Peroperative administration of tranexamic acid in Roux-en-Y and one-anastomosis gastric bypass to reduce haemorrhage in patients with morbid obesity: protocol for randomised controlled trial (PATRY trial).

INTRODUCTION: By implementation of Enhanced Recovery After Bariatric Surgery protocols and day-care surgery, early discharge poses a challenge if excessive bleeding occurs after bariatric surgery. Tranexamic acid (TXA) has demonstrated efficacy in other surgical fields and in bariatric pilot studies. This trial aims to assess the efficacy of peroperative administration of TXA in reducing haemorrhage in patients undergoing gastric bypass surgery. METHOD AND ANALYSIS: This is a multicentre, phase III, double-blind randomised controlled trial in six high-volume bariatric centres in the Netherlands. A total of 1524 eligible patients, aged 18 years or older, undergoing primary gastric bypass surgery (either Roux-en-Y gastric bypass or one-anastomosis gastric bypass) will be randomised between TXA and placebo (1:1, variable block, stratified for centre, day-care/overnight stay and type of surgery) after obtaining informed consent (2.5% less haemorrhage, power 80%, 2-sided-α 0.05 and 10% dropout). Exclusion criteria are pregnancy, amedical history of acute bleeding (without cause), venous thrombotic events (VTEs), epilepsy, anticoagulant use and iatrogenic bleeding during surgery (aside from staple line). The primary outcome is postoperative haemorrhage requiring intervention within 30 days postoperatively. Secondary outcome measures are staple line reinforcement, blood loss, duration of surgery, postoperative haemoglobin, vital parameters, minor and major complications, side effects of TXA (nausea, hypotension and VTE), length of hospital stay and directly made costs. ETHICS AND DISSEMINATION: Written informed consent will be obtained from all participants. The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 7 February 2023 (registration number: R22.102). Results will be disseminated through peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: NCT05464394.

The effect of preoperative use of anticoagulants on the hemostatic effect of intravenous application of tranexamic acid in PLIF: a case control study.

Intravenous application of tranexamic acid (TXA) in posterior lumbar interbody fusion (PLIF) can effectively reduce blood loss without affecting coagulation function. However, it has not been reported whether preoperative use of anticoagulants may affect the efficacy of TXA in PLIF. The purpose of this study is to observe the effect of preoperative use of anticoagulants on coagulation indicators and blood loss after PLIF receiving intravenous unit dose TXA. A retrospective analysis was conducted on data from 53 patients with PLIF between 2020.11 and 2022.9, who received intravenous application of a unit dose of TXA (1 g/100 mL) 15 min before the skin incision after general anesthesia. Those who used anticoagulants within one week before surgery were recorded as the observation group, while those who did not use anticoagulants were recorded as the control group. The main observation indicators include surgical time, intraoperative blood loss, postoperative drainage volume, blood transfusion, and red blood cell (RBC), hemoglobin (HB), and hematocrit (HCT) measured on the 1st, 4th, 7th, and last-test postoperative days. Secondary observation indicators included postoperative incision healing, deep vein thrombosis of lower limbs, postoperative hospital stay, and activated partial thrombin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), and platelets (PLT) on the 1st and 4th days after surgery. The operation was successfully completed in both groups, the incision healed well after operation, and no lower limb deep vein thrombosis occurred. There was no significant difference in surgical time, intraoperative blood loss, postoperative drainage volume, and blood transfusion between the two groups (p > 0.05). There was no significant difference in the RBC, HB, and HCT measured on the 1st, 4th, 7th, and last-test postoperative days between the two groups (p > 0.05). There was no statistically significant difference in APTT, PT, TT, FIB and PLT between the two groups on the 1st and 4th postoperative days (p > 0.05). There was no significant difference in postoperative hospital stay between the two groups (p > 0.05). The use of anticoagulants within one week before surgery does not affect the hemostatic effect of intravenous unit dose TXA in PLIF.

Effect of Intense Pulsed Light versus Intradermal Tranexamic Acid for the Management of Melasma.

