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Background and purpose: Risk factors for stroke differ between women and men in general populations. However, little is known about sex differences in secondary prevention. We investigated if sex interacted with modifiable risk factors for stroke in a large arterial disease cohort. Methods: Within the prospective UCC-SMART study, 13,898 patients (35% women) with atherosclerotic disease or high-risk factor profile were followed up to 23 years for stroke incidence or recurrence. Hypertension, smoking, diabetes, overweight, dyslipidemia, high alcohol use, and physical inactivity were studied as risk factors. Association between these factors and ischemic and hemorrhagic stroke incidence or recurrence was studied in women and men using Cox proportional hazard models and Poisson regression models. Women-to-men relative hazard ratios (RHR) and rate differences (RD) were estimated for each risk factor. Left-truncated age was used as timescale. Results: The age-adjusted stroke incidence rate was lower in women than men (3.9 vs 4.4 per 1000 person-years), as was the age-adjusted stroke recurrence rate (10.0 vs 11.7). Hypertension and smoking were associated with stroke risk in both sexes. HDL cholesterol was associated with lower stroke incidence in women but not in men (RHR 0.49; CI 0.27–0.88; and RD 1.39; CI − 1.31 to 4.10). Overweight was associated with a lower stroke recurrence in women but not in men (RHR 0.42; CI 0.23–0.80; and RD 9.05; CI 2.78–15.32). Conclusions: In high-risk population, sex modifies the association of HDL cholesterol on stroke incidence, and the association of overweight on stroke recurrence. Our findings highlight the importance of sex-specific secondary prevention. [ABSTRACT FROM AUTHOR]

Background: Acquiring a reliable estimate of glomerular filtration rate (eGFR) at the emergency department (ED) is important for clinical management and for dosing renally excreted drugs. However, renal function formulas such as CKD-EPI can give biased results when serum creatinine (SCr) is not in steady-state because the assumption that urinary creatinine excretion is constant is then invalid. We assessed the extent of this by analysing variability in SCr in patients who visited the ED of a tertiary care centre. Methods: Data from ED visits at the University Medical Centre Utrecht, the Netherlands between 2012 and 2019 were extracted from the Utrecht Patient Oriented Database. Three measurement time points were defined for each visit: last SCr measurement before visit as baseline (SCr-BL), first measurement during visit (SCr-ED) and a subsequent measurement between 6 and 24 hours during admission (SCr-H1). Non-steady-state SCr was defined as exceeding the Reference Change Value (RCV), with 15% decrease or 18% increase between successive SCr measurements. Exceeding the RCV was deemed as a significant change. Results: Of visits where SCr-BL and SCr-ED were measured (N = 47,540), 28.0% showed significant change in SCr. Of 17,928 visits admitted to the hospital with a SCr-H1 after SCr-ED, 27,7% showed significant change. More than half (55%) of the patients with SCr values available at all three timepoints (11,054) showed at least one significant change in SCr over time. Conclusion: One third of ED visits preceded and/or followed by creatinine measurement show non-stable serum creatinine concentration. At the ED automatically calculated eGFR should therefore be interpreted with great caution when assessing kidney function. [ABSTRACT FROM AUTHOR]

Background: Physical, cognitive and psychosocial functioning are frequently impaired in dialysis patients and impairment in these domains relates to poor outcome. The aim of this analysis was to compare the prevalence of impairment as measured by the Kidney Disease Quality of Life- Short Form (KDQOL-SF) subscales between the different age categories and to assess whether the association of these subscales with mortality differs between younger and older dialysis patients.Methods: This study included data from 714 prevalent hemodialysis patients, from 26 centres, who were enrolled in the CONvective TRAnsport STudy (CONTRAST NCT00205556, 09-12-2005). Baseline HRQOL domains were evaluated for patients <65 years, 65-74 years and over 75 years. Multivariable Cox proportional hazards analyses were performed to assess the relation between the separate domains and 2-year mortality.Results: Emotional health was higher in patients over the age of 75 compared to younger patients (mean level 71, 73 and 77 for increasing age categories respectively, p = 0.02), whilst physical functioning was significantly lower in older patients (mean level 60, 48 and 40, p < 0.01). A low level of physical functioning (Hazard Ratio (HR) 1.72 [95%Confidence Interval (CI) 1.02-2.73]), emotional health (HR 1.85 [95% 1.30-2.63]), and social functioning (HR 1.59 [95% CI 1.12-2.26]), was individually associated with an increased 2-year mortality within the whole population. The absence of effect modification suggests no evidence for different relations within the older age groups.Conclusions: In dialysis patients, older age is associated with lower levels of physical functioning, whilst the level of emotional health is not associated with age. KDQOL-SF domains physical functioning, emotional health and social functioning are independently associated with mortality in prevalent younger and older hemodialysis patients. [ABSTRACT FROM AUTHOR]

