Revisión sistemática de los ensayos clínicos sobre terapia antitrombótica con inhibidores del factor XI / Systematic review of clinical trials on the antithrombotic therapy with factor XI inhibitors

Antecedentes y objetivo La información proveniente de los ensayos clínicos fase 2 sugiere que los inhibidores del factor XI podrían mostrar un perfil de eficacia/seguridad más favorable que las terapias antitrombóticas actuales. El objetivo de esta revisión sistemática es analizar la evidencia disponible derivada de esos estudios. Métodos Se realizó una búsqueda bibliográfica en las bases de datos PubMed, Cochrane Library, Scopus y EMBASE, y en las plataformas de registro de ensayos clínicos Clinical Trials y Cochrane Central Register of Controlled Trials. Los resultados se publicaron según la declaración PRISMA. Resultados Se identificaron un total de 18 ensayos clínicos concluidos o en curso abordando múltiples escenarios, incluyendo fibrilación auricular, ictus, infarto de miocardio y tromboembolismo venoso. Se analizó la evidencia procedente de 8 estudios con resultados disponibles. En general, los estudios fase 2 con inhibidores del factor XI mostraron un perfil adecuado de eficacia y seguridad. El balance beneficio/riesgo fue más favorable en términos de reducción de tromboembolismo venoso en pacientes sometidos a artroplastia total de rodilla. Para esta indicación, los inhibidores del factor XI mostraron una reducción global del 50% en la tasa de complicaciones trombóticas y del 60% en la tasa de hemorragias comparado con enoxaparina. En los estudios de pacientes con fibrilación auricular, ictus e infarto de miocardio se observaron resultados más modestos. Conclusión Los inhibidores del Factor XI abren nuevas perspectivas en el tratamiento y la profilaxis antitrombótica. Los estudios fase 3 en curso permitirán definir los fármacos e indicaciones más idóneas. (AU)

Background and objective Data from phase 2 clinical trials suggest that factor XI inhibitors may exhibit a more favourable efficacy/safety profile than current antithrombotic therapies. This systematic review aims to analyze the available evidence derived from these studies. Methods A literature search in the PubMed, Cochrane Library, Scopus, EMBASE databases, and clinical trial registration platforms Clinical Trials and Cochrane Central Register of Controlled was conducted. The results were reported in accordance with the PRISMA statement. Results A total of 18 completed or ongoing clinical trials addressing multiple scenarios, including atrial fibrillation, stroke, myocardial infarction, and venous thromboembolism, were identified. Evidence from 8 studies with available results was analyzed. Overall, phase 2 studies with factor XI inhibitors demonstrated an acceptable efficacy and safety profile. The benefit-risk balance, in terms of reducing venous thromboembolism in patients undergoing total knee arthroplasty, was more favourable. For this scenario, factor XI inhibitors showed a 50% reduction in the overall rate of thrombotic complications and a 60% reduction in bleeding compared to enoxaparin. Modest results in studies involving patients with atrial fibrillation, stroke, and myocardial infarction were observed. Conclusions Factor XI inhibitors offer new prospects in antithrombotic treatment and prevention. Ongoing phase 3 studies will help define the most suitable drugs and indications. (AU)

Systematic review of clinical trials on antithrombotic therapy with factor XI inhibitors.

INTRODUCTION AND OBJECTIVE: Data from phase 2 clinical trials suggest that factor XI inhibitors may exhibit a more favorable efficacy/safety profile compared to current antithrombotic therapies. The aim of this systematic review is to analyze the available evidence derived from these studies. METHODS: A literature search in the PubMed, Cochrane Library, Scopus, EMBASE databases, and clinical trial registration platforms Clinical Trials and Cochrane Central Register of Controlled was conducted. In accordance with the PRISMA statement, results were reported. RESULTS: A total of 18 completed or ongoing clinical trials addressing multiple scenarios, including atrial fibrillation, stroke, myocardial infarction, and venous thromboembolism, were identified. Evidence from 8 studies with available results was analyzed. Phase 2 studies with factor XI inhibitors, overall, demonstrated an acceptable efficacy and safety profile. The benefit-risk balance, in terms of reducing venous thromboembolism in patients undergoing total knee arthroplasty, was more favorable. For this scenario, factor XI inhibitors showed a 50% reduction in the overall rate of thrombotic complications and a 60% reduction in the rate of bleeding compared to enoxaparin. Modest results in studies involving patients with atrial fibrillation, stroke, and myocardial infarction were observed. CONCLUSIONS: Factor XI inhibitors offer new prospects in antithrombotic treatment and prophylaxis. Ongoing phase 3 studies will help define the most suitable drugs and indications.

