The influence of comorbidity on the risk of access-related bacteremia in chronic hemodialysis patients.

Access-related bacteremia is an important cause of morbidity in chronic hemodialysis patients. The incidence of bacteremia is higher in patients dialyzing through a tunneled central venous catheter (TCVC) compared with an arteriovenous fistula (AVF). Our aim was to explore if this is explained by patient comorbidity. Two groups of chronic hemodialysis outpatients were compared: all patients who dialyzed through a TCVC at any time during 2003 and were fit enough to subsequently have a functioning AVF or renal transplant even if it was after 2003 (Group 1; n=93); and all patients who dialyzed through a TCVC in 2003 and were not fit enough to have a functioning AVF or renal transplant (Group 2; n=119). Episodes of bacteremia (n=71) were identified and those not related to access were excluded. Patients in Group 1 were younger than Group 2 (57.5 years vs. 64.8 years; P=0.001). The incidences of bacteremia in Groups 1 and 2 were, respectively, 0.31 and 0.44 episodes per 1000 patient days while dialyzing through an AVF (P=0.77), and 2.21 and 2.27 per 1000 days while dialyzing through a TCVC (P=0.91). The 3-year actual survival from January 1, 2003 to January 1, 2006 was significantly higher in Group 1 than in Group 2 (80.6% vs. 26.1%; P<0.0001) confirming the higher comorbidity of the patients in Group 2. Patients dialyzing through a TCVC (compared with an AVF) have a significantly higher risk of access-related bacteremia, irrespective of comorbidity.

Increasing Fruit and Vegetable Intake Has No Dose-Response Effect on Conventional Cardiovascular Risk Factors in Overweight Adults at High Risk of Developing Cardiovascular Disease

BACKGROUND: Improving diet and lifestyle is important for prevention of cardiovascular disease (CVD). Observational evidence suggests that increasing fruit and vegetable (FV) consumption may lower CVD risk, largely through modulation of established risk factors, but intervention data are required to fully elucidate the mechanisms by which FVs exert benefits on vascular health.

OBJECTIVE: The aim of this study was to examine the dose-response effect of FV intake on cardiovascular risk factors in adults at high CVD risk.

METHODS: This was a randomized controlled parallel group study involving overweight adults (BMI: >27 and ≤35 kg/m(2)) with a habitually low FV intake (≤160 g/d) and a high total risk of developing CVD (estimated ≥20% over 10 y). After a 4-wk run-in period where FV intake was limited to <2 portions/d (<160 g/d), 92 eligible participants were randomly assigned to 1 of 3 groups: to consume either 2, 4, or 7 portions (equivalent to 160 g, 320 g, or 560 g, respectively) of FVs daily for 12 consecutive weeks. Fasting venous blood samples were collected at baseline (week 4) and post-intervention (week 16) for analysis of lipid fractions and high-sensitivity C-reactive protein (hsCRP) concentrations. Compliance with the FV intervention was determined with use of self-reported FV intake and biomarkers of micronutrient status. Ambulatory blood pressure and body composition were also measured pre- and post-intervention.

RESULTS: A total of 89 participants completed the study and body composition remained stable throughout the intervention period. Despite good compliance with the intervention, no significant difference was found between the FV groups for change in measures of ambulatory blood pressure, plasma lipids, or hsCRP concentrations.

CONCLUSIONS: There was no evidence of a dose-response effect of FV intake on conventional CVD risk factors measured in overweight adults at high CVD risk. This trial was registered at clinicaltrials.gov as NCT00874341.

XBP 1-deficiency abrogates neointimal lesion of injured vessels via cross talk with the PDGF signaling

Objective: Smooth muscle cell (SMC) migration and proliferation play an essential role in neointimal formation after vascular injury. In this study, we intended to investigate whether the X-box-binding protein 1 (XBP1) was involved in these processes.

