Sprayable Zwitterionic Antibacterial Hydrogel With High Mechanical Resilience and Robust Adhesion for Joint Wound Treatment.

Wound healing in movable parts, including the joints and neck, remains a critical challenge due to frequent motions and poor flexibility of dressings, which may lead to mismatching of mechanical properties and poor fitting between dressings and wounds; thus, increasing the risk of bacterial infection. This study proposes a sprayable zwitterionic antibacterial hydrogel with outstanding flexibility and desirable adhesion. This hydrogel precursor is fabricated by combining zwitterionic sulfobetaine methacrylate (SBMA) with poly(sulfobetaine methacrylate-co-dopamine methacrylamide)-modified silver nanoparticles (PSBDA@AgNPs) through robust electrostatic interactions. About 150 s of exposure to UV light, the SBMA monomer polymerizes to form PSB chains entangled with PSBDA@AgNPs, transformed into a stable and adhesion PSB-PSB@Ag hydrogel at the wound site. The resulting hydrogel has adhesive strength (15-38 kPa), large tensile strain (>400%), suitable shape adaptation, and excellent mechanical resilience. Moreover, the hydrogel displays pH-responsive behavior; the acidic microenvironment at the infected wound sites prompts the hydrogel to rapidly release AgNPs and kill bacteria. Further, the healing effect of the hydrogel is demonstrated on the rat neck skin wound, showing improved wound closing rate due to reduced inflammation and enhanced angiogenesis. Overall, the sprayable zwitterionic antibacterial hydrogel has significant potential to promote joint skin wound healing.

Metallic-Polyphenolic Nanoparticles Reinforced Cationic Guar Gum Hydrogel for Effectively Treating Burn Wound.

The development of injectable hydrogel dressings which are long-term moisturizing, easy-to-apply, and effectively inhibiting infection and inflammatory is essential to promote burn wound repairing. Herein, an injectable hydrogel with moisturizing, antibacterial, and anti-inflammation abilities via multiple reversible interactions between cation guar gum (CG) and metallic-polyphenolic nanoparticles (PA-ZnII NPs) is developed. Specifically, PA-ZnII NPs is formed by synergistic complexation of protocatechualdehyde (PA) and zinc ion (Zn2+ ), provides CGPZ hydrogel with plentiful reversible interactions to inhibit the loss of moist. By interacting with PA-ZnII NPs, the CGPZ hydrogel can provide enhanced moisturization for more than 3 days. Moreover, the CGPZ hydrogel can maintain good adhesion for a period of time with injection and self-healing capabilities due to reversible interactions between CG and PA-ZnII NPs. In addition, CGPZ hydrogel exhibits outstanding broad spectrum antibacterial performance, as its killing efficiency against Escherichia coli and Staphylococcus aureus is all greater than 99.99%. Importantly, compared with commercial dressing, the CGPZ hydrogel can promote wound healing faster by inhibiting tissue damage from dysregulated inflammation and accelerating neovascularization. It is believed that the moisturizing CGPZ hydrogel with antibacterial and anti-inflammation performance can serve as a promising dressing for the effective treatment of burn wound.

Drug-Embedded Nanovesicles Assembled from Peptide-Decorated Hyaluronic Acid for Rheumatoid Arthritis Synergistic Therapy.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes endless pain and poor quality of life in patients. Usage of a lubricant combined with anti-inflammatory therapy is considered a reasonable and effective approach for the treatment of RA. Herein, inspired by glycopeptides, a peptide-decorated hyaluronic acid was synthesized, and the grafted Fmoc-phenylalanine-phenylalanine-COOH (FmocFF) peptide self-assembled with ß-sheet conformations could induce the folding of polymer molecular chains to form a vesicle structure in aqueous solution. The hydrophobic anti-inflammatory drug curcumin (Cur) could be embedded in the vesicle walls through π-π interactions with the FmocFF peptide. Furthermore, the inflammation suppression function of the Cur-loaded vesicles both in vitro and in vivo was demonstrated to be an effective treatment for RA therapy. This work proposes new insights into the folding and hierarchical assembly of glycopeptide mimics, providing an efficient approach for constructing intelligent platforms for drug delivery, disease therapy, and diagnostic applications.

Gait Asymmetry Variation in Kinematics, Kinetics, and Muscle Force along with the Severity Levels of Knee Osteoarthritis.

