Abstract

PURPOSE To compare the long-term clinical efficacy provided by intra-articular injections of either Pure Platelet-rich Plasma (P-PRP) or sham saline to treat knee osteoarthritis (KOA). METHODS This prospective, parallel-group, double-blind, multi-center, sham-controlled randomized clinical trial recruited participants with KOA from orthopedic departments at nine public hospitals (five tertiary medical centers, four secondary medical units) starting January 1, 2014, with follow-up completed on February 28, 2021. Participants were randomly allocated to interventions in a 1:1 ratio. Data were analyzed from March 1, 2021, to July 15, 2021. Three sessions (1 every week) of P-PRP or sham saline injected by physicians. The primary outcome was the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 3, 6, 12, 24, 60 months of follow-up. Secondary outcomes included the International Knee Documentation Committee (IKDC) subjective score, visual analogue scale (VAS) score, intra-articular biochemical marker concentrations, cartilage volume, and adverse events. Laboratory of each hospital analyzed the content and quality of P-PRP. RESULTS 610 participants (59% women) with KOA who received three sessions of P-PRP (n = 308, mean age 53.91 years) or sham saline (n = 302, mean age 54.51 years) injections completed the trial. The mean platelet concentration in PRP is 4.3-fold (95% confidence interval 3.6-4.5) greater than that of whole blood. Both groups showed significant improvements in IKDC, WOMAC, and VAS scores at 1 month of follow-up. However, only the P-PRP group showed a sustained improvement in clinical outcome measurements at month 24 (P < 0.001). There were statistically significant differences between the P-PRP and sham saline groups in all clinical outcome measurements at each follow-up time point (P < 0.001). The benefit of P-PRP was clinically better in terms of WOMAC-pain, WOMAC-physical function and WOMAC-total at 6, 12, 24, and 60 months of follow-up. No clinically significant differences between treatments were documented in terms of WOMAC-stiffness at any follow-up. A clinically significant difference favoring P-PRP group against saline in terms of IKDC and VAS scores was documented at 6, 12, 24 and 60 months of follow-up. At 6 months after injection, TNF-α and IL-1β levels in synovial fluid were lower in the P-PRP group (P < 0.001). Tibiofemoral cartilage volume decreased by a mean value of 1171 mm(3) in the P-PRP group and 2311 mm(3) in the saline group over 60 months and the difference between the group was statistically significant (intergroup difference, 1140 mm(3), 95% CI - 79 to 1320 mm(3); P < 0.001). CONCLUSIONS In this randomized clinical trial of patients with KOA, P-PRP was superior to sham saline in treating KOA. P-PRP was effective for achieving at least 24 months of symptom relief and slowing the progress of KOA, with both P-PRP and saline being comparable in safety profiles.

Abstract

OBJECTIVE There were limited randomized controlled trials (RCTs) of epsilon-aminocaproic acid (EACA) versus tranexamic acid (TXA) in total knee arthroplasty (TKA). The aim of the study was to compare the efficacy and safety of TXA and EACA in the combination of intravenous (IV) and intra-articular (IA) administration on reducing blood loss in patients following primary TKA. METHODS From January 2020 to January 2021, a total of 181 patients undergoing a primary unilateral TKA were enrolled in this prospective randomized controlled trial. Patients in the TXA group (n = 90) received 20 mg/kg of intravenous TXA preoperatively, 1 g of intra-articular TXA intraoperatively, and three doses of 20 mg/kg intravenous TXA at 0, 3, 6 h postoperatively. Patients in the EACA group (n = 91) received 120 mg/kg of intravenous EACA preoperatively, 2 g of intra-articular EACA intraoperatively, and three doses of 40 mg/kg intravenous EACA at 0, 3, 6 h postoperatively. The primary outcomes were total blood loss (TBL), transfusion rates and drop of hemoglobin (HB) level. The secondary outcomes included postoperative hospital stays and postoperative complications. The chi-square tests and Fisher's exact tests were utilized to compare categorical variables, while the independent-samples t-tests and Mann-Whitney tests were used to compare continuous variables. RESULTS The patients who received TXA averaged less TBL than the patients who received EACA (831.83 ml vs 1065.49 ml, P = 0.015), and HB drop in TXA group was generally less than that of EACA group on postoperative day 1 and 3 (20.84 ± 9.48 g/L vs 24.99 ± 9.40 g/L, P = 0.004; 31.28 ± 11.19 vs 35.46 ± 12.26 g/L, P = 0.047). The length of postoperative stays in EACA group was 3.66 ± 0.81 day, which is longer than 2.62 ± 0.68 day in TXA group (P < 0.001). No transfusions were required in either group. The risk of nausea and vomiting in TXA group was significantly higher than that in EACA group (11/90 vs 0/91, P < 0.01). CONCLUSION Although the TBL and HB drop were slightly greater in EACA group, these results were not clinically important, given that no transfusions were required. EACA could be an alternative to TXA, especially for patients with severe nausea and vomiting after using TXA postoperatively. Further studies are needed to adjust dosage of EACA to make better comparison of the two drugs.

