Unmet medical needs in intermittent Claudication with diabetes and coronary artery disease-A "real-world" analysis on 21 197 PAD patients.

BACKGROUND: Peripheral artery disease (PAD) is frequently co-prevalent with coronary artery disease (CAD) and diabetes (DM). The study aims to define the burden of CAD and/ or DM in PAD patients at moderate stages and further to evaluate its impact on therapy and outcome. METHODS: Study is based on health insurance claims data of the BARMER reflecting an unselected "real-world" scenario. Retrospective analyses were based on 21 197 patients hospitalized for PAD Rutherford 1-3 between 1 January 2009 to 31 December 2011, including a 4-year follow-up (median 775 days). RESULTS: In PAD patients, CAD is prevalent in 25.3% (n = 5355), DM in 23.5% (n = 4976), and both CAD and DM in 8.2% (n = 1741). Overall, in-hospital mortality was 0.4%, being increased if CAD was present (CAD alone: OR 1.849; 95%-CI 1.066-3.208; DM alone: OR 1.028; 95%-CI 0.520-2.033; CAD and DM: OR 3.115; 95%-CI 1.720-5.641). Both, CAD and DM increased long-term mortality (CAD alone: HR 1.234; 95%-CI 1.106-1.376; DM alone: HR 1.260; 95%-CI 1.125-1.412; CAD and DM: HR 1.76; 95%-CI 1.552-1.995). DM further increased long-term amputation risk (DM alone: HR 2.238; 95%-CI 1.849-2.710; DM and CAD: HR 2.199; 95%-CI 1.732-2.792), whereas CAD (alone) did not. CONCLUSIONS: In a greater perspective, the data identify also mild to modest stage PAD patients at particular risk for adverse outcomes in presence of CAD and/or DM. CAD and DM both are related with a highly increased risk of long-term mortality even in intermittent claudication, and DM independently increased amputation risk.

Impact of diabetes type on treatment and outcome of patients with peripheral artery disease.

BACKGROUND: The prevalence of diabetes mellitus and its associated complications such as peripheral artery disease is increasing worldwide. We aimed to explore the distinct impact of type 1 diabetes mellitus and type 2 diabetes mellitus on treatment and on short- and long-term outcome in patients with peripheral artery disease. METHODS: Retrospective analysis of anonymized data of hospitalized patients covered by a large German health insurance. Assessment of patient's characteristics (comorbidities, complications, etc.) and outcome using multivariable Cox regression and Kaplan-Meier curves. RESULTS: Among 41,702 patients with peripheral artery disease, 339 (0.8%) had type 1 diabetes mellitus and 13,151 (31.5%) had type 2 diabetes mellitus. Patients with diabetes mellitus had more comorbidities and complications than patients without diabetes mellitus ( p < 0.001). Type 1 diabetes mellitus patients exhibited the highest risk for limb amputation at 4-year follow-up (44.6% vs 35.1%, p < 0.001), while type 2 diabetes mellitus patients had higher mortality than type 1 diabetes mellitus (43.6% vs 31.0%, p < 0.001). CONCLUSION: Although the fraction of type 1 diabetes mellitus among patients with peripheral artery disease and diabetes mellitus is low, it represents a subset of patients being at particular high risk for limb amputation. Research focused on elaborating the determinants of limb amputation and mortality in peripheral artery disease patients with diabetes mellitus is warranted to improve the poor prognosis of these patients.

Prevalence and impact of critical limb ischaemia on in-hospital outcome in transcatheter aortic valve implantation in Germany.

