Nano-Micron Combined Hydrogel Microspheres: Novel Answer for Minimal Invasive Biomedical Applications.

Hydrogels, key in biomedical research for their hydrophilicity and versatility, have evolved with hydrogel microspheres (HMs) of micron-scale dimensions, enhancing their role in minimally invasive therapeutic delivery, tissue repair, and regeneration. The recent emergence of nanomaterials has ushered in a revolutionary transformation in the biomedical field, which demonstrates tremendous potential in targeted therapies, biological imaging, and disease diagnostics. Consequently, the integration of advanced nanotechnology promises to trigger a new revolution in the realm of hydrogels. HMs loaded with nanomaterials combine the advantages of both hydrogels and nanomaterials, which enables multifaceted functionalities such as efficient drug delivery, sustained release, targeted therapy, biological lubrication, biochemical detection, medical imaging, biosensing monitoring, and micro-robotics. Here, this review comprehensively expounds upon commonly used nanomaterials and their classifications. Then, it provides comprehensive insights into the raw materials and preparation methods of HMs. Besides, the common strategies employed to achieve nano-micron combinations are summarized, and the latest applications of these advanced nano-micron combined HMs in the biomedical field are elucidated. Finally, valuable insights into the future design and development of nano-micron combined HMs are provided.

Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is an age-related disease characterised by the accumulation of senescent chondrocytes, which drives its pathogenesis and progression. Senescent cells exhibit distinct features, including mitochondrial dysfunction and the excessive accumulation and release of reactive oxygen species (ROS), which are highly correlated and lead to a vicious cycle of increasing senescent cells. Stem cell therapy has proven effective in addressing cellular senescence, however, it still has issues such as immune rejection and ethical concerns. Microvesicles (MVs) constitute the primary mechanism through which stem cell therapy exerts its effects, offering a cell-free approach that circumvents these risks and has excellent anti-ageing potential. Nonetheless, MVs have a short in vivo half-life, and their secretion composition varies considerably under diverse conditions. This study aims to address these issues by constructing a ROS-responsive hydrogel loaded with pre-stimulant MVs. Through responding to ROS levels this hydrogel intelligently releases MVs, and enhancing mitochondrial function in chondrocytes to improving cellular senescence. RESULT: We employed Interferon-gamma (IFN-γ) as a stem cell-specific stimulus to generate IFN-γ-microvesicles (iMVs) with enhanced anti-ageing effects. Simultaneously, we developed a ROS-responsive carrier utilising 3-aminophenylboronic acid (APBA)-modified silk fibroin (SF) and polyvinyl alcohol (PVA). This carrier served to protect MVs, prolong longevity, and facilitate intelligent release. In vitro experiments demonstrated that the Hydrogel@iMVs effectively mitigated cell senescence, improved mitochondrial function, and enhanced cellular antioxidant capacity. In vivo experiments further substantiated the anti-ageing capabilities of the Hydrogel@iMVs. CONCLUSION: The effect of MVs can be significantly enhanced by appropriate pre-stimulation and constructing a suitable carrier. Therefore, we have developed a ROS-responsive hydrogel containing IFN-γ pre-stimulated iMVs to target the characteristics of ageing chondrocytes in OA for therapeutic purposes. Overall, this novel approach effectively improving mitochondrial dysfunction by regulating the balance between mitochondrial fission and fusion, and the accumulation of reactive oxygen species was reduced, finally, alleviates cellular senescence, offering a promising therapeutic strategy for OA.

Circular RNA circRNF169 functions as a miR-30c-5p sponge to promote cellular senescence.

