The volatile oil of Hyssopus cuspidatus Boriss (HVO) ameliorates OVA-induced allergic asthma via inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyssopus cuspidatus Boriss, a classic Uyghur medicine, is used to treat inflammatory lung diseases such as asthma. But the therapeutic effect and mechanism of the volatile oil of Hyssopus cuspidatus Boriss (HVO) in asthma therapy remain unclear. AIM OF THE STUDY: We aim to characterize the constituents of HVO, investigate the therapeutic effect in OVA-induced allergic asthmatic mice and further explore the molecular mechanism. MATERIALS AND METHODS: In this study, we applied two-dimensional gas chromatography quadrupole time-of-flight mass spectrometry (GC × GC-QTOF MS) to identify the ingredients of HVO. We established OVA-induced asthmatic model to investigate the therapeutic effect of HVO. To further explore the potential molecular pathways, we used network pharmacology approach to perform GO and KEGG pathways enrichment, and then built an ingredient-target-pathway network to identify key molecular pathways. Finally, LPS-induced RAW 264.7 macrophages and OVA-induced asthmatic model were used to validate the potential signaling pathways. RESULTS: GC × GC-QTOF MS analysis revealed the presence of 123 compounds of HVO. The sesquiterpenes and monoterpenes are the main constituents. The in vivo study indicated that HVO suppressed OVA-induced eosinophilic infiltration in lung tissues, inhibited the elevation of IgE, IL-4, IL-5, and IL-13 levels, downregulated the expressions of phosphorylated PI3K, Akt, JNK and P38, and maintained epithelial barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin. The in vitro study also revealed an inhibition of NO release and downregulation of phosphorylated PI3K, Akt, JNK and P38 levels. CONCLUSION: HVO alleviates airway inflammation in OVA-induced asthmatic mice by inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin.

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.

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.

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.

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.

Surgical management of hemophilic pseudotumor complicated by destructive osteoarthropathy.

Hemophilic pseudotumor gradually erodes bone and induces fracture or deformity, causing joint dysfunction or destructive osteoarthropathy. Reports about surgery for hemophilic pseudotumor complicated by destructive osteoarthropathy are scarce. The object of this study was to evaluate the results and complications of surgical management for patients of pseudotumor complicated by destructive osteoarthropathy. We retrospectively reviewed records from July 1996 to July 2013, and found eight patients with pseudotumor complicated by destructive osteoarthropathy. We recorded their demographic data, time of surgery, amount of blood loss and transfusion, bone union, and complications. Seven patients were diagnosed with hemophilia A and one with hemophilia B. The mean age at surgery was 31.9 ±â€Š8.3 years. Two of the eight underwent excision of the pseudotumor and metallic fixation, one had amputation, and five underwent autogenous or exogenous bone grafting and fixation with an absorbable screw. The median operating time was 170 min (135-315 min). The median amount of intraoperative blood loss was 1350 ml (100-4000 ml). The amount of red blood cells, plasma, and whole blood transfusion after surgery were 0-24 units, 0-2000 ml, and 0-4600 ml, respectively. After a median follow-up of 75 months, the numbers of pseudotumor recurrence, fracture nonunion, coagulation factor inhibitor formation, and wound complications were one, one, two, and four, respectively. Surgery is an effective treatment for hemophilic pseudotumor complicated by destructive osteoarthropathy. However, the incidences of wound infection, coagulation factor inhibitor formation, hemophilic pseudotumor recurrence, and fracture nonunion are high.

[The microbiology and antimicrobial susceptibility of the infected knee arthroplasty].

OBJECTIVES: To describe the microbiology, antimicrobial susceptibility of patients proven prosthetic joint infection (PJI) after primary total knee arthroplasty (TKA)and to provide reference for the diagnosis and treatment of this complication. METHODS: The medical data of the patients with infected knee arthroplasty, who were managed with revision surgery between January 1995 to December 2011 were reviewed. Twenty-nine cases were identified and majority of the patients were female (23/29). Diagnosis of PJI after primary TKA was between 1 week and 10 years (average 24.3 months). The microbiology and antimicrobial susceptibility were analyzed. RESULT: The overall positive rate of cultures was 65.5% (19/29). The most common organisms identified were Coagulase-negative Staphylococcus (CNS) (7/19) and Staphylococcus Aureus (SA) (5/19). Rare pathogens of Mycobacterium (2/19) and fungi (1/19) were also identified. Vancomycin was the most effective antibiotics with overall sensitivity rates of 100%.Resistant and rare pathogens were all in type IV infection. CONCLUSIONS: Gram-positive bacterias are the main pathogen, resistant and rare pathogens should be payed attention to. Antibiotic treatment for infected TKA should be based on the results of drug susceptibility. Vancomycin allows infected knee arthroplasties before the result.

[A meta-analysis of the effectiveness and safety of using tranexamic acid in spine surgery].