AIMS: Peripheral artery disease (PAD) is common in patients with aortic valve stenosis (AS). This study sought to assess the prevalence of critical limb ischaemia (CLI) and its impact on in-hospital outcome in patients undergoing transcatheter aortic valve implantation (TAVI) for severe AS. METHODS AND RESULTS: All isolated TAVI procedures for AS in Germany between 2007 and 2013 were analysed regarding the stage-specific prevalence of PAD, comorbidities, in-hospital complications and mortality using diagnostic and procedural codes. Among 32,044 patients with TAVI, 3,375 (10.5%) had PAD and 654 (2.0%) CLI. TAVI patients with PAD, particularly those with CLI, had a higher incidence of periprocedural stroke, bleeding and acute kidney injury (p<0.001). The overall in-hospital mortality among TAVI without PAD, non-CLI PAD and CLI was 6.1%, 8.4% and 14.7%, respectively (p<0.001). In a multivariate logistic regression analysis, CLI was an independent predictor of in-hospital mortality (odds ratio 1.96, 95% confidence interval 1.56-2.47; p<0.001). CONCLUSIONS: In patients undergoing TAVI, the presence of PAD is associated with an increased risk of periprocedural complications, while only CLI independently predicts increased in-hospital mortality. Whether CLI represents a marker of general poor health status resulting in poor outcome or is a modifiable risk factor whose treatment prior to TAVI can improve the outcome requires prospective studies.

Association of CKD with Outcomes Among Patients Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND AND OBJECTIVES: Despitethe multiple depicted associations of CKD with reduced cardiovascular and overall prognoses, the association of CKD with outcome of patients undergoing transcatheter aortic valve implantation has still not been well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from all hospitalized patients who underwent transcatheter aortic valve implantation procedures between January 1, 2010 and December 31, 2013 in Germany were evaluated regarding influence of CKD, even in the earlier stages, on morbidity, in-hospital outcomes, and costs. RESULTS: A total of 28,716 patients were treated with transcatheter aortic valve implantation. A total of 11,189 (39.0%) suffered from CKD. Patients with CKD were predominantly women; had higher rates of comorbidities, such as coronary artery disease, heart failure at New York Heart Association 3/4, peripheral artery disease, and diabetes; and had a 1.3-fold higher estimated logistic European System for Cardiac Operative Risk Evaluation value. In-hospital mortality was independently associated with CKD stage ≥3 (up to odds ratio, 1.71; 95% confidence interval, 1.35 to 2.17; P<0.05), bleeding was independently associated with CKD stage ≥4 (up to odds ratio, 1.82; 95% confidence interval, 1.47 to 2.24; P<0.001), and AKI was independently associated with CKD stages 3 (odds ratio, 1.83; 95% confidence interval, 1.62 to 2.06) and 4 (odds ratio, 2.33; 95% confidence interval, 1.92 to 2.83 both P<0.001). The stroke risk, in contrast, was lower for patients with CKD stages 4 (odds ratio, 0.23; 95% confidence interval, 0.16 to 0.33) and 5 (odds ratio, 0.24; 95% confidence interval, 0.15 to 0.39; both P<0.001). Lengths of hospital stay were, on average, 1.2-fold longer, whereas reimbursements were, on average, only 1.03-fold higher in patients who suffered from CKD. CONCLUSIONS: This analysis illustrates for the first time on a nationwide basis the association of CKD with adverse outcomes in patients who underwent transcatheter aortic valve implantation. Thus, classification of CKD stages before transcatheter aortic valve implantation is important for appropriate risk stratification.

The Impact of Chronic Kidney Disease on Hospitalized Patients With Peripheral Arterial Disease and Critical Limb Ischemia.

Peripheral arterial disease (PAD) and chronic kidney disease (CKD) are major public health problems worldwide. Evaluations of large-scale data on morbidity, outcome, and costs in patients having PAD with CKD are essential. Cross-sectional nationwide population-based analysis of all hospitalizations for PAD during 2009 in Germany focused on the stage-related impact of CKD on morbidity, in-hospital mortality, amputations, length of hospital stay, and health-related expenditure. The total number of hospitalizations was 483 961. Of those, 132 993 (27.5%) had CKD. Chronic kidney disease caused 1.8-fold higher amputation rate ( P < .001) with a stepwise increasing rate with higher CKD stage. Chronic kidney disease doubled in-hospital mortality of patients with PAD (7.8%; n = 10 421) versus 4.0% (n = 14 174, P < .001) with a stepwise increasing risk with higher CKD stage ( P < .001). The highest in-hospital mortality occurred in patients with coprevalence of CKD stage 4 and Fontaine stage IV (16.4%, n = 1176, P < .001). Chronic kidney disease caused 15% higher costs and 21% increased length of stay compared to the whole PAD cohort. This analysis demonstrates the stage-related influence of CKD on morbidity, in-hospital mortality, amputations, length of hospital stay, and reimbursement costs of hospitalized patients with PAD.

