Manejo del aneurisma de aorta abdominal sintomático no roto: últimos adelanto / Management of symptomatic unruptured abdominal aortic aneurysms: state of the art

RESUMEN El aneurisma de aorta abdominal (AAA) sintomático no roto es una patología que involucra a aquellos pacientes con AAA intacto, pero que presentan dolor abdominal y/o lumbar atribuido al aneurisma. Esta forma de presentación clínica es po tencialmente mortal dado que su etiopatogenia comprende cambios agudos en la pared aórtica, incluyendo inflamación, lo que incrementa la probabilidad de ruptura inminente. Está claro que estos pacientes deben ser derivados a reparación del AAA. Sin embargo, el momento de la intervención es controvertido. Por lo tanto, el objetivo del presente trabajo fue revisar la información actualizada sobre el abordaje diagnóstico-terapéutico del AAA sintomático no roto.

ABSTRACT Symptomatic unruptured abdominal aortic aneurysm (AAA) refers to a group of patients with intact AAA but who present abdominal and/or lumbar pain attributed to the aneurysm. This form of clinical presentation is potentially fatal since its etiopathogenesis, involving acute changes in the aortic wall, including inflammation, increases the probability of impending rupture. It is clear that these patients should be referred to AAA repair. However, the timing of the intervention is contro versial. Therefore, the aim of the present work was to review updated information on the diagnostic-therapeutic approach of symptomatic unruptured AAA.

Endoscopically Active Ulcerative Colitis Is Associated With Asymptomatic Atherosclerotic Vascular Disease: A Case-Control Study.

BACKGROUND: Chronic inflammation in immune-mediated conditions has been associated with an increased risk in atherosclerotic disease. There is paucity of evidence regarding the prevalence of asymptomatic atherosclerosis in patients with ulcerative colitis (UC) and its association with disease activity. We sought to compare the prevalence of asymptomatic atherosclerotic disease between young patients with UC with and without mucosal healing (MH) and healthy control individuals. METHODS: An observational study was conducted in 2 hospitals in Buenos Aires, Argentina. Patients with UC 18 to 50 years of age with at least 1 previous colonoscopy in the last year were enrolled, along with age- and sex-matched healthy control individuals. Carotid and femoral ultrasound assessments were performed to determine the prevalence of atherosclerotic lesions and abnormal intima-media thickness (IMT). We compared the prevalence of atherosclerotic disease and the prevalence of abnormally increased IMT in at least 1 vascular territory. RESULTS: Sixty patients with UC and 60 healthy control individuals were enrolled. Mean age was 38 years and 53.33% were men. Although the prevalence of atherosclerotic lesions was similar in patients with UC without MH when compared with both patients with UC with MH and control individuals (3.7% vs 0% vs 6.67%; P = .1), we found a significant increase in abnormal IMT in at least 1 vascular territory in UC patients without MH when compared with healthy control individuals (48.15% vs 26.67%; P = .05). CONCLUSIONS: Patients with UC with active mucosal inflammation showed a significantly increased odds of asymptomatic femoral or carotid vascular disease when compared with control individuals.

Young patients with endoscopically active ulcerative colitis showed a significantly higher prevalence of abnormal intima-media thickness when compared with control individuals. Among patients with ulcerative colitis, age, disease duration, and C-reactive protein were associated with increased odds of asymptomatic vascular lesions.

Calidad de vida en pacientes pediátricos tratados con quimioterapia por diagnóstico de leucemia linfoblástica aguda / Quality of life in pediatric patients treated with chemotherapy for the diagnosis of acute lymphoblastic leukemia

La leucemia es una patología neoplásica maligna que constituye un problema de salud que afecta fundamentalmente a la población infantil. Así, se realizó un proceso investigativo con el objetivo de describir la calidad de vida en pacientes pediátricos de LLA con edades entre 2 y 18 años, atendidos en 2019, en el Hospital Pediátrico Baca Ortiz y en el Hospital de Solca - Núcleo Quito, Ecuador; para lo cual se hizo un estudio observacional, transversal, descriptivo, con enfoque cuantitativo. Los datos fueron recopilados mediante la revisión de las historias clínicas de los 60 pacientes en el contexto de investigación. El 66,7% correspondió al sexo masculino, el 43,3% tenía edades entre 2 y 4 años, el 38,3% tuvo fiebre como síntoma inicial. El síndrome de Down resultó la comorbilidad más frecuente (6,7%). En 54 pacientes se diagnosticó LLA tipo B. El 66,7% recibía terapia psicológica, 22 de los enfermos estaban en la fase de inducción y mantenimiento. El 65% abandonó la escuela mientras se le administraba quimioterapia. Predomina-ron los que consideraron su calidad de vida como buena, seguido de los que tuvieron severa afectación. Las mayores afectaciones en los participantes fueron: dificultades con la alimentación, presencia de dolor, falta de comunicación, existencia de ansiedad y presencia de estrés por la preocupación debido a la posible infectividad del tratamiento.