OBJECTIVE: To compare the effectiveness of intense pulsed light (IPL) and intradermal tranexamic acid (TXA) in treating melasma. STUDY DESIGN: A cross-sectional analytical study. Place and Duration of the Study: Department of Dermatology, Dow International Medical College, Dow University Hospital, Karachi, Pakistan, from 15th January to 15th July 2023. METHODOLOGY: A total of 62 patients with melasma, aged 20-50 years, were divided into two groups. Group A (32 patients) received IPL (560 nm filter was used) treatment, and Group B (30 patients) received intradermal TXA. Each group underwent four treatment sessions with varying intervals. Melasma area and severity index (MASI) scores were used to compare the effects of treatment. RESULTS: After a 3-month treatment period, both groups showed reduced mMASI scores compared to baseline with a significant initial difference between Group A (8.6 ± 4.2) and Group B (5.4 ± 2.7, p <0.001). However, post-treatment, there was no significant difference in mMASI scores (Group A: 3.8 ± 2.6; Group B: 3.2 ± 2.0, p = 0.29). IPL treatment (Group A) demonstrated a significant reduction in mMASI scores (57.1 ± 19.7) compared to intradermal TXA treatment (Group B, 42.2 ± 18.8, p = 0.0034). CONCLUSION: Both IPL and intradermal TXA treatments effectively reduced melasma, with IPL exhibiting superior results. However, post-treatment outcomes converged, emphasising the need for personalised approaches considering the unique characteristics of South East Asian skin. KEY WORDS: Intense pulsed light, Melasma, Intradermal tranexamic acid.

Bleeding Reversal With Antifibrinolytics or Cryoprecipitate Following Thrombolysis for Acute Ischemic Stroke: A Case Series.

Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%. Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or ε-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another. In addition, compared to antifibrinolytics, cryoprecipitate is higher in cost and requires thawing before use. This case series seeks to characterize the management of thrombolytic reversal at a single institution as well as provide additional evidence for antifibrinolytics in this setting. Patients were included for a retrospective review if they met the following criteria: presented between January 2011-January 2017, were >18 years of age, were admitted for AIS, received a thrombolytic, and received TXA EACA, or cryoprecipitate. Twelve patients met the inclusion criteria. Ten (83.3%) developed an ICH, one (8.3%) experienced gastrointestinal bleeding, and one (8.3%) had bleeding at the site of knee arthroscopy. Eleven patients received cryoprecipitate (median dose: 10 units), three received TXA (median dose: 1,000 mg), and one patient received EACA (13 g). TXA was administered faster than the first blood product at a mean time of 19 min and 137 min, respectively. Hemorrhagic expansion (N = 8, 66.67%) and inhospital mortality (N = 7, 58.3%) were high. While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting.

Improved outcome with individualised antifibrinolytic therapy: what is the evidence?

Viscoelastic haemostatic testing (VHT) has been used to determine hyperfibrinolysis and hypofibrinolysis. When modified by addition of tissue plasminogen activator (tPA), VHT has been suggested to assess responses to antifibrinolytic therapy and to estimate the concentration of tranexamic acid in patients undergoing cardiac surgery. Despite some evidence that tPA-modified VHT might allow individualisation of antifibrinolytic therapy, further studies are warranted to prove its clinical benefit for postsurgical bleeding, transfusion of blood products, and thromboembolic events.

Effect of Tranexamic Acid on Intra- and Postoperative Bleeding in Eyelid Surgery: A Prospective, Randomized, Multicenter, Double-Masked, Control Trial.

PURPOSE: Pilot studies suggest that waiting 15 minutes after a subcutaneous tranexamic acid injection is associated with decreased intraoperative bleeding and postoperative ecchymosis in eyelid surgery. The outcomes of commencing eyelid surgery immediately after injection without a waiting period remain unexplored. METHODS: This prospective, randomized, multicenter, double-masked, controlled study examined bilateral symmetric upper and/or lower lid blepharoplasty or ptosis repair. Patients received tranexamic acid in 1 eyelid and control in the contralateral eyelid. The surgeon recorded the side with more intraoperative bleeding. Two masked graders evaluated periocular ecchymosis at postoperative day 0 and postoperative week 1 (POW 1) with a 5-point scale. At POW 1, patients reported subjective grading of bruising as increased on 1 side or similar on both sides. Results were analyzed with Wilcoxon signed-rank and sign tests. RESULTS: Of 130 patients, there was less eyelid ecchymosis on the tranexamic side at postoperative day 0 ( p = 0.001) and POW 1 ( p < 0.001). By surgery type, the 69 levator advancement surgeries had significantly less ecchymosis at postoperative day 0 ( p < 0.001) and POW 1 ( p = 0.001), while upper eyelid blepharoplasty, combined upper and lower lid blepharoplasty, and conjunctivomullerectomy trended toward significance. Of 68 patients reporting a POW 1 grading, 69% reported less bruising on the tranexamic side ( p < 0.001). Intraoperative bleeding was not significantly different between sides ( p = 0.930). CONCLUSIONS: Without a postinjection waiting period, subcutaneous tranexamic acid for eyelid surgery significantly decreased postoperative ecchymosis on postoperative day 0 and POW 1 but did not affect intraoperative bleeding. Subcutaneous tranexamic acid was not associated with any complications.

