Lithium Promotes Osteogenesis via Rab11a-Facilitated Exosomal Wnt10a Secretion and ß-Catenin Signaling Activation.

Both bone mesenchymal stem cells (BMSCs) and their exosomes suggest promising therapeutic tools for bone regeneration. Lithium has been reported to regulate BMSC function and engineer exosomes to improve bone regeneration in patients with glucocorticoid-induced osteonecrosis of the femoral head. However, the mechanisms by which lithium promotes osteogenesis have not been elucidated. Here, we demonstrated that lithium promotes the osteogenesis of BMSCs via lithium-induced increases in the secretion of exosomal Wnt10a to activate Wnt/ß-catenin signaling, whose secretion is correlated with enhanced MARK2 activation to increase the trafficking of the Rab11a and Rab11FIP1 complexes together with exosomal Wnt10a to the plasma membrane. Then, we compared the proosteogenic effects of exosomes derived from lithium-treated or untreated BMSCs (Li-Exo or Con-Exo) both in vitro and in vivo. We found that, compared with Con-Exo, Li-Exo had superior abilities to promote the uptake and osteogenic differentiation of BMSCs. To optimize the in vivo application of these hydrogels, we fabricated Li-Exo-functionalized gelatin methacrylate (GelMA) hydrogels, which are more effective at promoting osteogenesis and bone repair than Con-Exo. Collectively, these findings demonstrate the mechanism by which lithium promotes osteogenesis and the great promise of lithium for engineering BMSCs and their exosomes for bone regeneration, warranting further exploration in clinical practice.

Lithium prevents glucocorticoid-induced osteonecrosis of the femoral head by regulating autophagy.

Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC-ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC-ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC-induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC-ONFH was used for evaluating the therapeutic effect of oral lithium on GC-ONFH and underlying mechanism. Findings demonstrated that GC over-activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over-activated autophagy of GC-treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC-ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over-activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up-regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC-ONFH. Lithium may be a promising therapeutic agent for GC-ONFH. However, the role of autophagy in the pathogenesis of GC-ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC-ONFH, and the efficacy of lithium in the treatment of GC-ONFH and its underlying mechanisms.

Effects of a Modified Long-Acting Cocktail on Analgesia and Enhanced Recovery After Total Hip Arthroplasty: A Double-Blinded Randomized Clinical Trial.

BACKGROUND: We compared the efficacy and safety of a modified cocktail for postoperative analgesia and early functional rehabilitation in patients undergoing total hip arthroplasty (THA). METHODS: Magnesium sulfate and sodium bicarbonate were added to a cocktail of ropivacaine, epinephrine, and dexamethasone. Primary outcome measures were visual analog scale (VAS) pain scores at various intervals after surgery, morphine consumption for rescue analgesia after surgery, and time to first rescue analgesia. Secondary outcomes were hip function after surgery, daily walking distance, quadriceps muscle strength, and the incidence of postoperative adverse reactions. RESULTS: Morphine consumption was significantly lower in the modified cocktail group than in the control group in the first 24 hours after surgery (6.2 ± 6.0 versus 14.2 ± 6.4 mg, P < .001), as was total morphine consumption (10.0 ± 8.6 versus 19.2 ± 10.1 mg, P < .001). The duration of the first rescue analgesia was significantly prolonged (23.7 ± 10.3 versus 11.9 ± 5.8 mg, P < .001). Morphine consumption was also reduced in the magnesium sulfate and sodium bicarbonate groups over a 24-hour period compared to the control group (P < .001). The modified cocktail group had significantly lower resting VAS pain scores than the control group within 24 hours after surgery (P < .050). The VAS pain scores during movement within 12 hours after surgery were also lower (P < .050). The experimental groups showed better hip range of motion (P < .050) and longer walking distance (P < .050) on the first postoperative day, and levels of inflammatory markers were significantly reduced. The incidence of postoperative adverse reactions was similar among the 4 groups. CONCLUSIONS: The modified cocktail with a new adjuvant can prolong the duration of postoperative analgesia, reduce the dosage of rescue analgesics, and accelerate early postoperative functional recovery in patients undergoing THA.

