Papel del hierro endovenoso para el manejo de la anemia preoperatoria en cirugía ortopédica mayor dentro de un programa de ahorro de sangre

Objetivos La anemia preoperatoria es frecuente en cirugía ortopédica mayor y es un factor predictivo de transfusión y de peor evolución postoperatoria. El objetivo de este estudio es evaluar la utilidad y seguridad del hierro endovenoso como tratamiento de la anemia preoperatoria y ferropenia en cirugía ortopédica mayor, y valorar la respuesta según el hierro utilizado y/o el tipo de anemia de acuerdo con el algoritmo de actuación de nuestro programa de ahorro de sangre. Material y métodos Análisis retrospectivo de una base de datos prospectiva de los pacientes programados para prótesis total de cadera (PTC) y de rodilla (PTR), en los últimos 5 años. Utilizamos la base de datos online PAS (Programa de Ahorro de Sangre) en www.awge.org que incluye: edad, sexo, peso, ASA, metabolismo del hierro, evolución de la hemoglobina (Hb), efectos adversos y transfusión. Resultados Se incluyeron en el PAS 3.488 pacientes de los cuales 612 (17,5%) presentaban anemia preoperatoria y 169 (27,6%) fueron tratados con hierro endovenoso (HE) De los pacientes tratados con HE (169), 35 recibieron hierro sacarosa (HS) y 134 hierro carboximaltosa (HCM). De acuerdo con el algoritmo de tratamiento, 101 lo recibieron por anemia por déficit de hierro (ADH), 26 por ferropenia sin anemia (DH), 21 por anemia de proceso crónico (APC) y 21 en otros tipos de anemia. El incremento de la Hb fue de 1 ± 09 g/dl en el DH, de 1.7± 1 g/dl en ADH y de 2.1 ± 1 g/dl en APC y otras anemias (P<0.001). El grupo del HCM la adherencia al tratamiento fue superior y necesitaron menos visitas (p<0.001). Los efectos adversos fueron leves y similares en ambos grupos. Conclusiones El hierro endovenoso (HS o HCM) es un tratamiento eficaz y seguro de la anemia preoperatoria en cirugia ortopédica mayor, aunque el HCM tiene la ventaja de conseguir el mismo resultado con sólo una administración.

Early neurological impairment and severe anemia in a newborn with Pearson syndrome

BACKGROUND: Pearson marrow-pancreas syndrome (PS) is usually a fatal mitochondrial disease, mostly diagnosed during infancy or postmortem. PS is caused by the deletions or duplications of mitochondrial DNA (mtDNA). The tissue distribution and relative proportions of expressed abnormal mtDNA determine the phenotype and the clinical course. MATERIALS AND METHODS: We describe the case of a term baby boy who was diagnosed with PS early in the neonatal period due to severe aregenerative anemia and persistent lactic acidosis. RESULTS: His neurological examination was abnormal since birth. Brain magnetic resonance imaging (MRI) at term was abnormal, indicating that mitochondrial encephalopathy in PS can be already manifested in the neonatal period. To our knowledge, neonatal encephalopathy in PS has not been previously described. CONCLUSION: PS is a rare condition diagnosed in the newborn. It should be suspected in the presence of severe anemia and persistent lactic acidosis, and may manifest with early encephalopathy.

Disease-corrected haematopoietic progenitors from Fanconi anemia induced pluripotent stem cells

The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells andprovided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold greattherapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect,somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications.

A polymorphism in the leptin gene promoter is associated with anemia in patients with HIV disease.

To study factors associated with anemia and its effect on survival in HIV-infected persons treated with modern combined antiretroviral therapy (cART), we characterized the prevalence of anemia in the Veterans Aging Cohort Study (VACS) and used a candidate gene approach to identify proinflammatory gene single nucleotide polymorphisms (SNPs) associated with anemia in HIV disease. The study comprised 1597 HIV(+) and 865 HIV(-) VACS subjects with DNA, blood, and annotated clinical data available for analysis. Anemia was defined according to World Health Organization criteria (hemoglobin < 13 g/dL and < 12 g/dL in men and women, respectively). The prevalence of anemia in HIV(+) and HIV(-) subjects was 23.1% and 12.9%, respectively. Independent of HIV status, anemia was present in 23.4% and 8% in blacks and whites, respectively. Analysis of our candidate genes revealed that the leptin -2548 G/A SNP was associated with anemia in HIV(+), but not HIV(-), patients, with the AA and AG genotypes significantly predicting anemia (P < .003 and P < .039, respectively, logistic regression). This association was replicated in an independent cohort of HIV(+) women. Our study provides novel insight into the association between genetic variability in the leptin gene and anemia in HIV(+) individuals.