Lack of efficacy of aprotinin over tranexamic acid in type A aortic dissection repair.

BACKGROUND: The role of aprotinin in modern cardiac surgery is not well defined. While licensed for use in isolated coronary artery bypass grafting it is more commonly used for cases deemed to be at an increased risk of bleeding. The relative efficacy, and safety profile, of aprotinin as compared to other antifibrinolytics in these high-risk cases is uncertain. STUDY DESIGN AND METHODS: A retrospective observational study with propensity matching to determine whether aprotinin versus tranexamic acid reduced bleeding or transfusion requirements in patients presenting for surgical repair of type A aortic dissection (TAD). RESULTS: Between 2016 and 2022, 250 patients presented for repair of TAD. A total of 231 patients were included in the final analysis. Bleeding and transfusion were similar between both groups in both propensity matched and unmatched cohorts. Compared to tranexamic acid, aprotinin use did not reduce transfusion requirements for any product. Rates of bleeding in the first 12 h, return to theater and return to intensive care unit with an open packed chest were similar between groups. There was no difference in rates of renal failure, stroke, or death. CONCLUSION: Aprotinin did not reduce the risk of bleeding or transfusion requirements in patients undergoing repair of type A aortic dissections. Efficacy of aprotinin may vary depending on the type of surgery performed and the underlying pathology.

Quantum biochemical analysis of the TtgR regulator and effectors.

The recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs by numerous mechanisms, active efflux of the drugs is a critical concern. A single species of efflux pump can produce a simultaneous resistance to several drugs. One of the best-studied efflux pumps is the TtgABC: a tripartite resistance-nodulation-division (RND) efflux pump implicated in the intrinsic antibiotic resistance in Pseudomonas putida DOT-T1E. The expression of the TtgABC gene is down-regulated by the HTH-type transcriptional repressor TtgR. In this context, by employing quantum chemistry methods based on the Density Functional Theory (DFT) within the Molecular Fragmentation with Conjugate Caps (MFCC) approach, we investigate the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two broad-spectrum antimicrobial agents. Our quantum biochemical computational results show the: [i] convergence radius, [ii] total binding energy, [iii] relevance (energetically) of the ligands regions, and [iv] most relevant amino acids residues of the TtgR-QUE/TAC/CLM complexes, pointing out distinctions and similarities among them. These findings improve the understanding of the binding mechanism of effectors and facilitate the development of new chemicals targeting TtgR, helping in the battle against the rise of resistance to antimicrobial drugs. These advances are crucial in the ongoing fight against rising antimicrobial drug resistance, providing hope for a future where healthcare-associated infections can be more beneficially treated.

Safety-Catch Linkers for Solid-Phase Peptide Synthesis.

Solid-phase peptide synthesis (SPPS) is the preferred strategy for synthesizing most peptides for research purposes and on a multi-kilogram scale. One key to the success of SPPS is the continual evolution and improvement of the original method proposed by Merrifield. Over the years, this approach has been enhanced with the introduction of new solid supports, protecting groups for amino acids, coupling reagents, and other tools. One of these improvements is the use of the so-called "safety-catch" linkers/resins. The linker is understood as the moiety that links the peptide to the solid support and protects the C-terminal carboxylic group. The "safety-catch" concept relies on linkers that are totally stable under the conditions needed for both α-amino and side-chain deprotection that, at the end of synthesis, can be made labile to one of those conditions by a simple chemical reaction (e.g., an alkylation). This unique characteristic enables the simultaneous use of two primary protecting strategies: tert-butoxycarbonyl (Boc) and fluorenylmethoxycarbonyl (Fmoc). Ultimately, at the end of synthesis, either acids (which are incompatible with Boc) or bases (which are incompatible with Fmoc) can be employed to cleave the peptide from the resin. This review focuses on the most significant "safety-catch" linkers.