Aim Multiple interacting pathways contribute to progression of renal and cardiac damage in chronic kidney disease followed by chronic heart failure (renocardiac syndrome). We hypothesized that simultaneous pharmacological modulation of critical pathways implicated in renocardiac syndrome would effectively reduce fibrosis in and preserve function of heart and kidney. Methods Rats were subjected to subtotal nephrectomy followed 9 weeks later by coronary artery ligation. From week 11 until week 16, rats received vehicle or losartan, or a combination of the NF- kB inhibitor PDTC, the NO donor molsidomine and superoxide dismutase mimetic tempol, or a combination of all four of these plus metoprolol together. At week 16, renal and cardiac structure, function and gene expression were assessed. Results Individual and combined treatments were similarly effective in limiting cardiac fibrosis and further decline in systolic function. Combined treatment with all five drugs reduced renal fibrosis and CTGF gene expression more effectively than other strategies. Combining all five drugs reduced heart rate, inotropy and mean arterial pressure ( MAP). Conclusion Thus, in our model of chronic renocardiac syndrome, combined treatments similarly decreased cardiac fibrosis and stabilized systolic function as losartan alone, perhaps suggesting a dominant role for a single factor such as angiotensin II type 1 ( AT1) receptor activation or inflammation in the network of aberrant systems in the heart. However, tubulointerstitial fibrosis was most effectively reduced by a five-drug regimen, pointing to additive effects of multiple pathophysiological pathways in the kidney. [ABSTRACT FROM AUTHOR]

Left ventricular systolic dysfunction (LVSD) in patients with chronic kidney disease (CKD) is associated with poorer prognosis. Because patients with CKD often exhibit progressively decreased nitric oxide (NO) availability and inhibition of NO production can reduce cardiac output, we hypothesized that loss of NO availability in CKD contributes to pathogenesis of LVSD. Subtotally nephrectomized (SNX) rats were treated with a low dose of the NO synthase inhibitor Nω-nitro-L-arginine (L-NNA; 20 mg/I water; SNX+L-NNA) and compared with relevant control groups. To study permanent changes separate from hemodynamic effects, L-NNA was stopped after week 8 and rats were followed up to week 15, until blood pressure was similar in SNX+L-NNA and SNX groups. To study effects of NO depletion alone, a control group with high-dose L-NNA (L-NNA-High: 100 mg/I) was included. Mild systolic dysfunction developed at week 13 after SNX. In SNX+L-NNA, systolic function decreased by almost 50% already from week 4 onward, together with markedly reduced whole body NO production and high mortality. In L-NINA-High, LVSD was not as severe as in SNX+L-NNA, and renal function was not affected. Both LVSD and NO depletion were reversible in L-NNA-High after L-NNA was stopped, but both were persistently low in SNX+L-NNA. Proteinuria increased compared with rats with SNX, and glomerulosclerosis and cardiac fibrosis were worsened. We conclude that SNX+L-NNA induced accelerated and permanent LVSD that was functionally and structurally different from CKD or NO depletion alone. Availability of NO appears to play a pivotal role in maintaining cardiac function in CKD. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Patients with diabetes are characterised by endothelial dysfunction and cardiovascular mortality. In particular endothelium-derived nitric oxide has emerged as a first line mechanism against atherosclerosis. Hyperglycaemia causes oxygen radical stress but has also been associated with endothelial nitric oxide synthase uncoupling, both lead to decreased nitric oxide-availability. We recently showed that folate reverses eNOS uncoupling in vitro. Therefore we hypothesise that folate improves endothelial function in Type II (non-insulin-dependent) diabetes mellitus in vivo. Methods. Using forearm plethysmography, we evaluated the effect of local, intra-arterial administration of 5-methyltetrahydrofolate (5-MTHF, the active form of folic acid, 1 µg/100 ml FAV/min) on forearm blood flow in 23 patients with Type II diabetes and 21 control subjects, matched for age, sex, blood pressure, body mass index, weight and smoking habits. Serotonin as a stimulator of nitric oxide-dependent vasodilation and sodium nitroprusside as a stimulator of endothelium-independent vasodilation were infused. Results. Serotonin-induced vasodilation was blunted (53±30 vs 102±66 M/C%, p<0.005) and nitroprusside-induced vasodilation was mildly reduced (275±146 vs 391±203 M/C%, p<0.05) in patients with Type II diabetes compared to control subjects. 5-MTHF improved nitric oxide-mediated vasodilation (from 53±30 to 88±59 M/C%, p<0.05) in patients with Type II diabetes mellitus. As expected, 5-MTHF had no effect on forearm blood flow in control subjects. Conclusion/interpretation. These data imply that folate can be used to improve nitric oxide status and to restore endothelial dysfunction in patients with Type II diabetes. Our results provide a strong rationale for the initiation of studies that investigate whether supplementation with folic acid prevents future cardiovascular events in this patient group. [ABSTRACT FROM AUTHOR]

