional administration (IORA) of TXA in TKA and compare differences in perioperative blood loss between IORA of TXA, intravenous infusion of TXA, and combined IORA and intravenous infusion of TXA. METHODS AND ANALYSIS: This randomised controlled trial will enrol 105 patients with osteoarthritis who meet the inclusion criteria for unilateral TKA. Patients were randomly divided into three groups using the random number table method. Group A received 1.0 g of TXA via IORA, group B received 1.0 g of TXA via intravenous infusion 15 min prior to the tourniquet release, and group C received both IORA of 1.0 g of TXA and intravenous infusion of 1.0 g of TXA. The primary outcome measure is perioperative total blood loss. Secondary outcomes include bleeding events, venous thromboembolism events, inflammation reactions, other complications and knee function assessments. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Peking Union Medical College Hospital and registered in the Chinese Clinical Trial Registry. Informed consent will be obtained from all the patients before enrolment. The trial will be conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The results of this study will be disseminated through peer-reviewed publications, conference presentations and social media platforms. The findings will provide valuable insights into the use of IORA of TXA in TKA and may lead to the development of new strategies for perioperative blood management in joint replacement surgery. TRIAL REGISTRATION NUMBER: The Ethics Committee of Peking Union Medical College Hospital (approval number: K2371); Chinese Clinical Trial Registry (trial registration number: ChiCTR2200066293).

The impact of COVID-19 on hip and knee arthroplasty surgical volume in China.

PURPOSE: The reduction of hip and knee arthroplasty surgical volume has been reported in many countries during the COVID-19 pandemic. In China, there is no national joint registry system and the impact of COVID-19 towards surgical volume remains unclear. The aim of this study was to investigate the hip and knee arthroplasty surgical volume in China during the pandemic and evaluate its change trends. METHODS: Annual sale numbers of prostheses used in total knee arthroplasty (TKA), total hip arthroplasty (THA), and femoral head replacement (FHR) from 2011 to 2021 was collected from providers registered in National Medical Products Administration (NMPA). Annual surgical volume of TKA, THA, FHR, unicompartmental knee arthroplasty (UKA), and revision of hip/knee arthroplasty (RJA) was collected from member hospitals of Beijing Joint Society (BJS). We used linear regression to estimate the loss of surgical volume. Annual surgical volume obtained from Britain and Australian joint registries were used to make comparison. RESULTS: In China, the surgical volume of THA/FHR, TKA, and UKA in 2020 all decreased compared to the predicted value, with a reduction of 82,525 cases (13.46%), 165,178 cases (33.50%), and 151 cases (0.65%), respectively. All the three procedures showed significant recovery in 2021. The surgical volumes of THA/FHR and UKA were 68,813 and 9402 cases higher than predicted levels, respectively, while TKA volume remained slightly below the predicted level. The regional statistics in Beijing showed similar change mode. In 2020, the surgical volume of THA/FHR, TKA, FHR, and UKA all decreased compared to the predicted value, with a reduction of 5031 cases (43.37%), 5290 cases (40.69%), 620 cases (29.18%), and 925 cases (39.11%), respectively. In 2021, with the exception of FHR, the number of these procedures increased compared to 2020, but remained below the predicted value. Compared with the data from Britain and Australia, China experienced less reduction and faster recovery in the proportions of elderly people (> 65 years old) who undergo hip and knee arthroplasty during the COVID-19 pandemic. CONCLUSION: During the COVID-19 pandemic, although hip and knee arthroplasty surgical volume in China showed a similar "restoration-recovery" change pattern with other countries, China took fewer losses in this field.

Hepatic arterial infusion chemotherapy with or without lenvatinib for unresectable cholangiocarcinoma: a single-center retrospective study.

Aim: The purpose of this study is to compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil and leucovorin (FOLFOX) plus lenvatinib and FOLFOX-HAIC alone in patients with unresectable cholangiocarcinoma. Patients & methods: Retrospective analysis of patients receiving FOLFOX-HAIC with or without lenvatinib. Results: Forty-one patients were included, with 22 patients receiving HAIC alone and 19 patients receiving HAIC plus lenvatinib. Combination treatment significantly prolonged overall survival and progression-free survival compared with HAIC alone. Grade 1-2 adverse events were more frequent in the combination group but manageable. No severe AEs or treatment-related deaths were reported. Conclusion: FOLFOX-HAIC plus lenvatinib has the potential to be a treatment option for unresectable cholangiocarcinoma.