Circular RNAs (circRNAs), characterized as single-stranded closed circular RNA molecules, have been established to exert pivotal functions in various biological or pathological processes. Nonetheless, the effects and underlying mechanisms concerning circRNAs on the aging and aging-related diseases remain elusive. We herein compared the expression patterns of circRNAs in young and senescent mouse embryonic fibroblasts (MEFs), and uncovered that circRNF169 was dramatically up-regulated in senescent MEFs compared with that in young MEFs. Therefore, we further digged into the role and potential mechanisms of circRNF169 in the senescence of MEFs. The results of senescence-associate-ß-galactosidase staining and BrdU incorporation assay showed that silencing of circRNF169 significantly delayed MEFs senescence and promoted cell proliferation, while ectopic expression of circRNF169 exhibited the opposite effects. Moreover, the dual-luciferase reporter assay confirmed that circRNF169 acted as an endogenous miR-30c-5p sponge, which accelerated cellular senescence by sequestering and inhibiting miR-30c-5p activity. Taken together, our results suggested that circRNF169 exerted a crucial role in cellular senescence through sponging miR-30c-5p and represented a promising target for aging intervention.

Pre-Emptive Antifibrinolysis: Its Role and Efficacy in Hip Fracture Patients Undergoing Total Hip Arthroplasty.

BACKGROUND: We aimed to determine the efficacy of pre-emptive antifibrinolysis with tranexamic acid (TXA) in decreasing hidden blood loss (HBL) in the elderly hip fracture patients. METHODS: Ninety-six elderly hip fracture patients receiving hip arthroplasty were randomized to receive 100 mL of normal saline (group A) or 1.5 g of TXA (group B) intravenously q12 hours from postadmission day 1 (PAD1) to the day before surgery. Both groups were treated with 1.5 g of TXA q12 hours from postoperative day 1 (POD1) to POD3. HBL was calculated by formulas and recorded as the primary outcome. RESULTS: In overall analyses, no difference was found in HBL, while the decline of hemoglobin (ΔHb), allogeneic blood transfusion (ABT) rate, fibrinogen degradation product (FDP-on PAD2, PAD3, POD1, and POD2), and d-dimer (D-D-on PAD2, PAD3, and POD1) were lower in group B. In subgroup analyses for patients receiving intervention within 72 hours of injury, group B had lower postoperative HBL, ΔHb, ABT rate, FDP, and D-D levels (on PAD2, PAD3, POD1, and POD2). For patients receiving intervention over 72 hours after injury, no difference was detected in perioperative HBL, ΔHb, and ABT rate between the 2 groups. The FDP and D-D levels were lower in group B on PAD2 and PAD3. No difference was found in coagulation parameters, wound complications, venous thromboembolism rate, and 90-day mortality in all analyses. CONCLUSION: Early administration (within 72 hours of injury) of multidose of TXA is effective in reducing perioperative HBL in elderly hip fracture patients. Delayed use (over 72 hours after injury) of TXA was not beneficial.

Dose optimization of intravenous dexamethasone for total knee arthroplasty: when two is not better than one.

BACKGROUND: The optimal dose regimen of dexamethasone in total knee arthroplasty (TKA) has not been determined. This study was performed to evaluate the impact of a single preoperative high-dose dexamethasone compared with two perioperative low-dose dexamethasone in TKA. MATERIALS AND METHODS: We prospectively studied three regimens on dexamethasone: no dexamethasone (A), a single preoperative dose of 20-mg dexamethasone (B), and two perioperative doses of 10-mg dexamethasone (C). The primary outcome was postoperative pain level. The incidence of postoperative nausea and vomiting (PONV), use of analgesic and antiemetic rescue, interleukin-6 (IL-6) and C-reactive protein (CRP) levels, range of motion (ROM), and complications were also compared. RESULTS: The dynamic pain scores and CRP and IL-6 levels were significantly lower for Group B compared to Groups A and C on postoperative days 1 and 2 (POD 1 and 2). Such differences were also detected between Groups C and A. Besides, the pain scores at rest were significantly lower in Groups B and C than in Group A on POD 1 and 2. Patients in Groups B and C had a lower incidence of PONV, reduced use of analgesic and antiemetic rescue, and improved ROM than in Group A. No complications occurred in any group. CONCLUSION: Dexamethasone in TKA provides short-term advantages in analgesic, antiemetic and anti-inflammatory effects. Besides, regarding the effects of pain and inflammatory control on POD 1 and 2, a single preoperative high dose of 20-mg dexamethasone was more effective than two perioperative low doses of 10-mg dexamethasone. LEVEL OF EVIDENCE: I.