Kidney transplantation is the best treatment option for patients with end-stage renal failure. At present, approximately 800 Dutch patients are registered on the active waiting list of Eurotransplant. The waiting time in the Netherlands for a kidney from a deceased donor is on average between 3 and 4 years. During this period, patients are fully dependent on dialysis, which replaces only partly the renal function, whereas the quality of life is limited. Mortality among patients on the waiting list is high. In order to increase the number of kidney donors, several initiatives have been undertaken by the Dutch Kidney Foundation including national calls for donor registration and providing information on organ donation and kidney transplantation. The aim of the national PROCARE consortium is to develop improved matching algorithms that will lead to a prolonged survival of transplanted donor kidneys and a reduced HLA immunization. The latter will positively affect the waiting time for a retransplantation. The present algorithm for allocation is among others based on matching for HLA antigens, which were originally defined by antibodies using serological typing techniques. However, several studies suggest that this algorithm needs adaptation and that other immune parameters which are currently not included may assist in improving graft survival rates. We will employ a multicenter-based evaluation on 5429 patients transplanted between 1995 and 2005 in the Netherlands. The association between key clinical endpoints and selected laboratory defined parameters will be examined, including Luminex-defined HLA antibody specificities, T and B cell epitopes recognized on the mismatched HLA antigens, non-HLA antibodies, and also polymorphisms in complement and Fc receptors functionally associated with effector functions of anti-graft antibodies. From these data, key parameters determining the success of kidney transplantation will be identified which will lead to the identification of additional parameters to be included in future matching algorithms aiming to extend survival of transplanted kidneys and to diminish HLA immunization. Computer simulation studies will reveal the number of patients having a direct benefit from improved matching, the effect on shortening of the waiting list, and the decrease in waiting time. [ABSTRACT FROM AUTHOR]

Kidney tubuloids are cell models that are derived from human or mouse renal epithelial cells and show high similarities with their in vivo counterparts. Tubuloids grow polarized in 3D, allow for long-term expansion, and represent multiple segments of the nephron, as shown by their gene expression pattern. In addition, human tubuloids form tight, functional barriers and have been succesfully used for drug testing. Our knowledge of mouse tubuloids, on the other hand, is only minimal. In this study, we further characterized mouse tubuloids and differentiated them towards the collecting duct, which led to a significant upregulation of collecting duct-specific mRNAs of genes and protein expression, including the water channel AQP2 and the sodium channel ENaC. Differentiation resulted in polarized expression of collecting duct water channels AQP2 and AQP3. Also, a physiological response to desmopressin and forskolin stimulation by translocation of AQP2 to the apical membrane was demonstrated. Furthermore, amiloride-sensitive ENaC-mediated sodium uptake was shown in differentiated tubuloids using radioactive tracer sodium. This study demonstrates that mouse tubuloids can be differentiated towards the collecting duct and exhibit collecting duct-specific function. This illustrates the potential use of mouse kidney tubuloids as novel in vitro models to study (patho)physiology of kidney diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Olde Hanhof, Dilmen, Yousef Yengej, Latta, Ammerlaan, Schreurs, Hooijmaijers, Jansen, Rookmaaker, Orhon, Verhaar and Hoenderop.)

