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.

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.

Deletion of BCG_2432c from the Bacillus Calmette-Guérin vaccine enhances autophagy-mediated immunity against tuberculosis.

BACKGROUND: Mycobacterium bovis bacillus Calmette-Guérin (BCG) is an attenuated live vaccine that provides insufficient protection against tuberculosis (TB), the underlying mechanisms for which remain unknown. Assuming that the BCG vaccine inherits immune evasive strategies from virulent parent M. bovis strains, we aimed to identify the associated genes and assess their effects on the vaccine efficacy. METHODS: Three genes, BCG_3174, BCG_1782, and BCG_2432c, associated with immune evasion were first identified via bioinformatics analysis and then confirmed in the genome of M. bovis and 12 commercial BCG vaccine substrains using Polymerase Chain Reaction (PCR) and DNA sequencing. These genes were disrupted to develop mutant strains, and their effects on autophagy and their protective efficacy were further compared with the BCG vaccine in vitro and in vivo. RESULTS: Of the three identified genes, only the disruption of BCG_2432c, namely ΔBCG_2432c, conferred stronger protection against intranasal TB in vaccinated mice, when compared with the BCG vaccine. ΔBCG_2432c showed a stronger ability to trigger intracellular ROS-mediated complete autophagic flux in infected THP-1 cells that resulted in higher antigen presentation. The improved protection could be attributed to early and increased IFN-γ+ CD4+ TEM and IL-2+ CD4+ TCM cells in the spleens and lungs of ΔBCG_2432c-vaccinated mice. CONCLUSIONS: The insufficient efficacy of the BCG vaccine is attributable to the important autophagy-inhibition gene BCG_2432c that blocks the autophagosome-lysosome pathway of antigen presentation. ΔBCG_2432c provides a promising platform to either replace the current BCG vaccine or develop vaccines that are more effective against TB.

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 ).

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.

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.

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).

Robotic-assisted compared with conventional total hip arthroplasty: systematic review and meta-analysis.

BACKGROUND: Robotic-assisted total hip arthroplasty (THA) allows for accurate preoperative planning and component positioning, potentially enhancing implant survival and long-term outcomes. The relative efficacy and safety of robotic-assisted and conventional THA, however, are unclear. This systematic review and meta-analysis compared the safety and efficacy of robotic-assisted and conventional THA. METHODS: Medline, Embase and the Cochrane Library were comprehensively searched in September 2017 to identify studies comparing the safety and efficacy of robotic-assisted and conventional THA. Seven studies were included. Data of interest were extracted and analysed using Review Manager 5.3. RESULTS: The seven included studies involved 1516 patients, with 522 undergoing robotic-assisted and 994 undergoing conventional THA. Compared with conventional THA, robotic-assisted THA was associated with longer surgical time (not significant); lower intraoperative complication rates (OR: 0.12, 95% CI: 0.05 to 0.34, p<0.0001 I2); better cup placement, stem placement and global offset and a higher rate of heterotopic ossifications. Functional scores, limb length discrepancy and rates of revision and stress shielding were similar in the two groups. The relative amount of blood loss was unclear. CONCLUSION: The results of this meta-analysis suggest that robotic-assisted THA has certain advantages over conventional THA, including the results of component positioning and rates of intraoperative complications. Additional comparative studies are required to determine the long-term clinical outcomes of robotic-assisted THA.

OCIAD2 suppressed tumor growth and invasion via AKT pathway in Hepatocelluar carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive tumor and the third leading cause of cancer-related death worldwide. Ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) has been found frequently methylated in various cancers, including HCC. The aim of the present study was to investigate the role of OCIAD2 in HCC progression. We analyzed liver hepatocellular carcinoma patients' data from the Cancer Genome Atlas (TCGA), including data extracted from 371 HCC tissues and 50 adjacent normal liver tissues. The RNA sequencing and DNA methylation data revealed that OCIAD2 were significantly hypermethylated and its expression level in the tumor tissues was much lower than that in the corresponding adjacent normal tissues. The methylation level in the promoter was negatively correlated with the expression level of OCAID2. Treatment of HCC cell lines with the DNA methylation inhibitor 5-aza-2'-deoxycitydine (5-Aza) induced a significant increase in the OCIAD2 mRNA and protein. Knocking-down OCIAD2 led to an increased colony formation, migration and invasion dramatically, accompanying with an enhanced expression of MMP9 and activation of AKT and FAK. Inhibition of AKT signaling restored OCIAD2-mediated changes in HCC cell clonogenic growth, migration and invasion. Survival analysis of HCC patient's data indicated patients with a higher expression ratio of OCIAD2/MMP9 had a shorter overall survival than those with a lower expression ratio of OCIAD2/MMP9. Overall, our data indicate that reduced expression of OCIAD2 by DNA hypermethylation plays an important role in HCC tumor growth and invasion. Hypermethylation of OCIAD2 may contribute to HCC treatment development.

Prognostic value of intraoperative MEP signal improvement during surgical treatment of cervical compressive myelopathy.

