Intermolecular Addition of Carbon-Centered Radicals to Ynamides. A Regio- and Stereoselective Route to Persubstituted α-Iodo-enamides.

Rather surprisingly, C-C bond formation through "intermolecular" radical addition to internal ynamides has never been reported. Actually, ynamides are excellent acceptors for "electrophilic" carbon-centered radicals. These processes enable the introduction of functionalized alkyl chains at Cß, groups that have not yet been introduced via the addition of organometallics. Radical carboiodination affords persubstituted α-iodo-enamides in moderate to high yield. The addition is totally stereoselective. Theoretical support to the mechanism and the scope and limitation of the reaction are discussed.

Differential down-regulation of HLA-DR on monocyte subpopulations during systemic inflammation.

INTRODUCTION: Decreased expression of human leukocyte antigen class II (HLA-DR) on monocytes is a hallmark of altered immune status in patients with a systemic inflammatory response syndrome (SIRS). So far, the analyses were mainly performed without taking into account monocytes subpopulations. METHODS: We studied this modification on CD14HIGH and CD14LOW monocytes of 20 SIRS patients undergoing abdominal aortic surgery (AAS), 20 patients undergoing carotid artery surgery (CAS), and 9 healthy controls, and we investigated mediators and intracellular molecules that may be involved in this process. RESULTS: HLA-DR on CD14HIGH monocytes started to decrease during surgery, after blood reperfusion, and was further reduced post-surgery. In contrast, HLA-DR expression on CD14LOW cells only decreased after surgery, and to a lesser extent than on CD14HIGH monocytes. Negative correlations were found between the reduction of HLA-DR expression and the change in cortisol levels for both subpopulations, whereas a negative correlation between interleukin-10 (IL-10) levels and HLA-DR modulation was only observed for CD14HIGH cells. In accordance with these ex vivo results, HLA-DR on CD14HIGH and CD14LOW monocytes of healthy donors was reduced following incubation with hydrocortisone, whereas IL-10 only acted on CD14HIGH subpopulation. Furthermore, flow cytometry revealed that the expression of IL-10 receptor was higher on CD14HIGH versus CD14LOW monocytes. In addition, hydrocortisone, and to a lesser extent IL-10, reversed the up-regulation of HLA-DR induced by bacterial products. Finally, membrane-associated RING-CH-1 protein (MARCH1) mRNA, a negative regulator of MHC class II, was up-regulated in monocytes of AAS patients on Day 1 post-surgery, and in those of healthy subjects exposed to hydrocortisone. CONCLUSIONS: This study reveals that HLA-DR expression is modulated differently on CD14HIGH (classical) versus CD14LOW (inflammatory) monocytes after systemic inflammation.

Translocation of bacterial NOD2 agonist and its link with inflammation.

INTRODUCTION: The gut is often considered as the motor of critical illness through bacterial translocation, which amplifies the inflammatory response and alters the immune status. However, systemic bacterial translocation was rarely proven and endotoxin measurement only reflects translocation of Gram-negative-derived products. The process could be more frequently identified if peptidoglycan, derived from both Gram-negative and Gram-positive bacteria, was measured. METHODS: We developed a new tool to detect circulating peptidoglycan-like structure using a NOD2-transfected cell line. We also measured plasma and cell-associated endotoxin and different plasma markers of inflammation. We studied 21 patients undergoing abdominal aortic surgery (AAS), and 21 patients undergoing carotid artery surgery (CAS) were included as negative controls. Patients were sampled during surgery until two days post-surgery. RESULTS: In 90.5% of the AAS patients, a NOD2 agonist peak was detected in plasma before aortic clamping, but after gut manipulation by the surgeon, and persisted after blood reperfusion. As expected, no peak was detected in plasma from CAS patients (P = 0.003). Leukocyte-bound endotoxin appeared after blood reperfusion in 71% of the AAS patients, and circulating endotoxin was detected for 57% of them. The levels of interleukin (IL)-6, IL-10 and of inflammatory markers (C-reactive protein, procalcitonin) were maximal at postoperative day 1 or 2 in AAS patients. The levels of circulating NOD2 agonist positively correlated with those of cortisol and IL-10. CONCLUSIONS: The measurement of circulating NOD2 agonist gives a higher informative tool than that of circulating endotoxin for early and sensitive detection of the translocation of bacterial products. The data suggest that circulating NOD2 agonist contributes to further enhance the stress response following surgery.

Type IV thoracoabdominal aneurysm repair: predictors of postoperative mortality, spinal cord injury, and acute intestinal ischemia.