Aims: To determine the (cost)-effectiveness of blood pressure lowering, lipid-lowering, and antithrombotic therapy guided by predicted lifetime benefit compared to risk factor levels in patients with symptomatic atherosclerotic disease., Methods and Results: For all patients with symptomatic atherosclerotic disease in the UCC-SMART cohort (1996-2018; n = 7697) two treatment strategies were compared. The lifetime benefit-guided strategy was based on individual estimation of gain in cardiovascular disease (CVD)-free life with the SMART-REACH model. In the risk factor-based strategy, all patients were treated the following: low-density lipoprotein cholesterol (LDL-c) < 1.8 mmol/L, systolic blood pressure <140 mmHg, and antithrombotic medication. Outcomes were evaluated for the total cohort using a microsimulation model. Effectiveness was evaluated as total gain in CVD-free life and events avoided, cost-effectiveness as incremental cost-effectivity ratio (ICER). In comparison to baseline treatment, treatment according to lifetime benefit would lead to an increase of 24 243 CVD-free life years [95% confidence interval (CI) 19 980-29 909] and would avoid 940 (95% CI 742-1140) events in the next 10 years. For risk-factor based treatment, this would be an increase of 18 564 CVD-free life years (95% CI 14 225-20 456) and decrease of 857 (95% CI 661-1057) events. The ICER of lifetime benefit-based treatment with a treatment threshold of ≥1 year additional CVD-free life per therapy was €15 092/QALY gained and of risk factor-based treatment €9933/QALY gained. In a direct comparison, lifetime benefit-based treatment compared to risk factor-based treatment results in 1871 additional QALYs for the price of €36 538/QALY gained., Conclusion: Residual risk reduction guided by lifetime benefit estimation results in more CVD-free life years and more CVD events avoided compared to the conventional risk factor-based strategy. Lifetime benefit-based treatment is an effective and potentially cost-effective strategy for reducing residual CVD risk in patients with clinical manifest vascular disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background and Objectives: Elderly patients with end-stage kidney disease (ESKD) are at high risk for fractures. However, the prevalence of vertebral fractures and hyperkyphosis is not studied well. This is relevant, because in the general population, both vertebral fractures and hyperkyphosis are associated with poor outcome. Therefore, the primary aim of our study was to assess the prevalence of vertebral fractures and hyperkyphosis in the ESKD population. The secondary aim was to assess if patients with vertebral fractures and/or hyperkyphosis more often have poor outcome after starting dialysis, such as accidental falling, functional decline and mortality compared to the patients without vertebral fractures and/or hyperkyphosis., Design, Setting, Participants & Measurements: This study included patients ≥65 years with ESKD who were enrolled in the Geriatric assessment in Older patients starting Dialysis (GOLD) study of whom a lateral chest radiograph was available. Chest radiographs were scored independently by two observers for vertebral fractures (Genant ≥1) and hyperkyphosis (≥50 degrees). The relation between vertebral fractures and hyperkyphosis with clinical outcomes (falls, decline in ADL and IADL, mortality) was studied using the Chi-square test., Results: Of the 196 enrolled patients, chest radiographs were available for 160 patients. Mean age was 75.3 (SD ±6.9), and 35% were female. The prevalence of vertebral fractures was 43% and of hyperkyphosis 22%. Patients with hyperkyphosis had a higher one-year mortality compared to patients without hyperkyphosis (20% vs. 8%, p = 0.04). No differences were observed between patients with and without hyperkyphosis, vertebral fractures and the remaining outcomes after six months of follow-up., Conclusions: In patients ≥65 years old with ESKD starting dialysis, vertebral fractures are highly prevalent. In contrast to the general population, patients with vertebral fractures did experience poor outcome as often as patients without vertebral fractures. Remarkably, patients with hyperkyphosis did have a higher one-year mortality. However, these patients did not experience more functional decline or accidental falls., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Essentials Mortality due to bleeding vs. arterial thrombosis in dialysis patients is unknown. We compared death causes of 201 918 dialysis patients with the general population. Dialysis was associated with increased mortality risks of bleeding and arterial thrombosis. Clinicians should be aware of the increased bleeding and thrombosis risks., Summary: Background Dialysis has been associated with both bleeding and thrombotic events. However, there is limited information on bleeding as a cause of death versus arterial thrombosis as a cause of death. Objectives To investigate the occurrence of bleeding, myocardial infarction and stroke as causes of death in the dialysis population as compared with the general population. Methods We included 201 918 patients from 11 countries providing data to the ERA-EDTA Registry who started dialysis treatment between 1994 and 2011, and followed them for 3 years. Age-standardized and sex-standardized mortality rate ratios for bleeding, myocardial infarction and stroke as causes of death were calculated in dialysis patients as compared with the European general population. Associations between potential risk factors and these causes of death in dialysis patients were investigated by calculating hazard ratios (HRs) with 95% confidence intervals (CIs) by the use of Cox proportional-hazards regression. Results As compared with the general population, the age-standardized and sex-standardized mortality rate ratios in dialysis patients were 12.8 (95% CI 11.9-13.7) for bleeding as a cause of death (6.2 per 1000 person-years among dialysis patients versus 0.3 per 1000 person-years in the general population), 13.4 (95% CI 13.0-13.9) for myocardial infarction (22.5 versus 0.9 per 1000 person-years), and 12.4 (95% CI 11.9-12.9) for stroke (14.3 versus 0.7 per 1000 person-years). Conclusion Dialysis patients have highly increased risks of death caused by bleeding and arterial thrombosis as compared with the general population. Clinicians should be aware of the increased mortality risks caused by these conditions., (© 2018 International Society on Thrombosis and Haemostasis.)

