Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. AIM OF THE STUDY: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. MATERIALS AND METHODS: Based on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: A total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, as well as immune cells in the liver. CONCLUSION: XS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.

The Longest Known Follow-Up of Vitallium Mold Arthroplasty in China: A Case Report and Literature Review.

BACKGROUND: Before the advent of total hip arthroplasty, Vitallium mold arthroplasty had been widely performed. We present a case with a 42-year follow-up after Vitallium mold arthroplasty. To our knowledge, this case represents the longest known follow-up of Vitallium mold arthroplasty in China. CASE PRESENTATION: This was a 59-year-old male. He underwent Vitallium mold arthroplasty of the left hip 42 years ago because of osteonecrosis of the femoral head. He developed left hip pain 3 months ago and underwent total hip revision surgery. There was some clear synovial fluid in the hip joint. The mold was loosened entirely and taken out effortlessly. Gram-positive cocci could be observed occasionally in the synovial fluid smear, while the synovial fluid culture was negative. The inflammatory markers elevated perioperatively, and prophylactic cefuroxime and vancomycin were utilized successively. All elevated inflammatory markers fell since postoperative day 5, and there was no other sign of infection. The pain and function of the hip joint improved significantly after surgery. CONCLUSIONS: Although Vitallium mold arthroplasty was inferior to total hip arthroplasty in survival rate and functional outcome, it did provide an excellent long-term function of the hip joint.

A Retrospective, Long-term Follow-up of the Clinical Outcomes and Cost-effectiveness of Single-anesthetic Multiple Total Joint Procedures in Hemophilic Arthropathy.

OBJECTIVE: Although total joint replacement (TJR) procedures are efficacious, perioperative high-dose factors replacement therapy (FRT) to avoid catastrophic bleeding represents a significant hurdle, particularly for patients with multiple joint affection. Double simultaneous bilateral TJRs were reported as safe and cost-effective. However, little is known about multiple TJRs. The feasibility and effects remain debatable. Surgeons need to weigh the high cost of FRT against safety. Accordingly, we aimed to evaluate the clinical outcomes and cost-effectiveness of single-anesthetic multiple-joint procedures of lower limbs in end-stage hemophilic arthropathy. METHODS: Our retrospective cohort study retrieved data from an inpatient database of patients with hemophilia who underwent total knee arthroplasty (TKA), total hip arthroplasty (THA), and/or ankle arthrodesis from January 2000 to April 2016. Complications, hospital stays, transfusion, doses of clotting factor, medical costs, range of motion (ROM), Harris hip scores (HHSs) and Hospital for special surgery knee scores (HSSs) were recorded. A P value < 0.05 was considered significant. RESULTS: A total number of 81 patients were included in this study, among which 89 TKAs and 52 THAs were performed. Compared to the single TJR group, the simultaneous multiple TJR group showed a significantly higher rate of blood transfusions (P < 0.05). But no significant differences were found in the length of hospital stays, factor consumption, hospitalization costs excluding prosthesis expenses, and total complication rates. Finally, similar postoperative ROM, HHS, and HSS were witnessed in two groups (P value > 0.05). CONCLUSION: Our data indicated that simultaneous multiple TJRs are a safe and cost-effective choice for treating hemophilic patients with multiple HA-affected lower limb joints.

Description of surgical treatment methods of hip and knee periprosthetic joint infections in the Chinese mainland: a national multi-centre survey.

PURPOSE: Periprosthetic joint infection (PJI) is a serious hip and knee arthroplasty complication. Despite the increased incidence of primary joint replacements, there is no clear guideline for treating PJI in the Chinese mainland yet. We aim to measure the current situation and basis for surgical treatment methods of PJI in major orthopaedic hospitals in the Chinese mainland. METHODS: We conducted a national survey on PJI treatment in Mainland China. Forty-one top arthroplasty centers were included, with 82.9% (34/41) response rate. The data were analyzed using Microsoft Excel version 20.0 and described as numbers and percentages. RESULTS: For acute infections, prosthesis-preserving procedures (DAIR) are used in all centres. For hip and knee PJI, 20.5% (7/34) and 35% (12/34) of the centres used a one-stage exchange. If applied, this treatment will necessitate the previous patients' selection for a satisfactory outcome. All centres execute the two-stage exchange. Between phases, the majority of centres implant a cemented spacer. Revisions for infected hips included 21 (4.3%) cases of DAIR, 95 (19.9%) cases of single-stage exchange, 362 (75.2%) cases of two-stage exchange, and 2 (0.007%) cases of hip dissection. Revisions for infected knee comprised 88 (19.0%) cases of DAIR, 48 (10.3%) cases of single-stage exchange, 324 (69.8%) cases of two-stage exchange, and 5 (0.02%) cases of knee fusion. CONCLUSIONS: The centers do not have a uniform PJI standard. Most patients have two-stage revision with a cemented spacer in China. These concepts can help establish treatment guidelines.

