Valor de la genética en la era de la terapia triple frente al virus de la hepatitis C

Despite the introduction of protease inhibitors (PI) in the treatment of hepatitis C, the sensitivity of interferon continues to be essential to achieve a sustained virological response (SVR) and to eradicate the viral infection. Currently, pegylated interferon (PEG-IFN) and ribavirin (RBV) are required to avoid selection of PI-resistance mutations. The likelihood of obtaining an SVR with dual therapy in treatment-naïve patients with genotype 1 infection varies from 40% to 50%. That is, almost half of these patients would not require a PI, thus avoiding their adverse effects and considerably reducing the cost of the treatment. Identifying which patients could potentially respond to dual therapy is one of the main challenges in clinical practice. The genetic variability of the host is one of the main factors affecting the sensitivity of PEG-IFN and therefore in the response to current treatment. Other baseline factors related to the host, the virus and, especially, to intratreatment factors such as rapid virological response (RVR) are strongly associated with the probability of achieving an SVR. The evidence on the decision to prescribe dual or triple therapy according to the factors predictive of response is based on retrospective studies or post-hoc analyses of pivotal studies on PI. Study of the polymorphisms of the IFNL3 gene (IL28B), ITPA, IFN-stimulated genes (ISGs), TT/ΔG (ss469415590; IFNL4)) and RBV transporters could help in the decision to prescribe dual or triple therapy in treatment naïve patients.     

Papel de MICA en la patogenia de la artritis reumatoide

MICA and MICB are molecules that are not expressed in normal cells but are expressed in infected, transformed or stressed cells, allowing their elimination by the immune system. Expression of these molecules activates T lymphocytes and natural killer cells through the NKG2D activating receptor. It has been postulated that expression of NKG2D ligands must be strictly regulated, since inappropriate expression may trigger or exacerbate autoimmunity. In agreement with this notion, MICA and MICB have been reported to play a key role in the development of several T cell-mediated autoimmune diseases, such as insulin-dependent diabetes mellitus, multiple sclerosis, and celiac disease. Equally, aberrant expression of these molecules in the synovia of rheumatoid arthritis (RA) patients has recently been reported. This aberrant expression could lead to the activation of autoreactive CD4 T cells, which may cause autoreactive T cell stimulation, thus promoting or perpetuating RA. A further finding on the role of these molecules in the pathogenesis of RA is that the MICB gene, which is located in the MHC class III region, is associated with RA susceptibility independently of HLA-DR.     

Place de la chirurgie dans la maladie de Caroli monolobaire

Caroli’s disease is a segmental congenital cystic dilatation of the intrahepatic biliary tree. It is a rare cause of chronic cholestasis and intrahepatic gallstones. We report two cases of Caroli’s disease localized to the left half of the liver, revealed by recurrent atypical cholangitis. A left hepatectomy was performed at once in one case and after multiple unsuccessful endoscopic and surgical acts in the other case. The preoperative diagnosis was based on the imaging study, but only histopathology can confirm and track neoplasia. The logical treatment of the localized form of Caroli’s disease is the complete resection of the affected lobe, which can be successfully achieved by partial hepatectomy.     

El futuro de la enfermedad inflamatoria intestinal desde la perspectiva de la DDW 2012

The new information presented in Digestive Disease Week has allowed us to speculate on the future of inflammatory bowel disease. Manipulation of diet and the microbioma will probably play an increasingly important role in the treatment of this disease and, in the long term, in its prevention. Biological agents will probably be used earlier and more widely; new information on levels of biological agents, mucosal healing and new comparative studies will also allow these agents to be used in a more precise and personalized way. In addition to infliximab, adalimumab, natalizumab and certolizumab, other biological agents will be employed; among the first of these to be used will be ustekinumab, golimumab and vedolizumab. In the near future, biological agents will be used as frequently in ulcerative colitis as in Crohn's disease. New healthcare models will be developed that will progressively include greater participation among patients and nurses. The ability to predict new diagnostic and prognostic models will allow decisions to be more individualized.     

Enjeu de la prise en charge. Chirurgie de la FA

Atrial Fibrillation Surgery is wide spread today but the indications are still limited to associated procedures with other cardiac surgery. Minimally invasive approach is less aggressive and could be proposed to complex lone AF which are still resistant to percutaneous ablations.     