OBJECTIVE: To assess the effectiveness and safety of using tranexamic acid (TXA) in reducing blood loss in spine surgery through a meta-analysis. METHODS: Literatures before November 2009 were identified from the PubMed, EMBase, Cochrane library, CNKI and VIP databases. Relevant journals or conference proceedings were also searched manually. This study only enrolled high quality (Jadad scores ≥ 3) randomized controlled trials (RCTs). Two independent reviewers searched and assessed the literatures.Weighted mean difference (WMD) of blood loss and blood transfusions, odds ratio (OR) of transfusion rate and of deep vein thrombosis (DVT) rate in TXA-treated group versus placebo group were calculated across the studies. The statistical analysis were conducted by the software of RevMan 4.2. RESULTS: Four double-blinded RCTs met the inclusion criteria for meta-analysis. The total sample size of these studies was 295. The use of TXA significantly reduced total blood loss [WMD = -523.74, 95%CI (-778.92, -268.56), P < 0.01], blood volumes of transfusion [WMD = -242.28, 95%CI (-394.02, -90.54), P = 0.002] and proportion of patients requiring blood transfusion [OR = 0.57, 95%CI (0.34, 0.93), P = 0.020], while did not raise the risk of DVT, as compared with placebo group. CONCLUSIONS: This meta-analysis indicates that the use of TXA infusion for patients undergoing spine surgery is effective in reducing total blood loss, transfusion volumes and the rate of transfusion, yet doesn't raise the risk of postoperative DVT.

[The efficacy and complications of one stage posterior vertebral column resection for severe spinal deformities].

OBJECTIVE: to evaluate the outcomes and complications of posterior vertebral column resection in the treatment of severe and fixed spinal deformities. METHODS: from January 2008 to January 2010, 15 consecutive cases (4 males, 11 females) of severe and fixed spinal deformities managed by single posterior vertebral column resection with transpedicular instrumentation were investigated retrospectively. The diagnosis included congenital scoliosis in 10 cases, adolescent idiopathic scoliosis in 1 case, congenital kyphosis in 3 cases, tuberculous kyphosis 1 case. Radiographs were measured to determine the regional coronal and sagittal curve magnitude, and the coronal and sagittal balance preoperatively, postoperatively and at the final follow-up. Operative reports and patient charts were reviewed to record operation time, intraoperative blood loss and complications. RESULTS: the mean resected vertebrae was 1.8 (range, 1 - 5). The mean operation time was 331 min (range, 240 - 450 min) with an average blood loss of 1453 ml (range, 800 - 3000 ml). The average follow-up time was 13 months (range, 3 - 24 months). The regional scoliosis was corrected from 111° to 51°with a correction rate of 54.0%, and regional kyphosis from 104° to 39° with a correction rate of 62.5%. No obvious loss of correction was noted at the final follow-up. The coronal trunk shift improved from 19.5 mm preoperatively to 18.1 mm postoperatively and 12.4 mm at final follow-up. The sagittal balance improved from 20.0 mm preoperatively to -2.0 mm postoperatively and -1.1 mm at the final follow-up. Complications included partial pleural rupture requiring repair in 3 cases, transient muscle weakness of one lower limb after surgery but recovered completely at 6 month follow-up in 2 cases, and tightness of thorax after surgery in one case. CONCLUSIONS: posterior vertebral column resection is effective in treatment of severe and rigid spinal deformities. But it is a technique-demanding procedure with higher risks of major neurologic complications.

An analysis on transcriptional regulation activity of human XBP1 gene 5' upstream DNA sequences.

OBJECTIVE: To analyze the transcription activation and possible regulation mechanism of human X-box binding protein 1(XBP1)gene 5'upstream DNA sequence in different cell lines. METHODS: Six kinds of XBP1 promoter deletion mutants were cloned into pGEM-Teasy vector, which included XBP1 gene 5' upstream -1039 to 66 bp,-859 to 66 bp,-623 to 66 bp,-351 to 66 bp,-227 to 66 bp,-227 to -45 bp respectively. Every deletion mutant sequence was cut from Teasy-XBP1p by KpnI and Xho I, and subcloned into pCAT3-Basic to produce a set of constructs termed as p1-XBP1p, p2-XBP1p, p3-XBP1p, p4-XBP1p, p5-XBP1p, p6-XBP1p, respectively. The transcription activity of each construct was detected after transiently transfecting K562, HepG2,NIH-3T3 and L0(2)cell with FuGENE 6 transfection reagent. Cells transfected by pCAT3-Basic or pCAT3-Promoter were used as negative and positive controls. The activity of chloramphenicol acetyltransferase(CAT), which reflects the transcription activation of the XBP1 gene promoter, was detected by ELISA after 48 hours of transfection. RESULTS: The reporter vectors of six kinds of XBP1 promoter deletion mutants were successfully constructed, as confirmed by restriction enzyme digestion and sequencing. The activities of p4-XBP1p and p5-XBP1p were higher than the other deletion mutants in K562 and HepG2. And the activity of p5-XBP1p was the highest in HepG2. There was no activity detected from any transfected NIH-3T3. CONCLUSION: The XBP1 gene promoter can transactivate its downstream gene to transcription. The core sequence of XBP1 promoter was implied between -227 bp and 66 bp. This sequence was connected with the transcriptional activity of XBP1 promoter closely. Its transcription activity varies with different cell lines. XBP1 promoter might drive gene expression with cell-type specificity.