Effect of Different Cooking Methods on the Aroma and Taste of Chicken Broth.

A single combi oven, known for its versatility, is an excellent choice for a variety of chicken soup preparations. However, the impact of universal steam ovens on the flavor quality of chicken soup remains unclear. This study aimed to explore the impact of different cooking methods on the aroma and taste of chicken soup. Three cooking methods with various stewing times were compared: ceramic pot (CP), electric pressure cooker (EPC), and combi oven (CO). Analyses were conducted using electron-nose, electron-tongue, gas chromatography-ion mobility spectrometry (GC-IMS), automatic amino acid analysis, and chemometric methods. A total of 14 amino acids, including significant umami contributors, were identified. The taste components of CP and CO chicken soups were relatively similar. In total, 39 volatile aroma compounds, predominantly aldehydes, ketones, and alcohols, were identified. Aldehydes were the most abundant compounds, and 23 key aroma compounds were identified. Pearson's correlation analyses revealed distinct correlations between various amino acids (e.g., glutamic acid and serine) and specific volatile compounds. The aroma compounds from the CP and CO samples showed similarities. The results of this study provide a reference for the application of one-touch cooking of chicken soup in versatile steam ovens.

Multi-Omics Study on Molecular Mechanisms of Single-Atom Fe-Doped Two-Dimensional Conjugated Phthalocyanine Framework for Photocatalytic Antibacterial Performance.

Currently, photocatalysis of the two-dimensional (2D) conjugated phthalocyanine framework with a single Fe atom (CPF-Fe) has shown efficient photocatalytic activities for the removal of harmful effluents and antibacterial activity. Their photocatalytic mechanisms are dependent on the redox reaction-which is led by the active species generated from the photocatalytic process. Nevertheless, the molecular mechanism of CPF-Fe antimicrobial activity has not been sufficiently explored. In this study, we successfully synthesized CPF-Fe with great broad-spectrum antibacterial properties under visible light and used it as an antibacterial agent. The molecular mechanism of CPF-Fe against Escherichia coli and Salmonella enteritidis was explored through multi-omics analyses (transcriptomics and metabolomics correlation analyses). The results showed that CPF-Fe not only led to the oxidative stress of bacteria by generating large amounts of h+ and ROS but also caused failure in the synthesis of bacterial cell wall components as well as an osmotic pressure imbalance by disrupting glycolysis, oxidative phosphorylation, and TCA cycle pathways. More surprisingly, CPF-Fe could disrupt the metabolism of amino acids and nucleic acids, as well as inhibit their energy metabolism, resulting in the death of bacterial cells. The research further revealed the antibacterial mechanism of CPF-Fe from a molecular perspective, providing a theoretical basis for the application of CPF-Fe photocatalytic antibacterial nanomaterials.

Exploring the Integrated Role of miRNAs and lncRNAs in Regulating the Transcriptional Response to Amino Acids and Insulin-like Growth Factor 1 in Gilthead Sea Bream (Sparus aurata) Myoblasts.

In this study, gilthead sea bream (Sparus aurata) fast muscle myoblasts were stimulated with two pro-growth treatments, amino acids (AA) and insulin-like growth factor 1 (Igf-1), to analyze the transcriptional response of mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) and to explore their possible regulatory network using bioinformatic approaches. AA had a higher impact on transcription (1795 mRNAs changed) compared to Igf-1 (385 mRNAs changed). Both treatments stimulated the transcription of mRNAs related to muscle differentiation (GO:0042692) and sarcomere (GO:0030017), while AA strongly stimulated DNA replication and cell division (GO:0007049). Both pro-growth treatments altered the transcription of over 100 miRNAs, including muscle-specific miRNAs (myomiRs), such as miR-133a/b, miR-206, miR-499, miR-1, and miR-27a. Among 111 detected lncRNAs (>1 FPKM), only 30 were significantly changed by AA and 11 by Igf-1. Eight lncRNAs exhibited strong negative correlations with several mRNAs, suggesting a possible regulation, while 30 lncRNAs showed strong correlations and interactions with several miRNAs, suggesting a role as sponges. This work is the first step in the identification of the ncRNAs network controlling muscle development and growth in gilthead sea bream, pointing out potential regulatory mechanisms in response to pro-growth signals.

