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Emergency Medicine Journal : EMJ Jun 2024
PubMed: 38876769
DOI: 10.1136/emermed-2024-214194 -
Emergency Medicine Journal : EMJ Jun 2024Tranexamic acid (TXA) decreases mortality in injured patients and should be administered as soon as possible. Despite international guidelines recommending TXA in the...
BACKGROUND
Tranexamic acid (TXA) decreases mortality in injured patients and should be administered as soon as possible. Despite international guidelines recommending TXA in the prehospital setting, its use remains low. The aim of this study was to assess the prehospital administration of TXA for injured patients in a Swiss region.
METHODS
We conducted a retrospective observational study in Switzerland between 2018 and 2021. Inclusion criteria were injured patients ≥18 years for whom an ambulance or helicopter was dispatched. The exclusion criterion was minor injury defined by a National Advisory Committee for Aeronautics score <3. The primary outcome was the proportion of patients treated with TXA according to guidelines. The European guidelines were represented by the risk of death from bleeding (calculated retrospectively using the Bleeding Audit for Trauma and Triage (BATT) score). Factors impacting the likelihood of receiving TXA were assessed by multivariate analysis.
RESULTS
Of 13 944 patients included in the study, 2401 (17.2%) were considered at risk of death from bleeding. Among these, 257 (11%) received prehospital TXA. This represented 38% of those meeting US guidelines. For European guidelines, the treatment rate increased with the risk of death from bleeding: 6% (95% CI 4.4% to 7.0%) for low risk (BATT score 3-4); 13% (95% CI 11.1% to 15.9%) for intermediate risk (BATT score 5-7); and 21% (95% CI 17.6% to 25.6%) for high risk (BATT score ≥8) (p<0.01). Women and the elderly were treated less often than men and younger patients, irrespective of the risk of death from bleeding and the mechanism of injury.
CONCLUSION
The proportion of injured patients receiving TXA in the prehospital setting of the State of Vaud in Switzerland was low, with even lower rates for women and older patients. The reasons for this undertreatment are probably multifactorial and would require specific studies to clarify and correct them.
PubMed: 38876768
DOI: 10.1136/emermed-2023-213806 -
Medical Science Monitor : International... Jun 2024BACKGROUND This prospective study from a single center aimed to compare the perioperative blood loss (PBL) in 79 patients with intertrochanteric fractures (IF) treated... (Randomized Controlled Trial)
Randomized Controlled Trial
Perioperative Administration of Tranexamic Acid and Low Molecular Weight Heparin for Enhanced Blood Management in Intertrochanteric Fractures: A Randomized Controlled Study.
BACKGROUND This prospective study from a single center aimed to compare the perioperative blood loss (PBL) in 79 patients with intertrochanteric fractures (IF) treated with intramedullary nailing (IMN) using 3 regimens of combined tranexamic acid (TXA) and low molecular weight heparin (LMWH), proposing a novel therapy of 4-dose TXA. MATERIAL AND METHODS We recruited 79 patients and randomly divided them into 3 groups. The 4-dose TXA group (22 patients) received 1.0 g intravenous TXA 30 min before surgery and 1.0 g at intervals of 3, 6, and 9 h before surgery. The 1-dose TXA group (25 patients) received 1.0 g intravenous TXA 30 min before surgery, while the control group (32 patients) did not receive TXA. LMWH was applied 12 h after surgery in each group. The primary metrics evaluated included hidden blood loss (HBL), total blood loss (TBL), and the number and incidence rate of deep vein thrombosis (DVT). RESULTS Analysis of the HBL revealed that the 4-dose TXA group had the lowest average (583.13±318.08 ml), followed by the 1-dose TXA group (902.94±509.99 ml), and the control group showed the highest (1154.39±452.06 ml) (P<0.05). A similar result was observed for TBL (4-dose group: 640.86±337.22 ml, 1-dose group: 971.74±511.14 ml, control group: 1226.27±458.22 ml, P<0.05). Regarding DVT, the 4-dose TXA group had 5 cases (incidence rate 22.73%), the 1-dose TXA group had 6 cases (incidence rate 24.00%), and the control group had 8 cases (incidence rate 25.00%), with no significant difference among groups (P>0.05). CONCLUSIONS Treatment using 4-dose TXA and LMWH can effectively reduce PBL without increasing the DVT risk in IF patients with IMN.
