Genetic Abrogation of Adenosine A3 Receptor Prevents Uninephrectomy and High Salt-Induced Hypertension.

BACKGROUND: Early-life reduction in nephron number (uninephrectomy [UNX]) and chronic high salt (HS) intake increase the risk of hypertension and chronic kidney disease. Adenosine signaling via its different receptors has been implicated in modulating renal, cardiovascular, and metabolic functions as well as inflammatory processes; however, the specific role of the A3 receptor in cardiovascular diseases is not clear. In this study, gene-modified mice were used to investigate the hypothesis that lack of A3 signaling prevents the development of hypertension and attenuates renal and cardiovascular injuries following UNX in combination with HS (UNX-HS) in mice. METHODS AND RESULTS: Wild-type (A3 (+/+)) mice subjected to UNX-HS developed hypertension compared with controls (mean arterial pressure 106±3 versus 82±3 mm Hg; P<0.05) and displayed an impaired metabolic phenotype (eg, increased adiposity, reduced glucose tolerance, hyperinsulinemia). These changes were associated with both cardiac hypertrophy and fibrosis together with renal injuries and proteinuria. All of these pathological hallmarks were significantly attenuated in the A3 (-/-) mice. Mechanistically, absence of A3 receptors protected from UNX-HS-associated increase in renal NADPH oxidase activity and Nox2 expression. In addition, circulating cytokines including interleukins 1β, 6, 12, and 10 were increased in A3 (+/+) following UNX-HS, but these cytokines were already elevated in naïve A3 (-/-) mice and did not change following UNX-HS. CONCLUSIONS: Reduction in nephron number combined with chronic HS intake is associated with oxidative stress, chronic inflammation, and development of hypertension in mice. Absence of adenosine A3 receptor signaling was strongly protective in this novel mouse model of renal and cardiovascular disease.

Renal palliative care – where to after the PACKS study?

The PAlliative Care in chronic Kidney diSease study (PACKS study) is examining quality of life, decision making and decisional conflict, costs and mortality in patients with advanced chronic kidney disease who have opted for palliative care. It is also exploring the impact of the decision on the quality of life of carers. The study includes adult patients with end stage (stage 5) chronic kidney disease who have opted for palliative care, adult carers of these patients and renal physicians/clinical nurse specialists who have experience of treating patients with end stage chronic kidney disease who have opted for palliative care.
Early initial findings relate to clinician perspectives on patient decisional conflict, in making complex decisions between dialysis and conservative management. Interviews were conducted with nephrologists and clinical nurse specialists across 10 renal centres in the UK. Themes with associated subthemes include “Frequent changing of mind regarding treatment options,” “A paternalistic approach to decision-making and “Intricacy of the decision”. These findings will be presented and recommendations for future research and education made. Clinicians need to take a more patient centered approach to decision-making. Interventions aimed at increasing understanding of renal disease and its treatments may reduce decisional conflict and raise decisional quality but require testing in the renal specialty.

Outlier effects on robust joint modelling of longitudinal and survival data

Robust joint modelling is an emerging field of research. Through the advancements in electronic patient healthcare records, the popularly of joint modelling approaches has grown rapidly in recent years providing simultaneous analysis of longitudinal and survival data. This research advances previous work through the development of a novel robust joint modelling methodology for one of the most common types of standard joint models, that which links a linear mixed model with a Cox proportional hazards model. Through t-distributional assumptions, longitudinal outliers are accommodated with their detrimental impact being down weighed and thus providing more efficient and reliable estimates. The robust joint modelling technique and its major benefits are showcased through the analysis of Northern Irish end stage renal disease patients. With an ageing population and growing prevalence of chronic kidney disease within the United Kingdom, there is a pressing demand to investigate the detrimental relationship between the changing haemoglobin levels of haemodialysis patients and their survival. As outliers within the NI renal data were found to have significantly worse survival, identification of outlying individuals through robust joint modelling may aid nephrologists to improve patient's survival. A simulation study was also undertaken to explore the difference between robust and standard joint models in the presence of increasing proportions and extremity of longitudinal outliers. More efficient and reliable estimates were obtained by robust joint models with increasing contrast between the robust and standard joint models when a greater proportion of more extreme outliers are present. Through illustration of the gains in efficiency and reliability of parameters when outliers exist, the potential of robust joint modelling is evident. The research presented in this thesis highlights the benefits and stresses the need to utilise a more robust approach to joint modelling in the presence of longitudinal outliers.