High incidence of childhood hemolytic uremic syndrome in Switzerland is associated with indicators of livestock farming intensity

Background: Hemolytic-uremic syndrome (HUS) is a multisystem disorder associated with significant morbidity and mortality. Typically, HUS is preceded by an episode of (bloody) diarrhea mostly due to Shiga-toxin (Stx) producing Escherichia coli (STEC). The main reservoir for STEC is the intestine of healthy ruminants, mostly cattle, and recent studies have revealed an association between indicators of livestock density and human STEC infection or HUS, respectively. Nationwide data on HUS in Switzerland have been established through the Swiss Pediatric Surveillance Unit (SPSU) [Schifferli et al. Eur J Pediatr. 2010; 169:591-8]. Aims: Analysis of age-specific incidence rate of childhood HUS and possible association of Shiga-toxin associated HUS (Stx-HUS) with indicators of livestock farming intensity. Methods: Epidemiological and ecological analysis based on the SPSU data (1997-2003) and the database of the Swiss Federal Statistical Office (data on population and agriculture). Results: One hundred-fourteen cases were registered, 88% were ≤5 years old. The overall annual incidence rate was 1.42 (0.60-1.91) and 4.23 (1.76-6.19) per 100000 children ≤5 and ≤16 years, respectively (P = 0.005). Stx-HUS was more frequent compared to cases not associated with STEC (P = 0.002). The incidence rate for Stx-HUS was 3.85 (1.76-5.65) in children ≤5, compared to 0.27 (0.00-0.54) per 100'000 children 5-16 years (P = 0.002), respectively. The incidence rate of cases not associated with STEC infection did not significantly vary with age (P = 0.107). Compared to data from Scotland, Canada, Ireland, Germany, England, Australia, Italy, and Austria the annual incidence rate of HUS in young children is highest in Switzerland. Ecological analysis revealed strong association between the incidence rate of Stx-HUS and indicators of rural occupation (agricultural labourer / population, P = 0.030), farming intensity (livestock breeding farms / population, P = 0.027) and cattle density (cattle / cultivated area, P = 0.013). Conclusions: Alike in other countries, HUS in Switzerland is mostly associated with STEC infection and affects predominantly young children. However, the incidence rate is higher compared to countries abroad and is significantly correlated with indicators of livestock farming intensity. The present data support the impact of direct and indirect contact with animals or fecal contaminants in transmission of STEC to humans.

Interferon-gamma impacts at multiple points during the progression of autoimmune diabetes.

The role of interferon-gamma in autoimmune diabetes was assessed by breeding a null mutation of the interferon-gamma receptor alpha chain into the nonobese diabetic mouse strain, as well as into a simplified T cell receptor transgenic model of diabetes. In contrast to a previous report on abrogation of the interferon-gamma gene, mutation of the gene encoding its receptor led to drastic effects on disease in both mouse lines. Nonobese diabetic mice showed a marked inhibition of insulitis-both the kinetics and penetrance-and no signs of diabetes; the transgenic model exhibited near-normal insulitis, but this never evolved into diabetes, either spontaneously or after experimental provocation. This failure could not be explained by perturbations in the ratio of T helper cell phenotypes; rather, it reflected a defect in antigen-presenting cells or in the islet beta cell targets.

The V-region disease hypothesis: evidence from autoimmune encephalomyelitis.