Topics: Humans; Tranexamic Acid; Female; Male; Hip Fractures; Heparin, Low-Molecular-Weight; Aged; Blood Loss, Surgical; Venous Thrombosis; Prospective Studies; Middle Aged; Perioperative Care; Antifibrinolytic Agents; Aged, 80 and over; Fracture Fixation, Intramedullary
PubMed: 38875178
DOI: 10.12659/MSM.944063 -
Current Medicinal Chemistry Jun 2024microRNA (miRNA) levels are dysregulated in many cancers, suggesting that miRNA-based therapy may be effective. The molecular pathways of colorectal cancer (CRC)...
INTRODUCTION
microRNA (miRNA) levels are dysregulated in many cancers, suggesting that miRNA-based therapy may be effective. The molecular pathways of colorectal cancer (CRC) development are unknown.
METHOD
Understanding miRNAs implicated in CRC formation may reveal new diagnostic and therapeutic targets. Angiogenesis is a key mechanism in tumor growth. CRC treatment may involve inhibiting angiogenesis, but existing drugs can cause negative effects. Tranexamic acid, an FDA-approved medication, may reduce the adverse effects of angiogenesis inhibitors. This work examined miRNAs implicated in CRC angiogenesis and how miR-16 and tranexamic acid may synergistically decrease CRC cell migration and angiogenesis. We identified miRNAs targeting CRC angiogenesis genes using bioinformatic databases. Proteins were docked with tranexamic acid utilizing the PyRx software. Quantitative Real-time PCR was used to analyze the effects of overexpressed miRNA and tranexamic acid on the expression of target genes. Scratch, transwell migration, and Chicken Chorioallantoic Membrane (CAM) assays were used to evaluate the effect of selected miRNA and tranexamic acid on the invasion and angiogenesis of CRC cells. in silico studies identified hsa-miR-16-5p, -101-3p, and 34a-5p as possible CRC angiogenesis modulators.
RESULTS
The study found that miR-16 and tranexamic acid influence the expression of VEGFA, ANGPT2, MMP9, and HIF1A. miR-16 and tranexamic acid influenced CRC cell movement in scratch tests and transwell migration assays. Furthermore, the CAM assay results demonstrated that miR-16 and tranexamic acid can alter angiogenesis in CRC.
CONCLUSION
These findings highlight the potential of miR-16 and tranexamic acid as combination therapeutic agents for CRC, with the ability to simultaneously target tumorigenesis and angiogenesis.
PubMed: 38874036
DOI: 10.2174/0109298673300320240604062533 -
EClinicalMedicine Jul 2024To assess the equivalence of tranexamic acid (TRAN) versus synthetic oxytocin (OXY) in reducing post-partum blood loss, in full-term patients (37-42 weeks), at low risk...
BACKGROUND
To assess the equivalence of tranexamic acid (TRAN) versus synthetic oxytocin (OXY) in reducing post-partum blood loss, in full-term patients (37-42 weeks), at low risk of post-partum hemorrhage, with vaginal childbirth.
METHODS
Phase III, randomized (1:1), open-label, longitudinal, multi-center, prospective clinical trial (Prot. n 63209, ClinicalTrials.gov Identifier: NCT02775773). From January 7, 2020, to June 30, 2023, a total of 256 women were enrolled at two general urban community hospitals in Italy, serving a multi-ethnic patient population with National Health Insurance. The primary outcome was to explore a potential equivalence between the two treatments (OXY and TRAN) in preventing total blood loss. Therefore, we randomized 231 women into two groups: Group A (OXY), 127 women who were administered 10UI intramuscularly within 5 min from childbirth; Group B (TRAN), 104 women to whom 1-g slow intravenous infusion was administered within 5 min from childbirth.
FINDINGS
At the time of delivery, mean blood loss for OXY group versus TRAN group was 269.12 mL versus 263.88 mL, respectively, with equivalence between the two groups. Similarly, there was equivalence in total blood loss between the OXY and the TRAN group (397.66 mL versus 405.64 mL, respectively. No statistical differences between Hb levels at admission and discharge in the two groups were reported. No difference was found in terms of additional uterotonic and surgical therapies between the two groups of patients. Neither group showed thrombotic complications at check-up performed after 7 days or after a questionnaire regarding adverse effects, subjected after 40 days.
INTERPRETATION
The study shows the equivalence of tranexamic acid versus synthetic oxytocin in post-partum blood loss prophylaxis in term patients at low risk of PPH with vaginal childbirth. The safety profiles of OXY and TRAN were similar.
FUNDING
None.
PubMed: 38873634
DOI: 10.1016/j.eclinm.2024.102665 -
Zhonghua Yi Xue Za Zhi Jun 2024To evaluate the influence of thromboelastography-guided hemostatic algorithm on allogeneic transfusion requirements during pediatric hemispherectomy. Clinical data of...