Improvement of Mineral and Bone Metabolism Markers Is Associated with Better Survival in Haemodialysis Patients: the COSMOS Study

BACKGROUND: Abnormalities in serum phosphorus, calcium and parathyroid hormone (PTH) have been associated with poor survival in haemodialysis patients. This COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) analysis assesses the association of high and low serum phosphorus, calcium and PTH with a relative risk of mortality. Furthermore, the impact of changes in these parameters on the relative risk of mortality throughout the 3-year follow-up has been investigated. METHODS:COSMOS is a 3-year, multicentre, open-cohort, prospective study carried out in 6797 adult chronic haemodialysis patients randomly selected from 20 European countries. RESULTS:Using Cox proportional hazard regression models and penalized splines analysis, it was found that both high and low serum phosphorus, calcium and PTH were associated with a higher risk of mortality. The serum values associated with the minimum relative risk of mortality were 4.4 mg/dL for serum phosphorus, 8.8 mg/dL for serum calcium and 398 pg/mL for serum PTH. The lowest mortality risk ranges obtained using as base the previous values were 3.6-5.2 mg/dL for serum phosphorus, 7.9-9.5 mg/dL for serum calcium and 168-674 pg/mL for serum PTH. Decreases in serum phosphorus and calcium and increases in serum PTH in patients with baseline values of >5.2 mg/dL (phosphorus), >9.5 mg/dL (calcium) and <168 pg/mL (PTH), respectively, were associated with improved survival. CONCLUSIONS:COSMOS provides evidence of the association of serum phosphorus, calcium and PTH and mortality, and suggests survival benefits of controlling chronic kidney disease-mineral and bone disorder biochemical parameters in CKD5D patients.