Our purpose was to identify preoperative and intraoperative predictors of early mortality, spinal cord injury, or acute intestinal ischemia after repair of type IV thoracoabdominal aneurysm (TAA IV) as a basis for optimizing surgical indications and techniques. From January 1991 to June 2006 we operated on 171 patients for TAA IV. There were 149 men (87.1%) and 22 women (12.9%), with a mean age of 65.0 +/- 10.9 years (range 23-82). The underlying etiology was degenerative aneurysmal disease in 143 patients (83.6%). Twenty-two patients (12.8%) underwent emergent operation. Comorbidity included coronary disease in 72 patients (45.6%) including 39 who had undergone a revascularization procedure, arterial hypertension in 121 (70.1%), chronic obstructive pulmonary disease in 81 (47.4%), and chronic kidney insufficiency in 58 (33.9%). Seventy-six patients (44.4%) presented concurrent lesions involving at least one visceral artery. Spinal cord arteriography was performed in 91 patients (53.2%). In 25 cases (27.5%) arteriographic findings demonstrated the need for revascularization of the Adamkiewicz artery due to location of the ostium at or below the T12 level. Repair was carried out with cross-clamping only in 160 cases (93.6%). Partial cardiopulmonary bypass was used in 11 patients (6.4%). A total of 23 patients (13.4%) died postoperatively. The cause of death was acute intestinal ischemia in nine cases, multiple organ failure in seven, coagulation disorder in three, cardiac complications in two, and stroke in two. Spinal cord injury occurred in eight patients (4.7%) including two who died. According to univariate analysis, the significant predictors of early death were age over 70 years, degenerative aneurysmal disease, coronary artery disease, chronic renal insufficiency or visceral artery lesions, operator, duration of intestinal ischemia and use of a "complex" surgical technique. Although the only significant predictor of spinal cord injury was duration of digestive ischemia, an almost significant trend (p < 0.1) was observed for coronary artery disease, coronary bypass, and renal insufficiency. The significant predictors of acute intestinal ischemia were kidney insufficiency and visceral artery lesions, but coronary artery disease and previous coronary bypass were almost significant (p = 0.06). Frequent association of TAA IV with arteriosclerotic disease in elderly patients presenting coronary artery disease and chronic kidney insufficiency partly explains why early postoperative mortality remains high. The incidence of spinal cord injury suggests that preoperative spinal cord arteriography is mandatory for prevention. The frequency of intestinal ischemia is more problematic, but a better understanding of the underlying mechanism should enable development of preventive strategies.

Influence of renal dysfunction on the accuracy of procalcitonin for the diagnosis of postoperative infection after vascular surgery.

OBJECTIVE: Procalcitonin has been advocated as a specific biomarker for bacterial infection. We performed this study to determine whether accuracy of procalcitonin for diagnosis of postoperative bacterial infection is affected by renal function after aortic surgery. DESIGN: Single-center prospective study. SETTING: University hospital. PATIENTS: Two hundred seventy-six patients scheduled for elective major aortic surgery. INTERVENTIONS: Blood samples were taken before surgery and each day over the 5-day postoperative period, and measurement of serum procalcitonin was performed. Diagnosis of infection was performed by a blinded expert panel. Renal function was assessed using an estimate of creatinine clearance with the Cockcroft formulas. Renal dysfunction was defined as a creatinine clearance <50 mL x min(-1). MEASUREMENTS AND MAIN RESULTS: Infection was diagnosed in 67 patients. Seventy five patients (27%) had postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, with a peak reached at the fourth postoperative day, but it was significantly higher in patients with impaired renal function in both control and infected patients. The optimal threshold of procalcitonin markedly differed in patients with renal dysfunction compared with patients without renal dysfunction (2.57 vs. 0.80 ng x mL(-1), p < .05). The diagnostic accuracy of procalcitonin significantly increased (0.74 vs. 0.70, p < .05) when the threshold of procalcitonin was adapted to the renal function. The elevation of procalcitonin occurred 2 days before the medical team was able to diagnose infection. CONCLUSIONS: Procalcitonin is a valuable marker of bacterial infections after major aortic surgery, but renal function is a major determinant of procalcitonin levels and thus different thresholds should be applied according to renal function impairment.

The impact of postoperative discontinuation or continuation of chronic statin therapy on cardiac outcome after major vascular surgery.