This study compared the effectiveness and safety of two treatments for unresectable cholangiocarcinoma (CCA), a type of liver cancer. The first treatment involved a combination of hepatic arterial infusion chemotherapy (FOLFOX-HAIC) and lenvatinib, a targeted therapy drug. The second treatment was FOLFOX-HAIC alone. The study included 41 patients with CCA, and the results showed that the group receiving FOLFOX-HAIC plus lenvatinib had significantly longer overall survival (32.0 months) and progression-free survival (20.0 months) compared with the group receiving FOLFOX-HAIC alone. The combination treatment had manageable side effects, although some mild adverse events were more common in the combination group. The study suggests that FOLFOX-HAIC plus lenvatinib could be a potential treatment option for unresectable CCA.

Hepatic arterial infusion chemotherapy plus lenvatinib with or without programmed cell death protein-1 inhibitors for advanced cholangiocarcinoma.

Background: New treatment strategies are needed to improve outcomes for patients with advanced cholangiocarcinoma (CCA) due to the limited efficacy of current first-line chemotherapy regimens. Although the combination of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and programmed cell death protein-1 (PD-1) inhibitors has been extensively evaluated in the treatment of advanced hepatocellular carcinoma, their roles in advanced CCA remain poorly understood. The purpose of this study is to compare the efficacy and safety of HAIC plus lenvatinib with or without PD-1 inhibitors in patients with advanced CCA. Methods: Between March 2019 to June 2022, patients diagnosed with advanced CAA who received HAIC plus lenvatinib with or without PD-1 inhibitors treatment were reviewed for eligibility. Efficacy was evaluated according to survival and tumor response, and safety was evaluated according to the incidence of adverse events (AEs). Results: Fifty-five patients with advanced CCA were included in the study, and they were divided into the HAIC+lenvatinib (LEN)+PD-1 inhibitors (PD-1i) group (n = 35) and HAIC+LEN group (n = 20). The median follow-up time was 14.0 (5-42) months. Patients in the HAIC+LEN+PD-1i group had significantly better PFS (HR = 0.390; 95% CI 0.189-0.806; p = 0.001) and OS (HR = 0.461; 95% CI 0.229-0.927; p = 0.01) than those in the HAIC+LEN group. The HAIC+LEN+PD-1i group showed a higher objective response rate and disease control rate than the HAIC+LEN group but did not find a significant difference. The incidence of grade 1-2 and grade 3-4 AEs was not significantly higher in the HAIC+LEN+PD-1i group compared to the HAIC+LEN group, whereas two patients (5.7%) in the HAIC+LEN+PD-1i group experienced grade 5 immune-mediated pneumonia. Conclusion: HAIC plus lenvatinib with PD-1 inhibitors is safe and well-tolerated, and has the potential to prolong the survival of patients with advanced CCA. The addition of PD-1 inhibitors may enhance the efficacy of HAIC and lenvatinib. Therefore, the combined therapy has the potential to become a treatment option for advanced CCA.

Polyetheretherketone development in bone tissue engineering and orthopedic surgery.

Polyetheretherketone (PEEK) has been widely used in the medical field as an implant material, especially in bone tissue engineering and orthopedic surgery, in recent years. This material exhibits superior stability at high temperatures and is biosecured without harmful reactions. However, the chemical and biological inertness of PEEK still limits its applications. Recently, many approaches have been applied to improve its performance, including the modulation of physical morphology, chemical composition and antimicrobial agents, which advanced the osteointegration as well as antibacterial properties of PEEK materials. Based on the evolution of PEEK biomedical devices, many studies on the use of PEEK implants in spine surgery, joint surgery and trauma repair have been performed in the past few years, in most of which PEEK implants show better outcomes than traditional metal implants. This paper summarizes recent studies on the modification and application of biomedical PEEK materials, which provides further research directions for PEEK implants.

Case report: Be alert to herpes zoster after total knee arthroplasty.

An 88-year-old woman started complaining of severe pain at the right knee and above at three weeks after right total knee arthroplasty (TKA). The empirical treatment cannot effectively control the progress of pain. The lesion was eventually diagnosed to be due to herpes zoster (HZ). The finding of HZ was unexpected in this case, because HZ is extremely rare in patients after TKA.

Advances and Progress in Self-Healing Hydrogel and Its Application in Regenerative Medicine.

