Left ventricular assist device-related infections: a multicentric study.

OBJECTIVES: The implantable left ventricular assist device (LVAD) is a major therapeutic development for end-stage heart failure in selected patients. As their use is expanding, infectious complications are emerging, with limited data available to guide their management. We aimed to better characterize LVAD-related infections. METHODS: We enrolled all consecutive patients diagnosed with LVAD-related infections in three referral centres in France, using a standardized definition of infections in patients with LVAD. Data were collected from medical charts using a standardized questionnaire. RESULTS: Between 2007 and 2012, 159 patients received LVAD for end-stage heart failure. Among them, 36 (22.6%; 5 women, 31 men) presented at least one infectious complication, after a median time of 2.9 months from LVAD implantation (interquartile range, 1.8-7.5), with a median follow up of 12 months (interquartile range 8-17). Main co-morbidities were alcoholism (33%), diabetes (11%) and immunosuppression (11%). Mean age at implantation was 51 (±11) years. LVAD were implanted as bridge-to-transplantation (n=22), bridge-to-recovery (n=8), destination therapy (n=4), or unspecified (n=2). LVAD-related infections were restricted to the driveline exit site (n=17), had loco-regional extension (n=13), or reached the internal pump (n=3). The main bacteria isolated were Staphylococcus aureus (n=20), coagulase-negative staphylococci (n=7), Enterobacteriaceae (n=14), Pseudomonas aeruginosa (n=10) and Corynebacterium sp. (n=7), with polymicrobial infections in 19 cases. LVAD could be retained in all patients, with the use of prolonged antibacterial treatment in 34 (94%), and debridement in 17 (47%). One patient died due to LVAD-associated infection. CONCLUSIONS: LVAD-related infections are common after LVAD implantation, and may be controlled by prolonged antibiotic treatment.

Epidemiology and prevention of surgical site infections after cardiac surgery.

Deep sternal wound infection is the major infectious complication in patients undergoing cardiac surgery, associated with a high morbidity and mortality rate, and a longer hospital stay. The most common causative pathogen involved is Staphylococcus spp. The management of post sternotomy mediastinitis associates surgical revision and antimicrobial therapy with bactericidal activity in blood, soft tissues, and the sternum. The pre-, per-, and postoperative prevention strategies associate controlling the patient's risk factors (diabetes, obesity, respiratory insufficiency), preparing the patient's skin (body hair, preoperative showering, operating site antiseptic treatment), antimicrobial prophylaxis, environmental control of the operating room and medical devices, indications and adequacy of surgical techniques. Recently published scientific data prove the significant impact of decolonization in patients carrying nasal Staphylococcus aureus, on surgical site infection rate, after cardiac surgery.

Protective effects of transgenic human endothelial protein C receptor expression in murine models of transplantation.

Thrombosis and inflammation are major obstacles to successful pig-to-human solid organ xenotransplantation. A potential solution is genetic modification of the donor pig to overexpress molecules such as the endothelial protein C receptor (EPCR), which has anticoagulant, anti-inflammatory and cytoprotective signaling properties. Transgenic mice expressing human EPCR (hEPCR) were generated and characterized to test this approach. hEPCR was expressed widely and its compatibility with the mouse protein C pathway was evident from the anticoagulant phenotype of the transgenic mice, which exhibited a prolonged tail bleeding time and resistance to collagen-induced thrombosis. hEPCR mice were protected in a model of warm renal ischemia reperfusion injury compared to wild type (WT) littermates (mean serum creatinine 39.0 ± 2.3 µmol/L vs. 78.5 ± 10.0 µmol/L, p < 0.05; mean injury score 31 ± 7% vs. 56 ± 5%, p < 0.05). Heterotopic cardiac xenografts from hEPCR mice showed a small but significant prolongation of survival in C6-deficient PVG rat recipients compared to WT grafts (median graft survival 6 vs. 5 days, p < 0.05), with less hemorrhage and edema in rejected transgenic grafts. These data indicate that it is possible to overexpress EPCR at a sufficient level to provide protection against transplant-related thrombotic and inflammatory injury, without detrimental effects in the donor animal.