Mitigation of postoperative urinary retention among total joint replacement patients using the ERAS protocol and applying risk-stratified catheterization.

BACKGROUNDS: We intended to identify the incidence and risk factors (RFs) for Postoperative urinary retention (POUR) after applying a risk-stratified catheterization optimization method in enhanced recovery after surgery (ERAS)-total joint arthroplasty (TJA). METHODS: A total of 381 patients were prospectively monitored for POUR. POUR diagnosis was done by a perioperative specialist. Data on potential risk factors (RFs) for POUR were accumulated. Univariate analysis (UA) was conducted to identify possible indicators of POUR, followed by multivariate analysis (MA) of identified indicators. RESULTS: POUR occurred in 5.5% of cases, including 8 (3.4%) patients underwent total knee arthroplasty and 13 (10.4%) patients underwent total hip arthroplasty. In UA, age, sex, American Society of Anesthesiologists (ASA) score, and the type of operation were significantly different on UA (P = 0.046, P = 0.022, P = 0.000 and P = 0.049, respectively). Other additional predictors, including body mass index (BMI), international prostate symptom score (IPSS) score, preoperative haemoglobin (Hb), duration of operation, estimated intraoperative blood loss, intraoperative fluid volume, fluid infusion volume within 24 h postoperatively were not associated with POUR (P > 0.05). MA results demonstrated that age, ASA score, type of operation and standard intraoperative placement of an indwelling bladder catheter (SIP-IBC) were strongly associated with POUR development risk (P < 0.05). CONCLUSION: Overall, we had a low POUR incidence in our study cohort. However, with the shift from non-ERAS TJA to ERAS TJA protocol, it is crucial to closely monitor the male gender, advanced age, THA and SIP-IBC, as these variables can markedly enhance POUR risk.

Validation of CT-Based Three-Dimensional Preoperative Planning in Comparison with Acetate Templating for Primary Total Hip Arthroplasty.

OBJECTIVE: This study aims to compare the accuracy of CT-based preoperative planning with that of acetate templating in predicting implant size, neck length, and neck cut length, and to evaluate the reproducibility of the two methods. METHODS: This prospective study was conducted between August 2020 and March 2021. Patients who underwent elective primary total hip arthroplasty by a single surgeon were assessed for eligibility. The included patients underwent both acetate templating and CT-based planning by two observers after the operation. Each observer conducted both acetate templating and CT-based planning twice for each case. The outcome measures included the following: (1) the accuracy of surgical planning in predicting implant size, calcar length, and neck length, which was defined as the difference between the planned size and length and the actual size and length; (2) reproducibility of the two planning techniques, which were assessed by inter-observer and intra-observer reliability analysis; (3) the influence of potential confounding factors on planning accuracy, which was evaluated using generalized estimating equations. RESULTS: A total of 57 cases were included in the study. CT-based planning was more accurate than acetate templating for predicting cup size (93% vs 79%, p < 0.001) and stem size (93% vs 75%, p < 0.001). When assessed by mean absolute difference, the comparison between acetate templating and CT-based planning was 4.28 mm vs 3.74 mm (p = 0.122) in predicting neck length and 3.05 mm vs 2.93 mm (p = 0.731) in predicting neck cut length. In the inter-observer reliability analysis, an intraclass correlation coefficient (ICC) of 0.790 was achieved for predicting cup size, and an ICC of 0.966 was achieved for predicting stem size using CT-based planning. In terms of intra-observer reliability, Observer 1 achieved an ICC of 0.803 for predicting cup size and 0.965 for predicting stem size in CT-based planning. Observer 2 achieved ICC values of 0.727 and 0.959 for predicting cup and stem sizes, respectively. The average planning time was 6.48 ± 1.55 min for CT-based planning and 6.12 ± 1.40 min for acetate templating (p = 0.015). CONCLUSION: The CT-based planning system is more accurate than acetate templating for predicting implant size and has good reproducibility in total hip arthroplasty.