Washed microbiota transplantation for Crohn's disease: A metagenomic, metatranscriptomic, and metabolomic-based study.

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn's disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported. AIM: To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT. METHODS: We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure. RESULTS: Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT. CONCLUSION: WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient's microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

Efficacy and safety of tranexamic acid in patients undergoing thoracic surgery: a systematic review and PRIMSA-compliant meta-analysis.

OBJECTIVES: Perioperative bleeding poses a significant issue during thoracic surgery. Tranexamic acid (TXA) is one of the most commonly used antifibrinolytic agents for surgical patients. The purpose of the current study was designed to investigate the efficacy and safety of TXA in patients undergoing thoracic surgery. METHODS: An extensive search of PubMed, Web of Science (WOS), Cochrane Library (trials), Embase, OVID, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP electronic databases was performed to identify studies published between the inception of these databases and March 2023. The primary outcomes included perioperative blood loss and blood transfusions. Secondary outcomes of interest included the length of stay (LOS) in hospital and the incidence of thromboembolic events. Weighted mean differences (WMDs) or odds ratios (OR) with 95% confidence intervals (CI) were used to determine treatment effects for continuous and dichotomous variables, respectively. RESULTS: Five qualified studies including 307 thoracic surgical patients were included in the current study. Among them, 65 patients were randomly allocated to the group receiving TXA administration (the TXA group); the other 142 patients were assigned to the group not receiving TXA administration (the control group). TXA significantly reduced the quantity of hemorrhage in the postoperative period (postoperative 12h: WMD = -81.90 ml; 95% CI: -139.55 to -24.26; P = 0.005; postoperative 24h: WMD = -97.44 ml; 95% CI: -121.44 to -73.44; P< 0.00001); The intraoperative blood transfusion volume (WMD = -0.54 units; 95% CI: -1.06 to -0.03; P = 0.04); LOS in hospital (WMD = -0.6 days; 95% CI: -1.04 to -0.16; P = 0.008); And there was no postoperative thromboembolic event reported in the included studies. CONCLUSIONS: The present study demonstrated that TXA significantly decreased blood loss within 12 and 24 hours postoperatively. A qualitative review did not identify elevated risks of safety outcomes such as thromboembolic events. It also suggested that TXA administration was associated with shorter LOS in hospital as compared to control. To validate this further, additional well-planned and adequately powered randomized studies are necessary.

[Case series of hereditary angioedema patients and use of tranexamic acid treatments in prophylaxis and acute crisis, experience in Perú]. / Serie de casos de pacientes con angioedema hereditario y uso de ácido tranexámico como tratamiento profiláctico, y en crisis agudas: experiencia en Perú.

BACKGROUND: Hereditary Angioedema (HAE) is a rare disease characterized by episodes of swelling, HAE crisis could cause death by suffocation, and also affect the quality of life in these patients. There exists an important disparity of HAE specific treatments between countries, inclusive in the same region, currently in Perú we use moderate and high doses of Tranexamic Acid (TA) in prophylaxis therapy and in acute HAE crisis respectively. OBJECTIVE: To report our experience with TA in three types of HAE patients and be a guide to other countries with this therapy, where HAE specific treatments are not registered. CASE REPORT: Patient 1: Woman. 49 years old. HAE-1. Symptoms began at the age of 12. Her final diagnosis was at age 45. Usually presents an acute crisis every two months approximately, she receives 2 g IV of TA when lips, tongue, facial episodes is beginning, eventually she needed other 1 - 2 g IV (after 4 hours). She receives Long-Term Prophylaxis (LTP) with TA (500 - 750 mg)/12 h. Patient 2: Woman 47 years old, HAE nC1INH-FXII. Symptoms began at the age of 19, during her first pregnancy, her definitive diagnosis was at the age of 41 years. She maintains a prophylaxis treatment of TA (750 mg-1,5 g)/daily; upper airway attacks are treated immediately with TA doses (1 - 2 g) when the crisis is beginning. Patient 3: Woman 43 years old, HAE-nC1INH-U. Genetic study did not recognize SERPING1, PLG1, ANGPT1, KNG1, FXII, mutations. Symptoms began at age 4, and her final diagnosis was at age 36. When the attack is beginning, she immediately receives TA (500 - 750 mg) orally / 12 hours during 2 to 3 days with acceptable tolerance and control of the HAE episodes. While the patients receive TA prophylaxis treatment doses (500 - 750 mg) every 8 or 12 hours respectively, the HAE episodes are less symptomatic and resolve in a few days. CONCLUSIONS: We found this systematic review, used TA orally, on-demand and prophylaxis therapy, maximum cumulative dose 3 g/24 h1. In our HAE patients, we used TA up to 4 g (2 g - 2 g) intravenous for control of acute crisis in a interval of 4 hours, when decreases the reaction, the orally maintenance dose should be prescribed, 1 g/8 h with a progressive decrease of the dose in the next days. Tranexamic Acid treatment was useful in our different types of HAE patients. Most of our patients use high doses of TA to slow down and stop slowly the HAE crisis. TA is probably an option in countries where specific treatments are not registered, it could be administered orally and/or intravenous. High doses of TA were well tolerated and with acceptable response in HAE attacks.