BACKGROUND: Statins reduce cardiac morbidity in nonsurgical populations, and may benefit surgical patients. We sought to examine cardiac outcome in patients who continued, compared with those who discontinued, statin therapy after major vascular surgery. METHODS: Prospectively collected data were examined for an association between statin therapy and perioperative cardiac morbidity in patients undergoing infrarenal aortic surgery. Between January 2001 and December 2003, there were no guidelines for perioperative continuation of statins (discontinuation group, n = 491). From January 2004, guidelines were instituted whereby statin therapy was continued starting as soon as possible after surgery (continuation group, n = 178). The occurrence of cardiac myonecrosis (defined as an increase of cardiac troponin I more than the 99th percentile or 0.2 ng/mL) was analyzed. Intra-cohort (propensity score) and extra-cohort (Lee score) adjustments of the risk were performed. RESULTS: The median delay between surgery and resumption of statin therapy was 4 days and 1 day in the discontinuation and continuation groups (P < 0.001), respectively. Using propensity score matching for likelihood of preoperative treatment, the odds ratio associated with chronic statin treatment to predict myonecrosis for patients with versus without early postoperative statin resumption (continuation versus discontinuation groups) was 0.38 and 2.1 (relative risk reduction of 5.4; 95% confidence interval: 1.2-25.3, P < 0.001), respectively. The odds ratio after adjustment for the Lee score was 0.38 in the continuation group and 2.1 in the discontinuation group (relative reduction of 5.5; 95% confidence interval: 1.2-26.0, P < 0.001). Postoperative statin withdrawal (>4 days) was an independent predictor of postoperative myonecrosis (OR 2.9, 95% confidence interval 1.6-5.5). CONCLUSIONS: Discontinuation of statin therapy after major vascular surgery is associated with an increased postoperative cardiac risk, suggesting that statin therapy should be resumed early after major vascular surgery.

Early and delayed myocardial infarction after abdominal aortic surgery.

BACKGROUND: Although postoperative myocardial infarction (PMI) after vascular surgery has been described to be associated with prolonged ischemia, its exact pathophysiology remains unclear. METHODS: The authors used intense cardiac troponin I (cTnI) surveillance after abdominal aortic surgery in 1,136 consecutive patients to better evaluate the incidence and timing of PMI (cTnI > or = 1.5 ng/ml) or myocardial damage (abnormal cTnI < 1.5 ng/ml). RESULTS: Abnormal cTnI concentrations was noted in 163 patients (14%), of which 106 (9%) had myocardial damage and 57 (5%) had PMI. In 34 patients (3%), PMI was preceded by a prolonged (> 24 h) period of increased cTnI (delayed PMI), and in 21 patients (2%), the increase in cTnI lasted less than 24 h (early PMI). The mean times from end of surgery to PMI were 37 +/- 22 and 74 +/- 39 h in the early PMI and delayed PMI groups, respectively (P < 0.001). The mean time between the first abnormal cTnI and PMI in the delayed PMI group was 54 +/- 35 h, during which the cTnI profiles of the myocardial damage and delayed PMI groups were identical. In-hospital mortality rates were 24, 21, 7, and 3% for the early PMI, delayed PMI, myocardial damage, and normal groups, respectively. CONCLUSIONS: Intense postoperative cTnI surveillance revealed two types of PMI according to time of appearance and rate of increase in cTnI. The identification of early and delayed PMI may be suggestive of different pathophysiologic mechanisms. Abnormal but low postoperative cTnI is associated with increased mortality and may lead to delayed PMI.

Does preoperative coronary angioplasty improve perioperative cardiac outcome?

BACKGROUND: Percutaneous coronary intervention (PCI) is performed in patients with coronary artery disease who are undergoing major noncardiac procedures to reduce perioperative cardiac morbidity and mortality. However, the impact of this approach on postoperative outcome remains controversial. METHODS: The authors analyzed a cohort of 1,152 patients after abdominal aortic surgery in which 78 patients underwent PCI. A propensity score analysis was performed. Also, using a logistic regression model, the authors determined variables associated with a severe postoperative coronary event or a death in patients without PCI. Then, in patients with PCI, they compared the expected and observed outcome. RESULTS: Five variables (age > 75 yr, blood transfusion > 3 units, repeated surgery, preoperative hemodialysis, and previous cardiac failure) independently predicted (with 94% correctly classified) a severe postoperative coronary event, and five variables (age > 75 yr, repeated surgery, previously abnormal ST segment/T waves, previous hypertension, and previous cardiac failure) independently predicted (with 97% correctly classified) postoperative death. In the PCI group, the observed percentages of patients with a severe postoperative coronary event (9.0% [95% confidence interval, 4.4-17.4]) or death (5.1% [95% confidence interval, 2.0-12.5]) were not significantly different from the expected percentages (8.2 and 6.9%, respectively). When all patients were pooled together, the odds ratios of PCI were not significant. The propensity score analysis provided a similar conclusion. CONCLUSION: PCI did not seem to limit significantly cardiac risk or death after aortic surgery.