The Effect of a Local Injection of Flurbiprofen Ester Microspheres on Systemic Inflammatory Model Rats With a Closed Femoral Shaft Fracture.

Background: Periarticular injections with a combination of local anesthetics, non-steroidal anti-inflammatory analgesics (NSAIDs), and epinephrine are becoming increasingly popular in the perioperative analgesia of artificial joint replacement. However, data on the efficacy and safety of local injection NSAIDs are still scarce. The purpose of this study was to investigate the efficacy and safety of a local injection of Flurbiprofen Ester Lipid microspheres into the inflammatory model of femoral shaft closed fractures in rats. Methods: A systemic inflammatory model was induced in SD rats (60) by closed femoral shaft fracture; 12 non-fractured rats were used as the blank control group (group A). The systemic inflammation model of 60 rats was divided into 5 groups (12 in each group); Group B: intramuscular injectionof the same amount of normal saline at different time points as a negative control; Group C: intravenous injection of Flurbiprofen Ester microspheres (4.5 mg/kg) at different time points; Group D: intramuscular injection of Flurbiprofen Ester microspheres (2.25 mg/kg) at different time points; Group E: intramuscular injection of Flurbiprofen Ester microspheres (4.5 mg/kg) at different time points; Group F: intramuscular injection of Flurbiprofen Ester microspheres (9 mg/kg) at different time points. The behavioral test observed the behavior of the rats. Then, the inflammation factors of CRP, IL-6, COX-1, COX-2 and TNF-αby ELISA were recorded. Results: Through the behavioral test it could be found that the effect of the intramuscular and intravenous injections of Flurbiprofen Ester microspheres was similar. Fracture rats with a local injection of Flurbiprofen Ester microspheres showed lower inflammation levels measured by COX-1, CRP, and TNF-α compared with the control group. Pathological sections at 24, 48, and 96 h after surgery did not display any local muscle necrosis at the local injection site. These findings suggested that a Flurbiprofen Ester microsphere muscular injection exhibited a similar effect to an intravenous injection. Conclusion: The local injection of Flurbiprofen Ester microspheres significantly reduced the inflammatory response in fracture rats and did not increase the risk of muscle necrosis, suggesting its feasibility in local injection analgesia.

Local Release of TGF-ß Inhibitor Modulates Tumor-Associated Neutrophils and Enhances Pancreatic Cancer Response to Combined Irreversible Electroporation and Immunotherapy.

Pancreatic cancer is a deadly disease with little response to standard therapies. Irreversible electroporation (IRE) has emerged as a novel ablative technique for the clinical treatment of pancreatic cancer. Combinations of IRE and immunotherapies, including anti-programmed death 1 (αPD1) immune checkpoint blockade, have shown promising efficacy in both preclinical and clinical studies. However, tumor recurrence remains an obstacle that needs to be overcome. It herein is shown that IRE induces a substantial infiltration of neutrophils into pancreatic tumors. These neutrophils are then polarized into a protumor phenotype by immunosuppressive cues, in particular transforming growth factor ß (TGF-ß). Using glutathione-responsive degradable mesoporous silica nanoparticles loaded with SB525334, an inhibitor of TGF-ß1 receptor, it is demonstrated that local inhibition of TGF-ß within the tumor microenvironment promotes neutrophil polarization into an antitumor phenotype, enhances pancreatic cancer response to combined IRE and αPD1 therapy, and induces long-term antitumor memory. The therapeutic efficacy is also attributed to tumor infiltration by CD8+ cytotoxic T cells, depletion of regulatory T cells, and maturation of antigen-presenting dendritic cells. Thus, modulating neutrophil polarization with nanomedicine is a promising strategy for treating pancreatic cancer.

Degree of coronal alignment correction can't predict knee function in total knee replacement.

