RESUMEN

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is fundamental in all patients undergoing percutaneous coronary intervention (PCI) to prevent coronary thrombosis. In patients with atrial fibrillation (AF), an oral anticoagulant gives protection against ischemic stroke or systemic embolism. AF-PCI patients are at high bleeding risk and decision-making regarding the optimal antithrombotic therapy remains challenging. Dual antithrombotic therapy (DAT) has been shown to reduce bleeding events but at the cost of a higher risk of stent thrombosis. Further studies are needed to clarify the optimal duration of triple antithrombotic therapy (TAT) or DAT and the role of more potent antiplatelet drugs.

Asunto(s)

Anticoagulantes , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Humanos , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Administración Oral , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/cirugía , Terapia Antiplaquetaria Doble/métodos , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Trombosis Coronaria/prevención & control

RESUMEN

Patients with peripheral artery disease (PAD) who undergo lower extremity revascularization (LER) are at high risk for cardiovascular and limb-related ischemic events. The role of antithrombotic therapy is to prevent thrombotic complications, but this requires balancing increased risk of bleeding events. The dual pathway inhibition (DPI) strategy including aspirin and low-dose rivaroxaban after LER has been shown to reduce major adverse cardiovascular and limb-related events without significant differences in major bleeding. There is now a need to implement the broad adoption of DPI therapy in PAD patients who have undergone LER in routine practice.

Asunto(s)

Fibrinolíticos , Enfermedad Arterial Periférica , Humanos , Enfermedad Arterial Periférica/cirugía , Fibrinolíticos/uso terapéutico , Trombosis/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/cirugía , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificación

RESUMEN

Early mechanical reperfusion, primarily via percutaneous coronary intervention, combined with timely antithrombotic drug administration, constitutes the main approach for managing acute coronary syndrome (ACS). Clinicians have access to a variety of antithrombotic agents, necessitating careful selection to balance reducing thrombotic events against increased bleeding risks. This review offers a comprehensive update on current antithrombotic therapy in ACS, emphasizing the need for individualized treatment strategies.

Asunto(s)

Síndrome Coronario Agudo , Fibrinolíticos , Intervención Coronaria Percutánea , Humanos , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/cirugía , Fibrinolíticos/uso terapéutico , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Hemorragia/inducido químicamente , Hemorragia/prevención & control

RESUMEN

Antiplatelet therapy is integral to reduce the risk of future ischemic events following acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI); this aim must be balanced by limiting the risk of bleeding. Women with ACS or undergoing PCI have distinct platelet physiology, vascular anatomy, and clinical profiles that can influence the selection of an appropriate regimen. There are procedural techniques that can enhance safety in women. The poor inclusion of women in ACS and PCI trials limits our understanding of the ideal antiplatelet regimen in women, and future studies must find ways to increase the participation of female patients.

Asunto(s)

Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Humanos , Síndrome Coronario Agudo/cirugía , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Femenino , Hemorragia/inducido químicamente , Hemorragia/prevención & control

RESUMEN

BACKGROUND: Patients undergoing percutaneous coronary intervention mainly receive antiplatelet therapy. However, limited data are available regarding the optimal dual antiplatelet therapy (DAPT) following the implantation of new-generation drug-eluting stent (DES). OBJECTIVE: This study aimed to compare the clinical outcomes of short-term (1-3 months) DAPT and standard (12 months) DAPT after the implantation of a new-generation of DES. METHODS: We systematically searched PubMed, The Cochrane Library Database, Embase for trials that compared short-term (1-3 months) and standard DAPT after the implantation of next-generation DES were retrieved from all published studies in English until December 31, 2021. The primary endpoint was major bleeding. The secondary endpoints included all-cause mortality, cardiac death, myocardial infarction, stroke, stent thrombosis, and all bleeding. RESULTS: This study included a total of 7 randomized controlled trials, comprising 28,344 subjects. Regarding primary endpoints, short-term DAPT exhibited a significantly lower incidence of major bleeding compared with standard DAPT [relative risk (RR): 0.66, 95% confidence interval (CI): (0.54, 0.81), P < .0001]. For secondary endpoints, there were significant differences between short-term and standard DAPT in all bleeding [RR: 0.59, 95% CI: (0.50, 0.69), P < .00001]. However, no significant differences were identified in all-cause mortality [RR: 0.96, 95% CI: (0.77, 1.18), P = .27], myocardial infarction [RR: 0.98, 95% CI: (0.82, 1.18), P = .86], cardiac death [RR: 0.83, 95% CI: (0.63, 1.10), P = .20], stroke [RR: 1.08, 95% CI: (0.79, 1.47), P = .63], cerebrovascular [RR: 1.08, 95% CI: (0.79, 1.47), P = .63], and stent thrombosis [RR: 1.13, 95% CI: (0.80, 1.57), P = .49] between the 2 groups. CONCLUSION: In patients undergoing implantation of a new-generation of DES, short-term (1-3 months) DAPT exhibited no inferiority compared with standard (12 months) DAPT in terms of all-cause mortality, cardiac death, myocardial infarction, stroke, and definite or probable stent thrombosis compared with standard (12 months) DAPT. However, short-term DAPT appeared superior to standard DAPT in terms of major bleeding and all bleeding.