To evaluate the influence of thromboelastography-guided hemostatic algorithm on allogeneic transfusion requirements during pediatric hemispherectomy. Clinical data of 38 children who underwent hemispherectomy from January 1, 2011 to October 31, 2023 at Xuanwu Hospital of Capital Medical University were retrospective collected. Patients were divided into study group (=17) and control group (=21) according to whether thromboelastography was employed to guide hemostatic algorithm. Demographic data and surgical data were recorded. The primary outcomes were allogeneic transfusion rates, including RBC transfusion rate, plasma transfusion rate, and platelets transfusion rate. The second outcomes were estimated blood loss, postoperative seizures during hospitalization, thromboembolic events, and length of hospital stay. There were 13 boys and 4 girls with mean age of (5.7±3.3) years old in study group, and 16 boys and 5 girls with mean age of (7.4±3.4) years old in control group. The surgery duration, anesthesia duration and the proportion of prophylactic administration of tranexamic acid in study group were (424.5±98.5) min, (542.8±106.9) min, and 94.1% (16/17), which were higher than (353.1±85.3) min, (445.3±87.9) min, and 47.6% (10/21) in control group (all <0.05). The rates of intra- and perioperative allogeneic plasma transfusion in study group were 52.9% (9/17) and 64.7% (11/17) respectively, which were lower than 90.5% (19/21) and 95.2% (20/21) in control group (all <0.05). The ratio of fibrinogen concentrates administration in study group was 58.8% (10/17), which was higher than that in control group [4.8% (1/21), =0.001]. There were no statistically differences in intra- and perioperative allogeneic RBC transfusion rates between the two groups (all >0.05). No platelets were transfused in both groups. There were no statistically differences in estimated blood loss, postoperative seizures during hospitalization and the length of hospital stay between the two groups (all >0.05). No postoperative thromboembolic events were observed. Thromboelastography-guided hemostatic algorithm can reduce allogeneic plasma transfusion requirements but not RBC transfusion requirements during pediatric hemispherectomy.
Topics: Humans; Thrombelastography; Female; Male; Child; Retrospective Studies; Child, Preschool; Hemispherectomy; Algorithms; Blood Transfusion; Blood Loss, Surgical; Hemostasis
PubMed: 38871471
DOI: 10.3760/cma.j.cn112137-20231227-01495 -
International Journal of Pharmaceutics Jun 2024Tranexamic acid (TXA) is an anti-fibrinolysis agent widely used in postoperative blood loss management. As a highly water-soluble drug, TXA is suffering from rapid...
Tranexamic acid (TXA) is an anti-fibrinolysis agent widely used in postoperative blood loss management. As a highly water-soluble drug, TXA is suffering from rapid clearance from the action site, therefore, large amount of drug is required when administered either by intravenously or topically. In this study, a TXA preparation with prolonged action site residence was designed using the nano-micro strategy. TXA nanoparticles were dispersed in oil by emulsification followed by lyophilization to give a solid-in-oil suspension, which was used as the oil phase for the preparation of TXA-loaded solid-in-oil-in-water (TXA@S/O/W) system. The particle size of TXA in oil was 207.4 ± 13.50 nm, and the particle size of TXA@S/O/W was 40.5 μm. The emulsion-in-gel system (TXA@S/O/G) was prepared by dispersing TXA@S/O/W in water solution of PLGA-b-PEG-b-PLGA (PPP). And its gelling temperature was determined to be 26.6 ℃ by a rheometer. Sustained drug release was achieved by TXA@S/O/G with 72.85 ± 7.52 % of TXA released at 120 h. Formulation retention at the joint cavity was studied by live imaging, and the fluorescent signals dropped gradually during one week. Drug escape from the injection site via drainage and absorption was investigated by a self-made device and plasma TXA concentration determination, respectively TXA@S/O/G showed the least drug drainage during test, while more than 70 % of drug was drained in TXA@S/O/W group and TXA solution group. Besides, low yet steady plasma TXA concentration (less than 400 ng/mL) was found after injecting TXA@S/O/G into rat knees at a dosage of 2.5 mg/kg, which was much lower than those of TXA dissolved in PPP gel or TXA solution. In conclusion, sustained drug release as well as prolonged action site retention were simultaneously achieved by the designed TXA@S/O/G system. More importantly, due to the steady plasma concentration, this strategy could be further applied to other highly water-soluble drugs with needs on sustained plasma exposure.