OBJECTIVE: Knee osteoarthritis (OA) patients exhibit greater gait asymmetry than healthy controls. However, gait asymmetry in kinematics, kinetics and muscle forces across patients with different severity levels of knee OA is still unknown. The study aimed to investigate the changes of gait asymmetry in lower limb kinematics, kinetics, and muscle force across patients with different severity levels of knee OA. METHODS: This is a cross-sectional study. From January 2020 to January 2021, 118 patients with symptomatic and radiographic medial knee OA were categorized into three groups using the Kellgren and Lawrence scale (mild: grade 1 and 2, n = 37; moderate: grade 3, n = 31; severe: grade 4, n = 50). During self-paced walking, marker trajectories and ground reaction forces data were recorded. Musculoskeletal simulations were used to determine gait kinematics, kinetics, and muscle force. One-way analysis of variance with Tukey's post-hoc test was used to evaluate group difference. Paired-sample t-test was used to compared the between-limb difference. RESULTS: In the Severe group, significantly greater asymmetry index in knee flexion/extension range of motion (45%) was observed with a greater value on the contralateral side (p < 0.01), compared to the Mild (15%) and Moderate (15%) groups. Significantly higher peak hip contact force (JCF) on the contralateral side was found in the Mild (more affected side: 3.80 ± 0.67 BW, contralateral side: 4.01 ± 0.58 BW), Moderate (more affected side: 3.67 ± 0.56 BW, contralateral side: 4.07 ± 0.81 BW), and Severe groups (more affected side: 3.66 ± 0.79 BW, contralateral side: 3.94 ± 0.64 BW) (p < 0.05). Significantly greater gluteus medius muscle force on the contralateral side was found in Mild (more affected side: 0.48 ± 0.09 BW, contralateral side: 0.52 ± 0.12 BW), Moderate (more affected side: 0.45 ± 0.10 BW, contralateral side: 0.51 ± 0.15 BW), and Severe groups (more affected side: 0.42 ± 0.15 BW, contralateral side: 0.47 ± 0.12 BW) (p < 0.05). The contralateral side showing significantly higher peak knee adduction moment and medial knee JCF was only observed in the Mild group (p < 0.05). CONCLUSIONS: Gait asymmetry in kinematics and muscle forces increased from mild to severe knee OA. Asymmetrical gait pattern tends to transfer loads from the more affected side to the contralateral side. Peak hip JCF and gluteus medius muscle force can be used to detect this asymmetrical gait pattern in patients with knee OA, regardless of severity levels.

MRI-based pre-Radiomics and delta-Radiomics models accurately predict the post-treatment response of rectal adenocarcinoma to neoadjuvant chemoradiotherapy.

Objectives: To develop and validate magnetic resonance imaging (MRI)-based pre-Radiomics and delta-Radiomics models for predicting the treatment response of local advanced rectal cancer (LARC) to neoadjuvant chemoradiotherapy (NCRT). Methods: Between October 2017 and August 2022, 105 LARC NCRT-naïve patients were enrolled in this study. After careful evaluation, data for 84 patients that met the inclusion criteria were used to develop and validate the NCRT response models. All patients received NCRT, and the post-treatment response was evaluated by pathological assessment. We manual segmented the volume of tumors and 105 radiomics features were extracted from three-dimensional MRIs. Then, the eXtreme Gradient Boosting algorithm was implemented for evaluating and incorporating important tumor features. The predictive performance of MRI sequences and Synthetic Minority Oversampling Technique (SMOTE) for NCRT response were compared. Finally, the optimal pre-Radiomics and delta-Radiomics models were established respectively. The predictive performance of the radionics model was confirmed using 5-fold cross-validation, 10-fold cross-validation, leave-one-out validation, and independent validation. The predictive accuracy of the model was based on the area under the receiver operator characteristic (ROC) curve (AUC). Results: There was no significant difference in clinical factors between patients with good and poor reactions. Integrating different MRI modes and the SMOTE method improved the performance of the radiomics model. The pre-Radiomics model (train AUC: 0.93 ± 0.06; test AUC: 0.79) and delta-Radiomcis model (train AUC: 0.96 ± 0.03; test AUC: 0.83) all have high NCRT response prediction performance by LARC. Overall, the delta-Radiomics model was superior to the pre-Radiomics model. Conclusion: MRI-based pre-Radiomics model and delta-Radiomics model all have good potential to predict the post-treatment response of LARC to NCRT. Delta-Radiomics analysis has a huge potential for clinical application in facilitating the provision of personalized therapy.

