Athanasios Saratzis

Effect of Thiazolidinediones on Albuminuria and Proteinuria in Diabetes: A Meta-analysis

BACKGROUND Because of the major clinical and economic burden of diabetic nephropathy, new therapeutic tools to delay its progression are needed. Recent studies suggest that thiazolidinediones have renal benefits. We aimed to evaluate the effect of thiazolidinediones on urinary albumin and protein excretion in patients with diabetes mellitus. STUDY DESIGN Systematic review and meta-analysis by searching MEDLINE/PubMed, EMBASE, and Cochrane CENTRAL databases (1991 to September 2009). SETTING & POPULATION Patients with diabetes mellitus. SELECTION CRITERIA FOR STUDIES Randomized controlled trials. INTERVENTION Thiazolidinediones (rosiglitazone and pioglitazone) compared with placebo or other antidiabetic agents. OUTCOMES Weighted (WMDs) and standardized mean differences (SMDs) for changes in urine albumin or protein excretion between the thiazolidinedione and control groups. RESULTS Of 171 originally identified articles, 15 studies (5 with rosiglitazone and 10 with pioglitazone) involving 2,860 patients were included in the analysis. In participants with baseline normo- or microalbuminuria, the WMD of proportional changes between the thiazolidinedione and control groups in urinary albumin excretion measured using time-specified collections was -64.8% (95% CI, -75.6 to -53.9) and the WMD of changes in albumin-creatinine ratio was -24.8% (95% CI, -39.6 to -10.0). Overall, in participants with normo- and microalbuminuria, thiazolidinedione treatment was associated with a significant decrease in urinary albumin excretion (SMD, -0.6 units of standard deviation [SD]; 95% CI, -0.8 to -0.4). Similarly, thiazolidinediones were associated with a significant decrease in urinary protein excretion in patients with proteinuria (SMD, -1.1 units of SD; 95% CI, -1.8 to -0.4). LIMITATIONS Significant heterogeneity across included studies in several subgroup analyses; patient-level data not available. CONCLUSIONS Treatment with thiazolidinediones significantly decreases urinary albumin and protein excretion in patients with diabetes. This finding calls for clinical trials with hard renal outcomes to elucidate the potential benefits of thiazolidinediones on diabetic nephropathy.

Inflammation and atherosclerosis in rheumatoid arthritis.

Rheumatoid arthritis (RA) associates with increased cardiovascular mortality. This appears to be predominantly due to ischaemic causes, such as myocardial infarction and congestive heart failure. The higher prevalence of cardiac ischaemia in RA is thought to be due to the accelerated development of atherosclerosis. There are two main reasons for this, which might be inter-related: the systemic inflammatory load, characteristic of RA; and the accumulation in RA of classical risk factors for coronary heart disease, which is reminiscent of the metabolic syndrome. We describe and discuss in the context of RA the involvement of local and systemic inflammatory processes in the development and rupture of atherosclerotic plaques, as well as the role of individual risk factors for coronary heart disease. We also present the challenges facing the clinical and scientific communities addressing this problem, which is receiving increasing attention.

Anaconda Aortic Stent-Graft: Single-Center Experience of a New Commercially Available Device for Abdominal Aortic Aneurysms

Purpose: To report a retrospective evaluation of the efficacy and midterm clinical results of the Anaconda stent-graft in the endovascular repair of infrarenal abdominal aortic aneurysms. Methods: Fifty-one patients (48 men; mean age 71±8 years, range 62–89) were treated with the Anaconda stent-graft from January 2006 to September 2007. Six patients were considered at high risk for open repair (defined as ASA grade 3) and 10 had undergone previous laparotomy. The mean neck diameter and length were 26 mm (range 22–30) and 18.5 mm (range 14–35), respectively. Mean proximal neck angulation was 30° (range 5–60). Severe iliac artery tortuosity (>60°) was seen in 20 (39%) patients; 3 (6%) had a proximal aneurysm neck angle >45°. Results: The technical success rate was 100%; intraprocedurally, 7 (14%) stent-grafts were repositioned to address renal artery occlusion by the graft (n=1) or type I endoleak. This maneuver resolved 6 of the 7 situations; a remaining endoleak required a proximal cuff to seal it. The procedural success rate (no major complication at 30 days) was 94%. The mean follow-up was 16 months (range 1–21). Five (10%) endoleaks (1 type I, 4 type II) and 1 (2%) graft migration occurred. The overall reintervention rate was 6%. Two (4%) patients died in late follow-up. Conclusion: The Anaconda stent-graft appears both safe and effective in terms of midterm clinical outcome and compares favorably with previously reported EVAR results. The ability to reposition the stent-graft is a particular advantage.

Aortic and Iliac Fixation of Seven Endografts for Abdominal-aortic Aneurysm Repair in an Experimental Model Using Human Cadaveric Aortas

OBJECTIVE To evaluate the proximal and distal (iliac) fixation of seven self-expanding endografts, used in the endovascular treatment (EVAR) of abdominal-aortic aneurysm (AAA), by measuring the displacement force (DF) necessary to dislocate the devices from their fixation sites. METHODS A total of 20 human cadaveric aortas were exposed, left in situ and transected to serve as fixation zones. The Anaconda, EndoFit aorto-uni-iliac, Endurant, Powerlink, Excluder, Talent and Zenith stent grafts were deployed and caudal force was applied at the flow divider, through a force gauge. The DF needed to dislocate each device ≥ 20 mm from the infrarenal neck was recorded before and after moulding-balloon dilatation. Cephalad force was similarly applied to each iliac limb to assess distal fixation before and after moulding-balloon dilatation. RESULTS Endografts with fixation hooks or barbs displayed a significantly higher DF necessary to dislocate the proximal portion compared with devices with no such fixation modalities (p < 0.001). Balloon dilatation produced a significant increase in DF in both devices with (p < 0.001) or without (p = 0.003) hooks or barbs. Suprarenal support did not enhance proximal fixation (p = 0.90). Balloon dilatation significantly increased the DF necessary to dislodge the iliac limbs (p = 0.007). CONCLUSIONS Devices with fixation hooks displayed higher proximal fixation. Moulding-balloon dilatation increased proximal and distal fixation. Suprarenal support did not affect proximal fixation.

Aortoduodenal Fistulas after Endovascular Stent-Graft Repair of Abdominal Aortic Aneurysms: Single-Center Experience and Review of the Literature

Purpose: To report a single-center experience with aortoduodenal fistula (ADF) after successful endovascular aneurysm repair (EVAR) of an infrarenal abdominal aortic aneurysm (AAA). Methods: Five patients (all men; mean age 68.4 years, range 60–75) developed an ADF between 18 days to 1 year after successful EVAR using 3 types of commercially available endografts: 1 bifurcated Anaconda, 1 unibody Powerlink, and 3 EndoFit stent-grafts in a tubular (n=1) or aortomonoiliac configuration (n=2). The internal iliac artery was not occluded in any of the cases. Results: Hematemesis and diffuse abdominal pain constituted the main symptoms leading to the diagnosis of ADF, which was confirmed on computed tomography. Infection was the etiology of the ADF in 3 patients; all underwent emergency surgical exploration, but 1 died in hospital; the other 2 have survived from 1 to 3 years after an emergency procedure. The other 2 ADFs developed in patients with large type I endoleaks; 1 patient died before surgery could be performed and the other one 18 hours after laparotomy. All stent-grafts were removed; none displayed any defects. Conclusion: ADF is a rare but dangerous complication of EVAR. The sequela may be primarily attributed to graft infection, as seen in this series. However, the exact pathogenesis of the pathology remains largely unknown. Prompt diagnosis and intervention are crucial to avoid a fatal outcome.