Asunto(s)

Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Intervención Coronaria Percutánea/métodos , Terapia Antiplaquetaria Doble/métodos , Hemorragia/epidemiología , Hemorragia/inducido químicamente , Hemorragia/prevención & control

RESUMEN

Inherited bleeding disorders such as Glanzmann thrombasthenia (GT) lack prophylactic treatment options. As a result, serious bleeding episodes are treated acutely with blood product transfusions or frequent, repeated intravenous administration of recombinant activated coagulation factor VII (rFVIIa). Here we describe HMB-001, a bispecific antibody designed to bind and accumulate endogenous FVIIa and deliver it to sites of vascular injury by targeting it to the TREM (triggering receptor expressed on myeloid cells)-like transcript-1 (TLT-1) receptor that is selectively expressed on activated platelets. In healthy nonhuman primates, HMB-001 prolonged the half-life of endogenous FVIIa, resulting in its accumulation. Mouse bleeding studies confirmed antibody-mediated potentiation of FVIIa hemostatic activity by TLT-1 targeting. In ex vivo models of GT, HMB-001 localized FVIIa on activated platelets and potentiated fibrin-dependent platelet aggregation. Taken together, these results indicate that HMB-001 has the potential to offer subcutaneous prophylactic treatment to prevent bleeds in people with GT and other inherited bleeding disorders, with a low-frequency dosing regimen.

Asunto(s)

Anticuerpos Biespecíficos , Animales , Anticuerpos Biespecíficos/farmacología , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/inmunología , Humanos , Factor VIIa , Plaquetas/metabolismo , Plaquetas/efectos de los fármacos , Plaquetas/inmunología , Ratones , Modelos Animales de Enfermedad , Hemorragia/prevención & control , Hemorragia/tratamiento farmacológico , Agregación Plaquetaria/efectos de los fármacos , Trombastenia/tratamiento farmacológico , Trombastenia/inmunología , Ratones Endogámicos C57BL , Femenino , Masculino , Macaca fascicularis , Activación Plaquetaria/efectos de los fármacos

RESUMEN

BACKGROUND: There has been growing interest in exploring combined interventions to achieve a more effective heparin-free treatment approach. AIM: to evaluate combination of interventions compared to standard practice (intermittent flushes) to prevent clotting and consequently reduce premature interruptions of hemodialysis. METHODS: This open-label randomized controlled trial recruited chronic hemodialysis patients with contra-indication to systemic heparinization. Participants were randomized into one of five groups to receive different strategies of heparin-free hemodialysis treatment for up to three sessions. PRIMARY ENDPOINT: the successful completion of hemodialysis without clotting. SECONDARY OUTCOMES: the clotting of the air traps assessed by a semi-quantitative scale, online KT/V, and safety of the interventions. RESULTS: Forty participants were recruited and randomized between May and December 2020. Participants showed similar baseline biochemistry results and coagulation profiles. The highest success rates were observed in group 3 (heparin-coated dialyzers combined with intermittent flushes) (100%) and group 5 (hemodiafiltration with online predilution combined with heparin-coated dialyzers), with 91% vs. the control (intermittent flushes) (64%). Group 2 (heparin-coated dialyzers alone) had the poorest success rate, with 38% of the sessions being prematurely terminated due to clotting. KT/V and clotting scores were similar between groups. No adverse events related to the trial interventions were observed. CONCLUSIONS: The proposed combination of interventions may have had additive effects, leading to less frequent clotting and the premature termination of an HD/HDF session. Our study supports the feasibility of conducting a larger randomized controlled trial focusing on the efficacy of combined interventions for heparin-free HD in patients with a high risk of bleeding.

Asunto(s)

Anticoagulantes , Hemorragia , Heparina , Diálisis Renal , Humanos , Femenino , Masculino , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Hemorragia/prevención & control , Persona de Mediana Edad , Anciano , Heparina/administración & dosificación , Heparina/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos

RESUMEN

ABSTRACT: Neuraxial blockade procedures are essential for anesthesia and pain management but pose risks in patients with uncertain coagulation profiles. Traditional coagulation tests often fail to predict bleeding risks associated with neuraxial blockade. Thromboelastography (TEG) offers real-time insights into coagulation status, potentially improving safety outcomes. In this case series, six patients underwent neuraxial blockade guided by TEG analysis. An individualized anesthetic plan was formulated based on TEG findings to mitigate bleeding risks while ensuring pain management. Tailoring anesthetic techniques to real-time TEG data improved safety outcomes with minimized bleeding complications and satisfactory pain control. In conclusion, neuraxial blockade guided by TEG enhances safety in patients with uncertain coagulation profiles. Further studies are needed to validate benefits in broader clinical settings.

Asunto(s)

Tromboelastografía , Humanos , Tromboelastografía/métodos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Coagulación Sanguínea/efectos de los fármacos , Bloqueo Nervioso/métodos , Bloqueo Nervioso/efectos adversos , Anciano , Anestesia Epidural/efectos adversos , Anestesia Epidural/métodos , Manejo del Dolor/métodos , Hemorragia/prevención & control

RESUMEN

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers. However, the influence of patient-specific demographic, clinical, and other genetic factors on outcomes with genotype-guided DAPT has not been defined. In addition, the impact of genotype-guided de-escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no-function allele has not been investigated in a diverse, real-world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19-guided DAPT, evaluate the safety and effectiveness of CYP2C19-guided DAPT de-escalation following PCI in a real-world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real-world population.

Asunto(s)

Clopidogrel , Citocromo P-450 CYP2C19 , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Clorhidrato de Prasugrel , Medicina de Precisión , Sistema de Registros , Ticagrelor , Humanos , Intervención Coronaria Percutánea/efectos adversos , Citocromo P-450 CYP2C19/genética , Medicina de Precisión/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Ticagrelor/administración & dosificación , Ticagrelor/uso terapéutico , Clorhidrato de Prasugrel/administración & dosificación , Clorhidrato de Prasugrel/uso terapéutico , Clorhidrato de Prasugrel/efectos adversos , Terapia Antiplaquetaria Doble/métodos , Aspirina/administración & dosificación , Aspirina/efectos adversos , Aspirina/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/prevención & control

RESUMEN

Transfemoral access is nowadays required for an increasing number of percutaneous procedures, such as structural heart interventions, mechanical circulatory support, and interventional electrophysiology/pacing. Despite technological advancements and improved techniques, these devices necessitate large-bore (≥12 French) arterial/venous sheaths, posing a significant risk of bleeding and vascular complications, whose occurrence has been related to an increase in morbidity and mortality. Therefore, optimizing large-bore vascular access management is crucial in endovascular interventions. Technical options, including optimized preprocedural planning and proper selection and utilization of vascular closure devices, have been developed to increase safety. This review explores the comprehensive management of large-bore accesses, from optimal vascular puncture to sheath removal. It also discusses strategies for managing closure device failure, with the goal of minimizing vascular complications.

Asunto(s)

Cateterismo Periférico , Remoción de Dispositivos , Arteria Femoral , Técnicas Hemostáticas , Punciones , Dispositivos de Cierre Vascular , Humanos , Cateterismo Periférico/efectos adversos , Cateterismo Periférico/instrumentación , Técnicas Hemostáticas/instrumentación , Técnicas Hemostáticas/efectos adversos , Remoción de Dispositivos/efectos adversos , Factores de Riesgo , Resultado del Tratamiento , Hemorragia/prevención & control , Hemorragia/etiología , Lesiones del Sistema Vascular/etiología , Lesiones del Sistema Vascular/prevención & control , Dispositivos de Acceso Vascular , Diseño de Equipo , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación

RESUMEN

The role of aspirin in cardiovascular primary prevention remains controversial. There are physiological reasons to explore its potential benefits in patients with high levels of lipoprotein(a) [Lp(a)], mainly due to its antifibrinolytic properties and interactions with platelets. The primary objective of this systematic review was to evaluate the cardiovascular benefits and bleeding risks associated with aspirin use in patients who have elevated Lp(a) levels but no history of cardiovascular disease. This systematic review was conducted following PRISMA guidelines. We performed a literature search to identify studies assessing the cardiovascular benefits and bleeding risks of aspirin use in patients with elevated Lp(a) levels (or a related genetic variant) who have no history of cardiovascular disease. Five studies (49,871 individuals) were considered for this systematic review. Three studies assessed the impact of aspirin use in relation to genetic variants associated with elevated Lp(a) levels (SNP rs379822), while the remaining two studies directly measured plasma levels of Lp(a). The endpoints evaluated varied among the studies. Overall, the findings consistently show that carriers of the apolipoprotein(a) variant or patients with Lp(a) levels > 50 mg/dL experience a reduction in cardiovascular risk with aspirin use. No significant bleeding issues were observed, although such events were reported in only two studies. This systematic review suggests that aspirin use in patients with elevated Lp(a) levels and no prior cardiovascular history may reduce cardiovascular risk. The available data on bleeding risk is insufficient.

Asunto(s)

Aspirina , Enfermedades Cardiovasculares , Hemorragia , Lipoproteína(a) , Inhibidores de Agregación Plaquetaria , Humanos , Aspirina/uso terapéutico , Aspirina/efectos adversos , Lipoproteína(a)/sangre , Enfermedades Cardiovasculares/prevención & control , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Prevención Primaria/métodos , Medición de Riesgo/métodos

Asunto(s)

Anticoagulantes , Humanos , Administración Oral , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificación , Hemorragia/inducido químicamente , Hemorragia/prevención & control

RESUMEN

OBJECTIVE: Increasingly, medical schools integrate clinical skills into early didactic coursework. The Stop the Bleed® Campaign emphasizes prehospital hemorrhage control to reduce preventable deaths; however, this course overlooks team interactions. We assessed the impact of high-fidelity simulation during medical student orientation on identification and treatment of life-threatening hemorrhage in a team setting. DESIGN: In this mixed method, prospective pre-, post-, and follow-up survey analysis assessing student knowledge and attitudes, student teams encountered a standardized patient in a prehospital environment with pulsatile bleeding from an extremity wound. Individual students completed surveys assessing previous experience, willingness and ability to assist bleeding person(s), and knowledge and attitudes about tourniquets. Postscenario, faculty preceptors made qualitative observations on teamwork. SETTING: Medical student orientation at a tertiary care academic medical center with long-term follow-up. PARTICIPANTS: Medical students (N = 150). RESULTS: Ninety students (60%) completed both pre- and postsimulation questionnaires. Sixteen (17%) students had previous tourniquet training experience although none had applied a tourniquet outside of training. Postsimulation, students reported increased likelihood of providing treatment until additional help arrived (p = 0.035), improved ability to identify life-threatening hemorrhage (p < 0.001), and more favorable opinions about tourniquet use (p < 0.001) and potential for limb-salvage (p = 0.018). Long-term follow-up respondents (n = 34, 23%) reported increased ability to identify life-threatening hemorrhage (p = 0.010) and universal willingness to intervene until additional help arrived. Follow-up survey responses elicited themes in hemorrhage control including recognition of the importance of continuous pressure, appropriate use of tourniquets, a desire for repeated team training, and the recognition of clerkship rotations as an optimal setting for skill reinforcement. Preceptors noted variable team responses but uniformly endorsed the exercise. CONCLUSIONS: High-fidelity bleeding simulation during medical student orientation improved students' knowledge and attitudes about treating life-threatening hemorrhage and served as an introduction to team-based emergency care. Future studies should further explore team training and hemorrhage control education.