Efficacy of Oral Nefopam on Multimodal Analgesia in Total Knee Arthroplasty: A Prospective, Double-Blind, Placebo-Controlled, Randomized Trial.

BACKGROUND: Multimodal analgesia is central to pain management after total knee arthroplasty (TKA). This study aimed to evaluate the efficacy of adding oral nefopam to multimodal analgesia for post-TKA pain management. METHODS: In this prospective, double-blind, placebo-controlled, randomized trial, 100 patients who underwent TKA at our hospital were randomized to either the nefopam or the control group. After surgery, patients in the nefopam group received 200 mg of celecoxib, 150 mg of pregabalin, and 40 mg of nefopam twice daily to control postoperative pain. Patients in the control group received 200 mg of celecoxib, 150 mg of pregabalin, and a placebo. Oxycodone hydrochloride (10 mg) was used as the rescue analgesic. If the pain remained poorly controlled, 10 mg of morphine hydrochloride was injected subcutaneously as a secondary rescue analgesic. The primary outcome was the postoperative consumption of oxycodone and morphine as rescue analgesics. Secondary outcomes were postoperative pain assessed using the visual analogue scale (VAS), functional recovery assessed by the range of knee motion and ambulation distance, time until hospital discharge, indicators of liver function, and complication rates. RESULTS: Patients in the nefopam group had significantly lower postoperative oxycodone and morphine consumption within 24 hours after surgery and during hospitalization, lower VAS pain scores at rest and during motion within 24 h after surgery, better functional recovery on postoperative days 1 and 2, and a shorter hospital stay. However, the absolute reduction in 0 to 24 h opioid consumption, VAS pain scores, and knee range of motion did not exceed the reported minimal clinically important difference. Both groups had similar indicators of liver function and complication rates. CONCLUSIONS: Adding oral nefopam to multimodal analgesia resulted in statistically significant improvements in opioid consumption, VAS pain scores, and functional recovery. However, the amount of improvement may not be clinically important.

Minimum effective concentration of ropivacaine for ultrasound-guided transmuscular quadratus lumborum block in total hip arthroplasty: a randomized clinical trial.

OBJECTIVE: This trial aimed to identify the Minimum Effective Concentration (MEC90, defined as the concentration which can provide successful block in 90% of patients) of 30 mL ropivacaine for single-shot ultrasound-guided transmuscular Quadratus Lumborum Block (QLB) in patients undergoing Total Hip Arthroplasty (THA). METHODS: A double-blind, randomized dose-finding study using the biased coin design up-and-down sequential method, where the concentration of local anesthetic administered to each patient depended on the response from the previous one. Block success was defined as a Numeric Rating Scale (NRS) score during motion ≤ 3 at 6 hours after arrival in the ward. If the block was successful, the next subject received either a 0.025% smaller dose (probability of 0.11) or the same dose (probability of 0.89); otherwise, the next subject received a 0.025% higher ropivacaine concentration. MEC90, MEC95 and MEC99 were estimated by isotonic regression, and the corresponding 95% Confidence Intervals (95% CIs) were calculated by the bootstrapping method. RESULTS: Based on the analysis of 52 patients, MEC90, MEC95, and MEC99 of ropivacaine for QLB were estimated to be 0.352% (95% CI 0.334-0.372%), 0.363% (95% CI 0.351-0.383%), and 0.373% (95% CI 0.363-0.386%). The concentration of ropivacaine at 0.352% in a volume of 30 ml can provide a successful block in 90% of patients. CONCLUSIONS: For ultrasound-guided transmuscular QLB in patients undergoing THA, 0.352% ropivacaine in a volume of 30 ml can provide a successful block in 90% of patients. Further dose-finding studies and large sample size are required to verify the concentration.

Do Patients with Borderline Anemia Need Treatment before Total Hip Arthroplasty? A Propensity Score-Matched Cohort Study.