PubMed: 38871135
DOI: 10.1016/j.ijpharm.2024.124334 -
Spine Surgery and Related Research May 2024Tranexamic acid (TXA) has gained popularity in spinal surgery because of its potential to reduce blood loss. However, concerns regarding its safety and efficacy remain.... (Review)
Review
BACKGROUND
Tranexamic acid (TXA) has gained popularity in spinal surgery because of its potential to reduce blood loss. However, concerns regarding its safety and efficacy remain. This systematic review and meta-analysis aimed to evaluate the efficacy of TXA in reducing blood loss and its safety profile in spinal surgeries.
METHODS
A comprehensive search was conducted in electronic databases for randomized controlled trials and prospective studies evaluating the use of TXA in spinal surgery. The primary outcomes were intraoperative and total estimated blood loss (EBL), and the secondary outcomes included the incidence and types of complications associated with TXA use. Meta-analyses were performed using random-effects models.
RESULTS
Thirteen studies involving 1,213 participants were included in the meta-analysis. The use of TXA was associated with significant reductions in both intraoperative (mean difference: -46.56 mL [-73.85, -19.26], p<0.01]) and total EBL (mean difference: -210.17 mL [-284.93, -135.40], p<0.01) while also decreasing the need for blood transfusions (risk ratio: 0.68 [0.51, 0.90], p<0.01). No significant difference was found in the incidence and types of thrombotic complications when TXA was used in spinal surgery. Subgroup analysis showed consistent results in instrumentation and fusion surgery and different doses of TXA.
CONCLUSIONS
TXA is effective in reducing intraoperative and overall blood loss in spinal surgery without increasing the risk of complications. These findings support the use of TXA to improve patient outcomes. However, caution should be exercised because of the heterogeneity among the included studies. Further research is needed to confirm these findings and explore potential long-term complications.
PubMed: 38868794
DOI: 10.22603/ssrr.2023-0244 -
Journal of Cosmetic Dermatology Jun 2024Substances that can efficiently enhance skin penetration while exerting no adverse effect are useful for drug and cosmetics formulation.
BACKGROUND
Substances that can efficiently enhance skin penetration while exerting no adverse effect are useful for drug and cosmetics formulation.
OBJECTIVE
To investigate the safety and enhance skin penetration efficacy of Putocrin®, a combination containing 2% isosorbide dimethyl ether, 1% pentanediol, and 0.5% inositol.
METHODS
An in vitro keratinocyte cell assay using 3-(4,5-dimethylthiazolyl-2)-2,5 diphenyltetrazolium bromide (MTT), and an in vitro EpiKutis® skin study adopted hematoxylin and eosin staining, immunostaining, and liquid chromatography-mass spectrometry (LC-MS) analysis were carried out to investigate the safety of Putocrin®. A pigskin-Franz cell system experiment applied high-performance liquid chromatography (HPLC) to compare the skin penetration efficiency of fluorescein isothiocyanate (Fitc)-labeled tranexamic acid with or without the assistance of Putocrin®. The safety and efficacy of Putocrin® was further evaluated on zebrafish embryos.
RESULTS
The MTT assay showed that Putocrin® at concentration ≤2.5% did not significantly affect cell viability. The in vitro EpiKutis® skin study revealed that 2.5% Putocrin® did not affect skin morphology, filaggrin content, ceramide/protein, or fatty acid/protein ratios, but significantly increased loricrin content by 86.00% (p < 0.001). The pigskin-Franz cell penetration experiment demonstrated that Fitc-labeled tranexamic acid could barely penetrate the skin (with penetration rate of 1.121%), while Putocrin® significantly enhanced the penetration rate up to 83.983%, which was close to unlabeled tranexamic acid (90.013%). The zebrafish embryo study showed that 2.5% Putocrin® did not exert observable toxicity and obviously assisted the skin penetration of Fitc-labeled tranexamic acid into fish embryos. These results indicate the strong enhancing skin penetration potency of Putocrin®.
CONCLUSION
This study demonstrated the safety as well as the strong enhancing skin penetration potency of Putocrin® for cosmetics formulation use.
PubMed: 38867384
DOI: 10.1111/jocd.16409 -
BMJ (Clinical Research Ed.) Jun 2024call for greater use of this inexpensive generic drug that can improve surgical outcomes, avoid unnecessary blood transfusion, and conserve blood stocks
call for greater use of this inexpensive generic drug that can improve surgical outcomes, avoid unnecessary blood transfusion, and conserve blood stocks
Topics: Tranexamic Acid; Humans; Antifibrinolytic Agents; Blood Loss, Surgical
PubMed: 38866414
DOI: 10.1136/bmj-2024-079444