Abstract

OBJECTIVES We aimed to evaluate the optimal regimen, efficacy and safety of tranexamic acid (TXA) and aminocaproic acid (EACA) for patients after total hip arthroplasty (THA). METHODS The network meta-analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. The outcomes were total blood loss, transfusion rates, hemoglobin (HB) drop, and risk for pulmonary embolism (PE) or deep vein thrombosis (DVT). Subgroup analyses were performed among most effective regimens to determine the influences of timing and number of doses. RESULTS A total of 56 eligible RCTs with different regimens were assessed. For reducing total blood loss, all high doses of TXA and EACA except high dose of intra-articular (IA) TXA, as well as medium dose of combination of intravenous and intra-articular (combined IV/IA) TXA were most effective. All high doses of TXA, as well as medium dose of combined IV/IA TXA did not show inferiority in reducing transfusion rates and HB drop compared with other regimens. No regimens showed higher risk for PE or DVT compared with placebo, and no statistical differences were seen among most effective regimens in subgroup analyses. CONCLUSIONS As effective as high doses of EACA and TXA, medium dose (20-40 mg/kg or 1.5-3.0 g) of combined IV/IA TXA was enough to control bleeding for patients after THA without increasing risk for PE/DVT. TXA was at least 5 times more potent than EACA. Timing and number of doses had few influences on blood conserving efficacy. LEVEL OF EVIDENCE Level I.

Abstract

OBJECTIVE To explore the 3D-slicer software-assisted endoscopic treatment for patients with hypertensive cerebral hemorrhage. METHODS A total of 120 patients with hypertensive cerebral hemorrhage were selected and randomly divided into control group and 3D-slicer group with 60 cases each. Patients in the control group underwent traditional imaging positioning craniotomy, and patients in the 3D-slicer group underwent 3D-slicer followed by precision puncture treatment. In this paper, we evaluate the hematoma clearance rate, nerve function, ability of daily living, complication rate, and prognosis. RESULTS The 3D-slicer group is better than the control group in various indicators. Compared with the control group, the 3D-slicer group has lower complications, slightly higher hematoma clearance rate, and better recovery of nerve function and daily living ability before and after surgery. The incidence of poor prognosis is low. CONCLUSION The 3D-slicer software-assisted endoscopic treatment for patients with hypertensive intracerebral hemorrhage has a better hematoma clearance effect, which is beneficial to the patient's early recovery and reduces the damage to the brain nerve of the patient.