OBJECTIVE: Preoperative anemia has been identified as a modifiable risk factor for multiple adverse outcomes. In real clinical practice, considering treatment of anemia would increase costs and delay surgery. Patients undergoing total hip arthroplasty (THA) with mild anemia are usually neglected and still underdiagnosed or inadequately treated. This study investigated the effects of preoperative borderline anemia and anemia intervention before THA on perioperative outcomes. METHODS: We screened 706 patients from those receiving THA at our hospital from January 2020 to January 2022, with 112 in the borderline anemia group and 594 in the non-anemia group. The cohort for this retrospective study was created by using propensity score matching (PSM) and subgroup analysis. The primary outcome was perioperative blood loss, while secondary outcomes were the rate of allogeneic blood transfusion and human serum albumin transfusion, perioperative laboratory indicators, postoperative length of stay, and complications. The independent sample t-test and the Mann-Whitney U-test were used to analyze continuous data, and the Pearson χ2 -test or the Fisher exact test was used to analyze categorical variables. RESULTS: After PSM, there was no significant difference in perioperative blood loss between patients in the borderline anemia group and the non-anemia group. The primary outcomes of hidden (p = 0.004) and total (p = 0.005) blood loss were significantly lower in the intervention group than in the control group. No statistical differences were found in allogeneic blood transfusion, human serum albumin transfusion, postoperative length of stay, or complications (p > 0.05). CONCLUSIONS: Anemia treatments for patients with borderline anemia before THA significantly reduced hidden blood loss and total blood loss in the perioperative period and decreased the drop of hemoglobin and hematocrit without increasing postoperative complications.

Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial.

BACKGROUND: Many patients experience lower-extremity swelling following total knee arthroplasty (TKA), which impedes recovery. Diosmin is a semisynthetic flavonoid that is often utilized to treat swelling and pain caused by chronic venous insufficiency. We aimed to evaluate the efficacy and safety of diosmin in reducing lower-extremity swelling and pain as well as in improving functional outcomes following TKA. METHODS: This study was designed as a randomized, controlled multicenter trial and conducted in 13 university-affiliated tertiary hospitals. A total of 330 patients undergoing TKA were randomized to either receive or not receive diosmin postoperatively. The diosmin group received 0.9 g of diosmin twice per day for 14 consecutive days starting on the day after surgery, whereas the control group received neither diosmin nor a placebo postoperatively. The primary outcome was lower-extremity swelling 1, 2, 3, and 14 days postoperatively. The secondary outcomes were postoperative pain assessed with use of a visual analogue scale, Hospital for Special Surgery score, range of knee motion, levels of the inflammatory biomarkers C-reactive protein and interleukin-6, and complications. RESULTS: At all postoperative time points, diosmin was associated with significantly less swelling of the calf, thigh, and upper pole of the patella as well as with significantly lower pain scores during motion. However, no significant differences in postoperative pain scores at rest, Hospital for Special Surgery scores, range of motion, levels of inflammatory biomarkers, or complication rates were found between the diosmin and control groups. CONCLUSIONS: The use of diosmin after TKA reduced lower-extremity swelling and pain during motion and was not associated with an increased incidence of short-term complications involving the outcomes studied. However, further studies are needed to continue exploring the efficacy and safety of diosmin use in TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Minimum effective concentration of ropivacaine for ultrasound-guided transmuscular quadratus lumborum block in total hip arthroplasty: a randomized clinical trial

Abstract Objective: This trial aimed to identify the Minimum Effective Concentration (MEC90, defined as the concentration which can provide successful block in 90% of patients) of 30 mL ropivacaine for single-shot ultrasound-guided transmuscular Quadratus Lumborum Block (QLB) in patients undergoing Total Hip Arthroplasty (THA). Methods: A double-blind, randomized dose-finding study using the biased coin design up-and-down sequential method, where the concentration of local anesthetic administered to each patient depended on the response from the previous one. Block success was defined as a Numeric Rating Scale (NRS) score during motion ≤ 3 at 6 hours after arrival in the ward. If the block was successful, the next subject received either a 0.025% smaller dose (probability of 0.11) or the same dose (probability of 0.89); otherwise, the next subject received a 0.025% higher ropivacaine concentration. MEC90, MEC95 and MEC99 were estimated by isotonic regression, and the corresponding 95% Confidence Intervals (95% CIs) were calculated by the bootstrapping method. Results: Based on the analysis of 52 patients, MEC90, MEC95, and MEC99 of ropivacaine for QLB were estimated to be 0.352% (95% CI 0.334-0.372%), 0.363% (95% CI 0.351-0.383%), and 0.373% (95% CI 0.363-0.386%). The concentration of ropivacaine at 0.352% in a volume of 30 ml can provide a successful block in 90% of patients. Conclusions: For ultrasound-guided transmuscular QLB in patients undergoing THA, 0.352% ropivacaine in a volume of 30 ml can provide a successful block in 90% of patients. Further dose-finding studies and large sample size are required to verify the concentration.