Heart failure in young adults

Heart failure (HF) is a major health concern affecting 15 million people in Europe and around 900 000 people in the U.K. HF predominantly affects the elderly, with the mean age of patients with a diagnosis of HF between 70 and 80 years. Most previous HF studies have accordingly focused on older patients. Although HF is less common in younger adults (<65 years), 15% to 20% of patients hospitalised with HF are younger than 60 years of age. Very few studies have described the characteristics of younger adults with HF and its outcome. The aims of this thesis are to describe the clinical characteristics of younger adults with HF, explore the epidemiology of HF in younger adults and determine their short- and long-term outcomes. This was made possible by access multiple databases consisting of large patient cohorts with HF. The first chapter is a systematic literature review of younger adults with HF. Gaps in the current literature were identified and the thesis focused on some of these. The CHARM study allows detail characterisations of younger adults with HF. It recorded characteristics of patients with HF, including symptoms and signs of HF, electrocardiographic changes, chest radiographic findings, and also left ventricular ejection fraction. HF hospitalisations and its precipitating factors were also recorded systematically. Younger adults were more likely to have a third heart sound and hepatomegaly, but less likely to have pulmonary crackles and peripheral oedema. Similarly, radiological findings in younger adults were less likely to show interstitial pulmonary oedema or pleural effusion. Interestingly, younger adults aged <40 years not only have similar HF hospitalisation rate to older patients, however during their presentation with decompensated HF, they were less likely to have clinical pulmonary oedema and radiological signs of HF. Physicians managing younger adults with HF need to be aware of this. Younger adults were also less compliant with medications and lifestyle restriction resulting in hospitalisation with decompensated HF. Fortunately, despite these challenges, mortality rates in younger adults with HF were lower compared to older patients. To further substantiate the findings from the CHARM study, the MAGGIC study, a meta-analysis consists of over 40 000 patients with HF from large observational studies and randomised controlled trials, was examined. In both databases, the commonest aetiology of HF in younger adults was dilated cardiomyopathy. The ejection fraction was the lowest in younger adults. Similar to the CHARM study, mortality rates in younger adults were lower compared to older patients. However, in the MAGGIC study, by stratifying mortality into patients with preserved ejection fraction and with reduced ejection fraction, younger patients with preserved ejection fraction have a much lower mortality rate compared to patients with reduced ejection fraction. Findings from clinical trials are not always reflective of the real life clinical practice. The U.K. Clinical Practice Research Datalink (CPRD), a large and well-validated primary care database with 654 practices contributing information into the database representing approximated 8% of the U.K. population, is a rich dataset offering a unique opportunity to examine the characteristics, treatments, and outcomes of younger adults with HF in the community. In contrast to the CHARM and MAGGIC studies, younger adults aged <40 years were stratified into 20-29 and 30-39 years in the CPRD analysis. This is possible due to the larger number of younger adults with HF. Further stratifying the younger age groups demonstrated heterogeneity among younger adults with HF. In contrast to previous data showing younger adults have lower co-morbidities, the proportions of depression, chronic kidney disease, asthma, and any connective tissue disease were high among patients aged 20-29 years in the analysis from the CPRD. Surprisingly, the treatment rates for angiotensin converting enzyme (ACE) inhibitor, and aldosterone antagonist were the lowest in patients aged 20-29 years. With the exception of patients aged ≥80 years, treatment rate with beta-blocker was also the lowest in patients aged 20-29 years. With over two decades of follow up, long-term mortality rates in younger adults with HF can be determined. The mortality rates continued to decline from 1988 to 2011. Physicians managing younger adults with HF can now use this contemporary data to provide prognostic information to patients and their family. A hospital administrative database is the logical next platform to explore younger adults with HF. The Alberta Ministry of Health database links an outpatient database to a hospitalisation database providing ample data to examine the relationship between outpatient clinic visits and hospital admissions in younger adults with HF. Following a diagnosis of HF in the outpatient setting, younger adults were admitted to the hospital with decompensated HF much sooner than older patients. Younger adults also presented to emergency department more frequently following their first hospitalisation for HF. In conclusion, this thesis presented the characteristics and outcomes of younger adults with HF, and helped to extend our current understanding on this important topic. I hope the data presented here will benefit not only physicians looking after younger adults with HF, but also patients and their family.

Doença renal infantil : qualidade de vida

Introdução: A crescente incidência de doenças crónicas, nomeadamente a patologia renal, dificulta o desfrutar de uma vida normal, dadas as modificações ocorridas no quotidiano. Objetivos: Caracterizar a qualidade de vida percebida pelas crianças com patologia renal que frequentam campos de férias e analisar a relação entre as variáveis sociodemográficas e clínicas. Metodologia: Estudo Ibérico descritivo-correlacional e transversal, misto: quantitativo e qualitativo. A amostra é composta por 29 crianças espanholas e 13 portuguesas, com patologia renal crónica, que frequentaram campos de férias com idades entre 7 e 17 anos. Utilizou-se a escala KINDL (Bullinger & Ravens-Sieberer, 1998a, 1998b), que contempla 7 dimensões: Bem-estar Físico, Bem-Estar Emocional, Autoestima, Família, Amigos, Escola e Situação Clínica. Agregaram-se 6 questões sociodemográficas e um bloco de notas. Resultados: Os participantes revelaram uma perceção positiva da qualidade de vida. A dimensão “Autoestima” foi a melhor percecionada e o “Bem-estar Emocional” a pior. As crianças de nacionalidade espanhola percecionaram melhor qualidade de vida. Relativamente às restantes variáveis, as diferenças não foram estatisticamente significativas. Pela análise de conteúdo efetuada aos testemunhos, emergiram sentimentos positivos, o que nos permite inferir que o campo de férias foi uma atividade que contribuiu para a socialização e melhoria da qualidade de vida das crianças. Conclusão: Estes dados revelam que seria benéfico um acompanhamento individualizado, mais direcionado às necessidades específicas de cada criança, por uma equipa multidisciplinar. Os campos de férias enquanto formativos e lúdicos são essenciais. Palavras-chave: Qualidade de vida; Doença renal; Acampamento.