ANTECEDENTES: El Angioedema Hereditario (AEH) se caracteriza por episodios de hinchazón a niveles cutáneo y submucoso, una crisis podría causar muerte por asfixia. Además, afecta la calidad de vida de las personas que la padecen. Existe una disparidad importante de medicamentos específicos para el AEH entre países, inclusive en nuestra misma región. En Perú donde no son viables estos tratamientos, se utiliza el Ácido Tranexámico (AT) para las Profilaxis de Largo y Corto Plazo (PLP / PCP), y para las crisis agudas de AEH. OBJETIVO: Reportar la experiencia con el tratamiento de AT en tres tipos de pacientes con AEH, para que pueda ser usada como referencia en otros países en los que aún no se cuenta con medicamentos específicos para la enfermedad. REPORTE DE CASO: Paciente 1: Mujer de 49 años, AEH Tipo 1. Inició síntomas a los 12 años de edad. Diagnóstico definitivo a los 45 años. Actualmente, presenta crisis cada dos meses. Se le administran dosis de 2 g por IV de AT, cuando empieza crisis en cara, lengua y labios. Eventualmente ha necesitado entre 1 y 2 g por IV (después de cuatro horas), ella recibe PLP con AT (500 ­ 750 mg) cada 12 horas. Paciente 2: Mujer de 47 años, AEH-nC1INH-FXII. Inició síntomas a los 19 años durante su primer embarazo. Diagnóstico definitivo a los 41 años. Ella mantiene PLP con AT (750 mg ­ 1,5 g) diariamente. Los ataques de vía respiratoria alta son tratados inmediatamente con AT cuando la crisis inicia, con dosis de 1 a 2 g por IV. Paciente 3: Mujer de 43 años, AEH-nC1INH-D. Estudio genético no detecta mutación en SERPING1, PLG1, ANGPT1, KNG1 y FXII. Inició síntomas a los 4 años. Diagnóstico definitivo a los 36 años. Al iniciar las crisis, se administra AT por VO, entre 500 a 750 mg/12 horas durante dos o tres días con aceptable respuesta y tolerancia a los episodios de AEH. Mientras las pacientes reciban dosis de mantenimiento de AT, entre 500 y 750 mg cada 8 o 12 horas, las crisis suelen ser de menor intensidad y se resuelven en menos días. CONCLUSIONES: En esta revisión sistemática, utilizaron AT vía oral, a demanda y en tratamiento profiláctico, dosis máxima acumulada 3 g/24 h1. En nuestros pacientes con AEH, hemos utilizado AT hasta 4 g vía intravenosa en un intervalo de cuatro horas (2 g - 2 g); para el control de crisis agudas, cuando la reacción está cediendo, prescribimos la dosis de mantenimiento, 1 g/8 h con disminución progresiva de la dosis en los días siguientes. El tratamiento con ácido tranexámico ha sido de utilidad en nuestros pacientes con los distintos tipos de AEH. La mayoría de ellos utilizan altas dosis de AT para disminuir lentamente las crisis agudas de AEH. Se puede administrar vía oral o intravenosa. Es un medicamento que puede ser de ayuda en países donde no se tiene registro de tratamientos específicos para la enfermedad. Las dosis de AT han sido bien toleradas y con una respuesta aceptable en las crisis de estos pacientes con AEH.