Lithium prevents glucocorticoid­induced chondrocyte autophagy: An in vitro study.

Glucocorticoids can induce chondrocyte autophagy. Lithium is a classical regulator of autophagy. The present study aimed to determine whether lithium can prevent glucocorticoid­induced chondrocyte autophagy by regulating the PI3K/AKT/mTOR signaling pathway. For this purpose, rat and human chondrocytes were treated with dexamethasone (200 µM) or dexamethasone (200 µM) combined with lithium chloride at various concentrations (0.01, 0.1, 1 and 10 mM). CYTO­ID® autophagy fluorescence staining and transmission electron microscopy were used to detect the levels of autophagy in the chondrocytes. Reverse transcription­quantitative PCR and western blot analysis were used to measure the expression levels of the autophagy marker, LC3B and the autophagy regulatory signaling pathway (PI3K/AKT/mTOR signaling pathways) markers, AKT and mTOR. The viability of chondrocytes was measured using the Cell Counting Kit­8 assay. It was found that compared with that in the control group, dexamethasone induced the autophagy of chondrocytes, decreased the expression levels of AKT and mTOR, and reduced cell viability. Compared with the treatment with dexamethasone alone, lithium chloride (10 mM) + dexamethasone reduced the autophagy levels, increased the expression level of AKT and mTOR, and increased cell viability. In conclusion, the present study demonstrated that lithium can prevent glucocorticoid­induced autophagy by activating the PI3K/AKT/mTOR signaling pathway and preventing the glucocorticoid­induced decrease in chondrocyte viability.

Influencing factors of hidden blood loss after primary total hip arthroplasty through the posterior approach: a retrospective study.

BACKGROUND: Total hip arthroplasty (THA) is an excellent treatment for the end-stage hip disease, and perioperative blood management strategies have been effectively applied to this procedure. However, many patients still experience anemia after the operation, which is usually overlooked by orthopedic surgeons due to the hidden blood loss (HBL) in the perioperative period. Therefore, the objective of this study was to evaluate HBL in patients undergoing primary THA using the posterior approach and to explore its influencing factors. METHODS: A retrospective analysis of 707 patients who underwent primary THA through the posterior approach was conducted in our hospital from January 2020 to January 2022. By applying Gross's and Nadler's formula, the HBL was calculated. Six quantitative variables (age, body mass index, surgical duration, albumin loss, preoperative hemoglobin, and hemoglobin loss) as well as four qualitative variables (gender, American Society of Anesthesiologists class, major preoperative diagnosis, and hypertension) of patients were analyzed using multivariate linear regression. RESULTS: The HBL was recorded at 700.39 ± 368.59 mL. As a result of multivariate linear regression analysis, it was determined that body mass index, surgical duration, and hemoglobin loss were all significant risk factors for HBL, whereas preoperative hemoglobin was considered a protective factor. It has been demonstrated that HBL is not significantly correlated with age, albumin loss, gender, ASA class, or major preoperative diagnosis, but it also did not differ from HBL by hypertension. CONCLUSIONS: Hidden blood Loss (HBL) in patients after primary total hip arthroplasty (THA) using the posterior approach is large and significant. When optimizing the perioperative management of THA, orthopedic surgeons should keep in mind HBL and its influencing factors, especially for patients with high body mass indexes, long surgical durations, and low preoperative hemoglobin levels. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100053888) in 02/12/2021, http://www.chictr.org.cn .

Analgesic efficacy of anterior iliopsoas muscle space block combined with local infiltration analgesia after total hip arthroplasty: A prospective, double-blind, placebo-controlled study.

