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.

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.

Metabolic profiling integrated with pharmacokinetics to reveal the material basis of Xiaokeyinshui extract combination in the treatment of type 2 diabetes in rats.

Xiaokeyinshui extract combination (XEC), originating from a traditional Chinese formula Xiaokeyinshui (XKYS) recorded in ancient Bencao, has been reported to exert significant hypoglycemic effects. However, the chemical profiles, metabolic transformation and pharmacokinetic behavior of XEC in vivo were unclear. The research was to investigate the chemical constituents, metabolic profiles and pharmacokinetic behavior of XEC. A UPLC-QE-Orbitrap-HRMS qualification method was developed to identify the chemical constituents in XEC and xenobiotics of XEC in plasma, urine, feces and bile of rats after oral administration. A LC-MS quantification method was established and applied for the pharmacokinetic studies of major active compounds of XEC in normal and T2DM rats and Coptidis Rhizoma extracts (CRE) in T2DM rats. Fifty eight compounds in XEC and a total of 152 xenobiotics were identified in T2DM rats, including 28 prototypes and 124 metabolites. The metabolic pathways were demethylation, demethyleneization, reduction, hydroxylation, hydrolysis and subsequent binding reactions, including glucuronidation, sulfation and methylation. According to the results of chemical constituents and metabolites, 7 ingredients, including berberine, palmatine, coptisine, epiberberine, berberrubine, magnoflorine and aurantio-obtusin were suggested for markers to comparative pharmacokinetics study in normal rats and T2DM rats. Compared with normal rats, the Tmax of berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine was significantly longer. The value of Cmax for palmatine, coptisine, epiberberine and berberrubine was significantly decreased in XEC T2DM group. The value of AUC for alkaloids was higher in diabetic rats. After oral CRE, alkaloids including berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine could be detected in vivo. Compared with T2DM rats after oral administration of CRE, the value of Tmax and Cmax for berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine exhibited significant differences in XEC T2DM group. This research provided an overview of the chemical profiles and metabolic profiling of XEC and elucidated the effect of diabetic state and compatibility on pharmacokinetic behaviors of active components in XEC. This research also can provide the material basis of XEC for subsequent quality control research.

Effect of alendronate sodium plus vitamin D3 tablets on knee joint structure and osteoarthritis pain: a multi-center, randomized, double-blind, placebo-controlled study protocol.

BACKGROUND: Osteoarthritis (OA) is a major cause of pain and disability worldwide. Despite the relatively high burden of the disease, the currently available non-surgical treatment options are directed towards symptomatic relief. Therefore, we propose the use of alendronate as a disease modifying agent to help slow and prevent OA. In addition, this study will utilize Whole-Organ Magnetic Resonance Imaging Score (WORMS) to evaluate the structural integrity of cartilage in the study population. High-quality evidence, limited to a few well-conducted randomized trials, highlights contradictory results on the effect of bisphosphonates on knee function and progression of OA. Therefore, a placebo-controlled, randomized trial is needed to evaluate the combined effect of alendronate and vit D on the structure of cartilage utilizing the WORMS score and its ability to treat knee pain in OA patients. METHODS: This multicenter, randomized, double-blinded, placebo-controlled study will evaluate the efficacy and safety of alendronate in early OA. Patients will undergo a 1:1 double-blinded randomization to receive a one-year course of either alendronate sodium vitamin D3 or placebo. The primary outcome is to compare WORMS score of knee joint at 6 and 12 months between both groups. Secondary endpoints will include WORMS score at 24 months, knee pain, radiographic progression of OA, severity of OA, quality of life, and serum inflammatory biomarkers at different assessment timepoints. To detect a 2.2% difference in cartilage loss between both groups with power of 80%, a sample size of 60 (30 per group) is proposed. DISCUSSION: This trial will give helpful and high-quality evidence regarding the potential therapeutic role of alendronate sodium vitamin D3, as compared to placebo, in the management of patients with knee OA regarding its role on cartilage loss, radiographic progression of OA, severity of OA, knee pain, quality of life, and inflammatory biomarkers. If proven effective, this intervention would be a great option for providing beneficial outcomes with a reduced cost in this patient population. TRIAL REGISTRATION: This trial was registered on clinicaltrials.gov (registration number: NCT04739592 ).