Can local infiltration analgesia supplemented with tranexamic acid reduce blood loss during total knee arthroplasty?

PURPOSE: The aim of this study was to investigate the efficacy of TXA supplemented with local infiltration analgesia (LIA) for reducing blood loss in patients undergoing total knee replacement. MATERIALS: A retrospective study of 530 individuals with a mean age of 71.44 years was performed after posterior stabilized total knee arthroplasty. Patients were divided into three groups according to the method of bleeding control: I - patients without an additional bleeding protocol (control group); II - patients receiving IV TXA (TXA group); and III - patients receiving the exact TXA protocol plus intraoperative local infiltration analgesia (TXA + LIA group). Blood loss was measured according to the maximal decrease in Hb compared to the preoperative Hb level. RESULTS: The mean hospitalization duration was 7.02 (SD 1.34) days in the control group, 6.08 (SD 1.06) days in the TXA group, and 5.56 (SD 0.79) in the TXA + LIA group. The most significant decrease in haemoglobin was found in the control group, which was an average of 30.08%. The average decrease in haemoglobin was 25.17% (p < 0.001) in the TXA group and 23.67% (p < 0.001) in the TXA + LIA group. A decrease in the rate of allogeneic blood transfusions was observed: 24.4% in the control group, 9.9% in the TXA group, and 8% in the TXA + LIA group (p < 0.01). CONCLUSIONS: Compared to the separate administration of tranexamic acid, the combination of perioperative administration with local infiltration analgesia significantly reduced blood loss in patients after total knee replacement.

Tranexamic Acid and Tourniquet: Which Combination Reduces Blood Loss Most Effectively?

BACKGROUND: Blood loss during and after total knee arthroplasty (TKA) can lead to substantial morbidity and the need for blood transfusions. There are several methods to minimize blood loss and decrease transfusion rates in patients undergoing TKA. Tranexamic acid, an antifibrinolytic agent with known efficacy for achieving these goals, is combined with tourniquets to reduce bleeding in arthroplasty surgeries. Our study investigated the effects of various combinations of tranexamic acid and tourniquet use on bleeding in knee arthroplasty in 558 patients. AIM: We aimed to determine the method that would provide the least blood loss and transfusion need in knee arthroplasty surgery. METHODS: Between January 2018 and December 2022, 558 patients aged between 55 and 85 years underwent TKA surgery for grade 4 gonarthrosis in our clinic, and their decrease in hemoglobin value and whether they were transfused or not were analyzed. The patients were divided into four groups based on use of tranexamic acid and tourniquet. Demographic variables and patient data (body mass index, INR values, and preoperative hemoglobin values) were recorded. RESULTS: There were 558 patients with a mean age of 68.19 (67 ± 6.949) years. In group 1, tranexamic acid was not used in 128 patients and tourniquet was used only during cementation; in group 2, in 132 patients, tranexamic acid was not used and tourniquet was used throughout the surgery; in group 3, in 158 patients, tranexamic acid was used and tourniquet was used throughout the surgery; in group 4, in 140 patients, tranexamic acid was used and tourniquet was used only during cementation. The decrease in hemoglobin value and transfusion rate was lowest in group 3 and highest in group 1. Besides, there was a greater decrease in hemoglobin value in group 2 than in group 4 and the transfusion rate was similar. CONCLUSIONS: This clinical study showed that using tranexamic acid and a tourniquet throughout surgery significantly reduced the decrease in hemoglobin value and the need for transfusion.