Injectable sodium alginate hydrogel loaded with plant polyphenol-functionalized silver nanoparticles for bacteria-infected wound healing.

A novel injectable hydrogel dressing (GA@AgNPs-SA) with long-term antimicrobial effect is developed that can accelerate the closure of bacteria-infected wounds. The hydrogel dressing was prepared by cross-linking sodium alginate molecular chains and gallic acid functionalized silver nanoparticles (GA@AgNPs) via calcium ions to form a three-dimensional network. The hydrogel dressing demonstrates excellent biocompatibility and can achieve a sustainable release of silver ions, ensuring a long-term antibacterial activity and inhibiting biofilm formation. Moreover, an in vivo study demonstrates that the GA@AgNPs-SA hydrogel can effectively decrease the expression of IL-6 and TNF-α to alleviate the inflammatory response, and promote angiogenesis by upregulating CD31, α-SMA and VEGF expression, thus significantly accelerating the repair of infected wounds. Given these interesting properties, this antibacterial hydrogel has great potential for application in the clinical care of bacteria-infected wounds.

IRF1 expression might be a biomarker of CD8+ T cell infiltration in cutaneous melanoma.

OBJECTIVE: This study aimed to explore the expression profile of interferon regulatory factor (IRF) genes in skin cutaneous melanoma (SKCM), their association with CD8 + T cell infiltration, and the potential regulatory network in melanoma and non-melanoma cells. METHODS: Bioinformatic analysis was conducted using the SKCM subset of The Cancer Genome Atlas (TCGA) Pan-Cancer, Genotype-Tissue Expression Project (GTEx), and single-cell RNA-seq data from the Human Protein Atlas and Jerby-Arnon et al. 2018's dataset. RESULTS: IRF1 expression is robustly associated with moderate to strong CD8 + T cell infiltration in the tumor microenvironment. It is ubiquitously expressed in tumor and non-tumor cells in melanoma. Melanoma tumor cells and macrophages had 16/36 and 9/27 cell-specific IRF1-correlated genes, respectively. The methylation of four CpG sites (cg00255919, cg21138405, cg15375424, and cg27587780) within the IRF1 gene locus showed moderate to strong negative correlations with IRF1 expression. CONCLUSION: IRF1 expression might serve as a biomarker indicating CD8 + T cell infiltration in skin melanoma. It might exert different regulatory effects in melanoma and non-melanoma cells in the tumor microenvironment. Cg00255919, cg21138405, cg15375424, and cg27587780 are four critical CpG sites that might modulate the transcription of IRF1.

Multiplexed nanomaterial-assisted laser desorption/ionization for pan-cancer diagnosis and classification.

As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. By multiplexing mass spectrometry fingerprints from two independent nanostructured matrixes through machine learning for highly sensitive detection and high throughput analysis, we report a laser desorption/ionization (LDI) mass spectrometry-based liquid biopsy for pan-cancer screening and classification. The Multiplexed Nanomaterial-Assisted LDI for Cancer Identification (MNALCI) is applied in 1,183 individuals that include 233 healthy controls and 950 patients with liver, lung, pancreatic, colorectal, gastric, thyroid cancers from two independent cohorts. MNALCI demonstrates 93% sensitivity at 91% specificity for distinguishing cancers from healthy controls in the internal validation cohort, and 84% sensitivity at 84% specificity in the external validation cohort, with up to eight metabolite biomarkers identified. In addition, across those six different cancers, the overall accuracy for identifying the tumor tissue of origin is 92% in the internal validation cohort and 85% in the external validation cohort. The excellent accuracy and minimum sample consumption make the high throughput assay a promising solution for non-invasive cancer diagnosis.

Additional nerve blocks are not superior to multiple-site infiltration analgesia in total knee arthroplasty under adductor canal block.