Experimental allergic encephalomyelitis has been shown to have an immunological basis. In fact, the disease can be induced by T cells specific for myelin basic protein, a molecule found in abundance in the central nervous system. In this article, Ellen Heber-Katz and Hans Acha-Orbea discuss the T-cell receptor (TCR) repertoire of the encephalitogenic T-cell response, and show that a limited V gene pool, in fact a single V beta and two V alpha families, are being used by the PL/J and B10.PL mice and by every rat strain examined, even though the antigenic determinants and the major histocompatibility complex (MHC) molecules are different in all cases. This extraordinary finding suggests that the TCR is involved in encephalitogenicity in a way that not only involves the recognition of antigen in association with MHC, but also as an effector molecule that results in encephalitis. If this is true, it implies that TCRs, in general, play more than one role in mammalian physiology.

Anemia and chronic kidney disease are potential risk factors for mortality in stroke patients : a historic cohort study

Rapport de synthèseApproche et objectifL'objectif de la recherche était de préciser les relations existant entre l'insuffisance rénale chronique, l'anémie et l'accident vasculaire cérébral parmi des patients hospitalisés au Centre Hospitalier Universitaire Vaudois (CHUV) pour un accident vasculaire cérébral (AVC). Les auteurs ont déterminé la prévalence de l'anémie et de l'insuffisance rénale chronique parmi ces patients et examiné s'ils sont des facteurs de risque indépendants de la mortalité suite à un AVC.L'insuffisance rénale chronique est associée à un risque élevé de développer un AVC. L'anémie est une complication et une conséquence fréquente qui découle de l'insuffisance rénale chronique et est également un facteur de risque pour les maladies cérébro- et cardiovasculaires.MéthodeLa présente étude de cohorte rétrospective se base sur le registre des AVC du CHUV et inclut tous les patients traités suite à un premier AVC au service de neurologie du CHUV entre les années 2000 et 2003.Les variables utilisées pour l'analyse sont les caractéristiques démographiques, l'insuffisance rénale chronique, le débit de filtration glomérulaire.(GFR), l'anémie et d'autres facteurs de risque d'AVC. Ils ont été récoltés au moyen du système informatique du laboratoire du CHUV, d'entretiens téléphoniques (patients ou proches) et du registre des AVC du CHUV.L'insuffisance rénale chronique a été calculée sur base de la ,,Kidney Disease Outcomes Quality Initiative (K/DOQI)-CKD Classification", laquelle est divisée en cinq stades. L'anémie a été définie par une hémoglobine de < 120g/L pour les femmes et < 130g/L pour les hommes.Les analyses statistiques réalisées sont des tests Chi-carré, des tests de Τ ainsi que des courbes de Kaplan-Meier et le modèle de régression de Cox.RésultatsParmi 890 patients adultes avec un AVC, le GFR moyen était de 64.3 ml/min/1.73 m2, 17% souffraient d'anémie et 10% sont décédés pendant la première année après la sortie de l'hôpital, suite à l'"AVC index". Parmi ceux-ci, 61% avaient une insuffisance rénale chronique de stade 3-5 et 39% de stade 1 ou 2 selon les critères de K/DOQI.D'autre part un taux d'hémoglobine élevé a pu être associé à un risque moins élevé de mortalité un an après la sortie de l'hôpital.Conclusion et perspectiveNous avons constaté que l'anémie ainsi que l'insuffisance rénale chronique sont fréquents parmi les patients souffrant d'un AVC et qu'ils sont des facteurs de risque d'un taux de mortalité élevé après un an. En conséquence, il pourrait être utile de traiter les patients souffrant d'anémie et d'insuffisance rénale dès que possible afin de diminuer les complications et comorbidités résultants de ces maladies.La perspective est de rendre les cliniciens attentif à l'importance de l'insuffisance rénale et de l'anémie parmi les patients ayants développé un AVC, ainsi que d'initier le traitement approprié afin de diminuer les complications, les comorbidités ainsi que les récidives d'un AVC. L'efficacité et l'économicité des interventions visant à améliorer le pronostic chez les patients présentant un AVC et souffrant d'une insuffisance rénale chronique et / ou d'une anémie doivent être évaluées par des études appropriées.

Anemia on admission predicts short- and long-term outcomes in patients with acute ischemic stroke.