Asunto(s)

Competencia Clínica , Educación de Pregrado en Medicina , Hemorragia , Humanos , Hemorragia/terapia , Hemorragia/prevención & control , Estudios Prospectivos , Educación de Pregrado en Medicina/métodos , Femenino , Masculino , Estudios de Seguimiento , Autoinforme , Torniquetes , Enseñanza Mediante Simulación de Alta Fidelidad/métodos , Estudiantes de Medicina

RESUMEN

The development of efficient hemostatic materials is crucial for achieving rapid hemorrhage control and effective wound healing. Inorganic polyphosphate (polyP) is recognized as an effective modulator of the blood coagulation process. However, the specific effect of polyP chain length on coagulation is not yet fully understood. Furthermore, calcium ions (Ca2+) are essential for the coagulation process, promoting multiple enzyme-catalyzed reactions within the coagulation cascade. Hence, calcium ion-coupled polyphosphate powders with three different degrees of polymerization (CaPP-n, n = 20, 50, and 1500) are synthesized by an ion-exchange reaction. CaPP exhibits a crystalline phase at a low polymerization degree and transitions to an amorphous phase as the polymerization degree increases. Notably, the addition of Ca2+ enhances the wettability of polyP, and CaPP promotes hemostasis, with varying degrees of effectiveness related to chain length. CaPP-50 exhibits the most promising hemostatic performance, with the lowest blood clotting index (BCI, 12.1 ± 0.7%) and the shortest clotting time (302.0 ± 10.5 s). By combining Ca2+ with polyP of medium-chain length, CaPP-50 demonstrates an enhanced ability to accelerate the adhesion and activation of blood cells, initiate the intrinsic coagulation cascade, and form a stable blood clot, outperforming both CaPP-20 and CaPP-1500. The hemostatic efficacy of CaPP-50 is further validated using rat liver bleeding and femoral artery puncture models. CaPP-50 is proven to possess hemostatic properties comparable to those of commercial calcium-based zeolite hemostatic powder and superior to kaolin. In addition, CaPP-50 exhibits excellent biocompatibility and long-term storage stability. These results suggest that CaPP-50 has significant clinical and commercial potential as an active inorganic hemostatic agent for rapid control of bleeding.

Asunto(s)

Calcio , Hemorragia , Polimerizacion , Polifosfatos , Animales , Polifosfatos/química , Polifosfatos/farmacología , Calcio/química , Ratas , Hemorragia/prevención & control , Hemorragia/tratamiento farmacológico , Hemostáticos/química , Hemostáticos/farmacología , Coagulación Sanguínea/efectos de los fármacos , Ratas Sprague-Dawley , Masculino , Hemostasis/efectos de los fármacos , Iones/química

RESUMEN

INTRODUCTION: Retrograde Endovascular Balloon Occlusion of the Aorta (REBOA) is an effective management for the transient responder, but the ischemic consequences of complete aortic occlusion currently limit its use. Multiple DoD-funded preclinical studies have clearly demonstrated that partial REBOA reduces distal ischemia to potentially extend safe occlusion times, while still providing effective temporization of noncompressible torso hemorrhage. Early versions of REBOA devices were designed to completely occlude the aorta and had little ability to provide partial occlusion. Recently, a new REBOA device (pREBOA-PRO) was designed specifically to allow for partial occlusion, with the hypothesis that this may reduce the complications of aortic occlusion and extend safe occlusion times while maintaining the benefits on cardiac and cerebrovascular circulation as well as reductions in resuscitation requirements. MATERIALS AND METHODS: To ascertain the impact of a new purpose-built partial REBOA device on the extension of safe occlusion time, the Partial REBOA Outcomes Multicenter ProspecTive (PROMPT) trial compared available data from the pREBOA-PRO with existing data from 200 clinical uses of pREBOA-PRO and available data in the AAST AORTA Registry were reviewed to design primary endpoints and clinical evidence for a prospective multi-center trial, the PROMPT Study. Together with the endpoints identified in preclinical studies of partial REBOA, primary endpoints for the PROMPT study were identified and power analyses were conducted to determine the target patient enrollment goals. RESULTS: Results from the clinical implementation of partial REBOA at a single trauma center were used to conduct the initial power analysis for the primary endpoint of Acute Kidney Injury (AKI) after prolonged occlusion. The rate of AKI after complete REBOA was 55% (12/20) compared to 33% (4/12) after partial REBOA (Madurska et al., 2021). With an alpha of 0.05 and power (ß) of 0.8, the projected sample size for comparison on a dichotomous outcome is 85 patients for the assessment of AKI. Initial power and endpoint analyses have been confirmed and extended with the ongoing analysis of partial and complete REBOA reported in the AORTA database. These analyses confirm preclinical findings which show that compared to complete REBOA, partial REBOA is associated with extended occlusion time in zone 1 (complete: 31 min vs. partial: 45 min, P = 0.003), lower rates of AKI after zone 1 occlusion (complete: 33% vs. partial: 19%, P = 0.05) and reduced resuscitation requirements (e.g., 25% reduction in pRBC administration: complete: 18 units vs. partial: 13 units, P = 0.02). CONCLUSIONS: The DoD-funded PROMPT study of partial REBOA will provide prospective observational clinical data on patients being treated with pREBOA-PRO. Outcomes will be stratified based on partial or complete occlusion to address whether partial REBOA has additional clinical benefits over complete REBOA, such as decreased distal ischemia, extension of safe occlusion time, improved hemodynamics during transition to and from occlusion, and reduced interoperative bleeding and blood product use. The results from this study are expected to confirm previous data demonstrating reduction of ischemic sequalae, improved transition to reperfusion, and reduced resuscitative requirements compared to complete REBOA.