BACKGROUND: The present study aimed to evaluate the efficacy of ultrasound-guided anterior iliopsoas muscle space block (AIMSB) combined with local infiltration analgesia (LIA) for pain management and recovery in patients who have undergone total hip arthroplasty (THA) via a posterolateral approach. METHODS: In this prospective, double-blind, placebo-controlled study, 80 patients undergoing primary THA under general anesthesia were included in the final analysis between March 22, 2022, and June 1, 2022. All patients were randomly assigned to receive AIMSB combined with LIA (AIMSB group, n = 40) or sham AIMSB and LIA (Sham group, n = 40). The primary outcome was cumulative morphine consumption (mg) within 24 h after surgery. Secondary outcomes were pain scores on a visual analog scale (VAS) at rest or during motion after surgery, time to first rescue analgesia, cumulative morphine consumption during hospitalization, intraoperative consumption of opioids, postoperative recovery, and postoperative adverse effects. RESULTS: Patients in the AIMSB group consumed significantly less morphine than the Sham group within the first 24 h and throughout hospitalization, as well as smaller amounts of intraoperative opioids. Also, significantly lower pain scores were recorded at rest or during motion within 24 h after surgery in AIMSB patients. Patients in the AIMSB group recovered more quickly than Sham patients. No significant difference was observed in quadriceps strength and postoperative complications between the two groups. CONCLUSIONS: Compared to treatment with LIA alone, ultrasound-guided AIMSB combined with LIA can provide better postoperative pain relief, decrease opioid consumption, promote motor sparing, and enhance the recovery of THA patients.

Efficacy of Adding Acetaminophen to Preemptive Multimodal Analgesia in Total Knee Arthroplasty: A Double-blinded Randomized Study.

OBJECTIVE: Preemptive multimodal analgesia is a frequently utilized method for controlling pain after total knee arthroplasty (TKA). So far, no studies have specifically examined the efficacy of adding acetaminophen to preemptive multimodal analgesia in TKA. The current work aimed to assess the efficacy of adding acetaminophen to preemptive multimodal analgesia for clinical pain management after TKA. METHODS: This was a double-blinded randomized study including 80 cases randomized to the acetaminophen and control groups, respectively. The acetaminophen group was administered celecoxib at 400 mg, pregabalin at 150 mg, and acetaminophen at 300 mg 2 h before TKA. Control patients were administered celecoxib, pregabalin, and placebo. The primary outcome was postsurgical use of morphine hydrochloride for rescue analgesia. Secondary outcomes included the time to the initial rescue analgesia, postsurgical pain as determined by a visual analogue scale (VAS), functional recovery as reflected by the range of knee motion and ambulation distance, hospitalization duration, and complication rates. Continuous data with normal and skewed distributions were compared by the Student's t test and the Mann-Whitney U test, respectively. Categorical variables were compared by the Pearson's chi-squared test. RESULTS: The control and acetaminophen groups were comparable in postoperative 0-24 h morphine consumption (11.3 ± 6.5 mg vs 12.3 ± 7.7 mg, P = 0.445) and total morphine consumption (17.3 ± 10.1 mg vs 19.3 ± 9.4 mg, P = 0.242). Additionally, time to the initial rescue analgesia, postoperative VAS score at any time point, postoperative functional recovery of the knee, and hospitalization duration were similar in both groups. Both groups also had similar occurrence rates of postoperative complications. CONCLUSIONS: In this study, adding acetaminophen to preoperative preemptive multimodal analgesia did not decrease postoperative morphine use or ameliorate pain relief. The efficacy of adding acetaminophen to preemptive multimodal analgesia in TKA need to be further explored in future studies.

Comparison between Ultrasound-Guided Pericapsular Nerve Group Block and Local Infiltration Analgesia for Postoperative Analgesia after Total Hip Arthroplasty: A Prospective Randomized Controlled Trial.