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.

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.

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.

Network pharmacology analysis and experimental validation to explore the mechanism of Hanchuan Zupa Granule in asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Hanchuan Zupa Granule (HCZP) is a classic prescription of Uyghur medicine, that is used for cough and abnormal mucinous asthma caused by a cold and "Nai-Zi-Lai". AIM OF THE STUDY: This study aimed to explore the possible molecular mechanism of HCZP in the treatment of asthma, using a network pharmacology method and in vivo experiments. MATERIALS AND METHODS: First, we conducted qualitative analysis of the chemical composition of HCZP as a basis for network pharmacology analysis. Using network pharmacology tools, the possible signaling pathways of HCZP in the treatment of asthma were obtained. An OVA-sensitized asthma model was established, and HCZP was continuously administered for one week. BALF was collected for cell counting, and serum and lung tissues were collected to analyze the expression of IgE, IL-4, IL-5, IL-13 and IFN-γ. Hematoxylin & eosin (H&E) staining was performed to assess the pathological changes in the lung tissues. Related protein expression in the lung tissues was analyzed by Western blotting for molecular mechanism exploration. RESULTS: Fifty-six chemical compounds were identified by UPLC Q-TOF MS. According to the network pharmacology results, 18 active compounds were identified among the 56 compounds, and 68 target genes of HCZP in the treatment of asthma were obtained. A total of 19 pathways were responsible for asthma (P < 0.05) according to KEGG pathway analysis. In vivo results showed that OVA sensitivity induced increased respiratory system resistance and inflammatory responses, which included inflammatory cell infiltration and high levels of IgE, IL-4, IL-5 and IL-13 in serum and lung tissues. Furthermore, OVA upregulated p-PI3K, p-JNK and p-p38 expression in lung tissues. Moreover, HCZP treatment significantly downregulated respiratory system resistance, and the expression of IL-4, IL-5, IL-13 and IgE, as well as significantly improved inflammatory cell infiltration in lung tissues. Moreover, the protein expression of p-PI3K, p-JNK and p-p38 in lung tissues decreased after HCZP treatment. CONCLUSION: HCZP significantly inhibited the OVA-induced inflammatory response via the PI3K-Akt and Fc epsilon RI signaling pathways.

Microbiology of Periprosthetic Hip and Knee Infections in Surgically Revised Cases from 34 Centers in Mainland China.

BACKGROUND AND AIM: Periprosthetic joint infection (PJI) is one of the most devastating complications after total joint arthroplasty (TJA). However, the antibiotic resistance of infecting pathogens can significantly vary in different parts of the country. In the current study, we analyzed the demographic and microbiological profiles of knee and hip PJI over three years and compared the microbiological differences between them. METHODS: A multicenter retrospective study of PJI patients in 34 referral medical centers in mainland China from January 2015 to November 2017 was performed. RESULTS: A total of 925 PJI patients were recruited, 452 were identified as knee PJIs, and 473 were hip PJIs. The most common causative pathogens were Staphylococcus aureus (26.5%) and coagulase-negative staphylococci (14.3%). Methicillin-resistant staphylococci were involved in 25.6% (237/925) of all PJI cases. Mycobacterium and fungus only accounted for 6.5% (61) of all cases. Enteric gram-negative bacilli, anaerobes, and polymicrobial pathogens were more common in hip joint prostheses than in knee PJI (P = 0.014; P = 0.006; P = 0.002, respectively). CONCLUSION: While the majority of causative pathogens in PJI cases are staphylococcal species, the prevalence of atypical organisms and resistant pathogens should also be given attention and warrant the need for empiric antibiotic treatment.

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.

Progress of antibiotic-loaded bone cement in joint arthroplasty.