L’évaluation des déterminants des paramètres hémodynamiques centraux à l’aide de la cohorte populationnelle CARTaGENE.

Les maladies cardiovasculaires ont un impact considérable sur la vie des Canadiens, et de nombreux efforts ont permis d’identifier différents facteurs de risque associés à cette condition. L’hypertension artérielle représente un de ces facteurs modifiables les plus importants. Quoique l’hypertension est définie à l’aide de mesures de pression artérielle en périphérie, il devient de plus en plus apparent que la mesure de pression centrale et de ses composantes auraient des avantages au niveau de la prédiction de la survenue d’événements cardiovasculaires. Le présent mémoire vise à mieux caractériser deux déterminants de cette pression centrale, le traitement antihypertenseur à base de bêtabloqueurs et l’insuffisance rénale chronique précoce. En utilisant les données recueillies dans la banque de données populationnelle CARTaGENE, il a été possible à l’aide d’analyses statistiques par appariement basé sur le coefficient de propension de démontrer que l’utilisation d’agents antihypertensifs de type bêtabloqueurs était associée à un profil hémodynamique central défavorable. Ainsi, les individus recevant ces agents avaient une pression centrale et une amplification artérielle plus élevées que des individus du groupe contrôle apparié et ce, malgré une pression périphérique identique. Cet effet semblait être incomplètement expliqué par la réduction du rythme cardiaque associé à l’utilisation de bêtabloqueurs. Aussi, il a été démontré que l’insuffisance rénale chronique de stade 3 (débit de filtration glomérulaire estimé entre 30 et 60 mL/min/1.73m2) n’était pas associée à une élévation des paramètres hémodynamiques centraux, contrairement à ce qui avait déjà été décrit chez des individus avec insuffisance rénale chronique plus avancée. De plus, le niveau d’albuminurie ne serait également pas associé à un changement du profil central dans un sous-groupe de la cohorte CARTaGENE.

The impact of bariatric surgery on estimated glomerular filtration rate in patients with type 2 diabetes:a retrospective cohort study

Background: Diabetes mellitus is the most common cause of end-stage renal disease, which is associated with increased morbidity and mortality. The impact of bariatric surgery on chronic kidney disease is unclear. Objectives: Our primary aim was to assess the impact of bariatric surgery on estimated glomerular filtration rate (eGFR) in type 2 diabetes (T2D) patients. Our secondary aim was to compare the impact of bariatric surgery versus routine care on eGFR in patients with T2D. Setting: University Hospital, United Kingdom. Methods: A retrospective cohort analysis of adults with T2D who underwent bariatric surgery at a single center between January 2005 and December 2012. Data regarding eGFR were obtained from electronic patients records. eGFR was calculated using the Modification of Diet in Renal Disease formula. Data regarding patients with T2D who did not undergo bariatric surgery ("routine care") were obtained from patients attending the diabetes clinic at the same center from 2009 to 2011. Results: One hundred sixty-three patients were included (mean age 48.5±8.8 yr; baseline body mass index 50.8±9.1 kg/m2) and were followed for 3.0±2.3 years. Bariatric surgery resulted in an improvement in eGFR (median [interquartile range] 86.0 [73.0-100.0] versus 92.0 [77.0-101.0] mL/min/1.73 m2 for baseline versus follow-up, respectively; P = .003), particularly in patients with baseline eGFR≤60 mL/min/1.73 m2 (48.0 [42.0-57.0] versus 61.0 [55.0-63.0] mL/min/1.73 m2; P = .004). After adjusting for baseline eGFR, glycated hemoglobin (HbA1C), body mass index, age, and gender, bariatric surgery was associated with higher study-end eGFR compared with routine care (B = 7.787; P< .001). Conclusion: Bariatric surgery results in significant improvements in eGFR in T2D patients, particularly those with an eGFR≤60 mL/min/1.73 m2, while routine care was associated with a decline in eGFR.