Leukemia is a malignant neoplastic disease that constitutes a health problem that mainly affects children. Thus, this research aimed to describe the quality of life in pediatric ALL patients between 2 and 18 years of age, treated in 2019, at the Baca Ortiz Pediatric Hospital and at the Solca Hospital - Núcleo Quito, Ecuador. A cross-sectional, descriptive, and observational study with a quantitative approach. Data were collected by reviewing the medical records of the 60 patients in the research context. 66.7% were male, 43.3% were between 2 and 4 years old, 38.3% had fever as the initial symptom. Down syndrome was the most frequent comorbidity (6.7%). Type B ALL was diagnosed in 54 patients. 66.7% received psychological therapy. 22 of the patients were in the induction and maintenance phase. 65% dropped out of school while recei-ving chemotherapy. Those ones who considered their quality of life as good predominated, followed by those ones who were severely affected. The greatest effects on the participants were: difficulties with feeding, presence of pain, lack of communication, existence of anxiety and presence of stress due to worry due to the possible infectivity of the treatment.

Enhancing electrocardiographic analysis by combining a high-resolution 12-lead ECG with novel software tools.

INTRODUCTION: Signal-averaged electrocardiography is a non-invasive, computerized technique that amplifies, filters, and averages cardiac electrical signals reducing contaminating noise to obtain a high-resolution record. The most widely used signal averaging (SA) method involves a bipolar X, Y, and Z orthogonal lead system. Information is limited regarding its application in the standard resting 12-lead ECG. A novel system combining a high-resolution 12-lead ECG (HR-ECG) registered by SA with advanced analysis tools is presented. HISTORY: Original programming of a commercially available signal-averaged HR-ECG device was modified, introducing more exhaustive electrocardiographic assessment instruments. DESCRIPTION: Using SA techniques and placing surface electrodes in the standard 12-lead ECG positions, a HR-ECG is acquired within a bandwidth of 0.25 to 262 Hz at a rate of 1000 samples per second. It is advisable to average at least 200 cycles, taking three to five minutes to record. The package includes different optional high-frequency filters, manual calipers, zoom/superimposing/amplification functions. CLINICAL ROLE: The main strength lies in obtaining a low noise HR-ECG with zooming capabilities without definition loss. Other potential advantages are the greater ease in performing high precision analysis and comparing different ECG leads simultaneously. CURRENT PROBLEMS: The primary limitation is the inability to document intermittent or dynamic electrocardiographic disorders because of averaging similar electrical cardiac cycles. FUTURE DEVELOPMENTS: Adding artificial intelligence and further refinements in the averaging process could lead to software upgrades. CONCLUSION: Integrating HR-ECG, obtained through SA techniques, with novel advanced analysis tools can enhance the ability to detect electrocardiographic disorders of permanent expression expeditiously.

Baboon Envelope Pseudotyped "Nanoblades" Carrying Cas9/gRNA Complexes Allow Efficient Genome Editing in Human T, B, and CD34+ Cells and Knock-in of AAV6-Encoded Donor DNA in CD34+ Cells.

Programmable nucleases have enabled rapid and accessible genome engineering in eukaryotic cells and living organisms. However, their delivery into human blood cells can be challenging. Here, we have utilized "nanoblades," a new technology that delivers a genomic cleaving agent into cells. These are modified murine leukemia virus (MLV) or HIV-derived virus-like particle (VLP), in which the viral structural protein Gag has been fused to Cas9. These VLPs are thus loaded with Cas9 protein complexed with the guide RNAs. Highly efficient gene editing was obtained in cell lines, IPS and primary mouse and human cells. Here, we showed that nanoblades were remarkably efficient for entry into human T, B, and hematopoietic stem and progenitor cells (HSPCs) thanks to their surface co-pseudotyping with baboon retroviral and VSV-G envelope glycoproteins. A brief incubation of human T and B cells with nanoblades incorporating two gRNAs resulted in 40 and 15% edited deletion in the Wiskott-Aldrich syndrome (WAS) gene locus, respectively. CD34+ cells (HSPCs) treated with the same nanoblades allowed 30-40% exon 1 drop-out in the WAS gene locus. Importantly, no toxicity was detected upon nanoblade-mediated gene editing of these blood cells. Finally, we also treated HSPCs with nanoblades in combination with a donor-encoding rAAV6 vector resulting in up to 40% of stable expression cassette knock-in into the WAS gene locus. Summarizing, this new technology is simple to implement, shows high flexibility for different targets including primary immune cells of human and murine origin, is relatively inexpensive and therefore gives important prospects for basic and clinical translation in the area of gene therapy.

Identification of novel, clonally stable, somatic mutations targeting transcription factors PAX5 and NKX2-3, the epigenetic regulator LRIF1, and BRAF in a case of atypical B-cell chronic lymphocytic leukemia harboring a t(14;18)(q32;q21).

Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) is usually straightforward, involving clinical, immunophenotypic (Matutes score), and (immuno)genetic analyses (to refine patient prognosis for treatment). CLL cases with atypical presentation (e.g., Matutes ≤ 3) are also encountered, and for these diseases, biology and prognostic impact are less clear. Here we report the genomic characterization of a case of atypical B-CLL in a 70-yr-old male patient; B-CLL cells showed a Matutes score of 3, chromosomal translocation t(14;18)(q32;q21) (BCL2/IGH), mutated IGHV, deletion 17p, and mutations in BCL2, NOTCH1 (subclonal), and TP53 (subclonal). Quite strikingly, a novel PAX5 mutation that was predicted to be loss of function was also seen. Exome sequencing identified, in addition, a potentially actionable BRAF mutation, together with novel somatic mutations affecting the homeobox transcription factor NKX2-3, known to control B-lymphocyte development and homing, and the epigenetic regulator LRIF1, which is implicated in chromatin compaction and gene silencing. Neither NKX2-3 nor LRIF1 mutations, predicted to be loss of function, have previously been reported in B-CLL. Sequencing confirmed the presence of these mutations together with BCL2, NOTCH1, and BRAF mutations, with the t(14;18)(q32;q21) translocation, in the initial diagnostic sample obtained 12 yr prior. This is suggestive of a role for these novel mutations in B-CLL initiation and stable clonal evolution, including upon treatment withdrawal. This case extends the spectrum of atypical B-CLL with t(14;18)(q32;q21) and highlights the value of more global precision genomics for patient follow-up and treatment in these patients.

Alphaviruses: Serological Evidence of Human Infection in Paraguay (2012-2013).

INTRODUCTION: Alphaviruses can produce febrile illness and encephalitis in dead-end hosts such as horses and humans. Within this genus, the Venezuelan Equine Encephalitis virus (VEEV) complex includes pathogenic epizootic subtypes and enzootic subtypes that are not pathogenic in horses (except subtype IE, Mexican strains), although they can cause febrile symptoms in humans. The Rio Negro virus (RNV-VEEV subtype VI) circulates in Argentina, where it was associated with undifferentiated febrile illness. Mayaro (MAYV) and Una (UNAV) viruses belong to a different group, the Semliki Forest virus complex, with confirmed circulation. OBJECTIVE: The present study aimed to determine RNV, MAYV, and UNAV seroprevalences by plaque reduction neutralization test in 652 samples of Paraguayan individuals mainly from the Central Department, between years 2012 and 2013. METHODS: Samples with antibodies titer >1:20 against RNV were also tested for Mosso das Pedras-subtype IF, subtype IAB, and Pixuna (PIXV)-subtype IV viruses that belongs to VEEV antigenic complex. RESULTS: The overall seroprevalence of RNV was 3.83%, and for UNAV it was 0.46%, and no neutralizing antibodies were detected against MAYV in the studied population. Two of the twenty-seven heterotypic samples were positive for PIXV. The 50.1% of neutralizing antibody titers against RNV were high (equal to or greater than 1/640), suggesting recent infections. The effect of age on the prevalence of RNV was negligible. CONCLUSIONS: These results bring new information about neglected alphaviruses in South America, and these data will serve as the basis for future studies of seroprevalence of other VEEV, and studies to search potential hosts and vectors of these viruses in the region.

Brugada phenocopy induced by severe pneumothorax.

A Brugada phenocopy has been defined as a clinical situation that presents with an abnormal electrocardiogram identical to any of the electrocardiographic patterns found in Brugada syndrome in the absence of the characteristic congenital genetic abnormalities. The first confirmed case of type 1 Brugada phenocopy associated with severe left pneumothorax is presented. A provocative test with ajmaline, which proved to be negative, was performed to confirm the diagnosis. The presence of ST-segment elevation in the context of pneumothorax is most infrequent.

Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome.

Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by the obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L), which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L, as consequence of Stx-induced endothelium damage, participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions.

Ataxia espinocerebelosa tipo 2: diagnóstico clínico y molecular de dos casos atendidos en el Hospital de Especialidades de las Fuerzas Armadas N°1 / Spinocerebellar ataxia type 2: clinical and molecular diagnosis of two cases treated at the Armed Forces N°1 Hospital

La ataxia espinocerebelosa tipo 2 (SCA2) es una enfermedad neurodegenerativa causada por la expansión del trinucleótido CAG en el exón 1 del gen Ataxina-2 (ATXN2), situado en la región cromosómica 12q23-24. Este es el primer reporte de diagnóstico molecular realizado en Ecuador para esta enfermedad. Presentación de los casos Dos pacientes ecuatorianos de género masculino de 39 y 46 años de edad fueron remitidos al Servicio de Genética Médica del Hospital de Especialidades de las Fuerzas Armadas Nº1 para identifcar el tipo de ataxia espinocerebelosa presente en cada caso. Para ambos pacientes, la evaluación clínica evidenció síntomas compatibles con una SCA2, el análisis genealógico mostró un patrón de herencia autosómico dominante y el diagnóstico molecular confrmó que la ataxia espinocerebelosa presente era de tipo 2. Conclusión El diagnóstico específco de las ataxias espinocerebelosas debe basarse principalmente en una correlación fenotípica-genotípica, la cual involucra evaluaciones clínicas, análisis genealógico y estudios genéticos moleculares para cada caso. La SCA2 constituye un tipo de enfermedad cuyo diagnóstico implica complejidades clínicas y genéticas, concluyendo que este proceso debe efectuarse con la inclusión del asesoramiento genético familiar, siendo el comienzo del manejo integral de esta enfermedad

