Abstract

BACKGROUND Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion. METHODS Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test). RESULTS We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P<0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P<0.001). No statistical differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies. CONCLUSION The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries. TRIAL REGISTRATION ClinicalTrials.gov, NCT01597232.

Abstract

The traditional lateral "L" approach is common for managing calcaneal fractures with a drawback of significant blood loss. Yet there are no prospective studies on the hemostatic effect of the topical use of tranexamic acid (TXA) in calcaneal fracture surgeries. The purpose of this study was to evaluate the role of topical administration of TXA in reducing postoperative blood loss in calcaneal fractures. Forty participants were randomly distributed into the TXA group (n = 20) and the control group (n = 20). All participants underwent the same surgery via the lateral "L" approach. At the end of the operation, the surgical wound was irrigated with 80 mL 0.5 g/L TXA in the TXA group and 80 mL 0.9% sodium chloride in the control group, followed by the routine use of a drainage tube when closing the incision. Then, 20 mL 0.5 g/L TXA (TXA group) or 20 mL 0.9% sodium chloride solution (control group) was injected retrogradely into the wound through the drainage tube, which was clipped for 30 minutes thereafter. There were no significant differences in the baseline data between the 2 groups (p > .05). There was significantly less blood loss in the first 24 hours and total blood loss postoperation in the TXA group (p < .01). The surgical wounds healed well after surgery in both groups with no complication. We concluded that topical application of TXA in calcaneal fracture surgeries is a safe and useful method that can reduce postoperative blood loss.

Abstract

OBJECTIVE Tranexamic acid (TXA) plays a significant role in the treatment of traumatic diseases. However, its effectiveness in patients with traumatic brain injury (TBI) seems to be contradictory, according to the recent publication of several meta-analyses. We aimed to determine the efficacy of TXA treatment at different times and doses for TBI treatment. METHODS PubMed, MEDLINE, EMBASE, Cochrane Library, and Google Scholar were searched for randomized controlled trials that compared TXA and a placebo in adults and adolescents (≥ 15 years of age) with TBI up to January 31, 2022. Two authors independently abstracted the data and assessed the quality of evidence. RESULTS Of the identified 673 studies, 13 involving 18,675 patients met our inclusion criteria. TXA had no effect on mortality (risk ratio (RR) 0.99; 95% confidence interval (CI) 0.92-1.06), adverse events (RR 0.93, 95% Cl 0.76-1.14), severe TBI (Glasgow Coma Scale score from 3 to 8) (RR 0.99, 95% Cl 0.94-1.05), unfavorable Glasgow Outcome Scale (GOS < 4) (RR 0.96, 95% Cl 0.82-1.11), neurosurgical intervention (RR 1.11, 95% Cl 0.89-1.38), or rebleeding (RR 0.97, 95% Cl 0.82-1.16). TXA might reduce the mean hemorrhage volume on subsequent imaging (standardized mean difference, -0.35; 95% CI [-0.62, -0.08]). CONCLUSION TXA at different times and doses was associated with reduced mean bleeding but not with mortality, adverse events, neurosurgical intervention, and rebleeding. More research data is needed on different detection indexes and levels of TXA in patients with TBI, as compared to those not receiving TXA; although the prognostic outcome for all harm outcomes was not affected, the potential for harm was not ruled out. TRIAL REGISTRATION The review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42022300484).