Approach and Results: In vivo studies on femoral artery injury models revealed that vascular injury triggered an immediate upregulation of XBP1 expression and splicing in vascular SMCs and that XBP1 deficiency in SMCs significantly abrogated neointimal formation in the injured vessels. In vitro studies indicated that platelet-derived growth factor-BB triggered XBP1 splicing in SMCs via the interaction between platelet-derived growth factor receptor β and the inositol-requiring enzyme 1α. The spliced XBP1 (XBP1s) increased SMC migration via PI3K/Akt activation and proliferation via downregulating calponin h1 (CNN1). XBP1s directed the transcription of mir-1274B that targeted CNN1 mRNA degradation. Proteomic analysis of culture media revealed that XBP1s decreased transforming growth factor (TGF)-β family proteins secretion via transcriptional suppression. TGF-β3 but not TGF-β1 or TGF-β2 attenuated XBP1s-induced CNN1 decrease and SMC proliferation.

Conclusions: This study demonstrates for the first time that XBP1 is crucial for SMC proliferation via modulating the platelet-derived growth factor/TGF-β pathways, leading to neointimal formation.

Management of polycythaemia vera: a critical review of current data

Polycythaemia vera (PV) is a chronic blood cancer; its clinical features are dominated by myeloproliferation (erythrocytosis, often leucocytosis and/or thrombocytosis) and a tendency for thrombosis and transformation to myelofibrosis or acute myeloid leukaemia. In the past 10 years the pathophysiology of this condition has been defined as JAK/STAT pathway activation, almost always due to mutations in JAK2 exons 12 or 14 (JAK2 V617F). In the same time period our understanding of the optimal management of PV has expanded, most recently culminating in the approval of JAK inhibitors for the treatment of PV patients who are resistant or intolerant to therapy with hydroxycarbamide. It has also been demonstrated that life expectancy for many patients with PV is not normal, nor is their quality of life. We critically explore these findings and discuss their impact. In addition, we highlight persisting gaps in our current management strategy; for example, what is the optimal first line cytoreductive therapy and, indeed, which patients need cytoreductive drugs.

Investigating clinical predictors of arteriovenous fistula functional patency in a European cohort

Background: Arteriovenous fistula (AVF) failure to mature (FTM) rates contribute to excessive dependence on central venous catheters for haemodialysis. Choosing the most appropriate vascular access site for an individual patient is guided largely by their age, co-morbidities and clinical examination. We investigated the clinical predictors of AVF FTM in a European cohort of patients and applied an existing clinical risk prediction model for AVF FTM to this population.
Methods: A prospective cohort study was designed that included all patients undergoing AVF creation between January 2009 and December 2014 in a single centre (Belfast City Hospital) who had a functional AVF outcome observed by March 2015.
Results: A total of 525 patients had a functional AVF outcome recorded and were included in the FTM analysis. In this cohort, 309 (59%) patients achieved functional AVF patency and 216 (41%) patients had FTM. Female gender [P < 0.001, odds ratio (OR) 2.03 (CI 1.37–3.02)] and lower-arm AVF [P < 0.001, OR 4.07 (CI 2.77–5.92)] were associated with AVF FTM. The Lok model did not predict FTM outcomes based on the associated risk stratification in our population.
Conclusions: In this European study, female gender was associated with twice the risk of AVF FTM and a lower-arm AVF with four times the risk of FTM. The FTM risk prediction model was not found to be discriminative in this population. Clinical risk factors for AVF FTM vary between populations;we would recommend that units investigate their own clinical predictors of FTM to maximize AVF functional patency and ultimately survival in dialysis patients. Clinical predictors of AVF FTM may not be sufficient on their own to improve vascular access functional patency rates.

Preoperative radial artery volume flow is predictive of arteriovenous fistula outcomes

Objective: Guidelines recommend the creation of a wrist radiocephalic arteriovenous fistula (RAVF) as initial hemodialysis vascular access. This study explored the potential of preoperative ultrasound vessel measurements to predict AVF failure to mature (FTM) in a cohort of patients with end-stage renal disease in Northern Ireland

.Methods: A retrospective analysis was performed of all patients who had preoperative ultrasound mapping of upper limb blood vessels carried out from August 2011 to December 2014 and whose AVF reached a functional outcome by March 2015.