OBJECTIVES: Pericapsular nerve group (PENG) blocking is a novel nerve block modality for analgesia after total hip arthroplasty (THA); however, its analgesic efficacy is unclear. We aimed to compare the analgesic effect of ultrasound-guided PENG blocking and periarticular local infiltration analgesia after THA. METHODS: This study involved patients undergoing unilateral primary THA at our institution between October 2022 and December 2022. Based on a prospective double-blind, randomized approach, patients were randomly divided into two groups: the PENG and infiltration groups. The former received ultrasound-guided pericapsular nerve block before surgery while the latter received local anesthesia and local infiltration analgesia during surgery. The primary outcome was the amount of morphine used for rescue analgesia within 48 h after surgery and the visual analog scale (VAS) pain score at 3, 6, 12, 24, and 48 h after surgery. Secondary outcomes consisted of postoperative hip function on the first and second postoperative days, including hip extension angle and flexion, as well as distance traveled by the patient. Tertiary outcomes included length of hospital stay and postoperative adverse reactions. The data were analyzed using SPSS 26.0. Using the appropriate statistical methodology, continuous and categorical data were analyzed, and p < 0.05 was considered statistically significant. RESULTS: There was no clear difference in morphine requirements during the first 24 hours postoperatively (5.8 ± 5.9 vs. 6.0 ± 6.3, p = 0.910), in the total postoperative morphine consumption (7.5 ± 6.3 vs. 7.8 ± 6.6, p = 0.889), and in the postoperative resting VAS pain scores (p > 0.05). However, the exercise VAS score in the PENG group was significantly higher than that in the infiltration group within 12 hours after surgery (6.1 + 1.2 vs. 5.4 + 1.0, p = 0.008). There was no significant difference in hip function, length of hospital stay, or incidence of complications between the two groups. CONCLUSION: The analgesic effect and functional recovery of ultrasound-guided pericapsular nerve block for THA was not superior to that of periarticular local infiltration analgesia.

Comparison of Perioperative Outcomes and Early Complications Between a Direct Anterior Approach or Posterolateral Approach in Simultaneous Bilateral Total Hip Arthroplasty: A Retrospective Study.

Background: Controversies remain on the best surgical approaches for unilateral total hip arthroplasty (THA). There are little data on simultaneous bilateral THA via direct anterior approach (SimBDAA-THA) or posterolateral approach (SimBPA-THA). Purpose: We sought to assess differences in perioperative outcomes and early medical and surgical complications between SimBDAA-THA and SimBPA-THA. Methods: This retrospective study involved patients who underwent either SimBDAA-THA in a supine position (n = 73) or SimBPA-THA in a lateral position (n = 162) at our institution from January 2015 to November 2021. The 2 groups were compared in terms of clinical and demographic characteristics, surgical parameters, and complications during 6-months of follow-up. Results: There were no differences in clinical and demographic characteristics between the 2 groups prior to surgery. Simultaneous bilateral THA via direct anterior approach significantly shortened the length of both the operation (117.50 ±19.42 vs 143.97 ± 32.20 min) and the hospitalization (140.64 ± 43.22 vs 156.24 ± 56.64 h) but increased perioperative loss of hemoglobin (3.28 ± 1.01 vs 3.21 ± 2.26 g/dL). There were no significant differences between the two groups in transfusion rate; levels of interleukin-6, C-reactive protein or creatine kinase; or complications. Conclusion: This retrospective study of patients at a single institution found minimal differences in perioperative outcomes or early medical and surgical complications between SimBDAA-THA and SimBPA-THA except operative time and length of hospitalization. Larger studies with longer follow-up should be conducted to identify whether a direct anterior approach is superior to a posterolateral one.

Effects of magnesium sulfate on periarticular infiltration analgesia in total knee arthroplasty: a prospective, double-blind, randomized controlled trial.