Traitement de la maladie de Horton

Corticosteroids (CS) remain the main treatment for giant cell arteritis (GCA). The choice of initial prednisone dosage (from 0.5 to 1 mg/kg/d) takes into account the disease severity and comorbidities in order to reduce the drug side effects. Low-dose aspirin may benefit to patients suffering ischemic complications or with multiple cardiovascular risk factors. Randomised controlled trials are necessary to precise its benefit-to-risk ratio. Methotrexate has a moderate corticosteroid sparing effect but it does not prevent cephalic complications and there is no evidence of a reduced frequency of CS adverse effects with this drug. Hydroxychloroquine and infliximab or adalimumab did not prevent relapses in double blind controlled trials. High doses of intravenous methylprednisolone are often prescribed for severe ischemic complications though there is no evidence that such doses are superior to classical doses. In corticosteroid dependent patients, the benefit-to-risk ratio of immunosuppressive drugs is unknown. Dapsone is no longer prescribed due to severe adverse effects. Efficacy of tocilizumab is very promising but its benefit-to-risk ratio in old people is largely unknown. Finding a well tolerated corticosteroid sparing drug remains a challenge and further studies are necessary to reduce the long term rate of cardiovascular events and the burden of CS adverse effects.     

Signos de alarma de la lumbalgia

Low back pain is defined as pain located between the last rib and the gluteal area and can radiate to the lower extremities. Low back pain is a major health problem, especially in industrialized countries, with a prevalence of approximately 70%. This disorder generally consists of musculo-skeletal pain that is self-limiting within a defined period of time. However, history and physical examination are advisable in patients with low back pain to rule out other serious entities such as neoplasms, osteomyelitis, vertebral fractures, cauda equine syndrome, spinal stenosis, and ankylosing spondylitis, and thus make a correct diagnosis and prescribe appropriate treatment. Consequently, most clinical guidelines mention what are known as the “red flags” or warning signs of low back pain. A red flag is any sign or symptom in a patient with low back pain that could be related to the development of a serious disease. There are insufficient evidence-based studies on the distinct warning signs. When examining a patient with low-back pain, if fever, constitutional syndrome, previous neoplasm, inflammatory pain, previous traumatism, or bladder dysfunction, among other entities, are present, further investigation is warranted since the diagnosis could be secondary low back pain. The present article discusses the red flag signs of acute low back pain.     

Estudios sobre la velocidad de desaparición de la insulina exógena de la sangre en el perro II. efecto de la tiroxina

Résumé Nous avons étudié l'effet d'un traitement chronique sous-cutané avec thyroxine (100 µg/kg de poids corporel/jour, pendant 10 jours) sur le taux de disparition de l'insuline du sang chez le chien totalement dépancréatisé à jeun. Chaque chien a reçu une dose i.v. de 0,25 UI/kg de poids d'insuline crystalline, et depuis a été saigné cinq fois, pendant une période totale de 75 min. Nous avons déterminée l'insuline immunoréactive sérique aussi bien que la glycémie, d'après les méthodes de Melani et Coll. et de Nelson respectivement. Les résultats obtenus nous on montré que, chez le chien dépancréatisé, l'hyperthyroïdisme ne produit aucun changement, soit dans: a) le taux constant de disparition de l'insuline du sang; b) la moyenne générale d'insuline immunoréactive sérique après l'injection de glucose, ou c) l'espace de l'insuline.

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Summary A study of the effect of chronic subcutaneous thyroxine treatment (100 µg/kg body weight daily for 10 days) on the rate of exogenous insulin disapperance from blood in totally depancreatized dogs in the fasting condition was performed. Each animal received 0.25 IU crystalline insulin/kg body weight i.v. and was bled five times within 75 min. Serum IRI and blood sugar were assayed according to Melani et al. and to Nelson respectively. The results enable us to conclude that in depancreatized dogs hyperthyroidism fails to induce any change in: a) the rate-constant for insulin disappearance from the blood, b) the general serum IRI mean after insulin injection or c) the insulin space.

This work was partly supported by Research grant no. 2304-B from the Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina).