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INTRODUCTION: Nuwiq® (Human-cl rhFVIII) is a fourth generation recombinant FVIII, produced in a human cell line, without chemical modification or protein fusion. No inhibitors developed in studies with Nuwiq® in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq® in previously untreated patients (PUPs) with severe HA are being assessed in the ongoing NuProtect study. METHODS: The study, conducted across 38 centres worldwide, is evaluating 110 true PUPs of all ages and ethnicities enrolled for study up to 100 exposure days (EDs) or 5 years maximum. The primary objective is to assess the immunogenicity of Nuwiq® (inhibitor activity ≥0.6 BU) using the Nijmegen-modified Bethesda assay at a central laboratory. RESULTS: Data for 66 PUPs with ≥20 EDs from a preplanned interim analysis were analysed. High-titre (HT) inhibitors developed in 8 of 66 patients after a median of 11.5 EDs (range 6-24). Five patients developed low-titre inhibitors (4 transient). The cumulative incidence (95% confidence interval) was 12.8% (4.5%, 21.2%) for HT inhibitors and 20.8% (10.7%, 31.0%) for all inhibitors. During inhibitor-free periods, median annualized bleeding rates during prophylaxis were 0 for spontaneous bleeds and 2.40 for all bleeds. Efficacy was rated as "excellent" or "good" in treating 91.8% of bleeds. Efficacy of surgical prophylaxis was "excellent" or "good" for 8 (89%) procedures and "moderate" for 1 (11%). No tolerability concerns were evident. CONCLUSION: These interim data show a cumulative incidence of 12.8% for HT inhibitors and convincing efficacy and tolerability in PUPs treated with Nuwiq® .
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Hemofilia A/inmunología , Adolescente , Adulto , Animales , Niño , Preescolar , Perros , Humanos , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Children with acute lymphoblastic leukemia (ALL) have increased risk of thromboembolism (TE). However, the predictors of ALL-associated TE are as yet uncertain. OBJECTIVE: This exploratory, prospective cohort study evaluated the effects of clinical (age, gender, ALL risk group) and laboratory variables (hematological parameters, ABO blood group, inherited and acquired prothrombotic defects [PDs]) at diagnosis on the development of symptomatic TE (sTE) in children (aged 1 to ≤18) treated on the Dana-Farber Cancer Institute ALL 05-001 study. PROCEDURES: Samples collected prior to the start of ALL therapy were evaluated for genetic and acquired PDs (proteins C and S, antithrombin, procoagulant factors VIII (FVIII:C), IX, XI and von Willebrand factor antigen levels, gene polymorphisms of factor V G1691A, prothrombin gene G20210A and methylene tetrahydrofolate reductase C677T, anticardiolipin antibodies, fasting lipoprotein(a), and homocysteine). RESULTS: Of 131 enrolled patients (mean age [range] 6.4 [1-17] years) 70 were male patients and 20 patients (15%) developed sTE. Acquired or inherited PD had no impact on the risk of sTE. Multivariable analyses identified older age (odds ratio [OR] 1.13; 95% confidence interval [CI]: 1.01, 1.26) and non-O blood group (OR 3.64, 95% CI: 1.06, 12.51) as independent predictors for development of sTE. Patients with circulating blasts had higher odds of developing sTE (OR 6.66; 95% CI: 0.82, 53.85). CONCLUSION: Older age, non-O blood group, and presence of circulating blasts, but not PDs, predicted the risk of sTE during ALL therapy. We recommend evaluation of these novel risk factors in the development of ALL-associated TE. If confirmed, these easily accessible variables at diagnosis can help develop a risk-prediction model for ALL-associated TE.