A hydrogel is a three-dimensional structure that holds plenty of water, but brittleness largely limits its application. Self-healing hydrogels, a new type of hydrogel that can be repaired by itself after external damage, have exhibited better fatigue resistance, reusability, hydrophilicity, and responsiveness to environmental stimuli. The past decade has seen rapid progress in self-healing hydrogels. Self-healing hydrogels can automatically self-repair after external damage. Different strategies have been proposed, including dynamic covalent bonds and reversible noncovalent interactions. Compared to traditional hydrogels, self-healing gels have better durability, responsiveness, and plasticity. These features allow the hydrogel to survive in harsh environments or even to be injected as a drug carrier. Here, we summarize the common strategies for designing self-healing hydrogels and their potential applications in clinical practice.

The Ilizarov technique in the management of haemophilic knee flexion contracture.

INTRODUCTION: The Ilizarov technique has the potential to be an attractive option for severe knee flexion contracture (KFC) patients with a high risk of bleeding. However, studies on this technique in the management of haemophilic KFC are scarce. AIM: The purpose of this study was to review and analyse the results of the Ilizarov technique in correcting haemophilic KFC and to evaluate the safety and efficacy of this technique. METHODS: Twelve male haemophilia patients with severe KFC who underwent distraction treatment using the Ilizarov technique from June 2013 to April 2019 were included in this study. The hospital day, flexion contracture, range of motion (ROM) of the knees, complications and functional outcomes were recorded and analysed. Functional outcomes were evaluated according to the Hospital for Special Surgery (HSS) knee scores of the preoperation, end of distraction and last follow-up. RESULTS: The average preoperative flexion contracture and range of motion (ROM) of the knees were 55 ± 15° and 66 ± 18°, respectively. The average preoperative HSS knee score was 47 ± 5. The average duration of follow-up was 75.5 ± 30.1 months. All flexion contractures achieved full correction (≤5°) at the end of distraction, and the flexion contracture significantly decreased to 6 ± 5° at the last follow-up (p < .0001). The ROM of the knees was significantly increased at the last follow-up compared with that before distraction treatment (p < .0001). The HSS knee scores at the end of distraction and at the last follow-up were both significantly higher than the preoperative HSS knee score (p < .0001). No major complications were encountered. CONCLUSIONS: This study provided evidence for the safety and effectiveness of Ilizarov technique plus physical therapy in the management of haemophilic KFC and accumulated clinical experience for the proper application of this technology.

Advances in Mesenchymal Stem Cell Therapy for Osteoarthritis: From Preclinical and Clinical Perspectives.

The prevalence of osteoarthritis (OA), a degenerative disorder of joints, has substantially increased in recent years. Its key pathogenic hallmarks include articular cartilage destruction, synovium inflammation, and bone remodeling. However, treatment outcomes are unsatisfactory. Until recently, common therapy methods, such as analgesic and anti-inflammatory treatments, were aimed to treat symptoms that cannot be radically cured. Mesenchymal stem cells (MSCs), i.e., mesoderm non-hematopoietic cells separated from bone marrow, adipose tissue, umbilical cord blood, etc., have been intensively explored as an emerging technique for the treatment of OA over the last few decades. According to existing research, MSCs may limit cartilage degradation in OA by interfering with cellular immunity and secreting a number of active chemicals. This study aimed to examine the potential mechanism of MSCs in the treatment of OA and conduct a thorough review of both preclinical and clinical data.

Advances in Biomaterial-Mediated Gene Therapy for Articular Cartilage Repair.

Articular cartilage defects caused by various reasons are relatively common in clinical practice, but the lack of efficient therapeutic methods remains a substantial challenge due to limitations in the chondrocytes' repair abilities. In the search for scientific cartilage repair methods, gene therapy appears to be more effective and promising, especially with acellular biomaterial-assisted procedures. Biomaterial-mediated gene therapy has mainly been divided into non-viral vector and viral vector strategies, where the controlled delivery of gene vectors is contained using biocompatible materials. This review will introduce the common clinical methods of cartilage repair used, the strategies of gene therapy for cartilage injuries, and the latest progress.

Recent Developments and Current Applications of Organic Nanomaterials in Cartilage Repair.