Is there a role of tranexamic acid in rheumatoid arthritis with total knee arthroplasty? Findings from a multicenter prospective cohort study in China.

BACKGROUND: Tranexamic acid (TXA) has proven to be effective in reducing the blood loss associated with total knee arthroplasty (TKA) in patients with osteoarthritis. However, there still exists a paucity of evidence regarding the effectiveness of intravenous TXA in patients with rheumatoid arthritis. The aim of this study was to explore the efficacy and safety of intravenous TXA on blood loss after TKA in Chinese patients with rheumatoid arthritis. MATERIALS AND METHODS: A total of 405 patients with rheumatoid arthritis who had undergone TKA were categorized into two groups based on the protocol of TXA use. TXA group (n = 248): patients received 15 mg/kg TXA prior to operation. Control group (n = 157): patients received no TXA. The outcome measurements such as, total blood loss (TBL), intraoperative blood loss (IBL), hidden blood loss (HBL), transfusion, drainage, the timing of first ambulation, the length of stay (LOS), total hospitalization costs, the results of 12-Item Short Form Survey (SF-12), the incidence of thromboembolic events and other complications were recorded and compared. RESULTS: The mean TBL, IBL, HBL, volume of transfusion and drainage were significantly lower in TXA group than in Control group. The rate of transfusion was significantly lower in TXA group than in Control group. There was a favorable effect in early ambulation for patients in TXA group, compared with patients in Control group. In addition, TXA group had shorter LOS, lower hospitalization costs and higher postoperative SF-12 score than Control group. The incidence of deep venous thrombosis and other complications did not differ between the two groups. CONCLUSION: TXA can effectively diminish blood loss, reduce transfusion, shorten LOS and decrease hospitalization costs after TKA in Chinese patients with rheumatoid arthritis, without increasing the risk of complications.

Effectiveness of preemptive antifibrinolysis with tranexamic acid in rheumatoid arthritis patients undergoing total knee arthroplasty: a study protocol for a randomized controlled trial.

BACKGROUND: Patients with rheumatoid arthritis (RA) who have undergone total knee arthroplasty are at increased risk of requiring a blood transfusion. This study is designed to compare the effects of preemptive antifibrinolysis of single-dose and repeat-dose tranexamic acid (TXA) in in RA patients undergoing total knee arthroplasty (TKA). METHODS/DESIGN: The study will be a double-blind randomized controlled trial with two parallel groups of RA patients. Group A will be given 100 ml normal saline twice daily starting from 3 days before the operation, Group B will be given TXA 1.5 g twice daily starting from 3 days before the operation. All patients will be given TXA 1.5 g 30 min before the operation. The primary outcomes will be evaluated with total blood loss and hidden blood loss. Other outcome measurements such as, fibrinolysis parameters, inflammatory factors, visual analogue scale for post-operative pain, analgesia usage, coagulation parameters, transfusion, the length of stay (LOS), total hospitalization costs, the incidence of thromboembolic events and other complications will be recorded and compared. Recruitment is scheduled to begin on 1 August 2020, and the study will continue until 31 May 2021. DISCUSSION: In current literature there is a lack of evidence with regard to the efficacy of TXA in RA patients. The findings of this study, whether positive or negative, will contribute to the formulation of further recommendations on the use of TXA in RA patients undergoing TKA. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000029720 . Registered 14 February 2020.