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Biomarcadores/análisis , Terapia Combinada/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Trombosis/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Proyectos Piloto , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Trombosis/etiología , Trombosis/metabolismoRESUMEN
AIM: To assess whether a structured diabetes education programme, the Patient Empowerment Programme, was associated with a lower rate of all-cause hospitalization and emergency department visits in a population-based cohort of patients with Type 2 diabetes mellitus in primary care. METHODS: A cohort of 24 250 patients was evaluated using a linked administrative database during 2009-2013. We selected 12 125 patients with Type 2 diabetes who had at least one Patient Empowerment Programme session attendance. Patients who did not participate in the Patient Empowerment Programme were matched one-to-one with patients who did, using the propensity score method. Hospitalization events and emergency department visits were the events of interest. Cox proportional hazard and negative binomial regressions were performed to estimate the hazard ratios for the initial event, and incidence rate ratios for the number of events. RESULTS: During a median 30.5 months of follow-up, participants in the Patient Empowerment Programme had a lower incidence of an initial hospitalization event (22.1 vs 25.2%; hazard ratio 0.879; P < 0.001) and emergency department visit (40.5 vs 44%; hazard ratio 0.901; P < 0.001) than those who did not participate in the Patient Empowerment Programme. Participation in the Patient Empowerment Programme was associated with a significantly lower number of emergency department visits (incidence rate ratio 0.903; P < 0.001): 40.4 visits per 100 patients annually in those who did not participate in the Patient Empowerment Programme vs. 36.2 per 100 patients annually in those who did. There were significantly fewer hospitalization episodes (incidence rate ratio 0.854; P < 0.001): 20.0 hospitalizations per 100 patients annually in those who did not participate in the Patient Empowerment Programme vs. 16.9 hospitalizations per 100 patients annually in those who did. CONCLUSIONS: Among patients with Type 2 diabetes, the Patient Empowerment Programme was shown to be effective in delaying the initial hospitalization event and in reducing their frequency.
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Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Educación del Paciente como Asunto/organización & administración , Participación del Paciente , Atención Primaria de Salud/organización & administración , Adulto , Anciano , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos , Educación del Paciente como Asunto/normas , Participación del Paciente/métodos , Participación del Paciente/estadística & datos numéricos , Atención Primaria de Salud/métodosAsunto(s)
COVID-19 , Angiografía Coronaria/métodos , Oxigenación por Membrana Extracorpórea/métodos , Control de Infecciones , Intervención Coronaria Percutánea/métodos , Infarto del Miocardio con Elevación del ST , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/prevención & control , Cateterismo Cardíaco/métodos , Servicio de Cardiología en Hospital/organización & administración , Gestión del Cambio , Comorbilidad , Vías Clínicas/organización & administración , Vías Clínicas/tendencias , Femenino , Hong Kong/epidemiología , Humanos , Control de Infecciones/instrumentación , Control de Infecciones/métodos , Control de Infecciones/organización & administración , Masculino , Persona de Mediana Edad , SARS-CoV-2/aislamiento & purificación , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/epidemiología , Infarto del Miocardio con Elevación del ST/cirugíaRESUMEN
AIMS: To assess whether a structured diabetes education programme, the Patient Empowerment Programme (PEP), was associated with a lower risk of first cardiovascular disease (CVD) event and all-cause mortality in a population-based cohort of patients with type 2 diabetes mellitus (T2DM) in primary care. METHODS: A Chinese cohort of 27 278 patients with T2DM and without previous CVD events on or before the baseline study recruitment date was linked to the Hong Kong administrative database from 2008 to 2013. The PEP was provided to patients with T2DM treated at primary care outpatient clinics through community trained professional educators. PEP non-participants were matched one-to-one with the PEP participants using a propensity score method with respect to their baseline covariates. Cox proportional hazard regression was performed to estimate the associations of the PEP with the occurrence of first CVD event, coronary heart disease, stroke, heart failure and death from any cause, controlling for baseline characteristics. RESULTS: During a median of 21.5 months follow-up, 795 (352 PEP participants and 443 PEP non-participants) patients experienced a first CVD event. After adjusting for confounding variables, PEP participants had a lower rate of all-cause mortality [hazard ratio (HR) 0.564, 95% confidence interval (CI) 0.445-0.715; p < 0.001], first CVD (HR 0.807, 95% CI 0.696-0.935; p = 0.004) and stroke (HR 0.702; 95% CI 0.569-0.867; p = 0.001) than those without PEP. CONCLUSIONS: Enrolment in the PEP was associated with lower all-cause mortality and a lower number of first CVD events among patients with T2DM. The CVD benefit of PEP might be attributable to improving metabolic control through empowerment of self-care and the enhancement of quality of diabetes care in primary care.