Pig thrombomodulin binds human thrombin but is a poor cofactor for activation of human protein C and TAFI.

Incompatibility between pig thrombomodulin (TM) and primate thrombin is thought to be an important factor in the development of microvascular thrombosis in rejecting pig-to-primate xenografts. To examine this interaction at the molecular level, we cloned pig TM and measured its ability to bind human thrombin and act as a cofactor for the activation of human protein C and TAFI. The 579-residue pig TM protein showed approximately 69% sequence identity to human TM. Within the EGF domains necessary for binding of thrombin (EGF56), protein C (EGF4) and TAFI (EGF3), all of the amino acids previously identified as critical for the function of human TM, with the exception of Glu-408 in EGF5, were conserved in pig TM. Comparison of transfected cells expressing pig or human TM demonstrated that both proteins bound human thrombin and inhibited its procoagulant activity. However, pig TM was a poor cofactor for the activation of human protein C and TAFI, with domain swapping showing that EGF5 was the most important determinant of compatibility. Thus, while pig TM may be capable of binding thrombin generated in the vicinity of xenograft endothelium, its failure to promote the activation of human protein C remains a significant problem.

Cartilaginous metaplasia and calcification in aortic allograft is associated with transforming growth factor beta 1 expression.

BACKGROUND: Calcification of homografts and vascular conduits is poorly understood. Mechanisms leading to calcification were studied in a rat model of aortic allografts. METHODS: Rat aortas from Lew1W (RT1(u)) were transplanted into Lew1A (RT1(a)). Animals were killed at 30 days and 180 days, and aortic grafts were removed and analyzed for histologic and immunohistologic studies. RESULTS: Intimal surface increased progressively over 6 months and was the site of important modifications. Intimal cellular population changed from a leukocyte (CD45, OX1-OX30)- and macrophage (CD68, ED-1)-based population at 30 days to predominantly alpha-smooth muscle actin-expressing cells at 180 days. At 180 days, allografts were characterized by an abundant extracellular matrix composed of collagen and elastic fibers associated with extensive calcification (von Kossa staining) located in the intima and media. Osteoblastic activity was present in calcified lesion as shown by alkaline phosphatase activity. At 180 days, numerous chondrocytes (protein S100-positive and alpha-smooth muscle actin-negative) were present focally in the media. However, double immunostaining revealed that a cellular population within the media with a chondrocyte-like morphology was alpha-smooth muscle actin-positive and S100-negative. Active form of transforming growth factor beta1 was expressed from 30 to 80 days in the medial and intimal layers. CONCLUSIONS: These observations suggest that alpha-smooth muscle actin-positive cells within aortic allografts are eventually transformed to a chondrocyte-like structure, leading to vascular cartilaginous metaplasia associated with the expression of transforming growth factor beta1 and could be a potential pathway leading to extensive vascular wall calcification in allografts through endochondral ossification.

Early and 1 year angiographic evaluation of graft patency in off-pump coronary bypass surgery via sternotomy.

The goal of this study was to evaluate the early and 1 year postoperative angiographic results in patients who underwent coronary revascularisation for multivessel disease on beating heart via sternotomy. One hundred eleven consecutive patients receiving 272 grafts, operated by the same surgeon were studied (2.5 grafts/patient). The quality of the graft and the anastomoses was systematically evaluated by coronary angiography between 1 and 15 days after surgery. Eighty-seven patients (209 grafts) of the initial cohort (78.3%) were repeatedly controlled by angiography between 5 and 24 months. Angiographic findings were studied and classified according to Fitzgibbon classification. Overall early graft patency was 96.4%. Arterial graft patency was 96.4% and vein graft patency was 96.3% (P=1). Of the grafts (88.7%) were Grade A, 21 grafts (7.7%) Grade B and 10 grafts (3.6%) were occluded (Grade O). The second angiographic control revealed a patency rate of 94.8%, arterial graft patency was 95.4% and vein graft patency was 93.8% (P=0.9): 91.5% of patent grafts were graded (A), 3.3% graded (B) and 5.2% graded (O). A comparison between early and late angiograms revealed: two-stenosis de novo, three-occlusion de novo and decrease or disappearance of the stenosis in 13/21 graft, 11 arterial and two vein grafts (61.9%). In this study, the early and 1 year postoperative patency rate seems to be equivalent to coronary bypass with pump, however, a randomised study is needed to compare both approaches. Most of the stenosis detected at the early coronary angiography could decrease or disappear, especially in arterial grafts.