Repeat Doses of Dexamethasone up to 48 Hours Further Reduce Pain and Inflammation After Total Hip Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: The optimal dose regimen of dexamethasone in total hip arthroplasty (THA) is unclear. This study was conducted to compare the effects among 1-dose, 2-dose, and 3-dose dexamethasone in THA. METHODS: One hundred fifty patients were randomized to receive a single preoperative dose of 10-mg dexamethasone (group A, 50 patients), or another dose of 10-mg dexamethasone 24 hours later (group B, 50 patients), or another 2 doses of 10-mg dexamethasone 24 and 48 hours later (group C, 50 patients). The primary outcome was postoperative pain level. The use of analgesic and antiemetic rescue; incidence of postoperative nausea and vomiting; C-reactive protein and interleukin-6 levels; range of motion; and complications were also compared. RESULTS: The dynamic pain scores were lower for groups B and C compared to group A on postoperative days 2 and 3. Such difference was also detected between groups B and C on postoperative day 3. C-reactive protein and interleukin-6 levels were lower in groups B and C than in group A at 48 and 72 hours postoperatively. Such difference was also observed between groups B and C at 72 hours postoperatively. Patients in groups B and C had reduced rescue analgesic use, and improved range of motion compared to patients in group A. There were no differences among 3 groups regarding the rescue antiemetic use, postoperative nausea and vomiting occurrence, and complications. CONCLUSION: Additional administrations of dexamethasone after THA could provide sustained pain relief and inflammatory control. Besides, the 3-dose regimen was more effective than the 2-dose regimen in terms of the analgesic and anti-inflammatory effects. LEVEL OF EVIDENCE: I.

The antifibrinolytic and anti-inflammatory effects of a high initial-dose tranexamic acid in total knee arthroplasty: a randomized controlled trial.

PURPOSE: The aim of this study was to evaluate the effects of a high initial-dose (60 mg/kg) intravenous tranexamic acid (IV-TXA) on fibrinolysis and inflammation after total knee arthroplasty (TKA). METHODS: A total of 132 patients were categorized into two groups based on different TXA regimens: 20 mg/kg before incision (A) or 60 mg/kg before incision (B). All patients received five doses of 1 g TXA at three, six, 12, 18, and 24 hours after the first dose. The primary outcomes were peri-operative blood loss and transfusion rate. Other outcome measurements such as, haemoglobin level, fibrinolysis parameters [fibrin(-ogen) degradation products (FDP), D-dimer], inflammatory factors [C-reactive protein (CRP), interleukin-6 (IL-6)], visual analog scale (VAS) score, consumption of analgesic rescue, coagulation parameters [activated partial thromboplastin time (APTT), prothrombin time (PT), platelet count, thrombelastography (TEG), and anti-factor Xa activity (AFXa)] and complications, were also compared. RESULTS: There was a favourable effect in reducing peri-operative blood loss and transfusion rate for patients in Group B, compared with patients in Group A. In addition, the levels of FDP, D-dimer, CRP, IL-6, and dynamic pain in Group B were significantly lower than those in Group A on post-operative days one, two and three. There were no statistically significant differences in postoperative coagulation parameters and complications between the two groups. CONCLUSION: A high initial-dose (60 mg/kg) IV-TXA before surgery followed by five doses can further reduce blood loss, provide additional fibrinolysis and inflammation control, and ameliorate post-operative pain following TKA, without increasing the risk of treatment-related complications.

Tranexamic acid attenuates inflammatory effect and modulates immune response in primary total knee arthroplasty: a randomized, placebo-controlled, pilot trial.