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Pueblo Asiatico/estadística & datos numéricos , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/prevención & control , Participación del Paciente , Atención Primaria de Salud , Autocuidado , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Estudios de Seguimiento , Hong Kong/epidemiología , Humanos , Incidencia , Cooperación del Paciente , Educación del Paciente como Asunto , Evaluación de Programas y Proyectos de Salud , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
The Canadian Hemophilia Assessment and Resource Management System (CHARMS) tracks factor concentrates (FC) from the sole suppliers, Canadian Blood Services (CBS) and Hema-Quebec (HQ), to hospitals and to patients' homes. Patients FC infusion data are entered into CHARMS at Canadian Hemophilia Treatment Centres (HTCs) then exported to the national database (CentrePoint). From 2000 to 2009, 2260 registered haemophilia A or B patients received FVIII (1,009,097,765 IU) and FIX (272,406,859 IU). Over 91% of FVIII and over 84% of FIX was infused at home. Utilization of FVIII progressively increased; this was accounted for by an increase in the number of patients treated (r = 0.97; P < 0.001), there being a linear relationship between the increase in utilization and the increase in number of patients treated (P < 0.001). There was also a correlation with the annual amount used per patient (r = 0.95; P < 0.001). Utilization of FIX did not increase over time. The highest proportional utilization of both FVIII and FIX was for prophylaxis, and this proportion progressively increased being, in year 10 (2009), 77% and 66% for FVIII and FIX respectively. The proportion used for bleeding remained steady; in year 10 that proportion was 14% for FVIII and 26% for FIX, the use per patient for bleeding decreasing. The HTC-based CHARMS tracking system is essential, in Canada, for analysing indications for infusion, for predicting utilization and planning for future needs.
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Factores de Coagulación Sanguínea/uso terapéutico , Recursos en Salud/estadística & datos numéricos , Recursos en Salud/tendencias , Hemofilia A/tratamiento farmacológico , Factores de Coagulación Sanguínea/administración & dosificación , Canadá , Femenino , Humanos , MasculinoRESUMEN
Haemorrhagic manifestations in patients with haemophilia A and B are considered quite similar for comparable level of factor deficiency. We investigated the bleeding frequency and factor usage between HA and HB patients with comparable disease severities. We collected data on frequency of bleeds and factor concentrate utilization over 3 years, from January 2001 to December 2003. Information was gathered from home infusion logs recorded by patients or their parents, and treatment records from the Hemophilia Clinic or the Hospital Emergency Department. Data were available on 58 patients with severe HA (FVIII < 0.01 U mL(-1)), 10 with moderate HA (FVIII < 0.05 U mL(-1)), 15 with severe HB, and five with moderate HB who required treatment for episodic bleeds, postoperative haemostasis and for primary or secondary prophylaxis. The HA patients bled more frequently than HB patients (14.4 vs. 8.63 bleeds/patient/year), but used similar amounts of concentrate per year. HA patients underwent surgical procedures 3.2 times more frequently than HB patients to correct musculoskeletal complications. A total of 21,363,409 IU of recombinant FVIII was used by patients with HA (104,722 IU/patient/year) and 6,430, 960 IU of recombinant factor IX, by patients with HB (107,182 IU/patient/year). The difference in factor concentrate usage is not statistically significant (P > 0.05). The decrease in bleed frequency in haemophilia B indicates that the conclusions from randomized trials of prophylaxis in HA may not be accurately applied to HB.
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Coagulantes/administración & dosificación , Factor IX/administración & dosificación , Factor VIII/administración & dosificación , Hemofilia A/complicaciones , Hemofilia A/tratamiento farmacológico , Hemofilia B/complicaciones , Hemofilia B/tratamiento farmacológico , Hemorragia/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Humanos , Lactante , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , Estudios Retrospectivos , Adulto JovenRESUMEN
SUMMARY: Bleeding disorders may present during the neonatal period, however, absent patient history along with unique physical signs, physiologically decreased levels of plasma proteins and laboratory variations of platelet function tests may render any diagnosis difficult to establish. Intra cranial haemorrhage (ICH) may be the clinical presenting symptom of a severe coagulation factor deficiency. Haemophilia in the newborn period poses unique challenges in diagnosis and management, Data presented from the UDC and similar surveillance systems world-wide can be used to further clinical research and improve management strategies. Development haemostasis should be considered as well as laboratory variations of coagulation tests while evaluating and diagnosis neonates suspected of bleeding disorders. Therapy of bleeding episodes in the neonate relies upon proper replacement and repeated haemostatic evaluation of patients' status, while dealing with underlying etiological causes. This manuscript discusses the unique aspects of clinical presentation, laboratory assessment, and treatment of various bleeding disorders in neonates.