A comparison of intrathecal opioid and intravenous analgesia for the incidence of cardiovascular, respiratory, and renal complications after abdominal aortic surgery.

UNLABELLED: Major surgery evokes a stress response that can produce deleterious consequences, especially in a population at high risk for those complications. We tested the hypothesis that decreasing or eliminating one of the sources of stress by providing intense analgesia in the immediate postoperative period via application of neuraxial opioids would decrease major nonsurgical complications. Two-hundred-seventeen patients scheduled to undergo abdominal aortic surgery were randomly allocated to receive either general anesthesia alone (control) or general anesthesia combined with intrathecal opioid (1 micro g/kg sufentanil with 8 micro g/kg preservative-free morphine injected at the L4-5 interspace). Postoperative care was identical in the two groups, including patient-controlled analgesia. Each patient provided an assessment of postoperative pain using a visual analog scale. Postopera-tive complications were recorded according to criteria established a priori. The administration of intrathecal opioid provided more intense analgesia than patient-controlled analgesia during the first 24 h postoperatively (P < 0.05). There was no difference between groups for the incidence of combined major cardiovascular, respiratory, and renal complications (P > 0.05) or mortality (P > 0.05). The incidence of myocardial damage or infarction, as defined by abnormal plasma concentration of troponin I, did not differ between the two groups (P > 0.05). In patients undergoing major abdominal vascular surgery, decrease of one contributor to postoperative stress, by provision of intense analgesia for the intraoperative and initial postoperative period, via application of neuraxial opioid, does not alter the combined major cardiovascular, respiratory, and renal complication rate. IMPLICATIONS: Provision of intense analgesia for the initial postoperative period after major abdominal vascular surgery, via the administration of neuraxial opioid, does not alter the combined incidence of major cardiovascular, respiratory, and renal complications.

[Tailored endoprostheses for the endovascular treatment of aorto-iliac aneurysms: current features and perspectives]. / Endoprothèses artisanales sur mesure pour le traitement endovasculaire des anévrysmes aorto-iliaques: aspects actuels et perspectives.

We describe here our preliminary experience with the almost exclusive use of a range of made to measure stent-grafts home-made from commercially available components. From January 1996 to December 1999, 188 aortoiliac aneurysms (AIA) were treated with stent-grafts that were home-made to measure using Z autoexpandable stainless steel stents connected with polyester sutures and covered with commercially available polyester vascular prostheses. These stent-grafts were implanted through 18 to 24 (typically 20) Fr. commercially available introducers via a surgical remote access. Made to measure tubular, bifurcated, tapered, and/or blind stents combined with extra-anatomic bypass designs increased the rate of endovascular treatment (ET) of AIA in this series. This rate was further increased through the use of uncovered proximal or distal stents when dealing with short or tortuous necks near major side branches and through use of hybrid, partly surgical designs, one with stented and the other with stentless ends, the latter allowing for a surgically made anastomosis. The results of our experience with these techniques show that use of home-made to measure stent-grafts greatly increases the feasibility of the ET of AIA among unselected patients while offering enough efficiency and safety to deserve further investigation. Future perspectives are discussed.

The effect of universal leukodepletion of packed red blood cells on postoperative infections in high-risk patients undergoing abdominal aortic surgery.

UNLABELLED: We evaluated, by using a before-and-after study, the influence of leukoreduction by filtration on postoperative infections and adverse outcomes in patients undergoing elective major aortic surgery. From January 1995 to October 2000, all patients who underwent elective abdominal aortic surgery were included in the analysis. Before the introduction of systematic leukodepletion of packed red blood cells (RBCs), on April 1, 1998, 192 patients received standard or buffy-coat-depleted packed RBCs. Then, 195 patients were transfused with exclusively filtered leukodepleted packed RBCs. No major significant difference was observed between the groups of patients with regard to preoperative cardiac and pulmonary status, anesthetic and surgical techniques, or transfusion policy. No significant difference in mortality was observed between the two groups. The incidence of postoperative infections was 31% (95% confidence interval, 25%--38%) in the Control group versus 27% (95% confidence interval, 21%--33%) in the Leukodepleted group; severe infectious complications and pneumonia were not significantly different between the two groups of patients. Cardiovascular and respiratory outcomes were not significantly different between the groups. Data from this study suggest that the effect of using leukodepleted RBC on postoperative infections is not of obvious importance. IMPLICATIONS: We evaluated the influence of leukocyte reduction by filtration of packed red blood cells (RBC) on postoperative infections and adverse outcomes in patients undergoing elective major aortic surgery by comparing two epochs with and without filtration. Data from this study suggest that the effect of using filtered RBC on postoperative infections is not of obvious importance.