BACKGROUND: Adductor canal block (ACB) with additional nerve blocks (ANBs) is reported to provide adequate analgesia and enhanced functional rehabilitation in total knee arthroplasty (TKA). The present study aims to evaluate whether ANBs are superior to multiple-site infiltration analgesia (MIA) in patients undergoing TKA under ACB. METHODS: We enrolled 530 patients undergoing primary TKA from 2015 to 2019 at our institution in this retrospective cohort study. Patients were divided into two groups: Group A was treated with ANBs + ACB; Group B was treated with MIA + ACB. Primary outcomes were pain scores and morphine consumption. Functional recovery was the secondary outcome. Other outcomes included satisfaction score, cost-effectiveness, adverse events, and length of hospital stay (LOS). RESULTS: Pain scores at rest and morphine consumption were slightly lower in the ANBs + ACB group than in the MIA + ACB group. No significant difference was found in functional recovery, post-operative complications or LOS between the groups. Meanwhile, the cost of analgesic intervention in the MIA + ACB group was less than that in the ANBs + ACB group. CONCLUSION: The present study suggests that ANBs do not provide superior pain relief compared to MIA for patients undergoing TKA under ACB. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100043227. Registered 9 February 2021, https://www.chictr.org.cn/showproj.aspx?proj=121745 .

Incidence and risk factors associated with human albumin administration following total joint arthroplasty: a multicenter retrospective study.

BACKGROUND: Enhanced recovery after surgery (ERAS) program advocates implementation of perioperative goal-directed fluid therapy and reduced application of colloidal fluids. It should be used reasonably selectively in high-risk patients despite the clear efficacy of human albumin (HA). Therefore, it is vital to identify the risk factors for the use of HA. This study aims to determine the incidence and risk factors of HA administration in patients undergoing total hip or knee arthroplasty (THA, TKA). METHODS: We identified patients undergoing THA or TKA in multiple institutions from 2014 to 2016 and collected patient demographics and perioperative variables. The criterion of HA administration was defined as a postoperative albumin level < 32 g/L or 32 to 35 g/L for at-risk patients. We compared 14 variables between patients who received HA administration and those who did not after stratification by the preoperative albumin (pre-ALB) level. Multivariable regressions identified the independent risk factors associated with HA administration. RESULTS: In total, 958 (20.3%) of 4713 patients undergoing THA and 410 (9.7%) of 4248 patients undergoing TKA received HA administration. In addition to pre-ALB < 35 g/L, preoperative anemia (odds ratio [OR] 2.12, P = 0.001; OR 1.39, P < 0.001) and drain use (OR 3.33, P = 0.001; OR 4.25, P < 0.001) were also independent risk factors for HA administration after THA regardless pre-ALB < 35 g/L or not, and patients undergoing TKA diagnosed of rheumatoid arthritis or ankylosing spondylitis tended to receive HA administration regardless pre-ALB < 35 g/L or not (OR 3.67, P = 0.002; OR 2.06, P < 0.001). CONCLUSIONS: The incidence of HA administration was high in patients undergoing THA or TKA, and several variables were risk factors for HA administration. This finding may aid surgeons in preoperatively identifying patients requiring HA administration and optimizing perioperative managements.

Porous copper- and lithium-doped nano-hydroxyapatite composite scaffold promotes angiogenesis and bone regeneration in the repair of glucocorticoids-induced osteonecrosis of the femoral head.

Glucocorticoids-induced osteonecrosis of the femoral head (GIONFH) is a common refractory disease. In the present study, we aimed to synthesize the nano-hydroxyapatite-copper-lithium (Cu-Li-nHA) composite porous scaffold to promote osteogenesis and angiogenesis functions to repair GIONFH by regulating the Wnt/ß-catenin and HIF-1α/VEGF pathways. The physicochemical property of the scaffold was characterized and their osteogenic and angiogenic effects were tested through a serial of experimentsin vitroandin vivo. Results showed that 0.25% Cu-Li-nHA scaffolds possessed the highest mechanical and biocompatibilityin vitro. Then the 0.25% Cu-Li-nHA scaffolds significantly enhanced the new bone formation on defects in GIONFH rabbitsin vivo. Moreover, the scaffold could increase the expression of osteogenic and angiogenic factors along with the activation of factors in Wnt/ß-catenin and HIF-1α/VEGF pathwaysin vitroandin vivo. In conclusion, the 0.25% Cu-Li-nHA scaffold could improve the osteogenesis and angiogenesis by upregulating the Wnt/ß-catenin and HIF-1α/VEGF pathways which benefited to repair the GIONFH in rabbit models.

[Comparison of unicompartmental knee arthroplasty and total knee arthroplasty in the treatment of severe medial compartment osteoarthritis].