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Factores de Coagulación Sanguínea/análisis , Trastornos Hemorrágicos/complicaciones , Trastornos Hemorrágicos/diagnóstico , Hemorragias Intracraneales/etiología , Plaquetas/fisiología , Salud de la Familia , Hemofilia A/diagnóstico , Trastornos Hemorrágicos/metabolismo , Hemostasis , Humanos , Incidencia , Recién Nacido , Hemorragias Intracraneales/epidemiología , Diagnóstico PrenatalRESUMEN
Antithrombotic therapy has recently become more frequent for the treatment of venous thromboembolism (VTE) in the paediatric population. This can be explained by the increased awareness of morbidities and mortalities of VTE in children, as well as the improved survival rate of children with various kinds of serious illnesses. Considering the large number of years a child is expected to survive, associated morbidities such as postthrombotic syndrome and risk of recurrence can significantly impact on the quality of life in children. Therefore, timely diagnosis, evidence-based treatment and prophylaxis strategies are critical to avoid such complications. This review summarizes the current literature about the antithrombotic treatment for VTE in infants and children. It guides the paediatric medical care provider for making a logical and justifiable decision.
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Fibrinolíticos/uso terapéutico , Tromboembolia Venosa/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Procedimientos Quirúrgicos Cardíacos , Niño , Heparina/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Incidencia , Recién Nacido , Cuidados Paliativos , Trombosis/prevención & control , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/mortalidad , Tromboembolia Venosa/cirugíaRESUMEN
INTRODUCTION: The incidence of thromboembolic (TE)-pediatric pulmonary embolism (PPE) is increasing. We sought to evaluate current practice patterns and gaps in the management of TE-PPE. MATERIALS AND METHODS: After Institutional Review Board approval, SurveyMonkey® questions were sent to members of the Pediatric/Neonatal Thrombosis and Hemostasis Subcommittee, of the International Society on Thrombosis and Haemostasis and the Hemostasis and Thrombosis Research Society. RESULTS: Of 442 members of the two groups, 134 (30%) responded, and 125 (28%) complete responses were analyzed. Eighty percent practiced at a pediatric facility, 88% at academic centers, and 59% in the USA. Computed tomography pulmonary angiography (CTPA) was the preferred diagnostic modality (89%). D-dimer testing was variably used; 22% used clinical diagnostic prediction models and 8% had specific clinical care pathways for TE-PPE management. Prognostic stratification models were used to guide therapy by 4%. Indications for thrombolytic therapy varied considerably; 40% had a standardized protocol for thrombolysis, employing various modalities (45% systemic, 25% catheter-directed, 19% pharmaco-mechanical) and tissue plasminogen activator dose intensities. Duration of anticoagulation was variable with 58% prescribing anticoagulation for duration of >3â¯months-6â¯months; 61% followed for long-term adverse outcomes. CONCLUSION: This multinational survey of thrombosis/hemostasis specialists mainly based at pediatric academic centers demonstrates that antithrombotic management of TE-PPE (including duration of anticoagulation and use/non-use of thrombolysis) varies considerably. Furthermore, standardized care pathways to facilitate acute evaluation and management decisions are in place in a minority of centers. These findings help to inform the design of future clinical trials in TE-PPE.
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Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Tromboembolia/diagnóstico por imagen , Tromboembolia/diagnóstico , Humanos , Embolia Pulmonar/patología , Encuestas y CuestionariosRESUMEN
AIM: The current trend on diabetes management advocates replacing the paradigm from a uniform to an individualized patient-centered haemoglobin A1c (HbA1c) target, but there is no consensus on the optimal HbA1c level. The study aimed at examining the association between HbA1c and the risk of cardiovascular diseases (CVD) for diabetic patients with different characteristics, in order to identify patient-centered treatment targets. METHODS: A retrospective cohort study was conducted on 115,782 Chinese adult primary care patients with type 2 diabetes mellitus (DM) but no known CVD history, who were prescribed antidiabetic medications in 2010-2011. The cumulative mean HbA1c over a median follow-up period of 5.8 years was used to evaluate the relationship between HbA1c and CVD incidence using Cox analysis. Subgroup analyses were conducted by stratifying different baseline characteristics including gender, age, smoking status, diabetes duration, body mass index, Charlson's comorbidity index and DM treatment modalities. RESULTS: For patients with a DM duration of<2years, an exponential relationship between HbA1c and risk of CVD was identified, suggesting that there was no threshold HbA1c level for CVD risk. For other diabetic patients, an HbA1c level of 6.8-7.2% was associated with a minimum risk for CVD and a J-shaped curvilinear association between HbA1c. The risk of CVD increased in patients with HbA1c<6.5% or ≥7.5%. CONCLUSION: Among Chinese primary care patients at the early (<2years) disease stage, lower HbA1c targets (<6.5%) may be warranted to prevent CVD events whilst for all others, excessively lower HbA1c levels may not necessarily better and can potentially be harmful.