PURPOSE: The purpose of the current study was to evaluate the prognostic value of intraoperative improved transcranial motor evoked potential (MEP) after cervical cord decompressive surgery for cervical compressive myelopathy (CCM). METHOD: A consecutive series of 59 CCM patients who underwent cervical cord decompressive surgery were studied between December 2013 and April 2015 in this study. And all patients were divided into three subgroups: the patients with intraoperative improved MEP, without obvious MEP change and MEP degeneration. MEP and modified Japanese Orthopedic Association (mJOA) score were mainly utilized to assess intra-, pre- and post-operative neurologic function; all patients had reliable and stable MEP baseline. The early neurologic outcomes and the long-term mJOA improvement rate were evaluated after surgery. RESULTS: There were 21 patients with intraoperative monitoring improvement (MEP improved rate, 140 ± 76 %), 32 patients without obvious MEP change and six patients with MEP degeneration. The early motor or sensory outcome showed varying degrees of recovery in the MEP improvement group. The long-term mJOA improvement rate among the three groups was 59.5 ± 4.2, 48.9 ± 3.9 and 40.6 ± 7.4 %, respectively, after 6-month follow-up, and the improvement group was better than the other two groups with statistical significance (59.5 ± 4.2 vs. 48.9 ± 3.9 %, p < 0.05; 59.5 ± 4.2 vs. 40.6 ± 7.4, p < 0.05). CONCLUSION: Patients with intraoperative MEP improvement after cervical cord decompression have better prognosis in early and long-term neurologic recovery in CCM surgery.

Interclonal gradient of virulence in the Pseudomonas aeruginosa pangenome from disease and environment.

The population genomics of Pseudomonas aeruginosa was analysed by genome sequencing of representative strains of the 15 most frequent clonal complexes in the P. aeruginosa population and of the five most common clones from the environment of which so far no isolate from a human infection has been detected. Gene annotation identified 5892-7187 open reading frame (ORFs; median 6381 ORFs) in the 20 6.4-7.4 Mbp large genomes. The P. aeruginosa pangenome consists of a conserved core of at least 4000 genes, a combinatorial accessory genome of a further 10 000 genes and 30 000 or more rare genes that are present in only a few strains or clonal complexes. Whole genome comparisons of single nucleotide polymorphism synteny indicated unrestricted gene flow between clonal complexes by recombination. Using standardized acute lettuce, Galleria mellonella and murine airway infection models the full spectrum of possible host responses to P. aeruginosa was observed with the 20 strains ranging from unimpaired health following infection to 100% lethality. Genome comparisons indicate that the differential genetic repertoire of clones maintains a habitat-independent gradient of virulence in the P. aeruginosa population.

Characterization of p38 MAPK isoforms for drug resistance study using systems biology approach.

MOTIVATION: p38 mitogen-activated protein kinase activation plays an important role in resistance to chemotherapeutic cytotoxic drugs in treating multiple myeloma (MM). However, how the p38 mitogen-activated protein kinase signaling pathway is involved in drug resistance, in particular the roles that the various p38 isoforms play, remains largely unknown. METHOD: To explore the underlying mechanisms, we developed a novel systems biology approach by integrating liquid chromatography-mass spectrometry and reverse phase protein array data from human MM cell lines with computational pathway models in which the unknown parameters were inferred using a proposed novel algorithm called modularized factor graph. RESULTS: New mechanisms predicted by our models suggest that combined activation of various p38 isoforms may result in drug resistance in MM via regulating the related pathways including extracellular signal-regulated kinase (ERK) pathway and NFкB pathway. ERK pathway regulating cell growth is synergistically regulated by p38δ isoform, whereas nuclear factor kappa B (NFкB) pathway regulating cell apoptosis is synergistically regulated by p38α isoform. This finding that p38δ isoform promotes the phosphorylation of ERK1/2 in MM cells treated with bortezomib was validated by western blotting. Based on the predicted mechanisms, we further screened drug combinations in silico and found that a promising drug combination targeting ERK1/2 and NFκB might reduce the effects of drug resistance in MM cells. This study provides a framework of a systems biology approach to studying drug resistance and drug combination selection. AVAILABILITY AND IMPLEMENTATION: RPPA experimental Data and Matlab source codes of modularized factor graph for parameter estimation are freely available online at http://ctsb.is.wfubmc.edu/publications/modularized-factor-graph.php.

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 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.

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.

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.

[Comparison of blood loss during total knee arthroplasty between haemophilic arthropathy and osteoarthritis].

OBJECTIVE: To evaluate the amount of blood loss and the efficacy of clotting factor in controlling blood loss during total knee arthroplasty. METHODS: The medical documents of 18 patients with haemophilic arthritis (HA) secondary to haemophilia A and 19 patients with osteoarthritis (OA) were retrospectively reviewed. Demographic data,functional and hematological test results,the amount of blood loss and transfusion,and complications were analyzed. RESULTS: The median amounts of total and external blood loss were 2240 ml(1892-3415 ml) and 1326 ml(934-2256 ml)in the HA group, which were significant higher than those in the OA group [1746 ml(1259-2246 ml)and 846 ml (504-1217 ml), respectively]. The median amounts of external blood loss in the two groups were 680 ml(370-1330 ml)and 730 ml(200-1190 ml)and there was no significant difference(p=0.620). Moreover, more patients in the HA group required blood transfusion (84.2% vs. 47.4%), and more red cells were transfused per patient in the HA group (2.3 U vs. 0 U). CONCLUSIONS: The total blood loss and hidden blood loss are higher in the HA patients than in OA patients during total knee arthroplasty, although the external blood loss is basically the same. Management with more clotting factor may decrease the blood loss in HA patients.

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.