Development of a Mouse Model of Shiga Toxin 2 (Stx2) Intoxication for Testing Therapeutic Agents Against Hemolytic Uremic Syndrome (HUS).

BACKGROUND: Hemolytic Uremic Syndrome (HUS) caused by infections with Shiga toxin (Stx)-producing E. coli is a life-threatening complication characterized by acute renal failure, thrombocytopenia and hemolytic anemia. Stx is the main pathogenic factor. Therefore, the mouse model by intravenous administration of a single lethal dose of Stx is often used to explore its pathogenic mechanisms. OBJECTIVE: The aim of this work was to develop an alternative mouse model of Stx type 2 (Stx2) intoxication to evaluate new therapeutic strategies. METHODS AND RESULTS: One lethal dose of Stx2 was divided in four daily doses. We observed a dose-dependent toxicity characterized by neutrophilia, leukocytopenia and renal damage. Most importantly, we demonstrated that the polyclonal anti-Stx2 serum was able to protect mice from fatal evolution even when administered together the third dose of Stx2. CONCLUSION: This model would provide an advantage for evaluation of therapeutic strategies. Furthermore, the results presented herein suggest that appropriate treatment with anti-Stx2 agents following the appearance of initial clinical signs may block the ongoing outcome or may alleviate disease in patients who have just been diagnosed with HUS. However, the delay in the onset of therapy would be unsafe.

[Primary angioplasty in diabetic and non-diabetic patients with acute myocardial infarction: Predictors of mortality]. / Angioplastia primaria en diabéticos vs. no diabéticos con infarto agudo de miocardio: predictores de mortalidad.

BACKGROUND AND AIMS: Diabetes mellitus is one of the major risk factors for coronary artery disease. The aim of this study was to evaluate in-hospital mortality and during follow-up of diabetic patients with acute myocardial infarction treated with primary angioplasty and to determine its predictors. MATERIALS AND METHODS: Eight hundred and sixty six patients were retrospectively enrolled from January 1993 to December 2013. A hundred patients with a diagnosis of diabetes were evaluated. The median follow-up was 121 months in 90% of the population. RESULTS: Of the 100 diabetic patients included (11.56%) 86% were male and 50% older than 70 years. Overall, 76% presented with a Killip-Kimball grade of 1 at admission and 16% presented with a Killip-Kimball 4. The most frequent location of myocardial infarction was anterior and 65% had 2 or more coronary vessel disease. In-hospital mortality was 15%. The only independent variable significantly associated was the Killip-Kimball at admission. Mortality during follow up was 35% and its independent predictors were: age, Killip-Kimball at admission and use of angiotensin-converting enzyme inhibitors Interestingly, in the non-diabetic group, Killip-kimball at admission failed to predict long-term mortality CONCLUSION: This group of diabetic patients was older, and with a higher prevalence of 2 or more vessel disease. Cardiogenic shock on admission was the only independent predictor of in-hospital death and along with age and angiotensin-converting enzyme inhibitor use, an independent predictor of mortality during long term follow-up.

La importancia de un diagnóstico clínico temprano en la distrofia muscular de Duchenne: mutaciones encontradas en siete pacientes ecuatorianos / The importance of early clinical diagnosis in Duchenne muscular dystrophy: mutations found in seven Ecuadorian patients

Duchenne muscular dystrophy (DMD) is a recessive X-linked genetic disease caused by mutations in the dystrophin gene. In Ecuador, the procedure to diagnose this disease is not standardized by the public health system. The aim of this study was to propose an algorithm for DMD diagnosis in order to establish a standard protocol, emphasize early diagnosis and identify pathological mutations in affected patients. Subjects and methods We reported seven Ecuadorian male patients with clinical signs of DMD. They were evaluated by pediatricians, neurologists and geneticists, who made a medical record considering age of onset, pedigree, symptoms, serum CK levels and EMG analysis results. The confrmatory diagnosis and the type of mutations were identifed by molecular genetic testing. Results The most common symptoms reported from patients were frequent falls, unstable gait, diminished muscular strength, calf pseudohypertrophy and diffculty climbing stairs. Moreover, two types of mutations in DMD gene were found, duplications and deletions. The effects of mutations in the reading frame were out-of frame for all patients, except for one, whose mutations showed an in-frame effect on the gene. Conclusions It is important to emphasize the timely diagnosis of DMD to reduce the appearance of new cases, as well as the emotional impact on families. When there is a suspicion of a neuromuscular condition in male children, we recommend following the proposed algorithm in order to offer an early and effcient DMD diagnosis, confrm the disease and to provide an appropriate genetic counseling to patients and their families