Abstract

BACKGROUND To evaluate the efficacy and safety of recombinant human serum albumin /granulocyte colony-stimulating factor (rHSA/G-CSF) in breast cancer following receipt of cytotoxic agents. METHODS The phase 1b trial assessed the pharmacokinetics, pharmacodynamics, and safety of dose-escalation, ranging from rHSA/G-CSF 1800 μg, 2100 μg, and 2400 μg. Randomized controlled phase 2b trial was further conducted to ensure the comparative efficacy and safety of rHSA/G-CSF 2400 μg and rhG-CSF 5 μg/kg. In multicenter, randomized, open-label, parallel, phase 2 study, participants treated with anthracycline-containing chemotherapy were assigned in a ratio 1:1:1 to receive double delivery of rHSA/G-CSF 1200 μg, 1500 μg, and continuous rhG-CSF 5 μg/kg. RESULTS Between December 16, 2014, to July 23, 2018, a total of 320 patients were enrolled, including 25 individuals in phase 1b trial, 80 patients in phase 2b trial, and 215 participants in phase 2 study. The mean duration of agranulocytosis during the first chemotherapeutic intermission was observed as 1.14 ± 1.35 days in rHSA/G-CSF 1500 μg, which was comparable with that of 1.07 ± 0.97 days obtained in rhG-CSF control (P = 0.71). Safety profiles were assessed to be acceptable ranging from rHSA/G-CSF 1800 μg to 2400 μg, while the double delivery of HSA/G-CSF 2400 μg failed to meet the noninferiority in comparison with rhG-CSF. CONCLUSION The prospective randomized controlled trials demonstrated that rHSA/G-CSF was efficacious and well-tolerated with an approachable frequency and expense of application for prophylactic management of agranulocytosis. The double delivery of rHSA/G-CSF 1500 μg in comparisons with paralleling G-CSF preparations is warranted in the phase 3 trial. TRIAL REGISTRATION ClinicalTrials.gov identifiers: NCT02465801 (11/17/2014), NCT03246009 (08/08/2017), NCT03251768 (08/07/2017).

Abstract

BACKGROUND The effect of early vasopressin initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early start of vasopressin support within 6 h after the diagnosis on clinical outcomes in septic shock patients. METHODS We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of February 2021. We included studies involving adult patients (> 16 years)with septic shock. All authors reported our primary outcome of short-term mortality and in the experimental group patients in the studies receiving vasopressin infusion within 6 h after diagnosis of septic shock and in the control group patients in the studies receiving no vasopressin infusion or vasopressin infusion 6 h after diagnosis of septic shock, clearly comparing with clinically relevant secondary outcomes(use of renal replacement therapy(RRT),new onset arrhythmias, ICU length of stay and length of hospitalization). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). RESULTS Five studies including 788 patients were included. The primary outcome of this meta-analysis showed that short-term mortality between the two groups was no difference (odds ratio [OR] = 1.09; 95% CI, 0.8 to 1.48; P = 0.6; χ2 = 0.83; I2 = 0%). Secondary outcomes demonstrated that the use of RRT was less in the experimental group than that of the control group (OR = 0.63; 95% CI, 0.44 to 0.88; P = 0.007; χ2 = 3.15; I2 = 36%).The new onset arrhythmias between the two groups was no statistically significant difference (OR = 0.59; 95% CI, 0.31 to 1.1; P = 0.10; χ2 = 4.7; I2 = 36%). There was no statistically significant difference in the ICU length of stay(mean difference = 0.16; 95% CI, - 0.91 to 1.22; P = 0.77; χ2 = 6.08; I2 = 34%) and length of hospitalization (mean difference = -2.41; 95% CI, -6.61 to 1.78; P = 0.26; χ2 = 8.57; I2 = 53%) between the two groups. CONCLUSIONS Early initiation of vasopressin in patients within 6 h of septic shock onset was not associated with decreased short-term mortality, new onset arrhythmias, shorter ICU length of stay and length of hospitalization, but can reduce the use of RRT. Further large-scale RCTs are still needed to evaluate the benefit of starting vasopressin in the early phase of septic shock.