The presence of donor-specific anti-HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long-term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement-dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10-year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10-year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10-year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence., (© 2018 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Administration of mesenchymal stromal cells (MSCs) is a promising strategy to treat cardiovascular disease (CVD). As progenitor cells may be negatively affected by both age and comorbidity, characterization of MSC function is important to guide decisions regarding use of allogeneic or autologous cells. Definitive answers on which factors affect MSC function can also aid in selecting which MSC donors would yield the most therapeutically efficacious MSCs. Here we provide a narrative review of MSC function in CVD based on a systematic search. A total of 41 studies examining CVD-related MSC (dys)function were identified. These data show that MSC characteristics and regenerative potential are often affected by CVD. However, studies presented conflicting results, and directed assessment of MSC parameters relevant to regenerative medicine applications was lacking in many studies. The predictive ability of in vitro assays for in vivo efficacy was rarely assessed. There was no correlation between quality of study reporting and study findings. Age mismatch was also not associated with study findings or effect size. Future research should focus on assays that assess regenerative potential in MSCs and parameters that relate to clinical success.

The complement system, as part of the innate immune system, plays an important role in renal transplantation. Complement is involved in the protection against foreign organisms and clearance of apoptotic cells but can also cause injury to the renal allograft, for instance, via antibody binding or in ischemia-reperfusion injury. Numerous polymorphisms in complement factors have been identified thus far; some of them result in different functionalities or alter complement levels. In this review, we provide an overview of the literature on the role of complement polymorphisms in renal transplantation. Furthermore, we discuss functional complement polymorphisms that have not yet been investigated in kidney transplantation. By investigating multiple polymorphisms both in donor and recipient at the same time, a complotype can be constructed. Because the combination of multiple polymorphisms is likely to have a greater impact than a single one, this could provide valuable prognostic information., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: Quality of life (QoL) is an important outcome in evaluating treatment effect in severe limb ischemia. The randomized, double blind, placebo controlled JUVENTAS trial, investigating the effect of bone marrow derived mononuclear cell (BMMNC) administration in no option severe limb ischemia, showed an improved QoL at 6 months compared with baseline in both the treatment and placebo groups. The aim of the present study was to evaluate whether the improved QoL persisted beyond 6 months' follow up, whether this differed in both trial arms, and if major amputation influenced QoL., Methods: Short form 36 (SF-36) and EuroQol 5D (EQ5D), including the EQ Visual Analogue Scale (EQ-VAS), questionnaires were sent to JUVENTAS trial participants. In the JUVENTAS trial, a norm based scoring method was applied to report the results of the SF-36. The results of the long-term follow up were compared with baseline and 6 month follow up and the results of both trial arms were compared, as were the results of patients with and without amputation., Results: One hundred and nine patients (86.5% of surviving patients) responded to the questionnaires. Median follow up after inclusion was 33 months (interquartile range [IQR] 21.2-50.6) for