OBJECTIVE: To compare the effectiveness of unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) in the treatment of severe medial compartment osteoarthritis (OA). METHODS: A clinical data of 69 patients (69 knees), who underwent joint replacement due to severe medial compartment OA between February 2015 and September 2018 and met the selection criteria, was retrospectively analyzed. Among them, 38 cases were treated with UKA (UKA group) and 31 cases with TKA (TKA group). There was no significant difference in gender, age, body mass index, course of disease, lesion side, and preoperative visual analogue scale (VAS) score, Hospital for Special Surgery (HSS) score, Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score, Feller score, range of motion of knee, physiological and psychological scores of short-form 12 health survey scale (SF-12) between the two groups ( P>0.05). The femorotibial angle (FTA) of TKA group was bigger than that of UKA group, and hip-knee-ankle angle (HKA) was smaller, showing significant differences ( P<0.05). The operative time, incision length, blood loss, time for flexion 90°, ambulation time, hospital stay, and incidence of deep venous thrombosis of lower extremity were recorded and compared between the two groups. The VAS score, HSS score, WOMAC score, Feller score, range of motion, and physiological and psychological scores of SF-12 were used to evaluate patients' quality of life. FTA, HKA, and prosthesis looseness were observed by X-ray films. Kaplan-Merier survival analysis was used to evaluate the survival rate of prosthesis. RESULTS: All operations were successfully completed in both groups. Compared with TKA group, UKA group had shorter incision length, longer operative time, and less blood loss ( P<0.05). There was no significant difference in time for flexion 90°, ambulation time, hospital stay, and the incidence of deep venous thrombosis of lower extremity between the two groups ( P>0.05). The incisions in both groups healed by first intention. During follow-up, 3 patients in the UKA group and 1 patient in the TKA group developed mild anterior knee pain. Patients were followed up (30.7±9.6) months in the UKA group and (34.9±8.7) months in the TKA group, and the difference was not significant ( t=-1.832, P=0.071). At last follow-up, there were significant differences in the HSS score, Feller score, WOMAC score, range of motion, VAS score, and physiological and psychological scores of SF-12 between pre- and post-operation ( P<0.05). The range of motion in the UKA group was bigger than that in the TKA group ( Z=-2.666, P=0.008), and there was no significant difference in the other indexes between the two groups ( P>0.05). X-ray films showed that the alignment of the two groups recovered well, and the FTA and HKA of the two groups were improved at 1 week after operation ( P<0.05). No radiolucency was found around the prosthesis during follow-up, no prosthesis loosening and meniscal bearing dislocation occurred. The survival rates of the prostheses in the two groups were 100%. CONCLUSION: For severe medial compartment OA, the early survival rates of the two prostheses are similar, but UKA has less traumatic, can preserve the normal structure of the knee, and the range of motion of the knee after operation is significantly better than TKA.

Dressing Blood-Contacting Materials by a Stable Hydrogel Coating with Embedded Antimicrobial Peptides for Robust Antibacterial and Antithrombus Properties.

Although dressing blood-contacting devices with robust and synergistic antibacterial and antithrombus properties has been explored for several decades, it still remains a great challenge. In order to endow materials with remarkable antibacterial and antithrombus abilities, a stable and antifouling hydrogel coating was developed via surface-initiated polymerization of sulfobetaine methacrylate and acrylic acid on a polymeric substrate followed by embedding of antimicrobial peptides (AMPs), including WR (sequence: WRWRWR-NH2) or Bac2A (sequence: RLARIVVIRVAR-NH2) AMPs. The chemical composition of the AMP-embedded hydrogel coating was determined through XPS, zeta potential, and SEM-EDS measurements. The AMP-embedded antifouling hydrogel coating showed not only good hemocompatibility but also excellent bactericidal and antiadhesion properties against Gram-positive and Gram-negative bacteria. Moreover, the hydrogel coating could protect the AMPs with long-term bioactivity and cover the positive charge of the dotted distributed AMPs, which in turn well retained the hemocompatibility and antifouling capacity of the bulk hydrogels. Furthermore, the microbiological results of animal experiments also verified the anti-infection performance in vivo. Histological and immunological data further indicated that the hydrogel coating had an excellent anti-inflammatory function. Therefore, the present study might provide a promising approach to prevent bacterial infections and thrombosis in clinical applications of blood-contacting devices and related implants.

NT5DC2 promotes leiomyosarcoma tumour cell growth via stabilizing unpalmitoylated TEAD4 and generating a positive feedback loop.