Abstract

OBJECTIVE To construct and validate a nomogram composed of preoperative variables to predict intraoperative blood transfusion for gastric cancer surgery. BACKGROUND Intraoperative transfusion for gastric cancer surgery is a common medical procedure that is associated with increased postoperative complications. METHODS A total of 999 patients who underwent gastrectomy between January 2010 and June 2019 were randomly allocated into the primary and validation cohorts in a 2:1 ratio. In the primary cohort, logistic analyses were performed to identify independent predictors for transfusion. Using the Akaike information criterion, selected variables were incorporated to construct a nomogram. Validations of the nomogram were performed in the primary and validation cohorts. The discrimination ability of the nomogram was assessed by the concordance index (C-index), and calibration was assessed by calibration curves and the Hosmer-Lemeshow goodness-of-fit test. RESULTS The following risk factors for transfusion were identified and used to construct the nomogram: ASA status (III-IV vs I-II: odds ratio [OR] 1.74), comorbidities (yes vs no: OR 1.57), tumour location (diffuse vs lower: OR 4.05), cTNM stage (III vs I: OR 1.95), and a preoperative haemoglobin level less than 80 g/L (vs over 120 g/L: OR 35.30). The C-index was 0.859 and 0.850 in the primary and validation cohorts, respectively, which both indicated good discrimination of the nomogram. Additionally, both calibration curves and Hosmer-Lemeshow tests (p-value 0.184 and 0.887, respectively) demonstrated high agreement between the predictions and actual outcomes. CONCLUSION A nomogram composed of preoperative variables to predict blood transfusion for gastric cancer surgery was effectively developed and validated. This nomogram could be used to improve the utilisation of red blood cells for gastrectomy.

Abstract

BACKGROUND Studies have shown that the combined application of hyaluronic acid (HA) and platelet-rich plasma (PRP) can repair degenerated cartilage and delay the progression of knee osteoarthritis (KOA). The purpose of this study was to explore the efficacy and safety of the intra-articular injection of PRP combined with HA compared with the intra-articular injection of PRP or HA alone in the treatment of KOA. METHODS The PubMed, Cochrane Library, EMBASE and China National Knowledge Infrastructure (CNKI) databases were searched from inception to December 2019. Randomized controlled trials and cohort studies of PRP combined with HA for KOA were included. Two orthopaedic surgeons conducted the literature retrieval and extracted the data. Outcome indicators included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the Lequesne Index, the visual analogue scale (VAS) for pain, and adverse events (AEs). Review Manager 5.3 was used to calculate the relative risk (RR) or standardized mean difference (SMD) of the pooled data. STATA 14.0 was used for quantitative publication bias evaluation. RESULTS Seven studies (5 randomized controlled trials, 2 cohort studies) with a total of 941 patients were included. In the VAS comparison after 6 months of follow-up, PRP combined with HA was more likely to reduce knee pain than PRP alone (SMD: - 0.31; 95% confidence interval (CI): - 0.55 to - 0.06; P = 0.01 < 0.05). PRP combined with HA for KOA achieved better improvements in the WOMAC Function Score (SMD: -0.32; 95% CI: - 0.54 to - 0.10; P < 0.05) and WOMAC Total Score (SMD: -0.42; 95% CI: - 0.67 to - 0.17; P < 0.05) at the 12-month follow-up than did the application of PRP alone. In a comparison of Lequesne Index scores at the 6-month follow-up, PRP combined with HA improved knee pain scores more than PRP alone (SMD: -0.42; 95% CI: - 0.67 to - 0.17; P < 0.05). In terms of AEs, PRP combined with HA was not significantly different from PRP or HA alone (P > 0.05). CONCLUSIONS Compared with intra-articular injection of PRP alone, that of PRP combined with HA can improve the WOMAC Function Scores, WOMAC Total Score, 6-month follow-up VAS ratings, and Lequesne Index scores. However, in terms of the incidence of AEs, PRP combined with HA is not significantly different from PRP or HA alone.