BACKGROUND: To investigate whether adding magnesium sulfate to a periarticular infiltration analgesia (PIA) cocktail could improve pain control and functional outcomes in patients undergoing total knee arthroplasty (TKA). METHODS: Ninety patients were randomly assigned to the magnesium sulfate and control groups, with 45 patients in each group. In the magnesium sulfate group, patients were given a periarticular infusion of a cocktail of analgesics consisting of epinephrine, ropivacaine, magnesium sulfate, and dexamethasone. The control group received no magnesium sulfate. The primary outcomes consisted of visual analogue scale (VAS) pain scores, postoperative morphine hydrochloride consumption for rescue analgesia, and time to first rescue analgesia. Secondary outcomes were postoperative inflammatory biomarkers (IL-6 and CRP), postoperative length of stay, and knee functional recovery (assessed by knee range of motion, quadriceps strength, daily mobilization distance, and time to first straight-leg raising). Tertiary outcomes included the postoperative swelling ratio and complication rates. RESULTS: Within 24 h of surgery, patients in the magnesium sulfate group had markedly lower VAS pain scores during motion and at rest. After the addition of magnesium sulfate, the analgesic effect was dramatically prolonged, leading to a reduction in morphine dosage within 24 h and the total morphine dosage postoperatively. Postoperative inflammatory biomarker levels were significantly reduced in the magnesium sulfate group compared with the control. There were no considerable differences between the groups in terms of the postoperative length of stay and knee functional recovery. Both groups had similar postoperative swelling ratios and incidences of complications. CONCLUSIONS: The addition of magnesium sulfate to the analgesic cocktail for PIA can prolong postoperative analgesia, decrease the consumption of opioids, and effectively alleviate early postoperative pain after TKA. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200056549. Registered on 7 February 2022, https://www.chictr.org.cn/showproj.aspx?proj=151489 .

Efficacy of a Modified Cocktail for Periarticular Local Infiltration Analgesia in Total Knee Arthroplasty: A Prospective, Double-Blinded, Randomized Controlled Trial.

BACKGROUND: Periarticular local infiltration analgesia (LIA) is largely utilized for controlling pain after total knee arthroplasty (TKA). The present work aimed to assess the efficacy of a modified LIA cocktail for patients undergoing TKA. METHODS: Magnesium sulfate (MgSO4) and sodium bicarbonate (NaHCO3) were added to a conventional LIA cocktail comprising ropivacaine, epinephrine, and dexamethasone. After the safety of this modified cocktail was tested in rats, its efficacy and safety were evaluated in a prospective, double-blinded study including 100 individuals randomized to receive periarticular infiltration of the modified cocktail or a conventional cocktail. The primary outcome was postsurgical use of morphine hydrochloride for rescue analgesia. Secondary outcomes were the time until the first rescue analgesia, postsurgical pain (on a visual analog scale [VAS]), functional recovery (assessed by range of knee motion and ambulation distance), time to discharge, and complication rates. RESULTS: Adding NaHCO3 to the local anesthetics caused some instantaneous precipitation in all cases. Administering the modified cocktail to rats did not obviously damage the injected area of the nerve or surrounding tissues. Administration of the modified cocktail to patients was associated with markedly reduced postsurgical morphine use in the initial 24 hours (4.2 ± 5.0 versus 14.6 ± 8.9 mg, p < 0.001), reduced total morphine use (9.8 ± 8.4 versus 19.6 ± 11.4 mg, p < 0.001), prolonged time to the first rescue analgesia, lower VAS pain scores at rest and during motion at 12 and 24 hours following the operation, better functional recovery on postoperative days 1 and 2, and a shorter hospital stay. The modified and conventional cocktail groups had similar rates of complications. CONCLUSIONS: The present modification of a conventional cocktail significantly prolonged analgesia and reduced opioid consumption, which may substantially improve pain control in arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Minimum effective volume of ropivacaine for ultrasound-guided adductor canal + IPACK block in total knee arthroplasty: A double-blind, randomized dose-finding trial.