Recurrence risk of idiopathic venous thromboembolism. / Riesgo de recurrencia en el tromboembolismo venoso idiopático.

For patients with idiopathic venous thromboembolism (unprovoked), the risk of recurrence is high. Secondary prophylaxis with anticoagulant therapy reduces the thrombotic risk but at the expense of an increased risk of haemorrhage. A number of factors, such as the male sex and an increase in dimer-D concentrations after completing the anticoagulation therapy, are associated with an increased risk of recurrence. Other factors such as residual venous thrombosis have a more controversial and sometimes contradictory relationship. A number of models have been proposed for predicting thrombotic recurrence risk after anticoagulation therapy in unprovoked TVD. However, these models need external validation to determine their current usefulness in clinical practice. In this article, we analyse the risk factors for thrombotic recurrence and the existing prediction models.

A risk score for prediction of recurrence in patients with unprovoked venous thromboembolism (DAMOVES).

BACKGROUND: In patients with unprovoked venous thromboembolism (VTE), the optimal duration of anticoagulation is anchored on estimating the risk of disease recurrence. We aimed to develop a simple risk assessment model that improves prediction of the recurrence risk. METHODS: In a prospective cohort study, 398 patients with a first unprovoked VTE were followed up for a median of 21.3months after discontinuation of anticoagulation. We excluded patients with a strong thrombophilic defect. Preselected clinical and laboratory variables were analyzed based on the independent confirmation of the impact on the recurrence risk, simplicity of assessment, and reproducibility. Multivariable Cox regression analysis was used to develop a recurrence score that was subsequently internally validated by bootstrap analysis. RESULTS: A total of 65 patients (16.3%) had recurrent VTE. In all patients, VTE recurred spontaneously. Male sex (HR=2.89 [95% CI 1.21-6.90] P=0.016), age (HR=1.0310 per additional decade [95% CI 1.01-1.07] P=0.011), obesity (HR=3.92 [95% CI 1.75-8.75] P=0.0001), varicose veins (HR=4.14 [95% CI 1.81-9.43] P=0.0001), abnormal D-dimer during anticoagulation (HR=13.66 [95% CI 4.74-39.37] P=0.0001), high factor VIII coagulant activity (HR=1.01 [95% CI 1.00-1.02] P=0.028) and heterozygous of factor V Leiden and/or Prothrombin G20210A mutation (HR=13.86 [95% CI 5.87-32.75] P=0.0001) were related to a higher recurrence risk. Using these variables, we developed a nomogram [hereafter referred to as DAMOVES score (D-dimer, Age, Mutation, Obesity, Varicose veins, Eight, Sex)] for prediction of recurrence in an individual patient. CONCLUSIONS: The DAMOVES score can be used to predict recurrence risk in patients with a first unprovoked VTE and may be useful to decide whether anticoagulant therapy should be continued indefinitely or stopped after an initial treatment period of at least 3months.

Anemia perniciosa. Del pasado al presente / Pernicious anemia. From past to present

Actualmente, la anemia perniciosa es la causa más frecuente de déficit de vitamina B12 en los países occidentales. La lesión histológica sobre la que se sustenta es la gastritis crónica atrófica autoinmune. La destrucción de las células parietales provoca un déficit de factor intrínseco, proteína fundamental para que la vitamina B12 se absorba en el íleon terminal. Los avances que se han producido en las dos últimas décadas han reabierto el debate sobre una enfermedad que parecía olvidada por su aparente simplicidad. El nuevo papel del H. pylori, el valor de los anticuerpos anticélula parietal y antifactor intrínseco, la verdadera utilidad de los niveles séricos de vitamina B12, el riesgo de adenocarcinoma y carcinoides gástricos o el tratamiento con vitamina B12 oral, son algunos de los temas de actualidad que se analizan en profundidad en esta revisión (AU)