5'-Nucleotidase Domain Containing 2 (NT5DC2) is a novel oncoprotein, the regulatory effects of which have not been well characterized. This study aimed to investigate the expression profile and functional regulation of NT5DC2 and its potential interplay with TEAD4 in leiomyosarcoma (LMS). Bioinformatic analysis was conducted using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) program. LMS cell lines SK-LMS-1 and SK-UT-1 were used for both in vitro and in vivo analysis. Results showed that NT5DC2 is aberrantly upregulated in LMS. Its overexpression was associated with unfavourable survival. Deletion of NT5DC2 significantly reduced the expression of cyclin B1, cyclin A2, cyclin E1 and CDK1 and increased G1 phase arrest in LMS cell lines, and suppressed their proliferation both in vitro and in vivo. NT5DC2 interacted with unpalmitoylated TEAD4, and this association reduced TEAD4 degradation via the ubiquitin-proteasome pathway. TRIM27 is a novel E3 ubiquitin ligase that induces K27/48-linked ubiquitination of unpalmitoylated TEAD4 at Lys278. TEAD4 inhibition significantly suppressed LMS cell growth both in vitro and in vivo. Dual-luciferase assay demonstrated that TEAD4 could bind to the NT5DC2 promoter and activate its transcription. Based on these findings, we infer that the NT5DC2-TEAD4 positive feedback loop plays an important role in LMS development and might serve as a potential therapeutic target.

The efficacy and safety of ipriflavone in postmenopausal women with osteopenia or osteoporosis: A systematic review and meta-analysis.

OBJECTIVES: Ipriflavone (IP) is one of the over-the-counter drugs and found in foods, which is available for prevention of osteoporosis (OP) since 1989 in over 22 countries. Although some clinical trials have suggested that IP is appropriate for treatment of OP, there continues to be controversy regarding the efficacy and safety due to some contradictory reports. With the wide usage of IP for osteoporotic women, there is a critical need for evaluation of the evidence for IP in clinical practice. METHODS AND MATERIALS: We searched randomized control trials (RCTs) in PubMed, CENTRAL and CNKI which used the regimen of IP in postmenopausal women with osteopenia or OP. The efficacy referred to the absolute change and relative change in bone mineral density (BMD) and bone turnover markers. The safety profiles were associated with adverse events and the number of subject withdrawals due to adverse reactions. RESULTS: Eleven RCTs (n = 1605) met the eligibility criteria were included. The increase of the BMD in lumbar spine of the IP group is greater than that of the placebo group (random effect model: SMD = 0.36; 95%CI= (0.09, 0.62)). For safety profile, most frequent reactions are gastrointestinal symptoms, but withdrawals due to adverse reactions are similar in both the IP group and placebo control at the same time intervals. CONCLUSIONS: IP significantly increases BMD and has inhibitory effect on bone resorption markers in postmenopausal women with osteopenia or OP. Gastrointestinal symptoms may occur, but adverse drug withdrawal events were not statistically increased when compared with placebo group.

Systematic screening identifies a 2-gene signature as a high-potential prognostic marker of undifferentiated pleomorphic sarcoma/myxofibrosarcoma.

The Cancer Genome Atlas (TCGA) Research Network confirmed that undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) share a high level of genomic similarities and fall into a single spectrum of tumour. However, no molecular prognostic biomarkers have been identified in UPS/MFS. In this study, by extracting data from TCGA-Sarcoma (SARC), we explored relapse-related genes, their prognostic value and possible mechanisms of the dysregulations. After systematic screening, ITGA10 and PPP2R2B were included to construct a 2-gene signature. The 2-gene signature had an AUC value of 0.83 and had an independent prognostic value in relapse-free survival (RFS) (HR: 2.966, 95%CI: 1.995-4.410 P < .001), and disease-specific survival (DSS) (HR: 2.283, 95%CI: 1.358-3.835, P = .002), as a continuous variable. Gene-level copy number alterations (CNAs) were irrelevant to their dysregulation. Two CpG sites (cg15585341 and cg04126335) around the promoter of ITGA10 showed strong negative correlations with ITGA10 expression (Pearson's r < -0.6). Transcript preference was observed in PPP2R2B expression. The methylation of some CpG sites in two gene body regions showed at least moderate positive correlations (Pearson's r > .4) with PPP2R2B expression. Besides, the 2-gene signature showed a moderate negative correlation with CD4 + T cell infiltration. High-level CD4 + T cell infiltration and neutrophil infiltration were associated with significantly better RFS. Based on these findings, we infer that the 2-gene signature might be a potential prognostic marker in patients with UPS/MFS. Considering the potential benefits of immunotherapy for UPS/MFS patients, it is imperative to explore the predictive value of this signature in immunotherapeutic responses in the future.