Regeneration of cartilage is difficult due to the unique microstructure, unique multizone organization, and avascular nature of cartilage tissue. The development of nanomaterials and nanofabrication technologies holds great promise for the repair and regeneration of injured or degenerated cartilage tissue. Nanomaterials have structural components smaller than 100 nm in at least one dimension and exhibit unique properties due to their nanoscale structure and high specific surface area. The unique properties of nanomaterials include, but are not limited to, increased chemical reactivity, mechanical strength, degradability, and biocompatibility. As an emerging nanomaterial, organic nanocomposites can mimic natural cartilage in terms of microstructure, physicochemical, mechanical, and biological properties. The integration of organic nanomaterials is expected to develop scaffolds that better mimic the extracellular matrix (ECM) environment of cartilage to enhance scaffold-cell interactions and improve the functionality of engineered tissue constructs. Next-generation hydrogel technology and bioprinting can be used not only for healing cartilage injury areas but also for extensive osteoarthritic degenerative changes within the joint. Although more challenges need to be solved before they can be translated into full-fledged commercial products, nano-organic composites remain very promising candidates for the future development of cartilage tissue engineering.

Bone Density May Be a Promising Predictor for Blood Loss during Total Hip Arthroplasty.

BACKGROUND: Total hip arthroplasty (THA), which is performed mostly in elderly individuals, can result in substantial blood loss and thereby imposes a significant physical burden and risk of blood transfusion. The femoral neck cut and reamed acetabulum are the main sites of intraoperative bleeding. Whether the bone density in that region can be used to predict the amount of blood loss in THA is unknown. METHODS: We retrospectively analyzed adult patients undergoing primary THA in the Department of Orthopedics, Peking Union Medical College Hospital, from January 2018 to January 2020. All these patients underwent primary unilateral THA. Patients had their bone mineral density (BMD) recorded within the week before surgery and were stratified and analyzed for perioperative blood loss. Multivariable regressions were utilized to adjust for differences in demographics and comorbidities among groups. RESULTS: A total of 176 patients were included in the study. Intraoperative blood loss was 280.1 ± 119.56 mL. Pearson correlation analysis showed a significant correlation between blood loss and preoperative bone density of both the femoral greater trochanter (R = 0.245, p = 0.001) and the Ward's triangle (R = 0.181, p = 0.016). Stepwise multiple linear regression showed that preoperative bone density of the greater trochanter (p = 0.015, 95% CI: 0.004-0.049) and sex (p = 0.002) were independent risk factors for THA bleeding. The area under the receiver operating characteristic curve (AUROC) of the greater trochanter and Ward's triangle was 0.593 (95% CI: 0.507-0.678, p = 0.035) and 0.603 (95% CI: 0.519-0.688, p = 0.018), respectively. The cutoff T value on the femoral greater trochanter for predicting higher bleeding was -1.75. CONCLUSIONS: In THA patients, preoperative bone density values of the femoral greater trochanter and sex could be promising independent predictors for bleeding during surgery. Osteoporosis and female patients might have lower blood loss in the THA operation.

Carma3 Protects from Liver Injury by Preserving Mitochondrial Integrity in Liver Sinusoidal Endothelial Cells.

Carma3 is an intracellular scaffolding protein that can form complex with Bcl10 and Malt1 to mediate G protein-coupled receptor- or growth factor receptor-induced NF-κB activation. However, the in vivo function of Carma3 has remained elusive. Here, by establishing a Con A-induced autoimmune hepatitis model, we show that liver injury is exacerbated in Carma3 -/- mice. Surprisingly, we find that the Carma3 expression level is higher in liver sinusoidal endothelial cells (LSECs) than in hepatocytes in the liver. In Carma3 -/- mice, Con A treatment induces more LSEC damage, accompanied by severer coagulation. In vitro we find that Carma3 localizes at mitochondria and Con A treatment can trigger more mitochondrial damage and cell death in Carma3-deficient LSECs. Taken together, our data uncover an unrecognized role of Carma3 in maintaining LSEC integrity, and these results may extend novel strategies to prevent liver injury from toxic insults.

Immune Cells in Hyperprogressive Disease under Immune Checkpoint-Based Immunotherapy.

Immunotherapy, an antitumor therapy designed to activate antitumor immune responses to eliminate tumor cells, has been deeply studied and widely applied in recent years. Immune checkpoint inhibitors (ICIs) are capable of preventing the immune responses from being turned off before tumor cells are eliminated. ICIs have been demonstrated to be one of the most effective and promising tumor treatments and significantly improve the survival of patients with multiple tumor types. However, low effective rates and frequent atypical responses observed in clinical practice limit their clinical applications. Hyperprogressive disease (HPD) is an unexpected phenomenon observed in immune checkpoint-based immunotherapy and is a challenge facing clinicians and patients alike. Patients who experience HPD not only cannot benefit from immunotherapy, but also experience rapid tumor progression. However, the mechanisms of HPD remain unclear and controversial. This review summarized current findings from cell experiments, animal studies, retrospective studies, and case reports, focusing on the relationships between various immune cells and HPD and providing important insights for understanding the pathogenesis of HPD.