Pernicious anemia is currently the most common cause of vitamin B12 deficiency in Western countries. The histological lesion upon which this condition is based is autoimmune chronic atrophic gastritis. The destruction of parietal cells causes a deficiency in intrinsic factor, an essential protein for vitamin B12 absorption in the terminal ileum. Advances in the last two decades have reopened the debate on a disease that seemed to have been forgotten due to its apparent simplicity. The new role of H. pylori, the value of parietal cell antibodies and intrinsic factor antibodies, the true usefulness of serum vitamin B12 levels, the risk of adenocarcinoma and gastric carcinoids and oral vitamin B12 treatment are just some of the current issues analyzed in depth in this review (AU)

Pernicious anemia. From past to present. / Anemia perniciosa. Del pasado al presente.

Pernicious anemia is currently the most common cause of vitamin B12 deficiency in Western countries. The histological lesion upon which this condition is based is autoimmune chronic atrophic gastritis. The destruction of parietal cells causes a deficiency in intrinsic factor, an essential protein for vitamin B12 absorption in the terminal ileum. Advances in the last two decades have reopened the debate on a disease that seemed to have been forgotten due to its apparent simplicity. The new role of H. pylori, the value of parietal cell antibodies and intrinsic factor antibodies, the true usefulness of serum vitamin B12 levels, the risk of adenocarcinoma and gastric carcinoids and oral vitamin B12 treatment are just some of the current issues analyzed in depth in this review.

Clinical trial: a randomized controlled study on prevention of variceal rebleeding comparing nadolol + ligation vs. hepatic venous pressure gradient-guided pharmacological therapy.

BACKGROUND: Hepatic venous pressure gradient (HVPG) monitoring of therapy to prevent variceal rebleeding provides strong prognostic information. Treatment of nonresponders to beta-blockers +/- nitrates has not been clarified. AIM: To assess the value of HVPG-guided therapy using nadolol + prazosin in nonresponders to nadolol + isosorbide-5-mononitrate (ISMN) compared with a control group treated with nadolol + ligation. METHODS: Cirrhotic patients with variceal bleeding were randomized to HVPG-guided therapy (n = 30) or nadolol + ligation (n = 29). A Baseline haemodynamic study was performed and repeated within 1 month. In the guided-therapy group, nonresponders to nadolol + ISMN received nadolol and carefully titrated prazosin and had a third haemodynamic study. RESULTS: Nadolol + prazosin decreased HVPG in nonresponders to nadolol + ISMN (P < 0.001). Finally, 74% of patients were responders in the guided-therapy group vs. 32% in the nadolol + ligation group (P < 0.01). The probability of rebleeding was lower in responders than in nonresponders in the guided therapy group (P < 0.01), but not in the nadolol + ligation group (P = 0.41). In all, 57% of nonresponders rebled in the guided-therapy group and 20% in the nadolol + ligation group (P = 0.05). The incidence of complications was similar. CONCLUSIONS: In patients treated to prevent variceal rebleeding, the association of nadolol and prazosin effectively rescued nonresponders to nadolol and ISMN, improving the haemodynamic response observed in controls receiving nadolol and endoscopic variceal ligation. Our results also suggest that ligation may rescue nonresponders.

[Total enteral nutrition vs. total parenteral nutrition in patients with severe acute pancreatitis]. / Nutrición enteral total vs. nutrición parenteral total en pacientes con pancreatitis aguda grave.

OBJECTIVE: To compare the efficacy of early total enteral nutrition (TEN) vs. total parenteral nutrition (TPN) in patients with severe acute pancreatitis (SAP). METHODS: A total of 22 consecutive patients with SAP were randomized to receive TPN (group I) or TEN (group II). SAP was defined applying APACHE II score, C-reactive protein (CRP) measurements and/or Balthazar CT scan score. Acute inflammatory response (CRP, TNF-a, IL-6), visceral proteins (pre-albumin, albumin), complications (systemic inflammatory response syndrome, multiorgan failure, infections), surgical interventions, length of hospital stay and mortality were evaluated. RESULTS: No significant differences were found between the two groups in the APACHE II score, in CRP, TNF-a and IL-6 concentrations or in pre-albumin and albumin levels over the first 10 days. Seven patients in group I and 4 in group II suffered severe complications. Three patients in group I required surgical intervention. Length of hospital stay was alike in the two groups. Two patients from group I died in the course of the hospitalization. CONCLUSIONS: SAP patients with TEN feeding showed a tendency towards a better outcome than patients receiving TPN.