Abstract

Background: Tranexamic acid (TXA) has been widely applied to reduce perioperative bleeding. Recently, several studies focused on the administration of TXA in the treatment for with intertrochanteric fracture patients treated with intramedullary fixation. However, the efficacy and safety of TXA in these studies remain controversial. Therefore, we performed this systematic review and meta-analysis to investigate the efficacy and safety of TXA in intertrochanteric fracture patients treated with intramedullary fixation. Methods: We systematically searched electronic databases, including Cochrane, PubMed, and EMBASE, up to 16 May 2022. The efficacy and safety of TXA was evaluated in four aspects, which were bleeding-related outcomes, non-bleeding-related outcomes, thromboembolic events, and other complications. The outcomes of these studies were extracted and analyzed by RevMan Manager 5.4. Results: Finally, nine randomized controlled trials, involving nine hundred and seventy-two intertrochanteric fracture patients treated with TXA, were enrolled in this study. In the bleeding-related outcomes, TXA group was significantly lower than the control group in terms of total blood loss (MD = -219.42; 95% CI, -299.80 to -139.03; p < 0.001), intraoperative blood loss (MD = -36.81; 95% CI, -54.21 to -19.41; p < 0.001), hidden blood loss (MD = -189.23; 95% CI, -274.92 to -103.54; p < 0.001), and transfusion rate (RR = 0.64; 95% CI, 0.49 to 0.85; p = 0.002). Moreover, the postoperative hemoglobin on day 3 of the TXA group was significantly higher than that of the control group (MD = 5.75; 95% CI, 1.26 to 10.23; p = 0.01). In the non-bleeding-related outcomes, the length of hospital stays was significantly shorter in the TXA group (MD = -0.67; 95% CI, -1.12 to -0.23; p = 0.003). In terms of thromboembolic events, there was no significant differences between the TXA group and control group in deep vein thrombosis, pulmonary embolism, myocardial infarction, and ischemic stroke. As for complications and mortality, there was no significant differences between the TXA group and control group in respiratory infection, renal failure, and postoperative mortality within 1 year. Conclusion: TXA is an effective and safe drug for perioperative bleeding control in intertrochanteric fracture patients treated with intramedullary fixation. However, the long-term efficacy of TXA still needs to be investigated by large-scale multicenter randomized controlled trials. Level of evidence: II, Systematic review and Meta-analysis. Systematic Review Registration: https://inplasy.com/, identifier [INPLASY202280027].

Abstract

OBJECTIVES This study aimed to investigate the differences in the characteristics, management, and clinical outcomes of patients with and that of those without coronavirus disease 2019 (COVID-19) infection who had ST-segment elevation myocardial infarction (STEMI). METHODS Databases including Web of Science, PubMed, Cochrane Library, and Embase were searched up to July 2021. Observational studies that reported on the characteristics, management, or clinical outcomes and those published as full-text articles were included. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of all included studies. RESULTS A total of 27,742 patients from 13 studies were included in this meta-analysis. Significant delay in symptom onset to first medical contact (SO-to-FMC) time (mean difference = 23.42 min; 95% CI: 5.85-40.99 min; p = 0.009) and door-to-balloon (D2B) time (mean difference = 12.27 min; 95% CI: 5.77-18.78 min; p = 0.0002) was observed in COVID-19 patients. Compared to COVID-19 negative patients, those who are positive patients had significantly higher levels of C-reactive protein, D-dimer, and thrombus grade (p < 0.05) and showed more frequent use of thrombus aspiration and glycoprotein IIbIIIa (Gp2b3a) inhibitor (p < 0.05). COVID-19 positive patients also had higher rates of in-hospital mortality (OR = 5.98, 95% CI: 4.78-7.48, p < 0.0001), cardiogenic shock (OR = 2.75, 95% CI: 2.02-3.76, p < 0.0001), and stent thrombosis (OR = 5.65, 95% CI: 2.41-13.23, p < 0.0001). They were also more likely to be admitted to the intensive care unit (ICU) (OR = 4.26, 95% CI: 2.51-7.22, p < 0.0001) and had a longer length of stay (mean difference = 4.63 days; 95% CI: 2.56-6.69 days; p < 0.0001). CONCLUSIONS This study revealed that COVID-19 infection had an impact on the time of initial medical intervention for patients with STEMI after symptom onset and showed that COVID-19 patients with STEMI were more likely to have thrombosis and had poorer outcomes.