L’évaluation des déterminants des paramètres hémodynamiques centraux à l’aide de la cohorte populationnelle CARTaGENE

Les maladies cardiovasculaires ont un impact considérable sur la vie des Canadiens, et de nombreux efforts ont permis d’identifier différents facteurs de risque associés à cette condition. L’hypertension artérielle représente un de ces facteurs modifiables les plus importants. Quoique l’hypertension est définie à l’aide de mesures de pression artérielle en périphérie, il devient de plus en plus apparent que la mesure de pression centrale et de ses composantes auraient des avantages au niveau de la prédiction de la survenue d’événements cardiovasculaires. Le présent mémoire vise à mieux caractériser deux déterminants de cette pression centrale, le traitement antihypertenseur à base de bêtabloqueurs et l’insuffisance rénale chronique précoce. En utilisant les données recueillies dans la banque de données populationnelle CARTaGENE, il a été possible à l’aide d’analyses statistiques par appariement basé sur le coefficient de propension de démontrer que l’utilisation d’agents antihypertensifs de type bêtabloqueurs était associée à un profil hémodynamique central défavorable. Ainsi, les individus recevant ces agents avaient une pression centrale et une amplification artérielle plus élevées que des individus du groupe contrôle apparié et ce, malgré une pression périphérique identique. Cet effet semblait être incomplètement expliqué par la réduction du rythme cardiaque associé à l’utilisation de bêtabloqueurs. Aussi, il a été démontré que l’insuffisance rénale chronique de stade 3 (débit de filtration glomérulaire estimé entre 30 et 60 mL/min/1.73m2) n’était pas associée à une élévation des paramètres hémodynamiques centraux, contrairement à ce qui avait déjà été décrit chez des individus avec insuffisance rénale chronique plus avancée. De plus, le niveau d’albuminurie ne serait également pas associé à un changement du profil central dans un sous-groupe de la cohorte CARTaGENE.

Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants

Background: Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher. Methods: For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure. Findings: We pooled 1479 studies that had measured the blood pressures of 19·1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127·0 mm Hg (95% credible interval 125·7–128·3) in men and 122·3 mm Hg (121·0–123·6) in women; age-standardised mean diastolic blood pressure was 78·7 mm Hg (77·9–79·5) for men and 76·7 mm Hg (75·9–77·6) for women. Global age-standardised prevalence of raised blood pressure was 24·1% (21·4–27·1) in men and 20·1% (17·8–22·5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence. Interpretation: During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe.

Incidence and clinical impact of infective endocarditis after transcatheter aortic valve implantation

The aim of this study is to describe the characteristics of infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI). This study was performed using the GAMES database, a national prospective registry of consecutive patients with IE in 26 Spanish hospitals. Of the 739 cases of IE diagnosed during the study, 1.3% were post-TAVI IE, and these 10 cases, contributed by five centres, represented 1.1% of the 952 TAVIs performed. Mean age was 80 years. All valves were implanted transfemorally. IE appeared a median of 139 days after implantation. The mean age-adjusted Charlson comorbidity index was 5.45. Chronic kidney disease was frequent (five patients), as were atrial fibrillation (five patients), chronic obstructive pulmonary disease (four patients), and ischaemic heart disease (four patients). Six patients presented aortic valve involvement, and four only mitral valve involvement; the latter group had a higher percentage of prosthetic mitral valves (0% vs. 50%). Vegetations were found in seven cases, and four presented embolism. One patient underwent surgery. Five patients died during follow-up: two of these patients died during the admission in which the valve was implanted. Conclusions: IE is a rare but severe complication after TAVI which affects about 1% of patients and entails a relatively high mortality rate. IE occurred during the first year in nine of the 10 patients.