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Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/metabolismo , Anciano , Índice de Masa Corporal , Enfermedades Cardiovasculares/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Hong Kong/epidemiología , Humanos , Hipoglucemiantes/uso terapéutico , Incidencia , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been utilized as primary anticoagulants for thrombosis prophylaxis and treatment. However, a number of biophysical and safety limitations have led to development of new anticoagulants. Covalent antithrombin-heparin (ATH) complexes may address many of these issues. Early ATH products were prepared that had increased intravenous half-lives relative to UFH but lacked any improvement in anti-factor Xa activity or had no catalytic activity or reactivity against thrombin. However, a recent conjugate developed by Chan et al. has displayed a number of superior properties. Chan et al. ATH has an increased direct thrombin inhibition rate and can catalyze coagulant enzyme inhibition by exogenous antithrombin with very high specific activity. Unlike UFH, clot-bound thrombin is readily inhibited by ATH and, at similar antithrombotic efficacy, the ATH has improved bleeding profiles compared to heparins. Given the preclinical findings, Chan et al. ATH may warrant clinical trial testing for control of clot propagation.
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Anticoagulantes/química , Anticoagulantes/uso terapéutico , Antitrombinas/química , Antitrombinas/uso terapéutico , Heparina/química , Heparina/uso terapéutico , Animales , Anticoagulantes/aislamiento & purificación , Antitrombinas/aislamiento & purificación , Coagulación Sanguínea/efectos de los fármacos , Factor Xa/metabolismo , Heparina/aislamiento & purificación , Humanos , Técnicas In Vitro , Cinética , Sustancias MacromolecularesRESUMEN
BACKGROUND: Thrombin generation potential, a critical haemostatic measure, can be determined by continuous detection of total thrombin or direct subsampling. However, differences between methods exist in area under the curve or peak thrombin calculated. Also, impact of anticoagulants on thrombin generation may vary depending on mode of analysis. OBJECTIVE: We studied the effect of components on thrombin generation in the presence or absence of anticoagulants. METHODS: The continuous method was conducted with plasma +/- fibrin(ogen) +/- fibrin polymerization inhibitor. Plasma contained slow-reacting TG5134 substrate at 37 degrees C and reaction was started with dilute thromboplastin in CaCl(2)/Tris buffer. Absorbance (405 nm) was recorded over time and free thrombin calculated from total thrombin activity. For the subsampling method, similar plasma mixtures +/- TG5134 were reacted and free thrombin measured directly as the difference in activity against S2238 substrate of timed subsamples taken into EDTA or EDTA + antithrombin + heparin. RESULTS: Slow-reacting substrate in the continuous method acted as a competitor for thrombin, giving delayed but greater free thrombin than direct subsampling. These differences persisted to varying extents with all anticoagulants tested. In either method, presence of polymerization inhibitor increased the amount of free thrombin. Continuous method detection of alpha(2)macroglobulin complexes was hampered by sensitivity limits leading to inordinate free thrombin calculations. Especially with hirudin, although free thrombin remained at the end of the subsampling method, continuous method calculations assumed no residual free thrombin. CONCLUSION: In vitro plasma thrombin generation is delayed and increased by slow-acting substrate and fibrin polymerization inhibitor.