Aging and Outcome in Patients With Peripheral Artery Disease and Critical Limb Ischemia.

BACKGROUND, OBJECTIVES, DESIGN: Aging of the population is one of the major challenges facing public health systems. The impact of aging on acute and long-term outcome of patients with peripheral artery disease (PAD) and critical limb ischemia (CLI) is currently not sufficiently clarified. This analysis consists of comprehensive, anonymized data obtained from the largest public health insurance in Germany. RESULTS: A total of 41,740 PAD patients with an index hospitalization between January 1, 2009, and December 31, 2011, and a follow-up time up to 4 years were included (40-49 years: n = 1179; 50-59 years: n = 5415; 60-69 years: n = 10,565; 70-79 years: n = 13,313; 80-89 years: n = 9714; and 90-100 years: n = 1554). Advanced age was associated with female gender (men-women ratio up to 1:3.3), less smoking, less frequent obesity, more often chronic heart failure (up to 9-fold), chronic kidney disease (up to 4-fold), fewer angiographies (up to 0.8-fold), fewer endovascular (up to 0.5-fold) and surgical revascularizations (up to 0.9-fold), higher rates of amputation (up to 2.5-fold), acute renal failure (up to 3.7-fold), in-hospital mortality (up to 12-fold), myocardial infarction (up to 2.8-fold), ischemic stroke (up to 1.5-fold), infection (up to 1.4-fold), and sepsis (up to 1.8-fold) (each P < .001). During follow-up, advanced age was a highly significant independent predictor of long-term mortality, myocardial infarction, and stroke (each P < .001). Lengths of hospital stay (up to 1.3-fold longer) and reimbursement costs (up to 1.1-fold higher) were clearly associated with advanced age (each P < .001). CONCLUSIONS: This study demonstrates the impact of aging on morbidity, in-hospital treatment, complications, and acute and long-term outcome of PAD patients.

Amputations and mortality in in-hospital treated patients with peripheral artery disease and diabetic foot syndrome.

AIMS: The prevalence of diabetes mellitus (DM) and its associated complications such as peripheral artery disease (PAD) and diabetic foot syndrome (DFS) are increasing worldwide. We aimed to determine the contemporary acute and long-term outcome of patients with PAD and DFS in Germany. METHODS: Nationwide, anonymized data of 40,335 patients hospitalized for PAD and/or DFS from the years 2009-2011 were analyzed and followed up until 2013. Patients were classified into 3 groups: DFS, PAD+DM and PAD without DM. In-hospital and long-term outcome (1156days, 95% CI 1.151-1.161) regarding major and minor amputation and mortality was assessed. Cumulative amputation-free survival and overall survival rates were calculated using Kaplan-Meier analysis. RESULTS: The proportion of DFS, PAD+DM and PAD only was 17.3%, 21.5% and 61.2%, respectively. At index-hospitalization, DFS patients had the highest amputation (31.9% vs. 11.1% vs. 6.0%), yet the lowest revascularization rate (18.2% vs. 67.8% vs. 71.6%) compared to patients with PAD only and PAD+DM (P<0.001). Cumulative 4-year survival (57.4%, 60.8% and 70.0%) and amputation-free-survival (45.4%, 74.4% and 86.5%) were lowest for DFS followed by PAD+DM and PAD only (P<0.001). CONCLUSIONS: Patients with diabetes, particularly those with DFS, have persistent high rates of limb amputation and of mortality in a real-world setting. Our data emphasize the need for further dedicated research to identify and target the underlying causes of the extraordinary poor outcome in this high risk population.