BACKGROUND: It is still debatable whether anemia predicts stroke outcome. AIM: To describe the characteristics of patients with acute ischemic stroke (AIS) and anemia and identify whether hemoglobin status on admission is a prognostic factor of AIS outcome. METHODS: All 2439 patients of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) between January 2003 and June 2011 were selected. Demographics, risk factors, prestroke treatment, clinical, radiological and metabolic variables in patients with and without anemia according to the definition of the World Health Organization were compared. Functional disability and mortality were recorded up to 12 months from admission. RESULTS: Anemic patients (17.5%) were older, had lower body mass index, higher rates of coronary artery disease (CAD), atrial fibrillation, diabetes mellitus and peripheral artery disease. Anemia was associated with more severe stroke manifestations, lower systolic and diastolic blood pressure measurements, worse estimated glomerular filtration rate and elevated C-reactive protein concentrations upon admission and with increased modified Rankin scores during the follow-up. Anemic patients had higher 7-day, 3-month and 12-month mortality, which was associated with hemoglobin status and other factors, including age, CAD, stroke severity, and baseline C-reactive levels. Hemoglobin levels were inversely associated with recurrent stroke and mortality throughout the 12-month follow-up. CONCLUSION: Anemia is common among AIS patients and is associated with cardiovascular comorbidities. Low hemoglobin status independently predicts short and long-term mortality.

Anemia and chronic kidney disease are associated with poor outcomes in heart failure patients.

BACKGROUND: Chronic kidney disease (CKD) has been linked to higher heart failure (HF) risk. Anemia is a common consequence of CKD, and recent evidence suggests that anemia is a risk factor for HF. The purpose of this study was to examine among patients with HF, the association between CKD, anemia and inhospital mortality and early readmission. METHODS: We performed a retrospective cohort study in two Swiss university hospitals. Subjects were selected based the presence of ICD-10 HF codes in 1999. We recorded demographic characteristics and risk factors for HF. CKD was defined as a serum creatinine > or = 124 956;mol/L for women and > or = 133 micromol/L for men. The main outcome measures were inhospital mortality and thirty-day readmissions. RESULTS: Among 955 eligible patients hospitalized with heart failure, 23.0% had CKD. Twenty percent and 6.1% of individuals with and without CKD, respectively, died at the hospital (p < 0.0001). Overall, after adjustment for other patient factors, creatinine and hemoglobin were associated with an increased risk of death at the hospital, and hemoglobin was related to early readmission. CONCLUSION: Both CKD and anemia are frequent among older patients with heart failure and are predictors of adverse outcomes, independent of other known risk factors for heart failure.

Genes encoding tumor necrosis factor alpha and granzyme A are expressed during development of autoimmune diabetes.

Progressive destruction of the insulin-producing beta cells in nonobese diabetic mice is observed after infiltration of the pancreas with lymphocytes [Makino, S., Kunimoto, K., Muraoka, Y., Mizushima, Y., Katagiri, K. &amp; Tochino, Y. (1980) Exp. Anim. (Tokyo) 29, 1-13]. We show that the genes for tumor necrosis factor alpha and granzyme A, a serine protease associated with cytoplasmic granules of cytotoxic cells, are expressed during the development of spontaneous diabetes mellitus in the nonobese diabetic mouse. Granzyme A-positive cells are found both in and surrounding the islets, implying induction prior to islet infiltration. Tumor necrosis factor alpha expression is exclusively observed in the intra-islet infiltrate, predominantly in lymphocytes adjacent to insulin-producing beta cells, the targets of the autoimmune destruction, implying that tumor necrosis factor alpha expression is induced locally--i.e., in the islet. A considerable portion of cells expressing tumor necrosis factor alpha appear to be CD4+ T cells. This T-cell subset was previously shown to be necessary for development of the disease. Thus, these findings may be important for understanding the pathogenesis of autoimmune diabetes mellitus and potentially also for that of other T-cell-mediated autoimmune diseases.

Multiplex liquid chromatography-tandem mass spectrometry assay for simultaneous therapeutic drug monitoring of ribavirin, boceprevir, and telaprevir.

New directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. However, an assay for the simultaneous analysis of RBV and DAAs constitutes an analytical challenge because of the large differences in polarity among these drugs, ranging from hydrophilic (RBV) to highly lipophilic (telaprevir [TVR]). Moreover, TVR is characterized by erratic behavior on standard octadecyl-based reversed-phase column chromatography and must be separated from VRT-127394, its inactive C-21 epimer metabolite. We have developed a convenient assay employing simple plasma protein precipitation, followed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of levels of RBV, boceprevir, and TVR, as well as its metabolite VRT-127394, in plasma. This new, simple, rapid, and robust HPLC-MS/MS assay offers an efficient method of real-time TDM aimed at maximizing efficacy while minimizing the toxicity of antiviral therapy.