Abstract

OBJECTIVE The aim of this study was to evaluate the efficacy and safety of tranexamic acid (TXA) in elderly patients with intertrochanteric fracture undergoing intramedullary fixation surgery. METHODS We searched MEDLINE, the Cochrane Library and EMBASE for published randomized clinical trials relevant to use of TXA in elderly patients with intertrochanteric fracture treated with intramedullary fixation surgery. Meta-analysis was performed according to the guidelines of the Cochrane Reviewer's Hand book. RESULTS Five trials assessing 540 patients were included for meta-analysis. The pooled results showed that the mean total blood loss in TXA group was significant lower than that in the control group (mean difference - 172.83, 95% CI -241.43 to -104.23; p<0.00001, fixed-effect model). The intra- and postoperative transfusion rate for the TXA group was 34.4% (91/264) and for the control group was 49.27% (136/276), and the relative risk was 0.71 (95% CI 0.52 to 0.97; p<0.03, random-effect model) with substantial heterogeneity (I2=63%, p=0.03). The overall incidence of thrombotic events was 6.43% (17/264) in the intravenous TXA group, 7.63% (21/275) in the control group, with no significant difference (relative risk 0.84, 95% CI 0.46 to 1.54; p=0.57, fixed-effect model). CONCLUSION The present evidence shows that TXA can significantly reduce total and hidden blood loss, transfusion rate, and do not increase the risk of thrombotic events in elderly patients with intertrochanteric fracture undergoing intramedullary fixation surgery. However, the impact of TXA on thrombotic events needs to be researched in more high-quality, large-sample randomized clinical trials. LEVEL OF EVIDENCE Level I Therapeutic Study.

Abstract

Background: Catecholamines are commonly used in septic shock but face limitations of their hypo-responsiveness and adverse events due to high dose. Terlipressin is a synthetic vasopressin analog with greater selectivity for the V1-receptor. A meta-analysis was conducted to evaluate the efficacy and safety of terlipressin in septic shock. Methods: We searched for relevant studies in PubMed, Embase, and the Cochrane database from inception up to July 15, 2018. Randomized controlled trials (RCTs) were included if they reported data on any of the predefined outcomes in patients with septic shock and managed with terlipressin or any catecholamines. Results were expressed as risk ratio (RR) or mean difference (MD) with accompanying 95% confidence interval (CI). Heterogeneity, subgroup analysis, sensitivity analysis, and publication bias were explored. Results: Ten studies with 928 patients were included. Despite the shorter duration of mechanical ventilation, use of terlipressin did not reduce the risk of mortality (RR = 0.94; 95% CI, 0.85 to 1.05; I (2) = 0%; P = 0.28) when compared with control. This finding was confirmed by further subgroup and sensitivity analyses. In addition, lactate clearance, length of stay in ICU or hospital, total adverse events, digital ischemia, and arrhythmia were also similar between groups, while terlipressin was associated with shorter duration of mechanical ventilation and less norepinephrine requirements. Conclusions: Current results suggest terlipressin did not show added survival benefit in septic shock therapy when compared with catecholamines.

Abstract

PURPOSE The purpose of this meta-analysis was to compare platelet-rich plasma (PRP) and hyaluronic acid (HA) in patients with knee osteoarthritis (KOA). METHODS Randomized controlled trials (RCTs) comparing the use of PRP and HA in KOA patients were retrieved from each database from the establishment date to April 2018. Outcome measurements were the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analog scale (VAS), International Knee Documentation Committee, and Lequesne Index scores and adverse events. The pooled data were evaluated with Review Manager 5.3.5. RESULTS Fifteen RCTs (N = 1,314) were included in our meta-analysis. The present meta-analysis indicated that PRP injections reduced pain more effectively than HA injections in patients with KOA at six and 12 months of follow-up, as evaluated by the WOMAC pain score; the VAS pain score showed a significant difference at 12 months. Moreover, better functional improvement was observed in the PRP group, as demonstrated by the WOMAC function score at three, six, and 12 months. Additionally, PRP injections did not display different adverse event rates compared with HA injections. CONCLUSION In terms of long-term pain relief and functional improvement, PRP injections might be more effective than HA injections as a treatment for KOA. The optimal dosage, the timing interval and frequency of injections, and the ideal treatment for different stages of KOA remain areas of concern for future investigations.