Acute and chronic anemia and short- and long-term outcome of patients with peripheral arterial disease and critical limb ischemia.

BACKGROUND: Evident data about the additive effect of "the fifth cardiovascular risk factor" (anemia) and peripheral arterial disease (PAD) focused on morbidity and outcome of patients with PAD are currently still missing. METHODS AND RESULTS: A total of 41,882 PAD patients were included. Of these, 5566 (13.3%) suffered from anemia. Patients with anemia were older (P<0.001), suffered more often from chronic kidney disease (P<0.001), coronary artery disease (P<0.001), and more severe PAD (P<0.001). However, they received significantly less endovascular revascularizations (P<0.001), had higher amputation rates (acute anemia: 3.7-fold, P<0.001; nutritional, aplastic, and anemia in chronic disease: 2.9-fold, P<0.001), higher in-hospital mortality rates (acute anemia: 6.4-fold, P<0.001; nutritional, aplastic, and anemia in chronic disease: 4.6-fold; P<0.001), had significantly higher in-hospital complications (P<0.001) compared to those without anemia. During a follow-up time up to 4years (until Dec. 31st, 2012, median 775days, 25th-75th percentiles 469-1120days) nutritional, aplastic, and anemia in chronic disease and acute anemia were high significant predictors of long-term mortality and amputation (each P<0.001). Lengths of hospital stay and reimbursement costs were higher (nutritional, aplastic, and anemia in chronic disease: 2-fold higher (P<0.001), acute anemia: 3-fold higher (P<0.001)) than in patients without anemia. CONCLUSION: This study illustrates from a large, comprehensive database the association of acute, nutritional, aplastic, and anemia in chronic disease on morbidity, in-hospital treatment and complications, short- and long term outcome, and costs of patients with PAD.

Low Rates of Revascularization and High In-Hospital Mortality in Patients With Ischemic Lower Limb Amputation: Morbidity and Mortality of Ischemic Amputation.

BACKGROUND: To assess the nationwide contemporary burden of cardiovascular risk factors, comorbidities, and in-hospital mortality in patients with lower limb amputation (LLA) due to peripheral arterial disease and critical limb ischemia (CLI) in Germany. METHODS: German nationwide data for 2005 and 2009 were analyzed regarding in-hospital rates of major and minor ischemic LLA, risk factors, comorbidities, surgical and endovascular revascularizations, and in-hospital mortality. RESULTS: In 2005, a total of 22 479 major (7.8%) and 28 262 minor (9.8%) LLAs were performed with a relative decrease of -21.8% in major LLA, yet with a relative increase of +2% in minor LLA rate in 2009. The overall revascularization rate before amputation was 46% in 2005 and 57% in 2009. In-hospital mortality for non-CLI, minor, and major amputees was 3.3%, 4.6%, and 19.8%, respectively (P < .001 for major vs minor LLA and non-CLI). CONCLUSION: The total number of ischemic LLA and amputation-related in-hospital mortality remains high in Germany in the 21st century. The poor outcome of patients with CLI might in part be due to underuse of revascularizations prior to amputation.

Outcome of patients with reduced ankle brachial index undergoing open heart surgery with cardiopulmonary bypass.