Asunto(s)

Aorta , Oclusión con Balón , Humanos , Oclusión con Balón/métodos , Oclusión con Balón/normas , Oclusión con Balón/instrumentación , Oclusión con Balón/estadística & datos numéricos , Estudios Prospectivos , Masculino , Femenino , Adulto , Procedimientos Endovasculares/métodos , Procedimientos Endovasculares/instrumentación , Persona de Mediana Edad , Resucitación/métodos , Resucitación/instrumentación , Resucitación/normas , Resucitación/estadística & datos numéricos , Hemorragia/terapia , Hemorragia/prevención & control , Resultado del Tratamiento

RESUMEN

Apocynin (APO) is a naturally occurring acetophenone with eminent anti-inflammatory and anti-oxidant peculiarities. It suffers from poor bioavailability due to low aqueous solubility. Herein, APO was loaded in a Clove oil (CO) based Nanostructured lipid carrier (NSLC) system using a simple method (ultrasonic emulsification) guided by a quality-by-design approach (23 full factorial design) to optimize the formulated NSLCs. The prepared NSLCs were evaluated regarding particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). The optimal formula (F2) was extensively investigated through transmission electron microscope (TEM), Fourier transform infrared (FT-IR) spectroscopy, Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), in vitro release, and stability studies. Cytotoxicity against human urinary bladder carcinoma (T24) cell line and in vivo activity studies in rats with induced cystitis were also assessed. The results disclosed that the optimal formula (F2) had PS of 214.8 ± 5.8 nm with EE% of 79.3 ± 0.9%. F2 also exhibited a strong cytotoxic effect toward the T24 cancer cells expressed by IC50 value of 5.8 ± 1.3 µg/mL. Pretreatment with the optimal formula (orally) hinted uroprotective effect against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rat models, emphasized by histopathological, immunohistochemical, and biochemical investigations. In consideration of the simple fabrication process, APO-loaded CO-based NSLCs can hold prospective potential in the prophylaxis of oncologic and urologic diseases.

Asunto(s)

Acetofenonas , Aceite de Clavo , Portadores de Fármacos , Animales , Ratas , Humanos , Aceite de Clavo/química , Aceite de Clavo/farmacología , Portadores de Fármacos/química , Acetofenonas/química , Acetofenonas/farmacología , Acetofenonas/administración & dosificación , Línea Celular Tumoral , Tamaño de la Partícula , Lípidos/química , Nanoestructuras/química , Hemorragia/prevención & control , Masculino , Ratas Wistar , Cistitis Hemorrágica

Asunto(s)

Fibrilación Atrial , Diltiazem , Hemorragia , Metoprolol , Pirazoles , Piridonas , Rivaroxabán , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Piridonas/efectos adversos , Piridonas/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Diltiazem/efectos adversos , Diltiazem/uso terapéutico , Metoprolol/efectos adversos , Metoprolol/uso terapéutico , Femenino , Masculino , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Anciano , Persona de Mediana Edad