BACKGROUND: Whether neutral alignment brings better clinical outcomes is controversial. Consideration of the preoperative knee condition of patients and some limitations of previous studies, we suggested that other index may be more important than a generic target of 0° ± 3° of a neutral axis to reflect changes in coronal alignment after total knee replacement (TKR). The purpose of this study was to explore the relationship between alignment and functional outcome with a new grouping method and the concept of correction rate. METHODS: The study included 358 knees, the mean follow-up period was 3.62 years. A new grouping method was adopted to divide patients into three groups based on the degree of correction of mechanical femoral-tibial angle (MFTA): under-correction (n = 128), neutral (n = 209) and over-correction (n = 21). Hospital for Special Surgery (HSS) score were compared among the 3 groups (ANOVA with or without LSD t-test). In addition, we also attempt to further explore whether the concept of correction rate can predict postoperative functional score (Simple linear correlation analysis). RESULTS: HSS score showed significant improvement in all groups. There was no difference in HSS score (88.27 vs 88 vs 85.62) (p = 0.88) or incremental scores (26.23 vs 25.22 vs 22.88) (p = 0.25) based on the postoperative alignment category for the degree of correction of MFTA at the last follow-up. The correlational analyses also didn't show any positive results (r = -0.01 p = 0.95, r = -0.01 p = 0.97, r = 0.11 p = 0.15, r = 0.01 p = 0.90). CONCLUSION: Categorization of optimal coronal alignment after TKR may be impractical. But we still believe that the concept of correction rate and new grouping method are worthy of research which can reflects the preoperative knee condition and the change of coronal alignment. Perhaps it can be better used in TKR in the future. LEVEL OF EVIDENCE: III.

Role of Tetraspanins in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is characterized by high prevalence, morbidity, and mortality. Liver cancer is the sixth most common cancer worldwide; and its subtype, HCC, accounts for nearly 80% of cases. HCC progresses rapidly, and to date, there is no efficacious treatment for advanced HCC. Tetraspanins belong to a protein family characterized by four transmembrane domains. Thirty-three known tetraspanins are widely expressed on the surface of most nucleated cells and play important roles in different biological processes. In our review, we summarize the functions of tetraspanins and their underlying mechanism in the life cycle of HCC, from its initiation, progression, and finally to treatment. CD9, TSPAN15, and TSPAN31 can promote HCC cell proliferation or suppress apoptosis. CD63, CD151, and TSPAN8 can also facilitate HCC metastasis, while CD82 serves as a suppressor of metastasis. TSPAN1, TSPAN8, and CD151 act as prognosis indicators and are inversely correlated to the overall survival rate of HCC patients. In addition, we discuss the potential of role of the tetraspanin family proteins as novel therapeutic targets and as an approach to overcome drug resistance, and also provide suggestions for further research.

Multimodal Peri-articular Injection with Tranexamic Acid can reduce postoperative blood loss versus Intravenous Tranexamic Acid in Total Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: Tranexamic acid (TXA) has shown significant reductions in blood loss and transfusion rates in total knee arthroplasty (TKA). However, the optimal administration route continues to be debated. The aim of this trial was to compare the effectiveness of intravenous (IV) versus peri-articular injection (PAI) application of tranexamic acid in patients undergoing total knee arthroplasty. METHODS: We conducted a randomized controlled, double-blinded study. A total of 93 patients undergoing primary unilateral TKA were randomly distributed between 2 groups: the IV group (47 cases; 1 g TXA IV) and the PAI group (46 cases; 1 g TXA injected peri-articularly). The amount of total and hidden blood loss (HBL), drainage, transfusion rate, hemoglobin and hematocrit drift, and complications were recorded. RESULTS: Peri-articular injection of TXA reduced total blood loss (P < 0.001) and HBL more than IV use of TXA (P < 0.001). No patients in either group received a transfusion. No symptomatic deep venous thrombosis or other severe complications occurred. CONCLUSION: Peri-articular injection of TXA significantly reduced total blood loss and hidden blood loss to a greater degree than IV injection in total knee arthroplasty without reduction of drainage volume. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-INR-16010270 . Date of registration: December 27, 2016.