OBJECTIVES: In open heart surgery using cardiopulmonary bypass, perfusion of the lower extremities is markedly reduced which may induce critical ischaemia in patients with pre-existing peripheral artery disease. Whether these patients have an increased risk for amputation and should better undergo peripheral revascularization prior to surgery remains unclear. METHODS: From 1 January 2009 to 31 December 2010, 785 consecutive patients undergoing open heart surgery were retrospectively included. In 443 of these patients, preoperative ankle brachial index (ABI) measurements were available. The cohort was divided into four groups: (i) ABI < 0.5, (ii) ABI 0.5-0.69, (iii) ABI 0.7-0.89 or (iv) ABI ≥ 0.9. Follow-up data of 413 (93.2%) patients were analysed with regard to mortality and amputations. RESULTS: The groups differed significantly in terms of age, cardiac risk factors, performed cardiac surgery and renal function. Postoperative delayed wound healing was significantly associated with lower ABI (25.9, 15.2, 27.0 and 9.6% in Groups I-IV, respectively, P = 0.003), whereas 30-day mortality was not significantly higher in patients with lower ABI (0, 4.3, 8.1 and 3.9%, respectively, P = 0.4). Kaplan-Meier models showed a significantly lower long-term survival over 4 years in patients with reduced ABI (P = 0.001, long-rank test) while amputations occurred rarely with only one minor amputation in Group II (P = 0.023). CONCLUSIONS: Patients with reduced ABIs undergoing heart surgery showed more wound-healing disturbances, and higher long-term mortality compared with those with normal ABIs. However, no perioperative ischaemia requiring amputation occurred. Thus, reduced ABIs were not associated with increased peripheral risks in open heart surgery but ABI may be helpful in selecting the site for saphenectomy to potentially avoid delayed healing of related wounds in legs with severely impaired arterial perfusion.

Long-Term Mortality After Invasive Angiography and Endovascular Revascularization in Patients With PAD Having Chronic Kidney Disease.

Peripheral arterial disease (PAD) and chronic kidney disease (CKD) are associated with increased mortality rates. We assessed long-term outcomes of patients with PAD and CKD. Patients with PAD undergoing invasive angiography and/or endovascular revascularization between 2005 and 2010 were retrospectively classified into 5 CKD stages. A follow-up was performed and 572 patients were included, 116 patients (20%) had normal renal function, 245 were in CKD stage 2 (43%), 156 in CKD stage 3 (27%), and 55 in CKD stages 4 + 5 (10%). Diabetes mellitus, hypertension, and anemia were more frequent in higher CKD stages (P < .03). During follow-up (mean 1135 days; 95% confidence interval 1159-1259), cumulative mortality was 21% and increased with advanced CKD stages (9%, 16%, 29%, and 47%, respectively, P < .001). In multivariate Cox regression models, higher CKD stages were significantly associated with poor survival. Medication adherence for secondary prevention was significantly lower than recommended but irrespective of CKD stages. Kidney function is an independent predictor of worse long-term survival in patients with PAD. While standard medications were used less often than recommended, no differences between CKD stages were noted.

CKD and Acute and Long-Term Outcome of Patients with Peripheral Artery Disease and Critical Limb Ischemia.

BACKGROUND AND OBJECTIVES: Despite the many studies showing an association between CKD and a high risk of ischemic events and mortality, the association of CKD with peripheral arterial disease (PAD) still has not been well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This large cohort study assessed the association of CKD, even in the earlier stages, with morbidity, short- and long-term outcome, and costs among patients with PAD. RESULTS: We identified 41,882 patients with PAD who had an index hospitalization between January 1, 2009, and December 31, 2011. Of these, 8470 (20.2%) also had CKD (CKD stage 2: n=2158 [26%]; stage 3: n=3941 [47%]; stage 4: n=935 [11%]; stage 5: n=1436 [17%]). The ratio of women to men was 1:1.2. Compared with patients without known CKD, those with CKD had higher frequencies of coronary artery disease (1.8-fold higher; P<0.001), chronic heart failure (3.3-fold higher; P<0.001), and Rutherford PAD categories 5 and 6 (1.8-fold higher; P<0.001); underwent significantly fewer revascularizations (0.9-fold fewer; P<0.001); had a nearly two-fold higher amputation rate (P<0.001); had higher frequencies of in-hospital infections (2.1-fold higher; P<0.001), acute renal failure (2.8-fold higher; P<0.001), and sepsis (1.9-fold higher; P<0.001); had a 2.5-fold higher frequency of myocardial infarction (P<0.001); and had a nearly three-fold higher in-hospital mortality rate (P<0.001). In an adjusted multivariable Cox regression model, CKD remained a significant predictor of long-term outcome of patients with PAD during follow-up for up to 4 years (until December 31, 2012; median, 775 days; 25th-75th percentiles, 469-1120 days); the hazard ratio was 2.59 (95% confidence interval, 2.21 to 2.78; P<0.001). The projected mortality rates after 4 years were 27% in patients without known CKD and 46%, 52%, 72%, and 78% in those with CKD stages 2, 3, 4, and 5, respectively. Lengths of hospital stay and reimbursement costs were on average nearly 1.4-fold higher (P<0.001) in patients who also had CKD. CONCLUSIONS: This analysis illustrates the significant and important association of CKD with in-hospital and long-term mortality, morbidity, amputation rates, duration and costs of hospitalization, in-hospital treatment, and complications in patients with PAD.