Partial anomalous pulmonary venous connection: correction by intra-atrial baffle and cavo-atrial anastomosis.

The creation of intracaval conduits to repair partial anomalous pulmonary venous connection of the right lung into the superior vena cava can be complicated by arrhythmias and superior vena cava and pulmonary vein obstruction. An intra-atrial baffle, combined with cavo-atrial anastomosis, has been proposed to avoid these complications. The authors report their recent experience with this operative technique. From January 1997 to December 2000, 7 patients with a mean age of 13.5 +/- 9 (2-31) years were operated according to this technique. Only one child did not have an associated atrial septal defect. The mean number of pulmonary veins connected to the superior vena cava was 2.5 +/- 0.5. The immediate postoperative course was uneventful for the seven patients. The mean follow-up was 20 +/- 17 months. No patient developed arrhythmia or superior vena cava or pulmonary vein obstruction at echocardiography. This surgical technique appears to constitute an attractive alternative when pulmonary veins drain abnormally into the superior vena cava above the cavo-atrial junction.

Inhibition of graft arteriosclerosis development in rat aortas following heme oxygenase-1 gene transfer.

Heme oxygenase 1 (HO-1) is an enzyme which degrades heme into tree end products: biliverdin, free iron and carbon monoxide. This enzyme has recently been shown to have anti-inflammatory and tissue protective effects. HO-1 expression is involved in organ protection in pathological situations, and immunosuppressive treatments resulting in indefinite graft survival without chronic rejection have been associated with HO-1 expression by cells of the vessel wall. The aim of this study was to analyze the effect of specific HO-1 overexpression. We used a recombinant adenovirus coding for human HO-1 cDNA in a rat aorta chronic rejection model, 30 days after transplantation. Control groups included rats non treated or treated with a non-coding adenovirus Addl324. We first demonstrated that AdHO-1 was efficiently expressed in endothelial cells in vitro, and in rat aortas ex vivo after adenovirus gene transfer. We found that intimal thickening in AdHO-1 treated aortas (10.8 +/- 3.8%, n=5) was significantly decreased compared to untreated (21.2 +/- 5.6%, n = 5) or Addl324-treated (21.1 +/- 1.2%, n = 4) aortas. Immunohistology showed that treatment with AdHO-1 resulted in a significant reduction in leukocyte infiltration and a decreasing number of VSMC in the intima, compared to Addl324-treated aortas. However, this effect of HO-1 on chronic rejection did not imply modifications on numbers of apoptotic cells in the graft or of alloantibody levels. We have demonstrated, for the first time, that specific HO-1 overexpression following gene transfer of HO-1 inhibited chronic rejection by reducing leukocyte and VSMC infiltration of the aorta intima.

Left bronchial disruption and aortic rupture after blunt chest trauma.

A 25-year-old male who had been involved in a traffic accident presented with a neurological disorder, bilateral pneumothoraces, and pneumomediastinum. Bronchoscopy revealed a complex rupture of the left bronchial tract. MRI revealed a sinus valsalva aneurysm. The bronchial lesion was first repaired via left thoracotomy. 10 days later, the aorta was repaired via sternotomy. In cases of combined bronchial and aortic lesion, a concomitant repair is not mandatory, at least when the aortic lesion appears limited and shows no signs of dissection.

Resection of hepatic and pulmonary metastases in patients with colorectal cancer.