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Anticoagulantes/farmacología , Biopolímeros/metabolismo , Análisis Químico de la Sangre/métodos , Fibrina/antagonistas & inhibidores , Fibrina/metabolismo , Trombina/biosíntesis , Adulto , Antitrombinas/farmacología , Compuestos Cromogénicos , Fondaparinux , Heparina/farmacología , Heparina de Bajo-Peso-Molecular/farmacología , Humanos , Técnicas In Vitro , Polisacáridos/farmacología , Factores de TiempoAsunto(s)
Hemofilia A/tratamiento farmacológico , Cumplimiento de la Medicación , Adolescente , Adulto , Actitud del Personal de Salud , Canadá , Niño , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto JovenAsunto(s)
Inhibidores de Factor de Coagulación Sanguínea/sangre , Factor IX/uso terapéutico , Hemofilia B/tratamiento farmacológico , Hemofilia B/inmunología , Tolerancia Inmunológica/efectos de los fármacos , Adulto , Factor IX/antagonistas & inhibidores , Humanos , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The management of colorectal cancer with synchronous liver-limited metastases currently lacks randomised trial evidence to inform case selection for any of the bowel-first, liver-first or synchronous surgery routes. We examine the literature to report outcome data from reports utilising all three approaches. METHODS: A systematic review was conducted using OvidSP (including Embase, EBM Reviews and MEDLINE databases) to find articles reporting discrete peri-operative and long-term outcomes for patients undergoing sequential bowel-first, liver-first surgery or synchronous liver and bowel surgery. RESULTS: Of 223 unique citations, 3 cohort studies were identified comprising a pooled population of 1203 patients who completed treatment protocols between 1982 and 2011. Patients were allocated to bowel-first surgery (748 patients, 62.2%), liver-first surgery (75, 6.2%) or synchronous liver/bowel surgery (380, 31.6%). Minor complications were similar between procedures. Major complications were consistent with a pooled fixed estimate of 9.1% (95%CI: 7.6%-10.8%, I(2) = 48%). Post-operative death was rare and consistent with a pooled fixed effect estimate of 3.1% (95%CI: 2.2%-4.3%, I(2) = 0%). Median follow-up ranged from 25.1 to 40.0 months, with a pooled underlying 5-year survival fixed effect estimate of 44% (I(2) = 39%). CONCLUSION: This review assesses outcomes of patients with colorectal cancer with synchronous liver metastases managed by either synchronous, sequential liver-first or bowel-first surgery. Overall treatment-related mortality is low and survival is similar among the three groups. These findings provide support for the continued use of all three pathways until better evidence to guide selection of an individual treatment option is available.
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Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Quimioterapia Adyuvante , Colectomía , Neoplasias Colorrectales/tratamiento farmacológico , Hepatectomía , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Terapia Neoadyuvante , Neoplasia Residual , Selección de Paciente , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Covalent antithrombin-heparin complex (ATH) was covalently grafted to a polycarbonate urethane (Corethane) endoluminal graft (a kind gift of Corvita Corporation) after being activated using 0.3% m/m NaOCl in 0.15 M phosphate pH 6.0. ATH graft density (1.98 x 10(-7) mol/m2) was 6 times the maximum amount of unfractionated heparin (UFH) that could be bound to polycarbonate urethane surfaces. Surface-bound ATH could be stored in sterile 0.15 M NaCl at 4 degrees C for at least 2 months with good antithrombotic activity before being implanted into rabbits. Analysis of ATH-coated tubing showed that it contained significant direct thrombin inhibitory activity. In vivo testing in a rabbit model was compared to non-activated non-coated surfaces, activated-non-coated surfaces, hirudin-coated surfaces and antithrombin (AT)-coated surfaces. The weight of the clot generated in the ATH-coated graft tubing was significantly less than the weight of the clot generated within the hirudin-coated graft (p = 0.03 with a 1-tailed Student's t test). The anticoagulant nature of ATH grafts in vivo was shown to be due to bound ATH because boththe AT-coated surfaces and non-coated but activated surfaces showed similar thromboresistant efficacy to that of untreated material (ANOVA; p < 0.05). Apart from the direct antithrombin activity that contributed to much of the prolonged patency in vivo, surface-bound ATH likely catalyzed AT inhibition of thrombin, as evidenced by a significant number of 125I-AT binding sites (> or = 1.5 x 10(-8) mol/m2). Thus, ATH appears to be a good candidate for coating cardiovascular devices, such as endoluminal grafts, with high levels of substitution and significant long-term blood-compatibility.