Citations

Abstract Background: Inflammation in acute coronary syndrome (ACS) can identify those at greater long-term risks for heart failure (HF) and death. The present study assessed the performance of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) (cytokines involved in the activation and recruitment of leukocytes) in addition to known biomarkers [e.g., N-terminal pro-brain natriuretic peptide (NT-proBNP)] for predicting HF and death in an ACS population. Methods: In a cohort of 216 ACS patients, NT-proBNP (Elecsys®; Roche) and IL-6, IL-8, and MCP-1 (evidence investigator™; Randox) were measured in serial specimens collected early after symptom onset (n = 723). We collected at least 2 specimens from each participant: an early specimen (median 2 h; interquartile range 2–4 h) and a later specimen (9 h; 9–9 h), and used the later specimens’ biomarker concentrations for risk stratification. Results: An increase in both IL-6 and NT-proBNP was observed but not for IL-8 or MCP-1 early after pain onset. Kaplan–Meier analysis demonstrated that individuals with increased NT-proBNP (>183 ng/L) or cytokines (IL-6 > 6.4 ng/L; above upper limit of normal for IL-8 or MCP-1) had a greater probability of death or HF in the following 8 years (P <0.05). In a Cox proportional hazard model adjusted for both CRP and troponin I, increased IL-6, MCP-1, and NT-proBNP remained significant risk factors. Combining all 3 biomarkers resulted in a higher likelihood ratio for death or HF than models restricted to any 2 of these biomarkers. Conclusion: IL-6, MCP-1, and NT-proBNP are independent predictors of long-term risk of death or HF, highlighting the importance of identifying leukocyte activation and recruitment in ACS patients.

Resistin, a recently discovered proinflammatory cytokine, has been variably associated with insulin resistance, inflammation, and renal dysfunction. We investigated the association of plasma resistin with estimated glomerular filtration rate and albuminuria in 1575 hypertensive adults without known coronary heart disease or stroke (857 blacks and 718 non-Hispanic whites). Resistin was measured by a solid phase sandwich immunoassay, estimated glomerular filtration rate was estimated from serum creatinine, and albuminuria was expressed as urine albumin:creatinine ratio. After adjustment for coronary heart disease risk factors (age, sex, body mass index, smoking history, systolic blood pressure, diabetes, and total and high-density lipoprotein cholesterol) and use of renin-angiotensin blockers and statins, higher plasma resistin levels were associated with lower estimated glomerular filtration rate in both ethnic groups (each P <0.0001); the association remained significant after further adjustment for a marker of insulin resistance (homeostasis model assessment for insulin resistance) and a marker of inflammation (plasma C-reactive protein) and was seen in subjects with and without diabetes (each P <0.0001) in both ethnic groups. Higher plasma resistin levels were associated with a higher urine albumin:creatinine ratio in black subjects with diabetes ( P <0.0001) and non-Hispanic white subjects with diabetes ( P =0.032), independent of coronary heart disease risk factors, hypertension medication use, and statin use; the association remained significant after additional adjustment for homeostasis model assessment for insulin resistance and C-reactive protein. In adults with hypertension, higher circulating resistin levels were associated with a lower estimated glomerular filtration rate and with increased urine albumin:creatinine ratio in the presence of concomitant diabetes. This association was independent of coronary heart disease risk factors and markers of insulin resistance and inflammation.

The purpose of this study was to review the outcome of endovascular abdominal aortic aneurysm repair (EVAR) using custom-made aortouni-iliac (AUI) devices with femorofemoral bypass. Between June 1999 and March 2001, 23 consecutive patients (1 female, 22 male) at high risk of open aortic aneurysm repair underwent EVAR with custom devices in an AUI configuration. The mean follow-up was 37 months (range 2–72 months), and the mean age was 76.8 years (range 67.5–88.7 years). Increased surgical risk was evidenced by 92% and 69% of patients with significant pulmonary or cardiac disease, respectively. The preoperative mean aneurysm diameter ( n = 23) 62 ± 8.2 mm was significantly greater than the postoperative diameter, ( n = 23) 54 ± 16.4 mm. Ten endoleaks occurred. Migration of the stent graft occurred in 9% ( n = 2). Secondary interventions were necessary in 23%, whereas tertiary interventions were required in 9%. Patients at high risk of open aneurysm repair received sufficient protection from aneurysm rupture with custom-made AUI devices.