Incidence of deep venous thrombosis in patients with hemophilia undergoing bilateral simultaneous total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Hemophilic arthropathy usually affects the knees bilaterally. In order to reduce costs and improve rehabilitation, bilateral simultaneous total knee arthroplasty (TKA) can be performed. However, pharmacological prophylaxis for deep venous thrombosis (DVT) remains controversial in patients with severe hemophilia. The purpose of this study was to establish the incidence of DVT in severe hemophilia A patients undergoing bilateral simultaneous TKA without pharmacological thromboprophylaxis. METHODS: Consecutive patients with severe hemophilia A undergoing bilateral simultaneous TKA at a single center between January 2015 and December 2020 were retrospectively reviewed. All patients received a modified coagulation factor substitution regimen. Tranexamic acid (TXA) was used for hemostasis in all patients during surgery. All patients followed a standardized postoperative protocol with routine mechanical thromboprophylaxis, and none received anticoagulation. D-dimer was measured preoperatively, on the day of the operation and on postoperative days 1, 7 and 14. Ultrasound (US) of the lower extremities was performed before (within 3 days of hospitalization) and after surgery (days 3 and 14) to detect asymptomatic DVT. Patients were followed up until 2 years after surgery for the development of symptomatic DVT or pulmonary embolism (PE). RESULTS: 38 male patients with severe hemophilia A underwent 76 simultaneous TKAs. Mean (± standard deviation) age at the time of operation was 41.7 (± 17.1) years. Overall, 47.3% of patients had D-dimer concentrations above the threshold 10 µg/mL on day 7 and 39.5% on day 14. However, none of the patients had DVT detected on postoperative US, nor developed symptomatic DVT or PE during the 2-year follow-up. CONCLUSIONS: The risk of DVT in patients with severe hemophilia A after bilateral simultaneous TKA is relatively low, and routine pharmacological thromboprophylaxis may not be needed.

Assessing the feasibility of statistical inference using synthetic antibody-antigen datasets.

Simulation frameworks are useful to stress-test predictive models when data is scarce, or to assert model sensitivity to specific data distributions. Such frameworks often need to recapitulate several layers of data complexity, including emergent properties that arise implicitly from the interaction between simulation components. Antibody-antigen binding is a complex mechanism by which an antibody sequence wraps itself around an antigen with high affinity. In this study, we use a synthetic simulation framework for antibody-antigen folding and binding on a 3D lattice that include full details on the spatial conformation of both molecules. We investigate how emergent properties arise in this framework, in particular the physical proximity of amino acids, their presence on the binding interface, or the binding status of a sequence, and relate that to the individual and pairwise contributions of amino acids in statistical models for binding prediction. We show that weights learnt from a simple logistic regression model align with some but not all features of amino acids involved in the binding, and that predictive sequence binding patterns can be enriched. In particular, main effects correlated with the capacity of a sequence to bind any antigen, while statistical interactions were related to sequence specificity.

The efficacy and safety of different does of intravenous tranexamic acid on blood loss in fresh foot and ankle fractures: a prospective, randomized controlled study.

BACKGROUND: There are a few studies on the effectiveness and safety of intravenous administration of tranexamic acid(TXA) in patients who underwent foot and ankle surgery, especially for preoperative hidden blood loss in patients with freshfoot and ankle fractures. Thus, the aim of this study was to investigate whether intravenous administration of different doses of TXA can effectively reduce perioperative blood loss and blood loss before surgery and to determine its safety. METHODS: A total of 150 patients with fresh closed foot and ankle fractures from July 2021 to July 2023 were randomly divided into a control group (placebo controlled [PC]), standard-dose group (low-dose group [LD], 1 g/24 h; medium-dose group [MD], 2 g/24 h), and high-dose group (HD, 3 g/24 h; ultrahigh-dose group [UD], 4 g/24 h). After admission, all patients completed hematological examinations as soon as possible and at multiple other time points postsurgery. RESULTS: There was a significant difference in the incidence of hidden blood loss before the operation between the TXA group and the control group, and the effect was greater in the overdose groups than in the standard-dose groups. There were significant differences in surgical blood loss (intraoperative and postoperative), postoperative HGB changes, and hidden blood loss among the groups. The TXA groups showed a significant decrease in blood loss compared to that of the control group, and the overdose groups had a more significant effect than the standard-dose groups. A total of 9 patients in the control group had early wound infection or poor healing, while only 1 patient in the other groups had this complication, and the difference among the groups was significant. No patients in any group suffered from late deep wound infection, cardiovascular or cerebrovascular events or symptomatic VTE. CONCLUSION: This is the first study on whether TXA can reduce preoperative hidden blood loss in patients with freshfoot and ankle fractures. In our study, on the one hand, intravenous application of TXA after foot and ankle fractures as soon as possible can reduce preoperative blood loss and postoperative blood loss. On the other hand, TXA can also lower wound complications, and over-doses of TXA are more effective than standard doses. Moreover, overdoses of TXA do not increase the incidence of DVT.