The genetic basis for aortic aneurysmal disease

Aortic aneurysms are an important cause of cardiovascular death in elderly patients. At present, little is known of the pathobiology of aneurysmal disease and this limits the ability to develop non-surgical treatments to stabilise aneurysms. Both thoracic and abdominal aortic aneurysms (AAA) demonstrate a strong genetic component in their aetiology. Determination of the genetic variants associated with aneurysmal disease is one approach to increasing the understanding the pathways leading to aneurysmal degeneration of the aorta. In this review, we aim to summarise the current knowledge of the genetics underlying the two most common disease phenotypes, thoracic aortic aneurysm (TAA) and AAA. Genetically, AAA represent a multifactorial disease, with the likelihood that there are multiple variants of very low effect sizes contributing to the overall genetic disease risk. Non-syndromic TAA appears to be associated with a smaller number of risk loci with higher individual effect sizes at these loci. Candidate gene and genome-wide approaches have identified robust associations between AAA and variants in/nearby the SORT1, low-density lipoprotein receptor, DAB2IP, LRP1, ELN, CRP, TGFB and various matrix metallo-proteinase genes suggesting that aberrations of lipid metabolism and proteolytic pathways are the key contributors to disease. Some of these associations (eg, LRP1) are not associated with atherosclerosis, suggesting pathways unique to AAA. Genetic variants associated with non-syndromic TAA (ACTA2 and MYH11) are related to the TGFβ pathway, strongly implicated in syndromic TAA, thus suggesting a common pathway between syndromic and non-syndromic TAA.

Acute Kidney Injury After Endovascular Repair of Abdominal Aortic Aneurysm

Acute kidney injury (AKI) after any type of intervention negatively impacts mortality, length of hospitalization, and perhaps long-term survival. In the case of endovascular aneurysm repair (EVAR), the incidence of AKI ranges from 1% to 23% for elective and emergency procedures and is lower compared to open repair. The pathophysiology of AKI in EVAR is complex: contrast-induced nephropathy, renal microembolization, and acute tubular necrosis are all implicated. Prevention strategies include hydration, ischemic preconditioning, regional anesthesia, and pharmacological agents. There is no level I evidence regarding the prevention of AKI in EVAR, so this review sought to examine the mechanisms and prevention strategies for this potentially fatal complication.

Comparison of the impact of open and endovascular abdominal aortic aneurysm repair on renal function

OBJECTIVE The impact of any intervention on renal function is a crucial determinant of outcome. Open (OR) and endovascular (EVAR) abdominal aortic aneurysm (AAA) repair can affect renal function during the short and longer term. This study aimed to directly compare the effect of those different types of aneurysm repair during a period of 2 years. METHODS This was a nested case-control study including patients undergoing either OR or EVAR of an infrarenal AAA. Three groups were included: OR, EVAR with suprarenal endograft fixation, and EVAR with infrarenal fixation. These were matched for age (within 2 years), sex, AAA size (within 1 cm), hypertension, smoking, and proximal neck diameter (within 5 mm). The primary end point was change in estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration formula at baseline, 6 months, 12 months, and 2 years. RESULTS A total of 225 patients were included [(45 ORs matched vs 90 suprarenal and 90 infrarenal fixation EVARs; 35 women (16%); age, 71 ± 8 years; AAA size, 6.4 ± 1 cm]. Groups did not differ significantly in terms of diabetes, hypercholesterolemia, or baseline eGFR (P = .89). On average, those undergoing OR lost a mean 5.39 mL/min/1.73 m(2) (P = .48) within 1 year and 5.49 units (P = .42) after 2 years. The suprarenal fixation patients lost 5.58 units (P = .002) after 1 year and 6.57 units (P = .001) after 2 years. Finally, the infrarenal fixation patients lost 0.53 unit (P = .74) after 1 year and 2.24 units (P = .22) after 2 years. CONCLUSIONS OR and suprarenal fixation EVAR are associated with significant declines in renal function during 2 years, in contrast to infrarenal EVAR fixation. The patterns of eGFR decline in OR and suprarenal fixation EVAR are not similar, suggesting different causal mechanisms.