The Preinterventional Cystatin-Creatinine-Ratio: A Prognostic Marker for Contrast Medium-Induced Acute Kidney Injury and Long-Term All-Cause Mortality.

BACKGROUND/AIMS: Contrast medium-induced acute kidney injury (CI-AKI) is an important iatrogenic complication following the injection of iodinated contrast media. The level of serum creatinine (SCr) is the currently accepted 'gold standard' to diagnose CI-AKI. Cystatin C (CyC) has been detected as a more sensitive marker for renal dysfunction. Both have their limitations. METHODS: The role of the preinterventional CyC-SCr ratio for evaluating the risk for CI-AKI and long-term all-cause mortality was retrospectively analyzed in the prospective single-center 'Dialysis-versus-Diuresis trial'. CI-AKI was defined and staged according to the Acute Kidney Injury Network classification. RESULTS: Three hundred and seventy-three patients were included (average age 67.4 ± 10.2 years, 16.4% women, 29.2% with diabetes mellitus, mean baseline glomerular filtration rate 56.3 ± 20.2 ml/min/1.73 m(2) [as estimated by Chronic Kidney Disease Epidemiology Collaboration Serum Creatinine Cystatin C equation], 5.1% ejection fraction <35%). A total of 79 patients (21.2%) developed CI-AKI after elective heart catheterization, and 65 patients (17.4%) died during follow-up. Multivariate analyses by logistic regression confirmed that the preinterventional CyC-SCr ratio is independently associated with CI-AKI (OR 9.423, 95% CI 1.494-59.436, p = 0.017). Also, the Cox regression model found a high significant association between preinterventional CyC-SCr ratio and long-term all-cause mortality (mean follow-up 649 days, hazards ratio 4.096, 95% CI 1.625-10.329, p = 0.003). CONCLUSION: The preinterventional CyC-SCr ratio is independently associated with CI-AKI and highly significant associated with long-term mortality after heart catheterization.

Peripheral arterial disease and critical limb ischaemia: still poor outcomes and lack of guideline adherence.

AIMS: Only few and historic studies reported a bad prognosis of peripheral arterial disease (PAD) and critical limb ischaemia (CLI). The contemporary state of treatment and outcomes should be assessed. METHODS AND RESULTS: From the largest public health insurance in Germany, all in- and outpatient diagnosis and procedural data were retrospectively obtained from a cohort of 41 882 patients hospitalized due to PAD during 2009-2011, including a follow-up until 2013. Patients were classified in Rutherford categories 1-3 (n = 21 197), 4 (n = 5353), 5 (n = 6916), and 6 (n = 8416). The proportions of patients with classical risk factors such as hypertension, dyslipidaemia, and smoking declined with higher Rutherford categories (each P < 0.001) while diabetes, chronic kidney disease, and chronic heart failure increased (each P < 0.001). Angiographies and revascularizations were performed less often in advanced PAD (each P < 0.001). In-hospital amputations increased continuously from 0.5% in Rutherford 1-3 to 42% in Rutherford 6, as also myocardial infarctions, strokes, and deaths (each P < 0.001). Among 4298 amputated patients with CLI, 37% had not received any angiography or revascularization neither during index hospitalization nor the 24 months before. During follow-up (mean 1144 days), 7825 patients were amputated and 10 880 died. Kaplan-Meier models projected 4-year mortality risks of 18.9, 37.7, 52.2, and 63.5% in Rutherford 1-3, 4, 5, and 6, and for amputation of 4.6, 12.1, 35.3, and 67.3%, respectively. In multivariable Cox regression models, PAD categories were significant predictors of death, amputation, myocardial infarction, and stroke (each P < 0.001). Length of in-hospital stay (5.8 ± 6.7 days, 10.7 ± 11.1days, 15.2 ± 13.8 days and 22.1 ± 20.3 days; P < 0.001) and mean case costs (3662 ± 3186 €, 5316 ± 6139 €, 6021 ± 4892 €, and 8461 ± 8515 €; P < 0.001) increased continuously in Rutherford 1-3, 4, 5, and 6. While only 49% of the patients suffered from CLI, these produced 65% of in-hospital costs (141 million €), and 56% during follow-up (336 million €). CONCLUSION: Regardless of recent advances in PAD treatment, current outcomes remain poor especially in CLI. Despite overwhelming evidence for reduction of limb loss by revascularization, CLI patients still received significantly less angiographies and revascularizations.