AIMS: To explore the effect of intravenous tranexamic acid (IV-TXA) on inflammation and immune response following primary total knee arthroplasty (TKA). METHODS: Primary TKA patients (n = 125) were randomized into the following four groups: group A to receive placebo; group B to receive a single dose of 20 mg kg-1 IV-TXA and 20 mg of intravenous dexamethasone (IV-DXM); group C to receive six doses of IV-TXA (total dosage > 6 g); and group D to receive six doses of IV-TXA combined with three doses of IV-DXM (total dosage = 40 mg). The primary outcomes were C-reactive protein (CRP) and interleukin (IL)-6 levels and the secondary outcomes were complement C3 and C4 and T-cell subset levels, which were measured preoperatively and at 24 h, 48 h, 72 h, and 2 weeks postoperatively. RESULTS: The postoperative peak CRP and IL-6 levels in group C (93.7 ± 22.2 mg L-1, 108.8 ± 41.7 pg mL-1) were lower compared with those in group A (134.7 ± 28.8 mg L-1, P < 0.01; 161.6 ± 64.4 pg mL-1, P < 0.01). Groups B and D exhibited significantly lower CRP and IL-6 levels compared with groups A and C at 24 h, 48 h, and 72 h postoperatively (P < 0.05 for all). In group C, complement C3 and C4 levels were higher compared with those in group A at 48 h (0.967 ± 0.127 g L-1 vs. 0.792 ± 0.100 g L-1, P < 0.01; 0.221 ± 0.046 g L-1 vs. 0.167 ± 0.028 g L-1, P < 0.01) and 72 h (1.050 ± 0.181 g L-1 vs. 0.860 ± 0.126 g L-1, P = 0.01; 0.240 ± 0.052 g L-1 vs. 0.182 ± 0.036 g L-1, P < 0.01) postoperatively and CD3 and CD4 subset levels were higher compared with those in group B at 24 h postoperatively (66.78 ± 9.29% vs. 56.10 ± 12.47%, P < 0.05; 36.69 ± 5.78% vs. 28.39 ± 8.89%, P < 0.05). CONCLUSION: Six doses of IV-TXA could attenuate the inflammatory effect, modulate the immune response, and reduce immunosuppression caused by DXM in patients after TKA.

Additional benefits of multiple-dose tranexamic acid to anti-fibrinolysis and anti-inflammation in total knee arthroplasty: a randomized controlled trial.

BACKGROUND: Consensus is lacking regarding the dose and timing of tranexamic acid (TXA). The aim of this study was to determine whether multiple-dose intravenous TXA further reduced blood loss and attenuated inflammation after total knee arthroplasty (TKA). MATERIALS AND METHODS: We prospectively studied four regimens on TXA: no TXA (A), before incision, 3, 6, and 12 h later (B), before incision, 3, 6, 12, and 18 h later (C) and before incision, 3, 6, 12, 18, and 24 h later (D). The primary outcome was hidden blood loss (HBL). Other outcome measurements such as total blood loss (TBL), intraoperative blood loss (IBL), fibrinolysis parameters [fibrin(-ogen) degradation products, D-dimer], inflammatory factors (C-reactive protein, interleukin-6), visual analog scale (VAS) score, transfusion rate, length of stay (LOS) and complications were also compared. RESULTS: The mean HBL and TBL were significantly lower in Group D than in Groups C, B and A. The level of inflammatory factors and fibrinolysis parameters were significantly lower in Group D than in Groups C, B and A at 24 and 72 h postoperatively. The VAS score on postoperative days 1 and 3 (POD1 and POD3) was significantly lower in Group D than in Groups C, B and A. There was no significant difference in LOS among groups. No patient underwent blood transfusion. No episodes of deep venous thrombosis or pulmonary embolism occurred in all the groups. CONCLUSION: The repeated doses of TXA up to 24 h can further diminish HBL, provide additional fibrinolysis and inflammation control and ameliorate postoperative pain following TKA. LEVEL OF EVIDENCE: I.

Plasma Fibrin Degradation Product and D-Dimer Are of Limited Value for Diagnosing Periprosthetic Joint Infection.