La Distrofa Muscular de Duchenne (DMD) es una enfermedad genética recesiva ligada al cromosoma X, causada por mutaciones en el gen de la distrofna. En Ecuador, el procedimiento para diagnosticar esta enfermedad no ha sido estandarizado por el Sistema de Salud Pública. El objetivo de este estudio fue proponer un algoritmo para el diagnóstico de DMD con el fn de establecer un protocolo estándar, enfatizar el diagnóstico temprano e identifcar las mutaciones patológicas en los pacientes afectados. Sujetos y métodos Se reportaron siete pacientes ecuatorianos masculinos con signos clínicos de DMD. Estos fueron evaluados por pediatras, neurólogos y genetistas, quienes elaboraron una historia clínica incluyendo datos de la edad de inicio, árbol genealógico, síntomas, resultados de los niveles de CK en suero y el análisis del EMG. El diagnóstico confrmatorio de DMD y el tipo de mutaciones fueron identifcados con pruebas genéticas moleculares. Resultados Los síntomas más comunes reportados en los pacientes fueron caídas frecuentes, inestabilidad en la marcha, disminución de la fuerza muscular, pseudo-hipertrofa de pantorrillas y difcultad para subir escaleras. Además, dos tipos de mutaciones fueron halladas en el gen DMD: duplicaciones y deleciones. Los efectos de las mutaciones en el marco de lectura del gen de la distrofna fueron out-frame para todos los pacientes, excepto en uno, cuyas mutaciones tuvieron un efecto in-frame sobre el gen. Conclusiones Enfatizar en el diagnóstico temprano de DMD es importante para reducir la aparición de nuevos casos, así como el impacto emocional en las familias. Cuando existe la sospecha de una enfermedad neuromuscular en niños, recomendamos seguir el algoritmo propuesto con el fn de ofrecer un diagnóstico oportuno y efciente, confrmar el diagnóstico de la enfermedad y proveer el asesoramiento genético apropiado a los pacientes y sus familiares

Leukotriene C4 increases the susceptibility of adult mice to Shiga toxin-producing Escherichia coli infection.

Shiga toxin-producing Escherichia coli (STEC) is a food-borne pathogen that causes hemorrhagic colitis. Under some circumstances, Shiga toxin (Stx) produced within the intestinal tract enters the bloodstream, leading to systemic complications that may cause the potentially fatal hemolytic-uremic syndrome (HUS). Despite STEC human infection is characterized by acute inflammation of the colonic mucosa, little is known regarding the role of proinflammatory mediators like cysteine leukotrienes (cysLTs) in this pathology. Thus, the aim of this work was to analyze whether leukotriene C4 (LTC4) influences STEC pathogenesis in mice. We report that exogenous LTC4 pretreatment severely affected the outcome of STEC gastrointestinal infection. LTC4-pretreated (LTC4+) and STEC-infected (STEC+) mice showed an increased intestinal damage by histological studies, and a decreased survival compared to LTC4-non-pretreated (LTC4-) and STEC+ mice. LTC4+/STEC+ mice that died after the infection displayed neutrophilia and high urea levels, indicating that the cause of death was related to Stx2-toxicity. Despite the differences observed in the survival between LTC4+ and LTC4- mice after STEC infection, both groups showed the same survival after Stx2-intravenous inoculation. In addition, LTC4 pretreatment increased the permeability of mucosal intestinal barrier, as assessed by FITC-dextran absorption experiments. Altogether these results suggest that LTC4 detrimental effect on STEC infection is related to the increased passage of pathogenic factors to the bloodstream. Finally, we showed that STEC infection per se increases the endogenous LTC4 levels in the gut, suggesting that this inflammatory mediator plays a role in the pathogenicity of STEC infection in mice, mainly by disrupting the mucosal epithelial barrier.

River-derived humic substances as iron chelators in seawater.