Abstract

BACKGROUND Early lactate-guided resuscitation was endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease the mortality of patients admitted to the ICU department with septic shock. However, its effectiveness in elderly Asian patients is uncertain. METHOD We conducted a single-center trial to test the effectiveness of the early lactate-guided resuscitation of older Asian patients at the Second Hospital of Hebei Medical University. Eligible septic shock patients who consented to participation in the study were randomly assigned to receive early lactate-guided treatment or regular treatment as controls. RESULT A total of 82 patients met the hyperlactatemia criteria and participated in the trial. Forty-two patients received early lactate-guided treatment (lactate group) and 40 received regular treatment (control group). The lactate group received more fluids at initial 6 hours (3.3 ± 1.4 vs 2.4 ± 1.7 L, P = 0.01), but similar proportions of patients in both groups required the use of vasopressors and vasodilators. Patients in the lactate group showed significantly reduced ICU needs compared to the control group, which were weaned from mechanical ventilation more quickly (median 7, IQR 4 to 14 vs median 9, IQR 4.3 to 17.8, P = 0.02) and transferred out of the ICU earlier (median 4.5, IQR 2.8 to 7.3 vs median 6, IQR 3.2 to 8, P = 0.01). However, the hospital mortality (35.7% vs 42.5%, P = 0.35) and ICU mortality (31.0% vs 37.5%, P = 0.38) for both groups were not reduced. CONCLUSION For critically ill patients (elderly Asian patients) admitted to the ICU department with hyperlactatemia, early lactate-guided treatment reduced ICU needs but did not reduce mortality.

Abstract

BACKGROUND Elbow joint open arthrolysis is an effective method to release contracted tissue and débride heterotopic ossification in cases of post-traumatic elbow stiffness. Recurrence remains one of the most common concerns for surgeons. Soft tissue contracture may result from intra- and/or extra-articular bleeding, edema, effusion, and granulation. The increasing incidence of intraoperative and postoperative bleeding has caused uncertainty about surgical outcomes. Tranexamic acid (TXA) is effective for reducing surgery-related bleeding and effusions in total hip or knee arthroplasty. PURPOSE To investigate whether topical TXA can decrease blood loss and effusions in patients treated with elbow joint open arthrolysis and whether it affects final function. PATIENTS AND METHOD A prospective comparative study was conducted. Sixty-one patients with joint stiffness were enrolled and randomly divided into 2 groups: one consisting of 31 patients treated with topical TXA intraoperatively after open arthrolysis (experimental group) and the other consisting of 30 patients who received saline administration (control group). The operation time, tourniquet time, and intraoperative blood loss were recorded. Drainage volume, elbow rotation, elbow motion arc, Mayo Elbow Performance Score, and operation-related complications were followed up and recorded, whereas hematoma volume remaining in the joint space after drainage tube removal was assessed on ultrasonography. RESULTS Tourniquet time, intraoperative blood loss, and postoperative drainage were significantly lower in the TXA group than in the control group. However, no significant intergroup differences were found in the incidence of related complications and final function evaluated at the final follow-up. CONCLUSION Topical TXA improves surgical quality by controlling intraoperative bleeding, decreases the amount of blood loss soon after surgery, and could become a routine procedure in elbow joint open arthrolysis.