RESUMEN

Anticoagulation is common in patients undergoing routine musculoskeletal interventional maneuvers. Previous retrospective studies have established the safety of continuing anticoagulation with novel oral anticoagulants (NOACs) when performing this kind of interventions. Indeed, ultrasound (US)-guided interventional maneuvers have shown a superior safety profile compared to blind anatomical maneuvers. To evaluate prospectively the periprocedural bleeding events in NOAC-anticoagulated patients undergoing interventional articular or periarticular procedures. Consecutive patients diagnosed with inflammatory or degenerative rheumatologic pathology requiring interventional maneuvers were prospectively recruited. Group 1 was treated with NOACs, group 2 was treated with vitamin K antagonists, and group 3 was not anticoagulated. Prior to the international maneuver, NOAC therapy was continuously administered, in regimens dictated by the underlying anticoagulation indication. Demographics, comorbidities, laboratory parameters, locally administered medication (corticosteroids or viscosupplementation), interventional maneuver location, needle size, and local bleeding events were recorded. Post-procedural control was performed at 30 min, 48 h, and 7 days. No articular/periarticular bleeding event occurred in patients treated with NOACs, regardless of their type and dosage, locally administered medication, needle size, location, and number of interventions per individual. Several patients in all groups developed small superficial ecchymoses at the injection site. Our results suggest that NOACs are safe to be used in a continuous regimen prior to US-guided injections, even as dual antithrombotic therapy (in combination with aspirin). The use of lower gauge needles, chosen for viscosupplementation therapy, was not burdened with adverse effects on the procedural outcome. Key Points • Currently, no prospective studies have been performed to establish the safety of continuous NOAC anticoagulation when performing routine intra- or periarticular interventional maneuvers. • The study offers an extensive view on a wide spectrum of intra- and periarticular interventional maneuvers including anatomic targets and needle sizes that were not previously assessed. • The study offers a perspective into performing repetitive maneuvers in the same patient, both over a short time and at longer intervals. • The zero periprocedural bleeding risk observed in our study may reassure practitioners and suggest that US-guided interventional therapeutic interventions are safe in patients treated with a continuous regimen of different NOACs.

Asunto(s)

Anticoagulantes , Hemorragia , Humanos , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Masculino , Femenino , Estudios Prospectivos , Anciano , Persona de Mediana Edad , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Administración Oral , Anciano de 80 o más Años , Vitamina K/antagonistas & inhibidores , Ultrasonografía Intervencional

Asunto(s)

Síndrome Coronario Agudo , Aspirina , Terapia Antiplaquetaria Doble , Hemorragia , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Stents , Ticagrelor , Humanos , Ticagrelor/uso terapéutico , Ticagrelor/efectos adversos , Síndrome Coronario Agudo/terapia , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Aspirina/uso terapéutico , Aspirina/efectos adversos , Aspirina/administración & dosificación , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Terapia Antiplaquetaria Doble/métodos , Terapia Antiplaquetaria Doble/efectos adversos , Stents/efectos adversos , Resultado del Tratamiento , Quimioterapia Combinada , Factores de Tiempo

RESUMEN

Acute hemorrhage is a major cause of death in many emergency cases. Although many hemostatic materials have been studied in recent years, it is still necessary to develop new hemostatic materials with remarkable efficiency, biosafety, convenient preparation, low cost, and good biodegradability. In this work, novel chitosan (CS)/ß-glycerophosphate (ß-GP) composite porous microsphere with a uniform size of 210.00 ± 2.14 µm was fabricated through water-in-water (W/W) emulsion via microencapsulation, which can avoid the use of toxic crosslink chemicals and organic solvents to achieve facile and efficient preparation of microspheres. ß-GP could promote the formation of microspheres by enhancing the hydrogen-bonding interaction between CS chains, which contributed to the macro-porous structure. Owing to their large pore size (6.0 µm) and high specific surface area (37.8 m2/g), the CS/ß-GP microspheres could absorb water quickly and adsorb protein, red blood cells, and platelets through electrostatic forces to promote blood coagulation. Furthermore, the CS/ß-GP microspheres achieved a significantly shortened hemostatic time (45 s) and reduced blood loss (0.03 g) in a rat liver injury model. Rat tail amputation test also showed a satisfactory hemostatic effect. Overall, the green and porous CS/ß-GP microspheres can be used as a facile and topical rapid hemostatic material.

Asunto(s)

Quitosano , Emulsiones , Glicerofosfatos , Hemostáticos , Microesferas , Agua , Quitosano/química , Hemostáticos/química , Hemostáticos/farmacología , Animales , Porosidad , Emulsiones/química , Ratas , Agua/química , Glicerofosfatos/química , Hemorragia/tratamiento farmacológico , Hemorragia/prevención & control , Masculino , Ratas Sprague-Dawley