BACKGROUND: Although the Musculoskeletal Infection Society introduced the use of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as inflammatory markers for diagnosing periprosthetic joint infection (PJI), no single blood marker reliably detects infection before revision arthroplasty. We therefore posed 2 questions: (1) Are fibrin degradation product (FDP) and D-dimer of value for diagnosing PJI before revision arthroplasty? (2) What are their sensitivity and specificity for that purpose? METHODS: To answer these questions, we retrospectively enrolled 318 patients (129 with PJI [group A], 189 with aseptic mechanical failure [group B]) who underwent revision arthroplasty during 2013-2018. Receiver operating characteristic curves were used to determine maximum sensitivity and specificity of the 2 markers. Inflammatory and fibrinolytic markers were evaluated based on (1) the Tsukayama-type infection present and (2) the 3 most common PJI-related pathogens. RESULTS: FDP and D-dimer levels were higher in group A than in group B: 4.97 ± 2.83 vs 4.14 ± 2.67 mg/L and 2.14 ± 2.01 vs 1.51 ± 1.37 mg/L fibrinogen equivalent units (FEU), respectively (both P < .05). Based on the Youden index, 2.95 mg/L and 1.02 mg/L FEU are the optimal FDP and D-dimer predictive cutoffs, respectively, for diagnosing PJI. Sensitivity and specificity, respectively, were 65.12% and 60.33% (FDP) and 68.29% and 50.70% (D-dimer). ESR, CRP, and interleukin-6 values were diagnostically superior to those of FDP and D-dimer. CONCLUSION: The value of plasma FDP and D-dimer for diagnosing PJI is limited compared with traditional inflammatory markers (ESR, CRP, interleukin-6) before revision arthroplasty.

The efficacy and safety of multiple-dose oral tranexamic acid on blood loss following total hip arthroplasty: a randomized controlled trial.

PURPOSES: To explore the efficacy and safety of multiple-dose oral tranexamic acid (TXA) on blood loss following primary total hip arthroplasty (THA). METHODS: A total of 152 patients were randomized into three groups to receive 2 g of oral TXA two hours  pre-operatively (group A), or another bolus of 2 g of oral TXA four hours post-operatively (group B), or another three boluses of 2 g of oral TXA four, ten, and 16 hours post-operatively (group C). The primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and transfusion rate. The secondary outcomes were haemoglobin (Hb) and haematocrit (Hct) drop, the level of fibrinolysis parameters (fibrin degradation products, D-dimer), and complications (thrombotic diseases, stroke, cardiac infarction, and infection). RESULTS: The mean TBL and HBL in group C were lower than those in group A (p < 0.001 and p < 0.001) and group B (p = 0.012 and p = 0.029). The Hb drop on post-operative day one (POD1) and POD3 in group C was lower than those in group A (p < 0.001 and p = 0.029) and group B (p < 0.001 and p = 0.004). The difference was similar regarding Hct drop on POD3 (p < 0.001 and p = 0.014). Moreover, fibrin degradation products and D-dimer in group C were lower than in groups A and B on POD1 and POD3 (p < 0.001 and p < 0.001). The incidence of complications such as venous thromboembolism did not differ significantly among the three groups (p > 0.05). CONCLUSIONS: Multiple boluses of oral TXA could further reduce blood loss, Hb and Hct drop, and restrain post-operative fibrinolysis in primary THA without increasing the risk of complications. LEVEL OF EVIDENCE I: Therapeutic study.

Multiple Doses of Perioperative Dexamethasone Further Improve Clinical Outcomes After Total Knee Arthroplasty: A Prospective, Randomized, Controlled Study.