Tetraspanins: Novel Molecular Regulators of Gastric Cancer.

Gastric cancer is the fourth and fifth most common cancer worldwide in men and women, respectively. However, patients with an advanced stage of gastric cancer still have a poor prognosis and low overall survival rate. The tetraspanins belong to a protein superfamily with four hydrophobic transmembrane domains and 33 mammalian tetraspanins are ubiquitously distributed in various cells and tissues. They interact with other membrane proteins to form tetraspanin-enriched microdomains and serve a variety of functions including cell adhesion, invasion, motility, cell fusion, virus infection, and signal transduction. In this review, we summarize multiple utilities of tetraspanins in the progression of gastric cancer and the underlying molecular mechanisms. In general, the expression of TSPAN8, CD151, TSPAN1, and TSPAN4 is increased in gastric cancer tissues and enhance the proliferation and invasion of gastric cancer cells, while CD81, CD82, TSPAN5, TSPAN9, and TSPAN21 are downregulated and suppress gastric cancer cell growth. In terms of cell motility regulation, CD9, CD63 and CD82 are metastasis suppressors and the expression level is inversely associated with lymph node metastasis. We also review the clinicopathological significance of tetraspanins in gastric cancer including therapeutic targets, the development of drug resistance and prognosis prediction. Finally, we discuss the potential clinical value and current limitations of tetraspanins in gastric cancer treatments, and provide some guidance for future research.

Local Efficacy of Corticosteroids as an Adjuvant for Periarticular Cocktail Injection in Simultaneous Bilateral Total Knee Arthroplasty: A Prospective Randomized Double-Blind Controlled Trial.

Multimodal cocktail periarticular injections comprising corticosteroids are the most suggested therapy for postoperative discomfort and swelling following total knee arthroplasty (TKA). Nevertheless, previous findings cannot be applied to instances of unilateral total knee arthroplasty on bilateral knees. This randomized, prospective, double-blind, controlled clinical study examines the efficacy as well as safety of periarticular multimodal cocktail injection along or sans corticosteroids in certain situations. The 60 patients (120 knees) that experienced concurrent bilateral total knee arthroplasty were provided periarticular injections along additional betamethasone (7 mg) in the randomized knee, as well as the other knee, where corticosteroid was not administered. Key results were "pain scores at rest as well as in action" on a visual analogue scale of 11 pt. Other results included motion range, swelling of the thigh, Hospital for Special Surgery score (HSS score), and adverse effects were measured between the two sides. No statistically promising variations were found in the visual analogue scale ranking, motion range, girth of the thigh, and HSS score, as well as complications between the two sides. The impact on treatment outcomes was maintained between the knees on postoperative day 3 or at 3 months of follow-up. Multimodal periarticular injection without corticosteroid will alleviate postoperative swelling and pain. More studies are needed for the use of betamethasone as a corticosteroid in periarticular multimodal cocktail injections. This Chinese Clinical Trial Registry is registered with ChiCTR-OPC-17013503, dated 2017-11-23, available from http://www.chictr.org.cn/showproj.aspxproj=23146.

Interferon-γ induces tumor resistance to anti-PD-1 immunotherapy by promoting YAP phase separation.

Interferon-γ (IFN-γ)-mediated adaptive resistance is one major barrier to improving immunotherapy in solid tumors. However, the mechanisms are not completely understood. Here, we report that IFN-γ promotes nuclear translocation and phase separation of YAP after anti-PD-1 therapy in tumor cells. Hydrophobic interactions of the YAP coiled-coil domain mediate droplet initiation, and weak interactions of the intrinsically disordered region in the C terminus promote droplet formation. YAP partitions with the transcription factor TEAD4, the histone acetyltransferase EP300, and Mediator1 and forms transcriptional hubs for maximizing target gene transcriptions, independent of the canonical STAT1-IRF1 transcription program. Disruption of YAP phase separation reduced tumor growth, enhanced immune response, and sensitized tumor cells to anti-PD-1 therapy. YAP activity is negatively correlated with patient outcome. Our study indicates that YAP mediates the IFN-γ pro-tumor effect through its nuclear phase separation and suggests that YAP can be used as a predictive biomarker and target of anti-PD-1 combination therapy.