Efficacy and safety of tranexamic acid in geriatric hip fracture with hemiarthroplasty: a retrospective cohort study.

BACKGROUND: Geriatric hip fracture patients are particularly susceptible to blood loss and venous thromboembolism (VTE) during hemiarthroplasty, yet relatively few studies have examined the safety and efficacy of tranexamic acid (TXA) in these patients. METHODS: This cohort study of hip fracture patients (≥65 years) undergoing hemiarthroplasty between January 2013 and September 2016 involved 289 patients who received 15 mg/kg TXA prior to surgery and 320 who received no TXA. All patients underwent a fast-track program including nutrition, blood, and pain management; VTE prophylaxis; early mobilization; and early intake. The primary outcome was red cell transfusion requirement. Secondary outcomes included blood loss, hemoglobin (Hb) level, VTE, adverse events and length of hospital stay. Multivariate logistic regression and meta-analysis of the literature were also performed to control for confounding factors and identify risk factors of red cell transfusion. RESULTS: The proportion of patients receiving at least 1 U of erythrocytes was significantly lower in the TXA group (8.65%) than in the control group (24.06%, OR 0.299, p < 0.001). Mean Hb level was significantly higher in the TXA group on postoperative day 1 (111.70 ± 18.40 vs 107.29 ± 18.70 g/L, p = 0.008) and postoperative day 3 (108.16 ± 17.25 vs 104.22 ± 15.16 g/L, p = 0.005). A significantly higher proportion of TXA patients began to ambulate within 24 h after surgery (37.02% vs 26.25%, p = 0.004), and their length of hospitalization was significantly shorter (11.82 ± 4.39 vs 15.96 ± 7.30 days, p = 0.003). TXA did not increase risk of DVT (OR 0.70, 95%CI 0.25 to 1.97). Logistic regression showed that, after adjusting for covariates, TXA was associated with 62% lower risk of red blood cell transfusion (0.327, 95%CI 0.214 to 0.696), and a similar result was obtained in meta-analysis of unadjusted data from the present study and the literature (OR 0.33, 95%CI 0.25 to 0.43). CONCLUSION: TXA appears to be safe and effective for reducing blood loss and red blood cell transfusion in geriatric hip fracture patients undergoing fast-track hemiarthroplasty.

The effect of post-operative limb positioning on blood loss and early outcomes after primary total knee arthroplasty: a randomized controlled trial.

INTRODUCTION: The purpose of this study was to investigate the benefits of three different post-operative limb positions in primary total knee arthroplasty (TKA). METHODS: The trial was a single-surgeon, randomized, controlled trial, and 135 patients following primary TKA were randomized into three groups: group A (45 patients who were treated with the hip fixed at 50° and knee flexed at 90° for 6 hours post-operatively), group B (45 patients who were treated with the hip elevated at 30° and knee flexed at 45° for 6 hours  post-operatively), and group C (45 patients in whom the affected knee was fully extended after surgery). Tranexamic acid was used in all patients. RESULTS: The total blood loss and hidden blood loss in group A (921 ± 209 mL, 597 ± 213 mL) were significantly less than in groups B (1125 ± 222 mL, 784 ± 229 mL) and C (1326 ± 291 mL, 915 ± 301 mL) and less in group B compared with group C. The drain volume in groups A (158 ± 35 mL) and B (174 ± 45 mL) was significantly lower than in group C (249 ± 31 mL). The maximum haemoglobin drop in group A (3.1 ± 0.5 g/dL) was statistically significantly less than in groups B (3.6 ± 0.7 g/dL) and C (4.3 ± 0.4 g/dL). The range of motion (ROM) in groups A (102 ± 3°, 105 ± 2°) and B (100 ± 3°, 104 ± 2°) was significantly better than in group C (98 ± 3°, 102 ± 2°) at the time of discharge and one  month after surgery; it was also significantly less for group A (104.9 ± 2.1%, 108.0 ± 2.4%) compared with groups B (106.7 ± 3.1%, 108.3 ± 2.7%) and C (108.4 ± 3.2%, 110.6 ± 3.0%) with post-operative knee swelling. No differences in transfusion requirements and complications were observed among the three groups. CONCLUSIONS: The affected knee flexion position was superior to the use of a fully extended position for blood management, but it only contributed to better early functional recovery up to three  months post-operatively in TKA. In addition, by fixing the affected knee at a high flexion position of 90°, patients could achieve less blood loss, lower knee swelling, and better early results for ROM and patient satisfaction than the other two groups.

