RESUMEN
PCSK9-inhibitors belong to the new class of hypolipidemic agents. They enhance catabolism of low density lipoprotein cholesterol (LDL-C) through inhibiting activity of proprotein convertase subtilisin/kexin type 9 (PCSK9). They are monoclonal antibodies (alirocumab, evolocumab etc). Under clinical development are also other types of PCSK9-inhibitors which act at a subcellular level. The treatment with PCSK9-inhibitors can be beneficially combined with lipoprotein apheresis (LA). If such treatment using PCSK9-inhibitors is possible with regard to an individual patients genotype, the combination of LA and PCSK9-inhibitors leads to slowing the space of LDL-C increase between individual procedures of apheresis and enables attaining of the lowest possible values of LDL-cholesterolemia for the longest possible period of time. Due to high efficiency of PCSK9-inhibitors lowering LDL-C, but also their lower cost as compared to therapeutic LA, PCSK9-inhibitors now take precedence over the use of extracorporeal lipoprotein apheresis which, nonetheless, still remains the final method for hypolipidemic treatment of patients with severe hypercholesterolemia, who are resistant to conventional therapy while not reaching the target lipid values and at high cardiovascular risk. They belong to extracorporeal elimination methodologies which remove low density lipoprotein (LDL) cholesterol from circulating blood. LA in combination with higher doses of statins and ezetimib currently represents the most efficient method of treatment of homozygous and statin-refractory heterozygous familial hypercholesterolemia (FH). Residual cardiovascular risk in these patients still remains high, in particular because, despite the aforementioned treatment, the target values for lipids according to present recommendations cannot be reached. The combination of LA with the new drugs is promising, primarily due to its potential for further lowering of LDL-cholesterolemia between the individual apheresis procedures. Preliminary results of the ongoing studies indicate that the new hypolipidemic drugs in combination with LA, or when used separately, will substantially enrich and improve the treatment of refractory FH.Key words: alirocumab - atherosclerosis - evolocumab - hypercholesterolemia - cardiovascular disease - lipoprotein apheresis.
Asunto(s)
Anticolesterolemiantes , Eliminación de Componentes Sanguíneos , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Proproteína Convertasa 9 , Anticuerpos Monoclonales , Anticolesterolemiantes/uso terapéutico , LDL-Colesterol , Humanos , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/genética , Lipoproteínas , Inhibidores de PCSK9RESUMEN
Lipoprotein apheresis (LA) is an effective treatment method the patients with severe hypercholesterolemia, resistant to the standard therapy. LA is an extracorporeal elimination technique, which specifically removes low density lipoprotein (LDL) cholesterol from the circulation. At present, lipoprotein apheresis, combined with high-dose statin and ezetimibe therapy, is the best available means of treating patients with homozygous and statin refractory heterozygous familial hypercholesterolaemia (FH). However, the extent of cholesterol-lowering achieved is often insufficient to meet the targets set by current guidelines. The recent advent of new classes of lipid-lowering agents provides new hope that the latter objective may now be achievable. These compounds act either by reducing low density lipoprotein (LDL) cholesterol production by inhibiting apolipoprotein B synthesis with an antisense oligonucleotide (mipomersen), or by inhibiting microsomal triglyceride transfer protein (lomitapid), or by enhancing LDL catabolism via monoclonal antibody-mediated inhibition of the activity of proprotein convertase subtilisin/kexin 9 (PCSK9-alirocumab, evolocumab etc). The promising is the combination of LDL-apheresis with new drugs, namely for its potential to further decrease of LDL-cholesterol between apheresis. Depending on the outcome of current trials, it seems likely that these compounds, used alone or combined with lipoprotein apheresis, will markedly improve the management of refractory FH.
Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Hiperlipoproteinemia Tipo II/terapia , Lipoproteínas/sangre , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipoproteinemia Tipo II/sangre , Hipolipemiantes/uso terapéuticoRESUMEN
LDL-apheresis is an extracorporeal elimination technique, which specifically removes LDL-cholesterol from the circulation. There are six methods for the selective LDL-cholesterol removal these days. The main indications for LDL-apheresis are the diagnosis of homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia which is refractory the standard care and intolerance of routine care, and also patients with lipoprotein(a) increase resistant to the farmacotherapy. There is still debate which LDL-cholesterolemia is indication for LDL-apheresis therapy, and the recommendation differs among various countries. Despite large randomized trials are missing, there are several good quality studies to conclude, that the beneficial cardiovascular effects of LDL-apheresis in severe hypercholesterolemia are important and beneficial.
Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/terapia , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Humanos , Triglicéridos/sangreRESUMEN
OBJECTIVE: Levels of serum lipids are influenced by malnutrition and inflammation. The study aimed to find the relation of the lipidogram to positive and negative markers of inflammation in geriatric patients. Attention was paid to neopterin in urine as a non-protein positive bioindicator of inflammation. METHODS: It was a local, monocentric, prospective clinical study in hospitalized patients older than 80 y. The study included 101 patients (54 women, 47 men). The average age of the entire group was 85.37 +/- 4.88 y. The dependence of the values of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triacylglycerols (TAGs) on C-reactive protein (CRP), neopterin in urine, and prealbumin was examined. RESULTS: When we compared CRP and serum lipids, we found a statistically significant negative correlation between levels of CRP and total cholesterol (P < 0.05), HDL (P < 0.01), and LDL (P < 0.05). Also the level of neopterin in urine was negatively correlated with levels of total cholesterol (P < 0.05) and HDL (P < 0.01). A statistically highly significant interaction was demonstrated between levels of prealbumin and total cholesterol (P < 0.001), HDL (P < 0.001), LDL (P < 0.001), and TAG (P < 0.05). CONCLUSION: A significant negative correlation between levels of inflammation markers (neopterin in urine, CRP) and total cholesterol and HDL was found. LDL was influenced to a lesser extent. A close relation between serum lipids and prealbumin was also demonstrated. Total cholesterol, HDL, and LDL can be considered novel biomarkers of malnutrition and inflammation in geriatric patients.
Asunto(s)
Inflamación/diagnóstico , Lípidos/sangre , Desnutrición/diagnóstico , Neopterin/orina , Anciano de 80 o más Años , Biomarcadores/sangre , Biomarcadores/orina , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Hospitalización , Humanos , Inflamación/sangre , Inflamación/orina , Masculino , Desnutrición/sangre , Desnutrición/orina , Prealbúmina/análisis , Prealbúmina/metabolismo , Estudios Prospectivos , Triglicéridos/sangreRESUMEN
INTRODUCTION: The preferred treatment for acute cholecystitis is cholecystectomy, but for patients with precluded general anesthesia due to critical illness or multiple medical comorbidities it is not suitable. Cholecystostomy could be a minimally invasive therapeutic alternative. AIM: To retrospectively evaluate the indications, technical features, efficacy, complications, patients' development and relationships among monitored parameters of percutaneous computed tomography (CT)-guided cholecystostomies in cases of acute cholecystitis and find the role of this procedure in appropriate treatment selection. MATERIAL AND METHODS: Over the course of 10 years, 75 percutaneous cholecystostomy procedures in 69 patients were performed in cases with diagnosed acute cholecystitis, precluded general anesthesia and contraindicated cholecystectomy by an experienced surgeon and anesthesiologist. These interventions were done using only local anesthesia. The patients were men in 39 cases and women in 33 cases, aged 33 to 91 years. RESULTS: Technical success was achieved in all cases. The indications were sepsis in 34 (45.3%) cases, bridging acute gallbladder inflammatory status in 15 (20%) interventions, serious medical comorbidities in 8 (10.7%) cases, disseminated malignancy and cardiac failure in 6 cases each (both 8%) and neurological affections in 5 (6.5%) cases. Cholecystostomy was frequently the final solution in acalculous cholecystitis (79.3%). The 30-day mortality rate was determined at 10.7% and the overall complication rate was 21.3%, but all of these complications were managed conservatively or using minimally invasive treatment. CONCLUSIONS: Percutaneous CT-guided cholecystostomy is reserved for patients with a serious medical status for various reasons that preclude surgical treatment and general anesthesia. Simultaneously, technical success and efficacy are high and the complication rate is acceptable.
RESUMEN
RATIONALE, AIMS AND OBJECTIVES: Measuring self-reported adherence may contribute to minimizing the risk of therapy failure. Hence, the main aim of the study was to assess the psychometric properties of the Czech version of Medication Adherence Report Scale (MARS-CZ) and its appropriateness for use in long-term statin therapy where goal levels of low-density lipoprotein cholesterol (LDL-c) should be achieved. METHODS: Anonymous structured interview was performed to determine self-reported adherence by MARS-CZ in outpatients chronically treated with statins. At the same time, medication records were reviewed for inclusion of patients into groups of those who achieved and do not achieved LDL-c goal according to cardiovascular risk level. Reliability and validity of MARS-CZ were tested as well as the relationship between adherence and LDL-c goal achievement was examined. RESULTS: A total of 136 (86.6%) patients completed the interview; mean age was 66.1 years; 49.3% were male. The mean score of MARS-CZ was 24.4 and showed positive skewing. Satisfactory internal consistency (Cronbach's α=0.54), strong test-retest reliability (r=0.83, P<0.001; intra-class correlation=0.63, 95% confidence interval: 0.35-0.81) and positive correlation with eight-item Morisky Medication Adherence Scale (r=0.62, P<0.001) were indicated. Low validity values were found between MARS-CZ and 12-item Short Form Health Survey mental and physical subscales. MARS-CZ score significantly correlated with LDL-c goal achievement (P<0.05) when all patients who achieved LDL-c goal (35%) reported high adherence to statin. MARS-CZ score also correlated with cardiovascular risk level and doctor's judgments on adjusting treatment targets for each patient. CONCLUSION: This study proved MARS-CZ as an acceptable self-reported adherence measure. In routine clinical practice, MARS-CZ could be helpful to reveal medication non-adherence before the alteration of drug regimen and thereby contributing to enhancement of statin therapy management.