Risk-Stratified Venous Thromboembolism Prophylaxis after Total Joint Arthroplasty: Low Molecular Weight Heparins and Sequential Aspirin vs Aggressive Chemoprophylaxis.

OBJECTIVE: Venous thromboembolism (VTE) is a significant concern post total joint arthroplasty (TJA). However, the optimal prevention method of VTE remains controversial at present. This study aims to evaluate a risk-stratified VTE prophylaxis protocol for patients undergoing TJA. METHODS: A total of 891 TJA patients from January 2011 to November 2019 were retrospectively investigated. The study was divided into two cohorts. In cohort 1, 410 patients (250 females and 160 males, mean age 64.32 years) were treated with an aggressive VTE chemoprophylaxis protocol. In cohort 2, 481 patients were treated with a risk-stratified protocol that utilized low molecular weight heparins (LMWH) and sequential aspirin (ASA) for standard-risk patients (a total of 288 containing 177 females and 111 males, mean age 65.4 years), and targeted anticoagulation for high-risk patients (a total of 193 containing 121 females and 72 males, mean age 66.8 years). The patients were followed up at 2-4 weeks for an initial visit and at 6-10 weeks for a subsequent visit after surgery. A chart review of all patient medical records was performed to record the demographics, comorbidities, deep vein thrombosis, pulmonary embolus, superficial infection, deep infection, bleeding complications, and 90-day readmissions. RESULTS: The VTE rate was 1.71% (7/410) in cohort 1 and 1.46% (7/481) in cohort 2 respectively. For cohort 2, the VTE rate was 2.07% (4/193) in high-risk group and 1.04% (3/288) in standard-risk group. The readmission rate was 2.44% (10/410) in cohort 1 and 2.08% (10/481) in cohort 2. For cohort 2, the readmission rate was 2.07% (4/193) in high-risk group and 2.08% (6/288) in standard-risk group. The reasons for readmission were as follows: infection, 1.3% (5/410) in cohort 1 and 1.3% (6/481) in cohort 2; wound or bleeding complications, 0.48% (2/410) in cohort 1 and 0.2% (1/481) in cohort 2; trauma, 0.2% (1/410) in cohort 1 and 0.2% (1/481) in cohort 2; VTE, 0.2% (1/410) in cohort 1 and 0.2% (1/481) in cohort 2; others, 0.2% (1/410) in cohort 1 and 0.6% (3/481) in cohort 2. There was a decrease in VTE events and readmissions in the risk-stratified cohort, although this did not reach statistical significance. However, it was found that there was a significant reduction in costs (P < 0.001) with the use of LMWH/ASA, when compared with aggressive anticoagulation agents in the risk-stratified cohort. CONCLUSION: The use of LMWH/ASA in a risk-stratified TJA population is a safe and cost-effective method of VTE prophylaxis.

Accuracy of MRI Diagnosis of Meniscal Tears of the Knee: A Meta-Analysis and Systematic Review.

This study aimed to evaluate the overall diagnostic value of magnetic resonance imaging (MRI) in patients with suspected meniscal tears. PubMed, Cochrane, Embase database updated to November 2017 were searched by the index words to identify qualified studies, including prospective cohort studies and cross-sectional studies. Literature was also identified by tracking using reference lists. Heterogeneity of the included studies was reviewed to select proper effects model for pooled weighted sensitivity, specificity, and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) analyses were performed for meniscal tears. A total of 17 studies were involved in this meta-analysis to explore the diagnostic accuracy of MRI for meniscal tears. The global sensitivity and specificity of MRI of meniscal tears were 92.0% (95% confidence interval [CI]: 88.0-95.0%) and 90.0% (95% CI: 85.0-95.0%) in medial meniscal tears, and 80.0% (95% CI: 66.0-89.0%) and 95.0% (95% CI: 91.0-97.0%) in lateral meniscal tears, respectively. Moreover, the global positive and negative likelihood ratio of MRI of meniscal tears were 10.33 (95% CI: 6.04-17.67) and 0.09 (95% CI: 0.05-0.14) in medial meniscal tears; 16.48 (95% CI: 8.81-30.83) and 0.21 (95% CI: 0.12-0.37) in lateral meniscal tears, respectively. The global DOR was 81.69 (95% CI: 37.94-175.91) in medial meniscal tears and 56.59 (95% CI: 22.51-142.28) in lateral meniscal tears. The results of area under the SROC indicated high accuracy in medial meniscal tears (area under the curve [AUC] = 0.97, 95% CI: 0.95-0.98) and lateral meniscal tears (AUC = 0.96, 95% CI: 0.94-0.97). This review presents a systematic review and meta-analysis to evaluate the diagnostic accuracy of MRI of meniscal tears. Moderate-to-strong evidence suggests that MRI appears to be associated with higher diagnostic accuracy for detecting medial and lateral meniscal tears.