Comparison of three routes of administration of tranexamic acid in primary unilateral total knee arthroplasty: Analysis of a national database.

INTRODUCTION: The ideal route for the administration of tranexamic acid (TXA) remains undecided. This study aimed to compare the efficacy and safety of three routes of TXA following primary total knee arthroplasty (TKA). MATERIALS AND METHODS: We prospectively collected patients' data through the National Health Database from January 2013 to September 2017. The patients were divided into a control group, intravenous group, topical group, and combined group according to the different routes of TXA. The primary outcome was the incidence of transfusion, and secondary outcomes were total blood loss, hemoglobin level and extent of hemoglobin decrease on postoperative day 3, and incidence of complications. RESULTS: Of the total of 7133 primary TKA procedures collected, 4201 employed TXA and 2932 did not. The transfusion rate was 19.8% in the control group and 7.5% in the topical group, significantly higher than that in the intravenous (4.0%, p < 0.001) and combined (4.2%, p < 0.01) groups. The topical group had higher blood loss (0.97 ±â€¯0.47 L), greater reduction in hemoglobin level (31.2 ±â€¯10.1 g/L), and lower hemoglobin level (102.6 ±â€¯12.7 g/L) on postoperative day 3, compared with the intravenous and combined groups (p < 0.05 for all). The differences between the intravenous and combined groups were not significant (p > 0.05). The incidence of deep vein thrombosis in the topical group (1.1%) was significantly higher than that in the control (0.4%, p = 0.007) and intravenous groups (0.3%, p = 0.003). CONCLUSION: Intravenous and combined administration of TXA was equivalent in reducing blood loss and transfusion requirement, and superior to topical routes.

Tranexamic Acid Plus Low-dose Epinephrine Reduces Blood Loss in Total Knee Arthroplasty: A Systematic Review and Meta-analysis.

The present study assessed the effectiveness of the combined administration of tranexamic acid (TXA) plus low-dose epinephrine in primary total knee arthroplasty (TKA). We searched the following Chinese electronic databases: China National Knowledge Infrastructure and WanFang Data. We also searched the following English electronic databases: PubMed, Embase, Web of Science, and Central Register of Controlled Trials. To search for additional eligible studies, we also used Google's search engine. All randomized controlled trials (RCT) comparing TXA plus low-dose epinephrine (Combined group) and TXA alone in TKA were systematically searched. The primary outcomes were total blood loss, hidden blood loss, the requirement for transfusion, maximum hemoglobin (Hb) drop, and deep venous thrombosis (DVT). Drainage volume, operation time, length of stay, hospital for special surgery (HSS) score, and range of motion (ROM) were considered as secondary outcomes. Subgroup analyses were performed to assess the benefits of using a tourniquet and the application routes of topical or intravenous TXA between the two groups. Statistical analysis was assessed using RevMan 5.3 software. Four independent RCT were included involving 426 patients, with 213 patients in the Combined group and 213 patients in the TXA alone group. In the Combined group there was significant reduction in total blood loss (MD, 204.70; 95% CI, -302.76 to -106.63; P < 0.0001), hidden blood loss (MD, 185.63; 95% CI, -227.56 to -143.71; P < 0.00001), drainage volume (MD, 93.49; 95% CI, -117.24 to -69.74; P < 0.00001), and maximum Hb drop (MD, 5.33, 95% CI, -6.75 to -3.91; P < 0.00001). No statistical differences were found postoperatively in terms of the requirement for transfusion (risk ratio, 0.52; 95% CI, 0.26-1.04; P = 0.06), operation time (MD, 0.85; 95% CI, -2.62 to 4.31; P = 0.63), length of stay (MD, -0.02; 95% CI, -0.52 to 0.47; P = 0.93), HSS score (MD, 0.78; 95% CI, -0.36 to 1.92; P = 0.18), and ROM (MD, 1.40; 95% CI, -1.01 to 3.81; P = 0.26), and not increasing the risk of DVT (risk ratio, 1.00; 95% CI, 0.33 to 3.02; P = 1.00) in the two groups. This meta-analysis demonstrated that the administration of tranexamic acid plus low-dose epinephrine is a safe and efficacious treatment to reduce total blood loss, hidden blood loss, drainage volume, and maximum Hb drop in primary TKA, without increasing the risk of DVT in primary THA.