New prophylactic and therapeutic treatments to combat pathogenic Enterohaemorrhagic Escherichia coli

Bacterial diarrhoeal diseases have significant influence on global human health, and are a leading cause of preventable death in the developing world. Enterohaemorrhagic Escherichia coli (EHEC), pathogenic strains of E. coli that carry potent toxins, have been associated with a high number of large-scale outbreaks caused by contaminated food and water sources. This pathotype produces diarrhoea and haemorrhagic colitis in infected humans, and in some patients leads to the development of haemolytic uremic syndrome (HUS), which can result in mortality and chronic kidney disease. A major obstacle to the treatment of EHEC infections is the increased risk of HUS development that is associated with antibiotic treatment, and rehydration and renal support are often the only options available. New treatments designed to prevent or clear E. coli infections and reduce symptoms of illness would therefore have large public health and economic impacts. The three main aims of this thesis were: to explore mouse models for pre-clinical evaluation in vivo of small compounds that inhibit a major EHEC colonisation factor, to assess the production and role of two proteins considered promising candidates for a broad-spectrum vaccine against pathogenic E. coli, and to investigate a novel compound that has recently been identified as a potential inhibitor of EHEC toxin production. As EHEC cannot be safely tested in humans due to the risk of HUS development, appropriate small animal models are required for in vivo testing of new drugs. A number of different mouse models have been developed to replicate different features of EHEC pathogenesis, several of which we investigated with a focus on colonisation mediated by the Type III Secretion System (T3SS), a needle-like structure that translocates bacterial proteins into host cells, resulting in a tight, intimate attachment between pathogen and host, aiding colonisation of the gastrointestinal tract. As E. coli models were found not to depend significantly on the T3SS for colonisation, the Citrobacter rodentium model, a natural mouse pathogen closely related to E. coli, was deemed the most suitable mouse model currently available for in vivo testing of T3SS-targeting compounds. Two bacterial proteins, EaeH (an outer membrane adhesin) and YghJ (a putative secreted lipoprotein), highly conserved surface-associated proteins recently identified as III protective antigens against E. coli infection of mice, were explored in order to determine their suitability as candidates for a human vaccine against pathogenic E. coli. We focused on the expression and function of these proteins in the EHEC O157:H7 EDL933 strain and the adherent-invasive E. coli (AIEC) LF82 strain. Although expression of EaeH by other E. coli pathotypes has recently been shown to be upregulated upon contact with host intestinal cells, no evidence of this upregulation could be demonstrated in our strains. Additionally, while YghJ was produced by the AIEC strain, it was not secreted by bacteria under conditions that other YghJ-expressing E. coli pathotypes do, despite the AIEC strain carrying all the genes required to encode the secretion system it is associated with. While our findings indicate that a vaccine that raises antibodies against EaeH and YghJ may have limited effect on the EHEC and AIEC strains we used, recent studies into these proteins in different E. coli pathogens have suggested they are still excellent candidates for a broadly effective vaccine against E. coli. Finally, we characterised a small lead compound, identified by high-throughput screening as a possible inhibitor of Shiga toxin expression. Shiga toxin production causes both the symptoms of illness and development of HUS, and thus reduction of toxin production, release, or binding to host receptors could therefore be an effective way to treat infections and decrease the risk of HUS. Inhibition of Shiga toxin production by this compound was confirmed, and was shown to be caused by an inhibitory effect on activation of the bacterial SOS response rather than on the Shiga toxin genes themselves. The bacterial target of this compound was identified as RecA, a major regulator of the SOS response, and we hypothesise that the compound binds covalently to its target, preventing oligomerisation of RecA into an activated filament. Altogether, the results presented here provide an improved understanding of these different approaches to combating EHEC infection, which will aid the development of safe and effective vaccines and anti-virulence treatments against EHEC.