The speciation of iron(III) in oxic seawater is dominated by its hydrolysis and sedimentation of insoluble iron(III)-oxyhydroxide. As a consequence, many oceanic areas have very low iron levels in surface seawater which leads to iron deficiency since phytoplankton require iron as a micronutrient in order to grow. Fortunately, iron solubility is not truly as low as Fe(III) solubility measurements in inorganic seawater would suggest, since oceanic waters contain organic molecules which tend to bind the iron and keep it in solution. Various iron-binding organic ligands which combine to stabilize dissolved iron have been detected and thoroughly investigated in recent years. However, the role of iron-binding ligands from terrestrial sources remains poorly constrained. Blackwater rivers supply large amounts of natural organic material (NOM) to the ocean. This NOM (which consists mainly of vascular plant-derived humic substances) is able to greatly enhance iron bioavailability in estuaries and coastal regions, however, breakdown processes lead to a rapid decrease of river-derived NOM concentrations with increasing distance from land. It has therefore been argued that the influence of river-derived NOM on iron biogeochemistry in offshore seawater does not seem to be significant. Here we used a standard method based on 59Fe as a radiotracer to study the solubility of Fe(III)-oxyhydroxide in seawater in the presence of riverine NOM. We aimed to address the question how effective is freshwater NOM as an iron chelator under open ocean conditions where the concentration of land-derived organic material is about 3 orders of magnitude smaller than in coastal regions, and does this iron chelating ability vary between NOM from different sources and between different size fractions of the river-borne NOM. Our results show that the investigated NOM fractions were able to substantially enhance Fe(III)-oxyhydroxide solubility in seawater at concentrations of the NOM ≥ 5 µg L- 1. Terrigenous NOM concentrations ≥ 5 µg L- 1 are in no way unusual in open ocean surface waters especially of the Arctic and the North Atlantic Oceans. River-derived humic substances could therefore play a greater role as iron carriers in the ocean than previously thought.

Association of haemolytic uraemic syndrome with dysregulation of chemokine receptor expression in circulating monocytes.

Haemolytic uraemic syndrome (HUS) is the major complication of Escherichia coli gastrointestinal infections that are Shiga toxin (Stx) producing. Monocytes contribute to HUS evolution by producing cytokines that sensitize endothelial cells to Stx action and migration to the injured kidney. As CC chemokine receptors (CCRs) are involved in monocyte recruitment to injured tissue, we analysed the contribution of these receptors to the pathogenesis of HUS. We analysed CCR1, CCR2 and CCR5 expression in peripheral monocytes from HUS patients during the acute period, with healthy children as controls. We observed an increased expression of CCRs per cell in monocytes from HUS patients, accompanied by an increase in the absolute number of monocytes CCR1+, CCR2+ and CCR5+. It is interesting that prospective analysis confirmed that CCR1 expression positively correlated with HUS severity. The evaluation of chemokine levels in plasma showed that regulated on activation of normal T-cell-expressed and -secreted (RANTES) protein was reduced in plasma from patients with severe HUS, and this decrease correlated with thrombocytopenia. Finally, the expression of the higher CCRs was accompanied by a loss of functionality which could be due to a mechanism for desensitization to compensate for altered receptor expression. The increase in CCR expression correlates with HUS severity, suggesting that the dysregulation of these receptors might contribute to an increased risk of renal damage. Activated monocytes could be recruited by chemokines and then receptors could be dysregulated. The dysregulation of CCRs and their ligands observed during the acute period suggests that a chemokine pathway would participate in HUS development.

Differential expression of the fractalkine chemokine receptor (CX3CR1) in human monocytes during differentiation.

Circulating monocytes (Mos) may continuously repopulate macrophage (MAC) or dendritic cell (DC) populations to maintain homeostasis. MACs and DCs are specialized cells that play different and complementary immunological functions. Accordingly, they present distinct migratory properties. Specifically, whereas MACs largely remain in tissues, DCs are capable of migrating from peripheral tissues to lymphoid organs. The aim of this work was to analyze the expression of the fractalkine receptor (CX3CR1) during the monocytic differentiation process. Freshly isolated Mos express high levels of both CX3CR1 mRNA and protein. During the Mo differentiation process, CX3CR1 is downregulated in both DCs and MACs. However, MACs showed significantly higher CX3CR1 expression levels than did DC. We also observed an antagonistic CX3CR1 regulation by interferon (IFN)-γ and interleukin (IL)-4 during MAC activation through the classical and alternative MAC pathways, respectively. IFN-γ inhibited the loss of CX3CR1, but IL-4 induced it. Additionally, we demonstrated an association between CX3CR1 expression and apoptosis prevention by soluble fractalkine (sCX3CL1) in Mos, DCs and MACs. This is the first report demonstrating sequential and differential CX3CR1 modulation during Mo differentiation. Most importantly, we demonstrated a functional link between CX3CR1 expression and cell survival in the presence of sCX3CL1.

Angioplastia primaria en el infarto agudo de miocardio: predictores de eventos en el seguimiento a largo plazo / Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: Long-Term Predictors of Adverse Events