A Simple Diagnosis-Related Groups-Based Reimbursement System Is Cost Ineffective for Elderly Patients With Displaced Femoral Neck Fracture Undergoing Hemiarthroplasty in Beijing.

Displaced femoral neck fractures (FNF) in the elderly are a major public health concern that necessitates hemiarthroplasty (HA) as the mainstay treatment option. Diagnosis-Related Groups (DRG) are a patient classification system that categorizes patients based on the resources expended on them. The first objective of this study was to evaluate if a simplified DRG-based reimbursement system in Beijing would lower total HA treatment costs for elderly patients with displaced FNF. In addition, we aimed to determine how age, gender, year of admission, length of in-hospital stay, and the Charlson index affected total treatment costs. This retrospective study included 513 patients from the Peking Union Medical College Hospital. The patients were diagnosed with unilateral displaced femoral neck fractures and had HA. Medical information was gathered, including baseline demographic and clinical data, as well as treatment costs. Patients were classified into two groups: those who spent more than the predetermined cut-off cost and those who did not. The cost did not include the use of a bipolar prosthesis. Data from the two groups were compared, and multiple regression analysis models were constructed. The median total cost of treatment was ¥49,626 ($7,316). The majority of the patients (89.7%; 460/513) were categorized as exceeding the cost cut-off. Multiple linear regression analysis revealed that total treatment cost was positively correlated with age (p < 0.01) and the duration of in-hospital stay (p < 0.01) but not with gender (p = 0.160) or the Charlson index (p = 0.548). On implementing the DRG-based reimbursement system, the overall treatment costs increased by ¥21,028 ($3,099) (p < 0.01). The implementation of simplified DRG-prospective payment systems did not result in a significant reduction in total treatment costs for elderly patients with FNF who underwent HA in Beijing. The overall cost of treatment was associated with several factors, including age, length of hospitalization, and year of admission.

Usefulness of a Simple Preoperative Planning Technique using Plain X-rays for Direct Anterior Approach for Total Hip Arthroplasty.

OBJECTIVE: To examine the accuracy, reliability, and reproducibility of a simple preoperative planning technique using plain X-rays. METHODS: A retrospective analysis of 96 consecutive cases of primary direct anterior approach (DAA)-total hip arthroplasty (THA) from July 2015 to December 2018 was performed. The 96 patients included 24 males and 72 females, with an average age of 70 years. The standard AP pelvis radiographs with the patients' hips extended and internally rotated were obtained pre- and postoperatively. The preoperative planning was also completed on the standardized AP pelvic radiographs. The prearranged cup positioning was radiologically measured intraoperatively using fluoroscopy. The correct leg length was assessed intraoperatively, which was compared with the preoperative planning. The component positioning was measured by three independent researchers. Two of the researchers completed the measurements three times, and intra-observer and inter-observer reliability were calculated. All patients received at least 6 months follow-up (6 months-4 years). RESULTS: In all cases, the median leg length discrepancy (LLD) was 4.4 mm (range 1.6-15.9 mm), and 84 patients had an LLD smaller than 10 mm, of which 58 patients had an LLD of less than 5 mm. None of the patients had a critical LLD of 2 cm or larger. The multivariable logistic regression for LLD (safe range: yes/no) with the co-variables including gender, ASA classification, type of cup, the surgeon's experience level, and the presence of a total hip arthroplasty (THA) on the contralateral side did not present statistical significance. The median angle of the inclination of the acetabular component (IA) was 42.3° (range: 28.7°-52.2°). Ninety-one patients were within the defined safe range. The hit ratio for the cup to be within the safe zone was significantly higher for the Pinnacle cups than that for the Continuum cups (P < 0.05). However, there was no significant difference in gender, ASA classification, the surgeon's experience level, and the presence of a total hip arthroplasty (THA) on the contralateral side. The median of its anteversion (AA) was 20.6° (range: 10.6°-40.1°). Only 41 patients were within the defined safe range. None of the co-variables presented a statistical significance affecting the AA of the cup positioning. Meanwhile, the average fluoroscopy time for the cup positioning (n = 86, missing data in 10 cases) was 4 seconds (range: 1-74), with most of the patients (97.9%) having a fluoroscopy time of fewer than 20 seconds. CONCLUSIONS: The combination of correct preoperative planning and standardized intraoperative measurements can reestablish right leg length and assure the correct cup positioning.