the BMMNC and 36 months (IQR 21.4-50.9) for the placebo group. The improvement in QoL at 6 months persisted in both arms at a median follow up of 35 months. The long-term QoL did not differ between the BMMNC and placebo group in any of the SF-36 or EQ5D domains. Patients with and without a major amputation had similar QoL scores., Conclusions: The increased QoL in patients with no option severe limb ischemia persisted until 3 years after inclusion, but did not differ between the BMMNC and placebo arms or between patients with and without a major amputation., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective/background: Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease (PAD), and many patients with CLI are not eligible for conventional revascularization. In the last decade, cell based therapies have been explored as an alternative treatment option for CLI. A meta-analysis was conducted of randomized placebo controlled trials investigating bone marrow (BM) derived cell therapy in patients with CLI., Methods: The MEDLINE, Embase, and the Cochrane Controlled Trials Register databases were systematically searched, and all included studies were critically appraised by two independent reviewers. The meta-analysis was performed using a random effects model., Results: Ten studies, totaling 499 patients, were included in this meta-analysis. No significant differences were observed in major amputation rates (relative risk [RR] 0.91; 95% confidence interval [CI] 0.65-1.27), survival (RR 1.00; 95% CI 0.95-1.06), and amputation free survival (RR 1.03; 95% CI 0.86-1.23) between the cell treated and placebo treated patients. The ankle brachial index (mean difference 0.11; 95% CI 0.07-0.16), transcutaneous oxygen measurements (mean difference 11.88; 95% CI 2.73-21.02), and pain score (mean difference -0.72; 95% CI -1.37 to -0.07) were significantly better in the treatment group than in the placebo group., Conclusions: This meta-analysis of placebo controlled trials showed no advantage of stem cell therapy on the primary outcome measures of amputation, survival, and amputation free survival in patients with CLI. The potential benefit of more sophisticated cell based strategies should be explored in future randomized placebo controlled trials., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: The decision-making process of dialysis initiation in the elderly involves different considerations compared with younger patients. Cognitive, functional and psychosocial issues are likely to be more important than standard prognostic factors. To assess the role of these issues in the decision-making process regarding dialysis initiation in the elderly, a survey was conducted among nephrologists in the Netherlands., Methods: An internet-based survey was sent to all members of the Netherlands Federation of Nephrology., Results: Out of 298 invited, 94 Dutch nephrologists responded to the questionnaire. Reaching consensus with the patient and relatives and early withdrawal are difficult issues in the decision-making process in elderly end-stage renal disease patients. Geriatric impairments were considered (very) relevant issues (varying from 7- 0 on a scale from 1-10) in the context of dialysis initiation, with cognitive dysfunction being most relevant (median 10, range 6-10). The majority of nephrologists (56%) underlined the need for screening for geriatric problems when considering dialysis in the elderly. A total of 26% reported using some form of screening measurement for the determination of the presence of one or more geriatric impairments., Conclusions: Although cognitive, functional and psychosocial issues are considered relevant items in the context of dialysis initiation in the elderly, systematic assessment of these items is not standard of care in nephrology practice. Future research is needed to determine whether a more systematic screening for the presence of geriatric impairments can improve the decision-making process.