Recent Developments and Current Applications of Hydrogels in Osteoarthritis.

Osteoarthritis (OA) is a common degenerative joint disease that causes disability if left untreated. The treatment of OA currently requires a proper delivery system that avoids the loss of therapeutic ingredients. Hydrogels are widely used in tissue engineering as a platform for carrying drugs and stem cells, and the anatomical environment of the limited joint cavity is suitable for hydrogel therapy. This review begins with a brief introduction to OA and hydrogels and illustrates the effects, including the analgesic effects, of hydrogel viscosupplementation on OA. Then, considering recent studies of hydrogels and OA, three main aspects, including drug delivery systems, mesenchymal stem cell entrapment, and cartilage regeneration, are described. Hydrogel delivery improves drug retention in the joint cavity, making it possible to deliver some drugs that are not suitable for traditional injection; hydrogels with characteristics similar to those of the extracellular matrix facilitate cell loading, proliferation, and migration; hydrogels can promote bone regeneration, depending on their own biochemical properties or on loaded proregenerative factors. These applications are interlinked and are often researched together.

Bone metabolic indices: Promising predictors for assessing acromegaly.

Acromegaly is a chronic progressive endocrine disease that is often accompanied by joint and bone symptoms. The correlation between bone metabolism and acromegaly is still unclear. In this study, 31 patients with acromegaly at Peking Union Medical College Hospital were included. Bone metabolism indices, such as ß-CTX, TP1NP, T-25OHD, 1,25(OH)2D3, and SAGIT score, which represent the severity of acromegaly, were examined before operation, and the patients were followed up for at least 3 months after operation. The results showed that ß-CTX and TP1NP were significantly lower than those before surgery in the remission group (p < 0.001). In the nonremission group, CTX (p = 0.226) and TP1NP (p = 0.326) did not show significant differences from those before operation. In Pearson correlation analysis, ß-CTX was significantly correlated with SAGIT score (r = 0.356, p = 0.049). By multivariate linear regression analysis, it was found that ß-CTX was an independent risk factor of SAGIT score (p = 0.001). In conclusion, indicators of bone metabolism are closely related to changes in acromegaly, and the ß-CTX value can be used as an effective predictor for assessing acromegaly.

Nanomaterials as Promising Theranostic Tools in Nanomedicine and Their Applications in Clinical Disease Diagnosis and Treatment.

In recent decades, with the rapid development of nanotechnology, nanomaterials have been widely used in the medical field, showing great potential due to their unique physical and chemical properties including minimal size and functionalized surface characteristics. Nanomaterials such as metal nanoparticles and polymeric nanoparticles have been extensively studied in the diagnosis and treatment of diseases that seriously threaten human life and health, and are regarded to significantly improve the disadvantages of traditional diagnosis and treatment platforms, such as poor effectiveness, low sensitivity, weak security and low economy. In this review, we report and discuss the development and application of nanomaterials in the diagnosis and treatment of diseases based mainly on published research in the last five years. We first briefly introduce the improvement of several nanomaterials in imaging diagnosis and genomic sequencing. We then focus on the application of nanomaterials in the treatment of diseases, and select three diseases that people are most concerned about and that do the most harm: tumor, COVID-19 and cardiovascular diseases. First, we introduce the characteristics of nanoparticles according to the excellent effect of nanoparticles as delivery carriers of anti-tumor drugs. We then review the application of various nanoparticles in tumor therapy according to the classification of nanoparticles, and emphasize the importance of functionalization of nanomaterials. Second, COVID-19 has been the hottest issue in the health field in the past two years, and nanomaterials have also appeared in the relevant treatment. We enumerate the application of nanomaterials in various stages of viral pathogenesis according to the molecular mechanism of the complete pathway of viral infection, pathogenesis and transmission, and predict the application prospect of nanomaterials in the treatment of COVID-19. Third, aiming at the most important causes of human death, we focus on atherosclerosis, aneurysms and myocardial infarction, three of the most common and most harmful cardiovascular diseases, and prove that nanomaterials could be involved in a variety of therapeutic approaches and significantly improve the therapeutic effect in cardiovascular diseases. Therefore, we believe nanotechnology will become more widely involved in the diagnosis and treatment of diseases in the future, potentially helping to overcome bottlenecks under existing medical methods.