Anemia and brain oxygen after severe traumatic brain injury.

PURPOSE: To investigate the relationship between hemoglobin (Hgb) and brain tissue oxygen tension (PbtO(2)) after severe traumatic brain injury (TBI) and to examine its impact on outcome. METHODS: This was a retrospective analysis of a prospective cohort of severe TBI patients whose PbtO(2) was monitored. The relationship between Hgb-categorized into four quartiles (≤9; 9-10; 10.1-11; >11 g/dl)-and PbtO(2) was analyzed using mixed-effects models. Anemia with compromised PbtO(2) was defined as episodes of Hgb ≤ 9 g/dl with simultaneous PbtO(2) < 20 mmHg. Outcome was assessed at 30 days using the Glasgow outcome score (GOS), dichotomized as favorable (GOS 4-5) vs. unfavorable (GOS 1-3). RESULTS: We analyzed 474 simultaneous Hgb and PbtO(2) samples from 80 patients (mean age 44 ± 20 years, median GCS 4 (3-7)). Using Hgb > 11 g/dl as the reference level, and controlling for important physiologic covariates (CPP, PaO(2), PaCO(2)), Hgb ≤ 9 g/dl was the only Hgb level that was associated with lower PbtO(2) (coefficient -6.53 (95 % CI -9.13; -3.94), p < 0.001). Anemia with simultaneous PbtO(2) < 20 mmHg, but not anemia alone, increased the risk of unfavorable outcome (odds ratio 6.24 (95 % CI 1.61; 24.22), p = 0.008), controlling for age, GCS, Marshall CT grade, and APACHE II score. CONCLUSIONS: In this cohort of severe TBI patients whose PbtO(2) was monitored, a Hgb level no greater than 9 g/dl was associated with compromised PbtO(2). Anemia with simultaneous compromised PbtO(2), but not anemia alone, was a risk factor for unfavorable outcome, irrespective of injury severity.

AUTOIMMUNE PANCREATITIS

Autoimmune Pancreatitis (AIP) is a new nosological entity that was first reported by Sarles et al. in 1961 and then named by Yoshida et al. in 1995 in Japan. It was then ignored by many Western researchers and now, in the last decade; it appears to have been recognized worldwide. AIP is a distinct form a chronic pancreatitis with an immune mediated fibroinflammatory process that has unique histopathologic features that makes it distinguishable from other forms of pancreatitis. Moreover, AIP is the only type of pancreatitis that responds to steroid administration. The Honolulu consensus document that has recently been published by Chari et al. described the histopathologic and clinical subtypes of AIP. Indeed, it appears that there are two forms of AIP, with different prevalence in Europe and Asia and distinct clinical profiles. The first subtype, the most common type in Asia, has recently been named Lymphoplasmocytic sclerosing pancreatitis (LPSP) or type I AIP because of its histological features and its association with elevated IgG serum levels and various autoantibodies. The second one is called idiopathic duct centric pancreatitis, IDCP, or type II AIP, that barely exists in Japan, but more accounted in Caucasian people. IDCP is recognized by its particular histology that is a granulocytic epithelial lesion (GEL) which makes some people call it AIP with GEL. Still nowadays, the diagnosis of AIP is a challenge. AIP can only be definitively diagnosed by histological examination. The main differential diagnosis of AIP is, except chronic pancreatitis, pancreatic cancer. That explains why there are still some unnecessary resections. Several groups have proposed diagnostic criteria for AIP as in Japan, Korea, Germany, Italy and the United States. Thus, it is important to find an international consensus. Above all, it is important to find new criteria as specific markers in the serum and the pancreatic tissues, for example using proteomics, to be able to diagnosis both types of AIP, and distinguish AIP from pancreatic cancer in order to avoid surgical resection in patients with AIP. The aim of this project is to review all relevant studies about AIP and to document all the available diagnostic tools.