Abstract

BACKGROUND Patients with septic shock in whom Norepinephrine (NE) infusion alone is insufficient to raise blood pressure require the concomitant administration of Vasopressin (VP). However, current guidelines do not advise clinicians as to which vasoactive agent to discontinue first once the patient's septic shock begins to resolve. Moreover, there is controversial data guiding clinicians on how to discontinue vasopressors for septic shock patients who are receiving a combination therapy of NE and VP. METHODS The PubMed, Embase and Cochrane Central Register databases were searched from the database inception until October 18, 2018. Studies were limited to adult patients with septic shock who received concomitant NE and VP treatment, that included different orders of vasopressor discontinuation. The primary outcome was the incidence of hypotension. Overall mortality, ICU mortality and length of stay in the ICU (LOS) were secondary outcomes. Sensitivity and subgroup analyses, as well as trial sequential analysis (TSA), were performed. RESULTS One prospective randomized controlled trial and seven retrospective cohort studies were included in present meta-analysis. Compared with discontinuing VP first, the incidence of hypotension was significantly lower when NE was discontinued first (OR 0.3, 95% CI 0.10 to 0.86, P = 0.02; I = 91%). No significant difference was detected in either overall mortality (OR 1.28, 95% CI 0.77 to 2.10, P = 0.34) or ICU mortality (OR 0.99, 95% CI 0.74 to 1.34, P = 0.96) between these two groups. Furthermore, ICU length of stay (LOS) was also evaluated in five studies, and no statistical significance was observed between the two groups with different orders in weaning vasopressors (mean difference, 1.35, 95% CI -2.05 to 4.74, P = 0.44). The subgroup analyses suggested a significant association between hypotension and the practice of discontinuing VP first specifically in patients with a low usage rate of corticosteroids (OR 0.18, 95% CI 0.04 to 0.78, P = 0.02). The TSA indicated a lack of sufficient evidence to draw conclusions from the current results (RIS = 11,821). CONCLUSIONS In adults with septic shock treated with concomitant VP and NE therapy, discontinuing VP first may lead to a higher incidence of hypotension but is not associated with mortality or ICU LOS. Further prospective studies with larger sample sizes are warranted.

Abstract

BACKGROUND Intravenous crystalloid solutions are administered commonly for critically ill patients. We performed this meta-analysis of randomized trials with trial sequential analysis (TSA) to evaluate effects of chloride content of intravenous crystalloid solutions on clinical outcomes among critically ill adult patients. METHODS Electronic databases were searched up to June 1, 2018, for randomized trials of use of balanced crystalloids versus 0.9% saline solutions in critically ill adult patients. The outcome variables included mortality, renal outcomes, serum content alterations and organ function. Subgroup analysis was conducted according to patient settings, types or volume of crystalloid fluid, or among sepsis versus non-sepsis, TBI versus non-TBI or subpopulations by the categories of baseline kidney function. Random errors were evaluated by trial sequential analysis. RESULTS Eight studies with 19,301 patients were analyzed. A trend of in-hospital survival benefit with no statistical difference could be observed with balanced crystalloids compared with 0.9% saline (RR 0.92, 95% CI 0.85-1.0, p = 0.06). The use of balanced crystalloid solutions was associated with longer RRT-free days (SMD 0.09, 95% CI 0.06-0.12, p < 0.001), less risk of increase in serum concentrations of chloride (SMD - 1.23, 95% CI - 1.59 to - 0.87, p < 0.001) and sodium (SMD - 1.28, 95% CI - 1.65 to - 0.92, p < 0.001), less risk of decline in serum base deficit (SMD - 0.58, 95% CI - 0.98 to - 0.18, p = 0.004), longer ventilator-free days (SMD 0.08, 95% CI 0.05-0.11, p < 0.001) and vasopressor-free days (SMD 0.04, 95% CI 0.00-0.07, p = 0.02). Subgroup analysis showed that balanced crystalloid solutions were associated with a reduced in-hospital mortality rate among septic patients (RR 0.86, 95% CI 0.75-0.98; p = 0.02) and non-traumatic brain injury patients (RR 0.90, 95% CI 0.82-0.99, p = 0.02), while the TSA results indicated a larger sample size is still in need. CONCLUSIONS Limited evidence supported statistical survival benefit with balanced crystalloid solutions, while it benefited in reducing organ support duration and fluctuations in serum electrolyte and base excess and was associated with decreased in-hospital mortality in subpopulation with sepsis and non-TBI. Large-scale rigorous randomized trials with better designs are needed to provide robust evidence for clinical management. Trial registration The protocol for this meta-analysis was registered on PROSPERO International prospective register of systematic reviews (CRD42018102661), https://www.crd.york.ac.uk/prospero/#recordDetails.