Introducción: El infarto agudo de miocardio (IAM) es una de las principales causas de muerte cardiovascular. Los tratamientos de reperfusión, aplicados dentro de las primeras horas del evento, han contribuido a disminuir significativamente esa mortalidad. No existen en nuestro país registros con seguimiento a largo plazo de pacientes con IAM tratados con angioplastia transluminal coronaria primaria (ATCP). Objetivos: Evaluar los resultados intrahospitalarios y el pronóstico alejado de pacientes sometidos a ATCP por IAM con supra-desnivel del segmento ST (IAMCST) y su relación con las principales variables clínicas y terapéuticas aplicadas en diferentes décadas (1993-2002 vs. 2003-2012). Material y métodos: Estudio observacional y retrospectivo de todos los pacientes con diagnóstico de IAMCST a los que se les realizó una ATCP en dos hospitales de comunidad entre los años 1993 y 2012. Resultados: Se incluyeron 851 pacientes ingresados consecutivamente entre los años 1993 y 2012. La edad promedio fue de 61 ± 12 años y la mediana de seguimiento fue de 7,8 años en el 85% de la población. La mortalidad intrahospitalaria total fue del 6% y del 1,6% excluidos los pacientes con shock al ingreso; las variables independientes asociadas fueron la edad (OR 1,06, IC 1,03-1,09; p < 0,001), el sexo femenino (OR 3,1, IC 1,5-6,2; p < 0,002), la diabetes mellitus (OR 3,9, IC 1,86-8; p < 0,001) y la enfermedad de tres vasos coronarios (OR 4,3, IC 2,1-8,6; p < 0,001); el flujo final TIMI 3 fue una variable predictora de menor mortalidad intrahospitalaria (OR 0,28, IC 0,08-0,11; p < 0,008). La mortalidad global en el seguimiento fue del 14,3% y los predictores independientes fueron la edad (OR 3,1, IC 1,8-5,5; p < 0,001), la diabetes mellitus (OR 2,3, IC 1,25-4,3; p < 0,007) y la clase C o D de la clasificación de Killip y Kimball (KK) al ingreso (OR 4, IC 1,7-9; p < 0,001); la utilización de stent se asoció con menor mortalidad global alejada (OR 0,35, IC 0,21-0,6; p < 0,001). Conclusiones: En este grupo de pacientes con IAMCST, la ATCP aplicada adecuadamente y una elevada tasa de seguimiento alejado permitió obtener resultados intrahospitalarios favorables que se mantienen en el largo plazo. La edad avanzada al momento del IAMCST, la diabetes mellitus, el sexo femenino y la presencia de lesiones significativas en más de un vaso epicárdico mayor fueron los predictores de mortalidad intrahospitalaria, mientras que los dos primeros (edad y diabetes mellitus) y el KK C o D fueron predictores independientes de mortalidad en el seguimiento. Los pacientes asistidos durante la segunda década mostraron una tendencia no significativa a menor mortalidad intrahospitalaria en comparación con los de la primera década.

Introduction: Acute myocardial infarction (AMI) is one of the leading causes of cardiovascular death. Reperfusion treatments performed within the first hours have contributed to produce a significant reduction in mortality. In our country, there are no long-term follow-up registries of AMI patients treated with primary percutaneous coronary intervention (PCI). Objectives: The aim of this study is to evaluate the in-hospital results and long-term outcome of ST-segment elevation AMI (STEMI) patients undergoing primary PCI and their correlation with the main clinical and therapeutic variables applied in different decades (1993-2002 vs. 2003-2012). Methods: We performed an observational and retrospective study of all STEMI patients undergoing primary PCI in two community hospitals between 1993 and 2012. Results: The study included 851 patients consecutively admitted between 1993 and 2012. Mean age was 61 ± 12 years and median follow-up was 7.8 years in 85% of the population. In-hospital mortality was 6% and 1.6% when patients with shock at admission were excluded. It was independently associated with age (OR 1.06, CI 1.03-1.09; p < 0.001), female sex (OR 3.1, CI 1.5-6.2; p < 0.002), diabetes mellitus (OR 3.9, CI 1.86-8; p < 0.001) and three-vessel disease (OR 4.3, CI 2.1-8.6; p < 0.001). Conversely, final TIMI grade 3 flow predicted lower in-hospital mortality (OR 0.28, CI 0.08-0.11; p < 0.008). During follow-up, overall mortality was 14.3% and the independent predictors were age (OR 3.1, CI 1.8-5.5; p < 0.001), diabetes mellitus (OR 2.3, CI 1.25-4.3; p < 0.007) and Killip and Kimball (KK) class C or D at admission (OR 4, CI 1.7-9; p < 0.001); stent implant was associated with lower overall long-term mortality (OR 0.35, CI 0.21-0.6; p < 0.001). Conclusions: In this group of STEMI patients, the adequate use of primary PCI and the high rate of patients at long-term follow-up allowed the collection of favorable in-hospital and long-term results. Advanced age at the moment of STEMI, diabetes mellitus, female sex and multiple vessel disease were predictors of in-hospital mortality, while age, diabetes mellitus and KK class C or D were independent predictors of mortality during follow-up. Patients treated during the second decade showed a non-significant trend towards reduced in-hospital mortality compared with those of the first decade.