Impact of preexisting chronic kidney disease on acute and long-term outcome of critically ill patients on a medical intensive care unit.

BACKGROUND: Chronic kidney disease (CKD) increases acute and long-term mortality of many diseases. Limited data are available, in how far a preexisting non-dialysis dependent CKD affects the outcome of critically ill patients treated for non-renal causes. METHODS: In a retrospective study, we assessed the outcome of 524 patients with need for mechanical ventilation at our medical intensive care unit between 2002 and 2007. Patients were divided into 5 CKD stages depending on their calculated glomerular filtration rate at hospital admission excluding patients with pre-existing end-stage renal failure. In-hospital and long-term outcome up to 5 years were assessed. RESULTS: Advanced stages of CKD at admission were associated with higher age (p < 0.001) and diabetes (p = 0.003). Patients with higher CKD stages suffered more often from acute renal failure (p < 0.001), required longer renal replacement therapy (p < 0.001) and more often in-hospital resuscitation (p = 0.019). 405 patients died during follow-up (226 in-hospital). Multivariate Cox regression analysis identified eGFR as independent predictor of 30-day- (HRR 0.994, 95 % CI 0.990-0.998) and 1-year-mortality (HRR 0.996, 95 % CI 0.993-1.000). Long-term survival decreased significantly with increasing CKD stages (p = 0.004) and occurrence of acute renal failure (p < 0.001). CONCLUSIONS: In critically ill patients requiring mechanical ventilation, preexisting non-dialysis dependent CKD has marked impact on occurrence of acute renal failure, 30-day- and 1-year-mortality.

Recent trends in morbidity and in-hospital outcomes of in-patients with peripheral arterial disease: a nationwide population-based analysis.

AIMS: The prevalence of peripheral arterial disease (PAD) and especially of critical limb ischaemia (CLI) is announced to rise dramatically worldwide, with a considerable impact on the health care and socio-economic systems. We aimed to characterize the recent trends in morbidity and in-hospital outcome of PAD among all hospitalized patients in the entire German population between 2005 and 2009. METHODS AND RESULTS: Nationwide data of all hospitalizations in Germany in 2005, 2007, and 2009 were analysed regarding the prevalence of PAD, comorbidities, endovascular (EVR) and surgical revascularizations (SR), major and minor amputations, in-hospital mortality, and associated costs. From 2005 to 2009, total PAD cases increased by 20.7% (from 400 928 to 483 961), with an increase of CLI subset from 40.6 to 43.5%. Total EVR increased by 46%, while thromb-embolectomy, endarterectomy, and patch plastic increased by 67, 42, and 21%, respectively. Peripheral bypasses decreased by 2%. Major amputation decreased from 4.6 to 3.5%, while minor amputation slightly increased from 4.98 to 5.11%. The crude overall in-hospital mortality remained unchanged in claudicants (2.2%), while it decreased from 9.8 to 8.4% in CLI patients. However, mortality rate according to the Poisson model (n/1000 hospital residence days) increased significantly in claudicants (P < 0.001). Total reimbursement costs for PAD in-patient care increased by 21% with an average per case costs in 2009 of €4506 in a claudicant and €6791 in a CLI patient. CONCLUSION: This population-based analysis documents the significant rise of PAD, particularly of the CLI subset, and highlights the malign prognosis associated with PAD as indicated by high amputation and in-hospital mortality rates.