Bone cement, consisting of polymethyl methacrylate, is a bioinert material used for prothesis fixation in joint arthroplasty. To treat orthopedic infections, such as periprosthetic joint infection, antibiotic-loaded bone cement (ALBC) was introduced into clinical practice. Recent studies have revealed the limitations of the antibacterial effect of ALBC. Moreover, with the increase in high infection risk patients and highly resistant microbes, more researches and modification of ALBC are required. This paper reviewed latest findings about ALBC for most popular and destructive pathogens, summarized the influence of antibiotic kind, drug dosage, application method, and environment towards characteristic of ALBC. Subsequently, new cement additives and clinical applications of ALBC in joint arthroplasty were also discussed.

Transfusion-transmitted infections in hemophilia patients who underwent surgical treatment: a study from a single center in north China.

INTRODUCTION: Transfusion-transmitted infections (TTIs) continue to be a major challenge among hemophilia patients. This study was conducted to investigate the prevalence of TTIs including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and syphilis in patients with hemophilia who received surgical treatment due to bone or joint lesions in the Department of Orthopedics. MATERIAL AND METHODS: The present study was conducted from July 1996 to November 2016 in Beijing, China. A total of 189 patients who underwent orthopedic procedures were enrolled. Blood samples were obtained from the patients and were tested for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) and human immunodeficiency virus antibody (HIV Ab). RESULTS: Among 189 hemophilia patients included in the study, 54 (28.6%) tested positive for TTI. Seroprevalence for HBsAg was found in 8 (4.2%) cases, HCV Ab in 48 (25.4%) cases, HIV Ab in 2 (1.1%) cases, and syphilis in 1 (0.5%) case. No statistically significant difference in the numbers of patients with positive HCV Ab was seen between hemophilia A (26.0%) and B (20.0%) (p = 0.786). The seroprevalence of HCV Ab (12.1%) in 66 hemophilia patients diagnosed after 1995 was significantly lower than that (32.5%) among hemophilia patients diagnosed before or in 1995 (p = 0.003). CONCLUSIONS: Though few patients have become positive for HBsAg and HIV Ab, HCV is still the major virus of concern for hemophiliacs who have undergone orthopedic procedures. Hepatitis B vaccination should be given to the high-risk population including hemophilia patients as soon as possible.

The analgesic efficacy and safety of peri-articular injection versus intra-articular injection in one-stage bilateral total knee arthroplasty: a randomized controlled trial.

BACKGROUND: As an essential component of multimodal analgesia approaches after total knee arthroplasty (TKA), local infiltration analgesia (LIA) can be classified into peri-articular injection (PAI) and intra-articular injection (IAI) according to administration techniques. Currently, there is no definite answer to the optimal choice between the two techniques. Our study aims to investigate analgesic efficacy and safety of PAI versus IAI in patients receiving simultaneous bilateral TKA. METHODS: This randomized controlled trial was conducted from February 2017 and finished in July 2018. Sixty patients eligible for simultaneous bilateral total knee arthroplasty were randomly assigned to receive PAI on one side and IAI on another. Primary outcomes included numerical rating scale (NRS) pain score at rest or during activity at 3 h, 6 h, 12 h, 24 h, 48 h, and 72 h following surgery. Secondary outcomes contained active or passive range of motion (ROM) at 1, 2, and 3 days after surgery, time to perform straight leg raise, wound drainage, operation time, and wound complications. RESULTS: Patients experienced lower NRS pain scores of the knee receiving PAI compared with that with PAI during the first 48 h after surgery. The largest difference of NRS pain score at rest occurred at 48 h (PAI: 0.68, 95%CI[0.37, 0.98]; IAI: 2.63, 95%CI [2.16, 3.09]; P < 0.001); and the largest difference of NRS pain score during activity also took place at 48 h (PAI: 2.46, 95%CI [2.07, 2.85]; IAI: 3.90, 95%CI [3.27, 4.52]; P = 0.001). PAI group had better results of range of motion and time to perform straight leg raise when compared with IAI group. There were no differences in operation time, wound drainage, and wound complication. CONCLUSION: PAI had the superior performance of pain relief and improvement of range of motion to IAI. Therefore, the administration technique of peri-articular injection is recommended when performing local infiltration analgesia after total knee arthroplasty. TRIAL REGISTRATION: The trial was retrospectively registered in the Chinese Clinical Trial Registry as ChiCTR1800020420 on 29th December, 2018. LEVEL OF EVIDENCE: Therapeutic Level I.