BACKGROUND: Our previous study reported that when a respective 20 mL of ropivacaine was used for adductor canal block (ACB) combined with infiltration between the popliteal artery and capsule of the posterior knee (IPACK) block for patients undergoing total knee arthroplasty (TKA), the minimum concentration of 0.275% could provide successful block in almost all patients. Based on the results, the primary objective of this study was to investigate the minimum effective volume (MEV90, defined as the volume which can provide successful block in 90% of patients) of ACB + IPACK block. METHODS: This double-blind, randomized dose-finding trial was based on a biased coin up-and-down sequential design, where the volume of ropivacaine administered to a given patient depended on the previous patient's response. The first patient received 15 mL of 0.275% ropivacaine for ACB and again for IPACK. If the block failed, the next subject received a 1 mL higher volume for ACB and IPACK, respectively; otherwise, the next subject received either a 1 mL lower volume (probability of 0.11) or the same volume (probability of 0.89). The primary outcome was whether the block was successful. Block success was defined as the patient did not suffer significant pain and did not receive rescue analgesia within 6 h after surgery. Then the MEV90 was estimated by isotonic regression. RESULTS: Based on analysis of 53 patients, the MEV90 was 17.99 mL (95% CI 17.47-18.61 mL), MEV95 was 18.48 mL (95% CI 17.45-18.98 mL) and MEV99 was 18.90 mL (95% CI 17.38-19.07 mL). Patients whose blocks succeeded had significantly lower NRS pain scores, lower morphine consumption, and shorter hospitalization. CONCLUSION: 0.275% ropivacaine in 17.99 mL respectively can provide successful ACB + IPACK block in 90% of patients undergoing TKA. The minimum effective volume (MEV90) of ACB + IPACK block was 17.99 mL.

Connexin43 overexpression promotes bone regeneration by osteogenesis and angiogenesis in rat glucocorticoid-induced osteonecrosis of the femoral head.

Glucocorticoids induced osteonecrosis of the femoral head (GIONFH) is a devastating orthopedic disease. Previous studies suggested that connexin43 is involved in the process of osteogenesis and angiogenesis. However, the role of Cx43 potentiates in the osteogenesis and angiogenesis of bone marrow-derived stromal stem cells (BMSCs) in GIONFH is still not investigated. In this study, BMSCs were isolated and transfected with green fluorescent protein or the fusion gene encoding GFP and Cx43. The osteogenic differentiation of BMSCs were detected after transfected with Cx43. In addition, the migration abilities and angiogenesis of human umbilical vein endothelial cells (HUVECs) were been detected after induced by transfected BMSCs supernatants in vitro. Finally, we established GC-ONFH rat model, then, a certain amount of transfected or controlled BMSCs were injected into the tibia of the rats. Immunohistological staining and micro-CT scanning results showed that the transplanted experiment group had significantly promoted more bone regeneration and vessel volume when compared with the effects of the negative or control groups. This study demonstrated for the first time that the Cx43 overexpression in BMSCs could promote bone regeneration as seen in the osteogenesis and angiogenesis process, suggesting that Cx43 may serve as a therapeutic gene target for GIONFH treatment.

Different Doses of Intravenous Tranexamic Acid in Revision Total Knee Arthroplasty: A Retrospective Study.

PURPOSE: This article assessed the efficacy and safety of different doses of intravenous tranexamic acid (TXA) in revision total knee arthroplasty (TKA). METHODS: We retrospectively identified 122 patients in our institution who underwent revision TKA with a history of perioperative intravenous TXA utilization. According to the sum of intravenous TXA documented, all patients were divided into three groups: 1 g intravenous TXA, 2 g intravenous TXA, and equal or greater than 3 g intravenous TXA. The primary outcomes included total blood loss (TBL), hidden blood loss (HBL), transfusion rate, and the incidence of symptomatic venous thromboembolism among the three groups. A correlation analysis was conducted to analyze the correlation between the dose of TXA and the blood loss. RESULTS: In total, there was no significance difference in TBL and revised HBL (rHBL) between the first two groups (1 g/dL for intravenous TXA, 2 g/dL for intravenous TXA; p = 0.486; p = 0.525). Equal or greater than 3 g intravenous TXA (≥3 g/dL for intravenous TXA) reached a significant reduction in TBL, rHBL, and length of stay compared with the first two groups (p = 0.01; p = 0.01; p = 0.01). The rate of transfusion between the three groups did not differ significantly (p = 0.21). Due to the limitations in sample size, only one symptomatic venous thromboembolism was reported in the 1 g intravenous TXA group. CONCLUSION: Applying the dose of intravenous TXA equal or greater than 3 g in revision TKA might further reduce the blood loss and shorten the length of stay.