Impact of peripheral arterial occlusive disease on the development of contrast medium-induced acute kidney injury.

BACKGROUND/AIMS: Contrast medium-induced acute kidney injury (CI-AKI) is an important complication following the use of iodinated contrast media. It accounts for a significant number of hospital-acquired acute kidney injuries and is associated with increased in-hospital and long-term mortality and immense health care costs. We evaluated whether the presence of peripheral arterial occlusive disease (PAD) affects the incidence of CI-AKI following heart catheterization. METHODS: The impact of PAD on the frequency of CI-AKI after heart catheterization was analysed in the prospective single-centre Dialysis-versus-Diuresis trial (January 2001 to July 2004). The patients were retrospectively divided into 3 subgroups: patients with coronary heart disease (CHD), patients with PAD and patients without PAD or CHD. RESULTS: 412 patients were included (83.5% men, 29.1% diabetes mellitus, 4.9% ejection fraction <35%). Of these, 251 (60.9%) suffered from CHD but not from PAD, 77 (18.7%) from PAD and 84 (20.4%) had neither CHD nor PAD. After heart catheterization, 49 (11.9 %) patients developed CI-AKI. Patients with PAD suffered significantly more often from CI-AKI than those without PAD (32.7 vs. 16.8%, p = 0.008). Multivariate analyses by logistic regression confirmed PAD to be an independent predictor of a CI-AKI (odds ratio 2.013, 95% confidence interval 1.009-4.016, p = 0.047). The CHD was not significantly associated with CI-AKI. CONCLUSION: Patients with PAD significantly more often develop a CI-AKI after heart catheterization than those without PAD.

Complex cell rearrangements during intersegmental vessel sprouting and vessel fusion in the zebrafish embryo.

The formation of intersegmental blood vessels (ISVs) in the zebrafish embryo serves as a paradigm to study angiogenesis in vivo. ISV formation is thought to occur in discrete steps. First, endothelial cells of the dorsal aorta migrate out and align along the dorsoventral axis. The dorsal-most cell, also called tip cell, then joins with its anterior and posterior neighbours, thus establishing a simple vascular network. The vascular lumen is then established via formation of vacuoles, which eventually fuse with those of adjacent endothelial cells to generate a seamless tube with an intracellular lumen. To investigate the cellular architecture and the development of ISVs in detail, we have analysed the arrangement of endothelial cell junctions and have performed single cell live imaging. In contrast to previous reports, we find that endothelial cells are not arranged in a linear head-to-tail configuration but overlap extensively and form a multicellular tube, which contains an extracellular lumen. Our studies demonstrate that a number of cellular behaviours, such as cell divisions, cell rearrangements and dynamic alterations in cell-cell contacts, have to be considered when studying the morphological and molecular processes involved in ISV and endothelial lumen formation in vivo.

Slalom encodes an adenosine 3'-phosphate 5'-phosphosulfate transporter essential for development in Drosophila.

Sulfation of all macromolecules entering the secretory pathway in higher organisms occurs in the Golgi and requires the high-energy sulfate donor adenosine 3'-phosphate 5'-phosphosulfate. Here we report the first molecular identification of a gene that encodes a transmembrane protein required to transport adenosine 3'-phosphate 5'-phosphosulfate from the cytosol into the Golgi lumen. Mutations in this gene, which we call slalom, display defects in Wg and Hh signaling, which are likely due to the lack of sulfation of glycosaminoglycans by the sulfotransferase sulfateless. Analysis of mosaic mutant ovaries shows that sll function is also essential for dorsal-ventral axis determination, suggesting that sll transports the sulfate donor required for sulfotransferase activity of the dorsal-ventral determinant pipe.