Índice del perfil del donante renal (KDPI) como factor pronóstico del trasplante

La enfermedad renal crónica ha aumentado a nivel mundial y nacional, mientras que el número de donantes viene en descenso, y los pacientes en lista de espera aumentan. Los donantes cadavéricos son una opción para estos pacientes, y han sido utilizados en últimos años para aumentar los órganos disponibles. La evaluación de la calidad de estos es importante para optimizar su uso. Estudio analítico tipo cohorte retrospectiva, cálculo de KDPI en donantes cadavéricos, seguimiento función renal creatinina sérica 1 mes, 3 meses, 6 meses y un año. Correlación supervivencia del injerto, función renal, KDPI y EPTS. Análisis de supervivencia y regresión logística con variables del donante, receptor y acto quirúrgico.

Primary Joint Arthroplasty Surgery: Is the Risk of Major Bleeding Higher in Elderly Patients? A Retrospective Cohort Study

Increased risk of bleeding after major orthopedic surgery (MOS) has been widely documented in general population. However, this complication has not been studied in elderly patients. The purpose of this study is to determine whether the risk of major bleeding after MOS is higher in elderly patients, compared with those operated at a younger age. Methods: This retrospective cohort study included total hip and total knee arthroplasty patients operated during 5 consecutive years. The main outcome was the occurrence of major bleeding. Patients with other causes of bleeding were excluded. Relative risks (RRs) and confidence intervals (CIs) were calculated, anda multivariate analysis was performed. Results: A total of 1048 patients were included, 56% of patients were hip arthroplasties. At the time of surgery, 553 (53%) patients were older than 70 years. Patients aged >70 years showed an increased risk of major bleeding (RR: 2.42 [95% CI: 1.54-3.81]). For hip arthroplasty, the RR of bleeding was 2.61 (95%CI: 1.50-4.53) and 2.25 (95% CI: 1.03-4.94) for knee arthroplasty. After multivariate analysis, age was found to be independently associated with higher risk of major bleeding. Conclusion: According to European Medicines Agency criteria, patients aged 70 years are at a higher risk of major bleeding after MOS, result of a higher frequency of blood transfusions in this group of patients. Standardized protocols for blood transfusion in these patients are still required.

Factores de riesgo asociados al desarrollo de bacteriemia en pacientes adultos cirróticos hospitalizados

Introducción: La Bacteriemia en pacientes cirróticos es una causa importante de morbimortalidad, en gran parte favorecida por la especial vulnerabilidad de esta población ante procesos infecciosos. El objetivo fue determinar los factores asociados al desarrollo de bacteriemia primaria y secundaria en pacientes con Cirrosis, hospitalizados en la Fundación Cardioinfantil – Instituto de Cardiología entre 01 enero de 2010 y 31 enero de 2016. Materiales y Métodos: Estudio de casos y controles en pacientes mayores de 18 años con cirrosis hepática conocida o confirmada durante la hospitalización. Se realizó un análisis descriptivo, un análisis bivariado para determinar las diferencias entre los casos y los controles con respecto a las variables independientes un análisis de asociación mediante un modelo de regresión logística no condicional con variable dependiente bacteriemia. Los resultados se expresan en odds ratios con intervalos de confianza al 95%. Resultados: Las condiciones asociadas a bacteriemia como factores de riesgo fueron: Enfermedad renal crónica OR 9,1 (IC 95% 2,4-34), Escala Meld > 10 puntos OR 4,0 (IC 95% 2,-34), Infección previa OR 7,2 (IC 95% 2,1-24), presencia de catéter central OR 12,0 (IC 95% 1,8-80), presencia de sonda vesical OR 21,1 (IC 95% 1,6-276), estudio endoscópico OR 3,9 (IC 95% 1,1-14). Discusión: Factores relacionados con las condiciones clínicas del paciente evaluadas por las escalas Meld y Child-Pugh, el antecedente de infección previa y la presencia de dispositivos para monitorear el estado del paciente aumentan el riesgo de bacteriemia en pacientes hospitalizados con cirrosis.