BACKGROUND: This study aimed to evaluate the effect and safety of multiple doses of preoperative dexamethasone on pain and recovery after total knee arthroplasty (TKA). METHODS: Altogether, 182 patients undergoing TKA received 3 intravenous injections of normal saline (group A), 1 injection of high-dose dexamethasone (20 mg) and 2 injections of normal saline (group B), or 1 injection of high-dose dexamethasone and 2 injections of low-dose (10 mg) dexamethasone (group C). RESULTS: Visual analog scale was lower in group C than in group A or B and was different between groups A and B on postoperative days 1, 2, and 3 (all P < .05). Fewer group C patients required analgesic rescue and had lower total analgesic than those in group A or B, with the same difference between groups A and B (all P < .05). C-reactive protein and interleukin-6 levels were lower in groups B and C than in group A at 24, 48, and 72 hours postoperatively. C-reactive protein at 72 hours and interleukin-6 at 48 and 72 hours were lower in group C than in group B (all P < .05). Incidences of postoperative nausea and vomiting, number of patients requiring antiemetic rescue, and overall consumption of metoclopramide were lower in groups B and C than in group A (all P < .05). No surgical-site infections or gastrointestinal hemorrhages were detected in any group. CONCLUSION: Multiple dexamethasone doses further reduced postoperative pain, decreased consumption of analgesic drugs, and provided more powered inflammation control. These findings call for further studies to further evaluate its safety.

Multiple Low-Dose Dexamethasone Further Improves Clinical Outcomes Following Total Hip Arthroplasty.

BACKGROUND: The recommended dose regimen of dexamethasone in total hip arthroplasty (THA) has not been determined. This study was performed to assess the effects of multiple low-dose dexamethasone on clinical outcomes after THA. METHODS: Two hundred ten patients undergoing THA received 3 doses of normal saline (Group A), 2 doses of intravenous dexamethasone and 1 dose of normal saline (Group B), or 3 doses of intravenous dexamethasone (Group C). The primary outcome was the visual analog scale (VAS) score for pain and nausea. The incidence of postoperative nausea and vomiting, use of analgesic and antiemetic rescue, C-reactive protein (CRP) level, range of motion, length of stay (LOS), and complications were also compared. RESULTS: The VAS score (dynamic pain and nausea) on postoperative day 1 was significantly lower in Groups C and B than Group A. On postoperative day 2, the VAS score (dynamic pain and nausea) was lower in Group C than Groups A and B. In Group C, patients had a lower incidence of postoperative nausea and vomiting and reduced use of analgesic and antiemetic rescue. The CRP level was lower in Group B than Group A. Group C had the lowest CRP level among all 3 groups. LOS was shorter in Group B than Group A, while Group C had an even shorter LOS than Group B. Range of motion was greater in Group C. No complications occurred in any group. CONCLUSION: The 3-dose dexamethasone regimen can further relieve postoperative pain, ameliorate postoperative nausea, provide additional inflammatory control, enhance mobility, and shorten LOS following THA.

Multiple-Dose Intravenous Tranexamic Acid Further Reduces Hidden Blood Loss After Total Hip Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: The most appropriate dose of tranexamic acid in total hip arthroplasty (THA) has not been decided. This study was conducted to evaluate the clinical effects of multiple-dose intravenous tranexamic acid (IV-TXA) in THA. METHODS: One hundred fifty patients were randomized to receive one dose of IV-TXA before incision, followed by 2 doses of IV-TXA (group A), or 3 doses of IV-TXA (group B), or 4 doses of IV-TXA (group C) at 3-hour intervals. The primary outcome was hidden blood loss (HBL). Other outcome measurements such as total blood loss, maximum hemoglobin (Hb) drop, postoperative lowest Hb level, fibrinolysis parameter (D-dimer), inflammatory factor (interleukin-6), transfusion rate, length of stay, and complications were also compared. RESULTS: The mean HBL, total blood loss, and maximum Hb drop were significantly lower in group C than in groups B and A. Such differences were also detected between groups B and A. The postoperative lowest Hb level was significantly higher in group C. D-dimer and interleukin-6 in group C were significantly lower than in groups B and A at 24 and 48 hours postoperatively. Such differences were also significant between groups B and A. There was no significant difference in length of stay among groups. No patient underwent blood transfusion during hospitalization. No episodes of deep venous thrombosis or pulmonary embolism occurred in all cases. CONCLUSION: The 5-dose IV-TXA regimen can further diminish HBL, decrease maximum Hb drop, provide additional fibrinolysis control, and ameliorate postoperative inflammatory response following THA.