AbstractThe AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.06]. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% CI, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1416–21)

OBJECTIVE—Type 1 and type 2 diabetes are characterized by an ∼98 and ∼65% loss of pancreatic β-cells, respectively. Efforts to reverse either form of diabetes increasingly focus on the possibility of promoting β-cell replacement and/or regeneration. Islet transplantation has been explored, but it does not provide long-term insulin independence. One possible source of β-cell regeneration is hematopoietic stem cells. In mice, there are conflicting data as to whether hematopoietic stem cells contribute to pancreatic β-cells. We sought to establish whether hematopoietic stem cells (derived from adult donors) transdifferentiate into pancreatic β-cells in adult humans. RESEARCH DESIGN AND METHODS—We addressed this in 31 human pancreata obtained at autopsy from hematopoietic stem cell transplant recipients who had received their transplant from a donor of the opposite sex. RESULTS—Whereas some donor-derived cells were observed in the nonendocrine pancreata, no pancreatic β-cells were identified that were derived from donor hematopoietic stem cells, including two cases with type 2 diabetes. CONCLUSIONS—We conclude that hematopoietic stem cells derived from adult donors contribute minimally to pancreatic β-cells in nondiabetic adult humans. These data do not rule out the possibility that hematopoietic stem cells contribute to pancreatic β-cells in childhood or in individuals with type 1 diabetes.

The middle mesenteric artery is a rare anomalous mesenteric vessel that may supply variable segments of the colon. Occlusion of this artery during endovascular aortic aneurysm repair may bear a significant risk of bowel ischemia. We report the successful interventional treatment of a patient with a 5.3 cm infrarenal abdominal aortic aneurysm, sparing a dominant middle mesenteric artery.

Currently available aortic stent-grafts require bilateral femoral incisions for device deployment. The incidence of morbidity (infection, lymphatic complications, breakdown) of vertical, infrainguinal incisions used in endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs) was assessed, and the natural history of asymptomatic groin fluid collections following such procedures was determined. Between June 1999 and February 2001, 77 consecutive patients underwent EVAR for AAAs utilizing bilateral vertical femoral incisions. Fifty-nine (77%) bifurcated stent-grafts (BSGs), and 18 (23%) aortouniiliac (AUI) devices, with femorofemoral bypass were performed. Patients returned at 2 weeks, 1 month, and 6 months for physical examination, and 1 month and 6 months for abdominal and pelvic computed tomography (CT) scans. The presence of fluid collections was determined from the dictation report of the attending radiologist. Data are reported as (n) mean ± SE. Patient characteristics were compared using Fisher's exact test; p <0.05 considered significant. There were 72 males and 5 females, age 75 ±6.4 years and aneurysm size (77) 5.6 ±0.8 cm. There were no cases of wound breakdown or lymph fistula. Wound infections occurred in 3/150 incisions (2%), 2/34 AUI incisions (6%), and 1/1 16 BSG incisions (0.86%). There was no statistical difference (p =0.13) between graft types (BSG vs AUI). All infections were diagnosed clinically before the 1-month CT scan, treated without operative intervention or hospitalization, and resolved. There was a significant decrease in the BSG group and overall in asymptomatic wound fluid collections from 1 to 6 months postoperatively. At 1 and 6 months, respectively, the BSG group had 17 (14.6%) and 3 (2.6%) fluid collections out of 116 incisions (p = 0.003); the AUI group had 6 (17.6%) and 1 (2.9%) fluid collection(s) out of 34 incisions (p = 0. 13); and overall 23 (15.3%) and 4 (2.6%) out of 150 incisions (p = 0.004). The present study demonstrates that bilateral vertical femoral incisions used in EVAR have a wound infection rate of 2.0%. Infections are usually detected and treated clinically and empirically without the need for hospitalization or surgery. Asymptomatic groin wound fluid collections resolve significantly within 6 months without intervention. Therefore, surgical femoral artery exposure adds little morbidity to the endovascular repair of abdominal aortic aneurysms.

Carotid-carotid bypass grafting is a procedure only rarely performed. However, in selected cases it may provide an excellent treatment alternative. The authors report on two patients who were treated by carotid-carotid bypass. The first patient had recurrent cerebral emboli from a chronic aortic dissection extending into the right innominate, common carotid, and internal carotid artery. The second patient was symptomatic from a recurrent high-grade internal carotid artery stenosis and an ulcerated plaque in the right common carotid artery following radical neck dissection and radiotherapy. The indications for this procedure are described and the related literature is reviewed.