Nutrición enteral total vs. nutrición parenteral total en pacientes con pancreatitis aguda grave / Total enteral nutrition vs. total parenteral nutrition in patients with severe acute pancreatitis

Objetivo: comparar la eficacia de la instauración precoz de nutrición enteral total (NET) frente a nutrición parenteral total (NPT) en pacientes con pancreatitis aguda grave (PAG). Métodos: estudio prospectivo aleatorio. Se incluyeron consecutivamente 22 pacientes con PAG aplicando los criterios APACHE II, valores de PCR y graduación de Balthazar en la TC. El grupo I (n = 11) recibió NPT y el grupo II (n = 12) NET. Se valoró la respuesta inflamatoria (PCR, TNF-alfa, IL-6), las proteínas viscerales (pre-albúmina, albúmina), la tasa de complicaciones (síndrome de respuesta inflamatoria sistémica, fallo multiorgánico, infecciones), las intervenciones quirúrgicas, la estancia hospitalaria y la mortalidad. Resultados: no hubo diferencias significativas en los primeros 10 días entre los dos grupos en la evolución de los criterios APACHE II, en las concentraciones de PCR, TNF-alfa e IL-6 ni tampoco en los valores de pre-albúmina y albúmina. Siete pacientes del grupo I presentaron complicaciones graves frente a 4 del grupo II. Requirieron intervención quirúrgica 3 pacientes del grupo I. La estancia hospitalaria fue similar en los dos grupos. Dos pacientes del grupo I fallecieron. Conclusiones: se ha observado una tendencia a una mejor evolución de los pacientes con PAG que utilizaron NET frente a los que utilizaron NPT

Objective: to compare the efficacy of early total enteral nutrition (TEN) vs. total parenteral nutrition (TPN) in patients with severe acute pancreatitis (SAP). Methods: a total of 22 consecutive patients with SAP were randomized to receive TPN (group I) or TEN (group II). SAP was defined applying APACHE II score, C-reactive protein (CRP) measurements and/or Balthazar CT scan score. Acute inflammatory response (CRP, TNF-alpha, IL-6), visceral proteins (pre-albumin, albumin), complications (systemic inflammatory response syndrome, multiorgan failure, infections), surgical interventions, length of hospital stay and mortality were evaluated. Results: no significant differences were found between the two groups in the APACHE II score, in CRP, TNF-alpha and IL-6 concentrations or in pre-albumin and albumin levels over the first 10 days. Seven patients in group I and 4 in group II suffered severe complications. Three patients in group I required surgical intervention. Length of hospital stay was alike in the two groups. Two patients from group I died in the course of the hospitalization. Conclusions: SAP patients with TEN feeding showed a tendency towards a better outcome than patients receiving TPN

Tratamiento del episodio agudo de hemorragia digestiva varicosa / No disponible

No disponible

Hemodiálisis como tratamiento de elección de la acidosis láctica asociada a metformina / Hemodyalisis as therapy of choice in lactic acidosis associated with metformine

No disponible

Lesiones escleróticas diseminadas / Disseminated sclerotic lesions

No disponible

Endocarditis por Actinobacillus actinomycetemcomitans / Endocarditis causes by actinobacillus actinomycetemcomitans

Las endocarditis del grupo HACEK son poco prevalentes en la población general. Suelen originar endocarditis subagudas con aparición de vegetaciones grandes, embolismos periféricos, desarrollo de insuficiencia cardiaca, necesitando con frecuencia el recambio valvular. Describimos un caso de endocarditis por Actinobacillus actinomycetemcomitans (AA), sin las características típicas de este grupo de endocarditis y que evolucionó favorablemente con tratamiento médico (AU)