The efficacy and safety of two low-dose peri-operative dexamethasone on pain and recovery following total hip arthroplasty: a randomized controlled trial.

PURPOSE: To evalute the efficacy and safety of two low-dose peri-operative dexamethasone on pain and recovery following total hip arthroplasty (THA). METHODS: One hundred ten patients received two-dose of 10 mg IV-dexamethasone (group dexa) or IV-isotonic saline (group placebo). The level of C-reactive protein (CRP) and interleukin-6 (IL-6), pain at rest and during mobilization, incidence of post-operative nausea and vomiting (PONV), intensity of nausea, post-operative fatigue, consumption of analgesic and antiemetic rescue, range of motion (ROM), post-operative length of stay (post-operative LOS), wound problems and complications were recorded and compared. RESULTS: The level of inflammation markers (CRP, IL-6) in group dexa was lower than group placebo at 24, 48, 72 hours post-operatively. Dynamic pain VAS score at 24 hours was lower in group dexa (P = 0.002), however, there was no significant effect on pain at rest. In group dexa, patients had a lower incidence of PONV (P = 0.003), as well as a lower VAS score of nausea (P = 0.044). The post-operative fatigue (P < 0.001) was relieved and the consumption of analgesic and antiemetic rescues were reduced. Furthermore, patients had better maximum hip flexion (P < 0.001) and abduction (P = 0.017), with shorter post-operative LOS (P = 0.006). There is no difference between groups in wound problems. No surgical site infection or gastrointestinal haemorrhage was detected in both groups. CONCLUSIONS: The administration of two low-dose peri-operative dexamethasone can effectively reduce the post-operative level of CRP and IL-6, provide additional pain and nausea control, ameliorate post-operative fatigue, enhance mobility, and shorten post-operative LOS following THA, without increasing the risk of infection and gastrointestinal hemorrhage. LEVEL OF EVIDENCE: I.

The efficacy and safety of multiple-dose intravenous tranexamic acid on blood loss following total knee arthroplasty: a randomized controlled trial.

PURPOSE: To assess the efficacy and safety of multiple-dose intravenous tranexamic acid (IV-TXA) on blood loss following total knee arthroplasty (TKA). METHODS: One hundred fifty nine patients received one bolus of IV-TXA before skin incision and two boluses three and six hours later (group A), or another bolus nine hours later (group B), or another two boluses nine and 12 hours later (group C). The primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum haemoglobin (Hb) drop. Other outcome measurements such as fibrinolysis parameters [fibrin(-ogen) degradation products (FDP), D-dimer], inflammatory factors [interleukin-6 (IL-6)], transfusion rate, range of motion (ROM), length of hospital stay (LOH), and complications were also recorded and compared. RESULTS: The mean TBL, HBL and maximum Hb drop in group C (p < 0.001, p < 0.001, p = 0.025) and group B (p = 0.025, p = 0.025, p = 0.044) were lower than those in group A. FDP and D-Dimer in group C was lower than in group A and B on post-operative day one. IL-6 in group A, B and C showed a downward tendency on post-operative days one and three (POD1 and POD3). Moreover, the ROM and LOH were better in group C. No episodes of transfusion or deep venous thrombosis (DVT) were detected in all groups. CONCLUSIONS: The 5-dose TXA regimen can further reduce the blood loss, diminish the maximum Hb drop, minimize inflammation, enhance mobility, and shorten LOS following TKA, without increasing the risk of complications. An additional dose could be requisite when fibrinolysis maintains after 5-dose regimen has already been performed. LEVEL OF EVIDENCE: I.