Acid Sphingomyelinase Contributes to the Control of Mycobacterial Infection via a Signaling Cascade Leading from Reactive Oxygen Species to Cathepsin D.

Tuberculosis, caused by Mycobacterium tuberculosis, is one of the most severe diseases worldwide. The initial pulmonary localization of the pathogen often develops into systemic infection with high lethality. The present work investigated the role of sphingolipids, specifically the function of acid sphingomyelinase (Asm) and ceramide, in infection of murine macrophages in vitro and mice in vivo with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In vitro, we investigated macrophages from wild-type (wt) and Asm deficient (Asm-/-) mice to define signaling events induced by BCG infection and mediated by Asm. We demonstrate that infection of wt macrophages results in activation of Asm, which increases reactive oxygen species (ROS) via stimulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. ROS promote BCG degradation by cathepsin D. Asm deficiency in macrophages abrogates these effects. In vivo studies reveal that wt mice rapidly control BCG infection, while Asm-/- mice fail to control the infection and kill the bacteria. Transplantation of wt macrophages into Asm-/- mice reversed their susceptibility to BCG, demonstrating the importance of Asm in macrophages for defense against BCG. These findings indicate that Asm is important for the control of BCG infection.

Continuous block at the proximal end of the adductor canal provides better analgesia compared to that at the middle of the canal after total knee arthroplasty: a randomized, double-blind, controlled trial.

BACKGROUND: The optimal position for continuous adductor canal block (ACB) for analgesia after total knee anthroplasty (TKA) remians controversial, mainly due to high variability in the localization of the the adductor canal (AC). Latest neuroanatomy studies show that the nerve to vastus medialis plays an important role in innervating the anteromedial aspect of the knee and dives outside of the exact AC at the proximal end of the AC. Therefore, we hypothesized that continuous ACB at the proximal end of the exact AC could provide a better analgesic effect after TKA compared with that at the middle of the AC (which appeared to only block the saphenous nerve). METHODS: Sixty-two adult patients who were scheduled for a unilateral TKA were randomized to receive continuous ACB at the proximal end or middle of the AC. All patients received patient-controlled intravenous analgesia with sufentanil postoperatively. The primary outcome measure was cumulative sufentanil consumption within 24 h after the surgery, which was analyzed using Mann-Whitney U tests. P-values < 0.05 (two-sided) were considered statistically significant. The secondary outcomes included postoperative sufentanil consumption at other time points, pain at rest and during passive knee flexion, quadriceps motor strength, and other recovery related paramaters. RESULTS: Sixty patients eventually completed the study (30/group). The 24-h sufentanil consumption was 0.22 µg/kg (interquartile range [IQR]: 0.15-0.40 µg/kg) and 0.39 µg/kg (IQR: 0.23-0.52 µg/kg) in the proximal end and middle groups (P = 0.026), respectively. There were no significant inter-group differences in sufentanil consumption at other time points, pain at rest and during passive knee flexion, quadriceps motor strength, and other recovery related paramaters. CONCLUSIONS: Continuous ACB at the proximal end of the AC has a better opioid-sparing effect without a significant influence on quadriceps motor strength compared to that at the middle of the AC after TKA. These findings indicates that a true ACB may not produce the effective analgesia, instead, the proximal end AC might be a more suitable block to alleviate pain after TKA. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov ( NCT03942133 ; registration date: May 06, 2019; enrollment date: May 11, 2019).