Asunto(s)
LDL-Colesterol/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Cumplimiento de la Medicación/psicología , Cumplimiento de la Medicación/estadística & datos numéricos , Autoinforme , Anciano , República Checa , Femenino , Objetivos , Conductas Relacionadas con la Salud , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Factores de Riesgo , Factores SocioeconómicosRESUMEN
Varicella zoster virus typically causes a benign disease in childhood called varicella (chickenpox) and can reactivate in adults as a dermatomally distributed, painful rash illness known as herpes zoster (HZ). Infection with VZV can however lead to severe complications in immunocompromised patients that can result in hospitalization and, occasionally, death. Here we describe a patient, who acquired primary VZV infection during a 3-week-long treatment regimen with corticosteroids. The disease took a fulminant course, leading to a liver failure and severe coagulopathy. The patient died 9 days following hospital admission, despite intensive antiviral and supportive treatment. Wild-type VZV DNA was detected from multiple samples from esophagus, liver and skin. Genotypic analysis based on single nucleotide polymorphism profiles in open reading frames (ORFs) 21, 22 and 50 identified this strain as a clade 4 isolate, which is typically found in tropical countries. This is the first description of a clade 4 strain from a patient in the Czech Republic.
Asunto(s)
Varicela/complicaciones , Hepatitis/complicaciones , Herpesvirus Humano 3/fisiología , Huésped Inmunocomprometido , Adulto , República Checa , Resultado Fatal , Femenino , Genes Virales/genética , Genotipo , Hepatitis/patología , Herpesvirus Humano 3/clasificación , Herpesvirus Humano 3/genética , Humanos , Inmunosupresores/efectos adversosRESUMEN
A wound-healing agent developed in the European Union is based on the combination of organic hyaluronan with inorganic iodine. The aim of this pilot study was to assess the efficacy and safety of hyaluronate-iodine in the treatment of sternal wounds. Eight patients with sternal wound dehiscence were entered into the study. After debridement, wounds were dressed with gauze soaked in hyaluronate-iodine. In one patient with an epipleural abscess, hyaluronate-iodine was instilled directly into the abscess cavity daily. Complete healing was achieved in 7 patients, and 1 patient underwent a reconstructive operation for wound closure. The mean (SD) length of treatment was 136 (114.2) days. No adverse effects or complications were apparent in this group. Hyaluronate-iodine is safe and effective in healing sternal wound dehiscence. Randomized controlled trials are needed for further validation.
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Procedimientos Quirúrgicos Cardíacos/métodos , Esternotomía/efectos adversos , Dehiscencia de la Herida Operatoria/tratamiento farmacológico , Administración Tópica , Anciano , Anciano de 80 o más Años , Antiinfecciosos Locales/administración & dosificación , Vendajes , Procedimientos Quirúrgicos Cardíacos/efectos adversos , República Checa/epidemiología , Combinación de Medicamentos , Femenino , Humanos , Ácido Hialurónico , Incidencia , Yodo , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Retrospectivos , Dehiscencia de la Herida Operatoria/epidemiología , Dehiscencia de la Herida Operatoria/etiología , Factores de Tiempo , Resultado del Tratamiento , Cicatrización de Heridas/efectos de los fármacosRESUMEN
BACKGROUND: Cholesterol is an essential component of cell membranes, precursor of steroids, biliary acids and other components of serious importance in live organism. Cholesterol synthesis is a complicated and energy-demanding process. Real daily need of cholesterol and mechanisms of decline cholesterol levels in critical ill are unknown. During stressful situations a significant hypocholesterolaemia may be found. Hypocholesterolemia has been known for a number of years to be a significant prognostic indicator of increased morbidity and mortality connected with a whole spectrum of pathological conditions. The aim of article is the elucidation of the role and importance of hypocholesterolaemia during the intensive care. METHODS AND RESULTS: We examined studies that are engaged in problems of hypocholesterolemia in critically ill. Very low levels of total as well as LDL cholesterol are most frequently found in serious polytrauma, after extensive surgery, in serious infections, in protracted hypovolemic shock. It is still not clear whether hypocholesterolemia reflects only a serious metabolic disorder, which results from a life-threatening condition, or whether it has an active role in evolution and outcome. CONCLUSIONS: Hypocholesterolemia is commonly observed in critically ill patients. Nevertheless, it is not known whether it is a secondary manifestation of disease, or whether it actively contributes to deterioration of the disease. Although the contribution of hypocholesterolemia to mortality is modest compared with known risk factors such as increased severity of illness and the development of nosocomial infection, low serum lipid concentrations represent a potential therapeutic target in sepsis.