The resection of liver and lung metastases is now regarded as valid therapy, although the surgical procedure of both metastatic sites has not been clearly defined. Nine consecutive patients who underwent resection of both liver and lung metastases from colorectal cancer (5 Dukes' stage B, 3 C, 1 D) between 1986 and 1999 were studied retrospectively. A total of 19 resections were performed: 8 hepatectomies, 2 liver wedge resections, and 9 lung lobectomies. No operative or hospital deaths occurred, and mean postoperative hospital stay per procedure was 12 days. Mean survival after resection of the primary colorectal tumor was 66.3 (range: 26-96) months. The median interval was 24.2 (range: 2-39) months from resection of the liver metastasis and 30.4 (range: 3-45) months from resection of the lung metastasis. At the last follow-up, 6 patients were still alive, 4 of whom were free of recurrence 59, 69, 74, and 76 months, respectively, after resections. Three patients died with metastases. Aggressive treatment of liver and lung secondaries from colorectal cancer was performed without hospital mortality and acceptable morbidity. Longer survival times warrant the use of this alternative therapy for selected patients. In association with new effective chemotherapies, it will be possible to select patients who will benefit from surgery.

[Surgical treatment of pulmonary metastases of colorectal cancers. 8-year survival and main prognostic factors]. / Traitement chirurgical des métastases pulmonaires des cancers colorectaux. Survie à 8 ans et principaux facteurs pronostiques.

OBJECTIVE: In order to achieve a better definition of the indications for surgical excision of pulmonary metastases in colorectal cancer (CCR), a retrospective study of the eight year survival of patients who had been operated on was carried out with reference to the principal prognostic factors. METHODS AND RESULTS: Between May 1986 and December 1997, 38 patients had an excision for pulmonary metastases for CCR. The mean delay between diagnosis of the metastases and surgical treatment of the CCR was 39 +/- 24 months (0-98). Thirty two patients (84%) had a single pulmonary metastasis. The mean diameter of the metastasis was 38 +/- 22 mm. Twenty metastases had a diameter < 30 mm. Five patients had a locoregional recurrence of their CCR before pulmonary surgery. Fourteen patients had an abnormally elevated level of carcinoembrionic antigen (ACE-CEA) before the pulmonary excision. Five pneumonectomies, 23 lobectomies, 1 bilobectomy and 11 atypical resections were carried out. A lymph node clearance was performed in 25 cases. Six patients (16%) had an associated excision of an hepatic metastasis. The in-hospital mortality was 2.6%. Chemotherapy was associated with a pulmonary excision in 17 patients (46%). The mean survival was 2.7 years (0.13-8.7 years). The survival at one year was 89 +/- 5.2% and at five years 35.2 +/- 10.1% and at eight years 18.8% +/- 10.3%. Age, sex, histological stage of the primary tumor, the size and the delay in appearance in the pulmonary metastases, the number of metastases, the preoperative CEA, the operative technique and the perioperative chemotherapy did not influence the levels of survival at five years. At the same time associated excision of an hepatic metastasis did not worsen the prognosis at five years. CONCLUSION: Complete excision of pulmonary metastases in a colorectal cancer allows for significantly longer survival. This study associated with a literature review may help in advancing towards better selection of surgical candidates.

Quantitative porosity profiles and wettability contrast visualisation in sandstone by CPMG imaging.

CPMG imaging is applied to the visualisation of porosity and wetting heterogeneities in water saturated sandstone samples at 0.1 T. Porosity profiles from NMR imaging are in agreement within 1% with the standard core analysis. T2 calculated profiles show a factor greater than two between water-wet and oil-wet samples; thus, wettability contrast can be easily visualised.

Characterisation of wetting heterogeneities in sandstone rocks by MRI.

MRI is applied to the visualisation of wetting heterogeneities evidenced by water proton T1 contrast at 0.1 T. Water saturated Fontainebleau sandstone samples were examined either in their original water-wet condition, or after silanation. T1, T2Hahn, and T2CPMG were measured for several porosities. T1 and T2CPMG of hydrophobic samples are both twice longer than those of hydrophilic ones. This good contrast allows us to observe wetting heterogeneities in T1-profiles and T1-weighted images.