Results: There were 152 patients (97% white) who had ultrasound mapping andan AVF functional outcome recorded; 80 (54%) had an upper arm AVF created, and 69 (46%) had a RAVF formed. Logistic regression revealed that female gender (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.12-5.55; P = .025), minimum venous diameter (OR, 0.6; 95% CI, 0.39-0.95; P = .029), and RAVF (OR, 0.4; 95% CI, 0.18-0.89; P = .026) were associated with FTM. On subgroup analysis of the RAVF group, RAVFs with an arterial volume flow <50 mL/min were seven times as likely to fail as RAVFs with higher volume flows (OR, 7.0; 95% CI, 2.35-20.87; P < .001).

Conclusions: In this cohort, a radial artery flow rate <50 mL/min was associated with a sevenfold increased risk of FTM in RAVF, which to our knowledge has not been previously reported in the literature. Preoperative ultrasound mapping adds objective assessment in the clinical prediction of AVF FTM.

Beneficial effect of a polyphenol-rich diet on cardiovascular risk: a randomised control trial

OBJECTIVES: There is previous epidemiological evidence that intake of polyphenol-rich foods has been associated with reduced cardiovascular disease risk. We aimed to investigate the effect of increasing dietary polyphenol intake on microvascular function in hypertensive participants.

METHODS: All participants completed a 4-week run-in phase, consuming <2 portions of fruit and vegetables (F&V) daily and avoiding berries and dark chocolate. Subjects were then randomised to continue with the low-polyphenol diet for 8 weeks or to consume a high-polyphenol diet of six portions F&V (including one portion of berries/day and 50 g of dark chocolate). Endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside) vasodilator responses were assessed by venous occlusion plethysmography. Compliance with the intervention was measured using food diaries and biochemical markers.

RESULTS: Final analysis of the primary endpoint was conducted on 92 participants. Between-group comparison of change in maximum % response to ACh revealed a significant improvement in the high-polyphenol group (p=0.02). There was a significantly larger increase in vitamin C, carotenoids and epicatechin in the high-polyphenol group (between-group difference p<0.001; p<0.001; p=0.008, respectively).

CONCLUSIONS: This study has shown that increasing the polyphenol content of the diet via consumption of F&V, berries and dark chocolate results in a significant improvement in an established marker of cardiovascular risk in hypertensive participants.

Epidemiology of painful procedures performed in neonates: A systematic review of observational studies

Procedural pain in neonates has been a concern in the last two decades. The purpose of this review was to provide a critical appraisal and a synthesis of the published epidemiological studies about procedural pain in neonates admitted to intensive care units. The aims were to determine the frequency of painful procedures and pain management interventions as well as to identify their predictors. Academic Search, CINAHL, LILACS, Medic Latina, MEDLINE and SciELO databases were searched for observational studies on procedural pain in neonates admitted to intensive care units. Studies in which neonatal data could not be extracted from the paediatric population were excluded. Eighteen studies were included in the review. Six studies with the same study duration, the first 14 days of the neonate life or admission in the unit of care, identified 6832 to 42,413 invasive procedures, with an average of 7.5-17.3 per neonate per day. The most frequent procedures were heel lance, suctioning, venepuncture and insertion of peripheral venous catheter. Pharmacological and nonpharmacological approaches were inconsistently applied. Predictors of the frequency of procedures and analgesic use included the neonate's clinical condition, day of unit stay, type of procedure, parental presence and pain assessment. The existence of pain protocols was not a predictor of analgesia. Painful procedures were performed frequently and often with inadequate pain management. Unlike neonate clinical factors, organizational factors may be modified to promote a context of care more favourable to pain management. © 2015 European Pain Federation - EFIC®

Chick heart/hemangioblast progenitor 12 (chep 12: study of a novel gene expressed in the heart/hemangioblast percursors cells

Dissertação de mest., Ciências Biomédicas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2009

Effects of vitamin K deficiency and its mechanisms in vertebrate's early development: zebrafish as a model

Disertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

Energia e medicina : Mayer e Helmholtz

Tese de doutoramento, História e Filosofia das Ciências, Universidade de Lisboa, Faculdade de Ciências, 2014

The Impact of R10-Hydroxywarfarin on CYP2C9-Mediated S-Warfarin Metabolism

Thesis (Master's)--University of Washington, 2014

Cuidados paliativos ao doente em fim de vida num serviço de urgência básico

Tese de mestrado, Cuidados Paliativos, Faculdade de Medicina, Universidade de Lisboa, 2015