Rates of periprosthetic infection and surgical revision in Beijing (China) between 2014 and 2016: a retrospective multicenter cross-sectional study.

BACKGROUND: Periprosthetic joint infection (PJI) is a rare but devastating complication after total joint arthroplasty. There is a paucity of data on the incidence and prevalence of periprosthetic infection in mainland China. This study aimed to analyze the rates of surgical revision after arthroplasty due to PJI and the procedures followed in Beijing, China. METHODS: The study involved a retrospective multicenter cross-sectional survey of patients undergoing revisions for periprosthetic infection after hip/knee arthroplasty at nine hospitals in Beijing from 2014 to 2016. Age, gender, body mass index, primary diagnosis, comorbidity, primary surgery, treatment methods, and post-revision complications were analyzed. RESULTS: A total of 38,319 hip/knee arthroplasties and 366 (0.96%) revisions for PJI were identified. Of these, 161 (161/14,110; 1.14%) revisions involved hip arthroplasty, whereas 205 (205/24,209; 0.85%) revisions were due to knee arthroplasty. Procedures for revisions of infected hip included 7 (4.3%) cases of open debridement and prosthesis retention, 32 (19.9%) cases of one-stage exchange, 121 (75.2%) cases of two-stage exchange, and 1 (0.007%) case of hip dissection. As for the infected knee, the procedures included 45 (22.0%) cases of open debridement and prosthesis retention, 13 (6.3%) cases of one-stage exchange, 143 (69.8%) cases of two-stage exchange, and 4 (0.02%) cases of knee fusion. CONCLUSIONS: The study found the rates of revision due to PJI to be low. Nonetheless, the incidence of PJI in mainland China could be higher and calls for more elaborate studies in geographically and socioeconomically diverse health institutions.

Incidence of Symptomatic Venous Thromboembolism in Patients with Hemophilia Undergoing Hip and Knee Joint Replacement without Chemoprophylaxis: A Retrospective Study.

OBJECTIVE: To establish the prevalence of clinically significant venous thromboembolic events (VTE) in hemophilia patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) without chemoprophylaxis and a modified coagulation factor substitution. METHODS: A cohort of patients who underwent THA and TKA from June 2002 to April 2017 were included. Based on World Federation of Hemophilia (WFH) guidelines, a modified coagulation factor substitution regimen was adopted. All patients were under a standardized postoperative protocol with routine mechanical prophylaxis against VTE. None of the patients received prophylactic anticoagulation. Only symptomatic patients were referred for radiological examination to exclude VTE. We evaluated the patient demographics and calculated the prevalence of VTE in our cohort. RESULTS: A total of 98 patients were reviewed. The patients were all men. Thirty-one patients underwent primary THA with 39 hip arthroplasties (only 1 case with hemophilia B) and 67 patients underwent primary TKA with 101 knee arthroplasties (5 cases with hemophilia B). The mean age was 34.2 ± 7.8 years. The mean body mass index was 21.2 ± 5.7 kg/m2 . There was 100% compliance to mechanical prophylaxis. The mean time to ambulation was 6.8 days (±2.5 days), and the mean hospital stay was 32.4 days (±7.1 days). There was only 1 hemophilia B patient with clinically significant VTE. None of the other 97 surgical cases had symptomatic VTE within 6 months after the procedure. This translates to a prevalence of 1.02%. CONCLUSION: Given the low incidence (1.02%) of clinically significant VTE in our cohort, routine chemoprophylaxis in hemophilia patients undergoing THA and TKA may not be needed.

Role of Parecoxib Sodium in the Multimodal Analgesia after Total Knee Arthroplasty: A Randomized Double-blinded Controlled Trial.