Angioplastia primaria en el infarto agudo de miocardio: predictores de eventos en el seguimiento a largo plazo / Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: Long-Term Predictors of Adverse Events

Introducción: El infarto agudo de miocardio (IAM) es una de las principales causas de muerte cardiovascular. Los tratamientos de reperfusión, aplicados dentro de las primeras horas del evento, han contribuido a disminuir significativamente esa mortalidad. No existen en nuestro país registros con seguimiento a largo plazo de pacientes con IAM tratados con angioplastia transluminal coronaria primaria (ATCP). Objetivos: Evaluar los resultados intrahospitalarios y el pronóstico alejado de pacientes sometidos a ATCP por IAM con supra-desnivel del segmento ST (IAMCST) y su relación con las principales variables clínicas y terapéuticas aplicadas en diferentes décadas (1993-2002 vs. 2003-2012). Material y métodos: Estudio observacional y retrospectivo de todos los pacientes con diagnóstico de IAMCST a los que se les realizó una ATCP en dos hospitales de comunidad entre los años 1993 y 2012. Resultados: Se incluyeron 851 pacientes ingresados consecutivamente entre los años 1993 y 2012. La edad promedio fue de 61 ± 12 años y la mediana de seguimiento fue de 7,8 años en el 85% de la población. La mortalidad intrahospitalaria total fue del 6% y del 1,6% excluidos los pacientes con shock al ingreso; las variables independientes asociadas fueron la edad (OR 1,06, IC 1,03-1,09; p < 0,001), el sexo femenino (OR 3,1, IC 1,5-6,2; p < 0,002), la diabetes mellitus (OR 3,9, IC 1,86-8; p < 0,001) y la enfermedad de tres vasos coronarios (OR 4,3, IC 2,1-8,6; p < 0,001); el flujo final TIMI 3 fue una variable predictora de menor mortalidad intrahospitalaria (OR 0,28, IC 0,08-0,11; p < 0,008). La mortalidad global en el seguimiento fue del 14,3% y los predictores independientes fueron la edad (OR 3,1, IC 1,8-5,5; p < 0,001), la diabetes mellitus (OR 2,3, IC 1,25-4,3; p < 0,007) y la clase C o D de la clasificación de Killip y Kimball (KK) al ingreso (OR 4, IC 1,7-9; p < 0,001); la utilización de stent se asoció con menor mortalidad global alejada (OR 0,35, IC 0,21-0,6; p < 0,001). Conclusiones: En este grupo de pacientes con IAMCST, la ATCP aplicada adecuadamente y una elevada tasa de seguimiento alejado permitió obtener resultados intrahospitalarios favorables que se mantienen en el largo plazo. La edad avanzada al momento del IAMCST, la diabetes mellitus, el sexo femenino y la presencia de lesiones significativas en más de un vaso epicárdico mayor fueron los predictores de mortalidad intrahospitalaria, mientras que los dos primeros (edad y diabetes mellitus) y el KK C o D fueron predictores independientes de mortalidad en el seguimiento. Los pacientes asistidos durante la segunda década mostraron una tendencia no significativa a menor mortalidad intrahospitalaria en comparación con los de la primera década.(AU)

Introduction: Acute myocardial infarction (AMI) is one of the leading causes of cardiovascular death. Reperfusion treatments performed within the first hours have contributed to produce a significant reduction in mortality. In our country, there are no long-term follow-up registries of AMI patients treated with primary percutaneous coronary intervention (PCI). Objectives: The aim of this study is to evaluate the in-hospital results and long-term outcome of ST-segment elevation AMI (STEMI) patients undergoing primary PCI and their correlation with the main clinical and therapeutic variables applied in different decades (1993-2002 vs. 2003-2012). Methods: We performed an observational and retrospective study of all STEMI patients undergoing primary PCI in two community hospitals between 1993 and 2012. Results: The study included 851 patients consecutively admitted between 1993 and 2012. Mean age was 61 ± 12 years and median follow-up was 7.8 years in 85% of the population. In-hospital mortality was 6% and 1.6% when patients with shock at admission were excluded. It was independently associated with age (OR 1.06, CI 1.03-1.09; p < 0.001), female sex (OR 3.1, CI 1.5-6.2; p < 0.002), diabetes mellitus (OR 3.9, CI 1.86-8; p < 0.001) and three-vessel disease (OR 4.3, CI 2.1-8.6; p < 0.001). Conversely, final TIMI grade 3 flow predicted lower in-hospital mortality (OR 0.28, CI 0.08-0.11; p < 0.008). During follow-up, overall mortality was 14.3% and the independent predictors were age (OR 3.1, CI 1.8-5.5; p < 0.001), diabetes mellitus (OR 2.3, CI 1.25-4.3; p < 0.007) and Killip and Kimball (KK) class C or D at admission (OR 4, CI 1.7-9; p < 0.001); stent implant was associated with lower overall long-term mortality (OR 0.35, CI 0.21-0.6; p < 0.001). Conclusions: In this group of STEMI patients, the adequate use of primary PCI and the high rate of patients at long-term follow-up allowed the collection of favorable in-hospital and long-term results. Advanced age at the moment of STEMI, diabetes mellitus, female sex and multiple vessel disease were predictors of in-hospital mortality, while age, diabetes mellitus and KK class C or D were independent predictors of mortality during follow-up. Patients treated during the second decade showed a non-significant trend towards reduced in-hospital mortality compared with those of the first decade.(AU)