Aims: Atherosclerotic plaque development is accelerated in patients with diabetes. Bone marrow-derived smooth muscle-like cells have been detected in neointima and diabetes has a numerical and functional effect on circulating vascular progenitor cells. We hypothesized that an increased number of bone marrow-derived smooth muscle-like cells correlates with accelerated atherosclerosis in diabetic apoE-deficient mice., Methods: ApoE(-/-) mice were subjected to total body irradiation and transplanted with bone marrow cells from GFP-transgenic mice. Mice were rendered diabetic by streptozotocin injection and examined after 4, 8, 11 and 15 weeks of diabetes., Results: Diabetic mice showed a larger plaque area and a higher number of smooth muscle-like cells compared to non-diabetic mice at 11 and 15 weeks after diabetes induction. Bone marrow-derived smooth muscle-like cells were detected in atherosclerotic plaques of both diabetic and control mice, but numbers were higher in plaques of diabetic mice 11 weeks after induction of diabetes. The higher number of bone marrow-derived smooth muscle-like cells in plaque was associated with an increase in in vitro differentiation of smooth muscle-like cells from spleen mononuclear cells in diabetic mice., Conclusions: Diabetes increases the number of bone marrow-derived smooth muscle-like cells in atherosclerotic plaques and the differentiation of mononuclear cells towards smooth muscle-like cells, which may contribute to accelerated atherosclerotic plaque development in diabetic apoE(-/-) mice., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Critical limb ischemia (CLI) continues to form a substantial burden on Western health care. Despite recent advances in surgical and radiological vascular techniques, a large number of patients is not eligible for these revascularisation procedures and faces amputation as their ultimate treatment option. Growth factor therapy and stem cell therapy - both therapies focussing on augmenting postnatal neovascularisation - have raised much interest in the past decade. Based on initial pre-clinical and clinical results, both therapies appear to be promising strategies to augment neovascularisation and to reduce symptoms and possibly prevent amputation in CLI patients. However, the underlying mechanisms of postnatal neovascularisation are still incompletely understood. Both fundamental research as well as large randomised trials are needed for further optimisation of these treatment options, and will hopefully lead to needed advances in the treatment of no-option CLI patients in the near future.

A total of 3 patients, a female aged 66 years, a male aged 67 years and a female aged 82 years, presented with rest pain or gangrene of their lower extremities as a result of critical limb ischemia (CLI). Radiographic studies showed non-reconstructable arterial obstructive disease in the 66-year-old female patient, who underwent an uncomplicated primary amputation and subsequent rehabilitation. Bypass surgery was initially performed in the male patient. However, failed reconstruction and progression of ischaemia necessitated transfemoral amputations to be performed, which was followed by impaired rehabilitation. In the 82-year-old female patient gangrene was the indication for primary amputation. She died due to progressive sepsis following surgery. In about 40% of patients with CLI, major lower extremity amputation is the ultimate solution. The morbidity, mortality and rehabilitation potential in CLI and the factors that influence these outcomes are discussed. The most clinically relevant determinants of morbidity, mortality and rehabilitation following major lower extremity amputation are comorbidity, age, preoperative mobility and amputation level.

More women die of cardiovascular disease than men; in women, cardiovascular mortality is 1.5 times greater than cancer mortality. The pathophysiology of cardiovascular disease has female-specific aspects such as fragile coronary arteries and microvascular ischaemia. Women with acute coronary syndromes are more likely to present with atypical symptoms such as dyspnoea, nausea or fatigue. With regard to diagnostic tests in women, exercise ECG can be difficult to interpret and a normal coronary angiogram does not exclude coronary heart disease. Myocardial perfusion scintigraphy may be considered for high-risk women who are clinically suspected of having coronary heart disease and have a normal or inconclusive exercise ECG and angiogram. Women are less likely to be treated according to guidelines than men, and their prognosis after a myocardial infarction or a coronary intervention is worse. Female-specific aspects such as gestational hypertension and diabetes allow for early detection and treatment of women at risk for cardiovascular disease.

The implementation of the intriguing concept of the polypill to prevent cardiovascular events remains doubtful due to a lack of evidence, expected adherence problems, the inevitable overtreatment and undertreatment of individuals, and potential side effects. Lifestyle changes and individual interventions are more preferable strategies.