Helical EndoStaples enhance endograft fixation in an experimental model using human cadaveric aortas

OBJECTIVE This study evaluated the contribution of Aptus EndoStaples (Aptus Endosystems, Sunnyvale, Calif) in the proximal fixation of eight endografts used in the endovascular repair of abdominal aortic aneurysms (EVAR). METHODS Nine human cadaveric aortas were exposed, left in situ, and transected to serve as fixation zones. The Zenith (Cook, Bloomington, Ind), Anaconda (Vascutek, Inchinnan, Scotland, UK), Endurant (Medtronic, Minneapolis, Minn), Excluder (W. L. Gore and Associates, Flagstaff, Ariz), Aptus (Aptus Endosystems), Aorfix (Lombard Medical, Didcot, UK), Talent (Medtronic), and AneuRx (Medtronic) stent grafts were proximally deployed and caudal displacement force (DF) was applied via a force gauge, recording the DF required to dislocate each device ≥20 mm from the infrarenal neck. Measurements were repeated after four and six EndoStaples were applied at the proximal fixation zone, as well as after a Dacron graft was sutured at the proximal neck in standard fashion. Finally, a silicone tube was used as a control fixation zone to test the DF of grafts with EndoStaples in a material that exceeded the integrity of a typical human cadaveric aorta and provided a consistent substrate to examine the differential effect of variable degrees of EndoStaple implantation using zero, two, four, and six EndoStaples. RESULTS In the cadaveric model, the mean DF required to dislocate the endografts without the application of EndoStaples was 19.73 ± 12.52 N; this increased to 49.72 ± 12.53 N (P < .0001) when four EndoStaples where applied and to 79.77 ± 28.04 N when six EndoStaples were applied (P = .003). The DF necessary to separate the conventionally hand-sutured Dacron graft from the aorta was 56 N. In the silicone tube model, the Aptus endograft without EndoStaples withstood 3.2 N of DF. The DF increased to 39 ± 3 N when two EndoStaples were added, to 71 ± 6 N when four were added, and to 98 ± 5 N when six were added. In eight of the 13 cadaver experiments conducted with four and six EndoStaples, the displacement occurred as a result of complete aortic transection proximal to the fixation site, indicating that aortic tissue integrity was the limiting factor in these experiments. CONCLUSIONS The fixation of eight different endografts was increased by a mean of 30 N with four Aptus EndoStaples and by a mean of 57 N with six EndoStaples in this model. Endostaples can increase endograft fixation to levels equivalent or superior to that of a hand-sewn anastomosis. The application of six EndoStaples results in aortic tissue failure above the fixation zone, demonstrating fixation strength that exceeds inherent aortic integrity in these cadavers.

Suprarenal graft fixation in endovascular abdominal aortic aneurysm repair is associated with a decrease in renal function

INTRODUCTION Suprarenal endograft fixation is routinely used in the endovascular repair of abdominal aortic aneurysms (EVAR) to enhance proximal endograft attachment but can be associated with an adverse outcome in renal function. This prospective study assessed the effect of suprarenal fixation on serum creatinine concentration and estimated glomerular filtration rate (eGFR), calculated by the Modified Diet in Renal Disease equation, 12 months after elective EVAR. METHODS Patients undergoing elective EVAR were divided into suprarenal vs infrarenal fixation groups matched for age, sex, smoking, and aneurysm diameter. Serum creatinine and eGFR were measured at baseline, 6, and 12 months. RESULTS Included were 92 patients (two women) with a mean age of 71 ± 7 years, with 46 in each group. No device-related complications were noted. Serum creatinine did not differ significantly between groups at 6 (P = .24) or 12 (P = .08) months but significantly increased in the suprarenal group at 12 months (1.08 ± 0.36 to 1.16 ± 0.36 mg/dL; P < .001) vs baseline. The eGFR (mL/min/1.73 m(2)) did not differ significantly at baseline between the suprarenal (85 ± 27) and infrarenal (80 ± 28; P = .33) groups or at 6 months (88 ± 29 vs 77 ± 24, respectively; P = .07). At 12 months, the suprarenal group had a lower eGFR (73 ± 23) than the infrarenal group (84 ± 26; P = .027). The eGFR at 12 months showed a significant decrease in the suprarenal (80 ± 28 to 73 ± 23; P < .001) but not in the infrarenal group (85 ± 27 to 84 ± 26; P = .48). The drop in eGFR differed significantly at 12 months in the infrarenal vs the suprarenal (0.82 vs -6.94; P < .001) group. No patient progressed to end-stage renal disease or disclosed a drop in eGFR > 30%. CONCLUSIONS In contrast to previous studies, this study suggests that suprarenal endograft fixation in elective EVAR is associated with a drop in eGFR at 12 months.