OBJECTIVE: Total knee arthroplasty (TKA) is an established surgical technique and is the standard treatment for degenerative knee joint diseases. However, severe pain after TKA makes it difficult for many patients to perform early postoperative rehabilitation and functional exercise, which might result in subsequent unsatisfactory recovery of knee joint function and great reduction in patients' satisfaction and quality of life. Orthopaedic surgeons have tried a large variety of analgesics and analgesic modes to relieve patients' pain after TKA. There are many analgesic regimens available in clinical practice but all have some deficiencies. Parecoxib sodium, a highly selective inhibitor of cyclooxygenase-2 (COX-2), can reduce the synthesis of peripheral prostaglandin to exert the effect of analgesia, and relieve inflammation and prevent central sensitization through inhibition of peripheral and central COX-2 expression. In addition, it can be used as a preemptive analgesic without affecting platelet aggregation. However, there does seem to be conflicting evidence in the current research as to whether parecoxib sodium can be used successfully as a preemptive analgesic; the effect of preemptive analgesia with parecoxib sodium in multimodal analgesia is still controversial. This research investigated the effects of parecoxib sodium in a preemptive multimodal analgesic regimen. METHODS: Eighty-eight patients were randomized into two groups. The experimental group received parecoxib (46 patients) and the control group received saline (42 patients), administered 30 min before the initiation of the surgical procedure. A patient-controlled analgesia (PCA) pump was applied within 48 h after surgery. The visual analogue scale (VAS), drug consumption through the PCA pump, use of salvaging analgesia, range of motion (ROM) of the knee joints, and postoperative complications were observed. RESULTS: The VAS score in the post-anesthesia care unit (PACU) of the parecoxib group was significantly lower than that of the control group (P = 0.039). There was no significant difference in the demographic profiles, duration of operation, hemorrhage in surgery, postoperative hemorrhage, postoperative drainage, VAS at different time points, function of knee joints, length of hospital stay, use of salvaging analgesia, and postoperative drug consumption through the PCA between the two groups (P > 0.05). CONCLUSION: In preemptive multimodal analgesia regimens, parecoxib sodium can significantly decrease the VAS score in the short term, relieve pain shortly after surgery, and does not increase the incidence of complications. Parecoxib sodium is a safe and effective drug in the perioperative analgesic management for TKA.

Preemptive Analgesia with Parecoxib in Total Hip Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Total hip arthroplasty (THA) is a well-accepted surgical treatment for terminal hip diseases. OBJECTIVE: To evaluate the effect of preemptive analgesia with parecoxib in patients undergoing primary unilateral THA. STUDY DESIGN: A randomized, double-blind, placebo-controlled study. SETTING: This study was conducted at Peking Union Medical College Hospital and Beijing Jishuitan Hospital in Beijing, China. METHODS: A total of 94 patients scheduled for primary unilateral THA in 2 centers (Peking Union Medical College Hospital and Beijing Jishuitan Hospital) were randomly assigned to receive 40 mg parecoxib (n = 48) or 0.9% normal saline solution (n = 46) 30 minutes before incision. All patients received standardized intravenous patient-controlled analgesia (PCA) postoperatively. Preoperative baseline data, surgery-related conditions, postoperative Visual Analog Scale (VAS) pain score, cumulative narcotic consumption of PCA, and complications were compared between the parecoxib group and the placebo group. RESULTS: There were no significant differences in postoperative VAS pain score, cumulative narcotic consumption of PCA, proportion of analgesic remedy, and complications between the 2 groups. LIMITATIONS: Only a single dose of parecoxib was used without including a dose-dependent control group. CONCLUSION: A single dose of parecoxib 30 minutes before incision did not provide effective preemptive analgesia for the management of postoperative pain after primary unilateral THA. The possible effect of preemptive analgesia with parecoxib needs further investigation. KEY WORDS: Total hip arthroplasty, pain, parecoxib, COX-2 selective inhibitor, preemptive analgesia, clinical trial, patient-controlled analgesia, analgesics.