Does obesity influence the results in Transvaginal Hybrid-NOTES cholecystectomy?

BACKGROUND: Morbidly obese patients are usually excluded from studies that compare Transvaginal Hybrid-NOTES Cholecystectomy (TVC) with traditional laparoscopic cholecystectomy. Therefore, these study results cannot necessarily be transferred to this group of patients. In this study, we have analyzed and compared the outcomes of the procedure with obese and non-obese patients. METHODS: Data from a prospectively maintained database were retrospectively analyzed. All the TVCs performed in our clinic since 2008 were divided into groups according to their body mass index (BMI). Within these groups, we evaluated the following outcome parameters: age, ASA classification, procedural time, number of percutaneous trocars, intra- and postoperative complications, and postoperative hospital stay. Additionally, the posthospital surgical and gynecological follow-up was evaluated for additional complications and patients with class III obesity were contacted to determine further parameters. RESULTS: Six underweight, 76 normal weight, 72 overweight, 48 class I obesity, 15 class II obesity, and 20 class III obesity patients were analyzed. ASA classification (P < 0.001), procedural time (P < 0.001), and number of percutaneous trocars (P < 0.001) significantly increased with the BMI. By contrast, intra- and postoperative complications (P = 0.134 and P = 0.571), as well as postoperative hospital stay (P = 0.076) did not depend on the BMI. Neither did the classification according to Clavien/Dindo show a significant relation (P = 0.640). Lethality was zero. All posthospital gynecological follow-ups were inconspicuous. Telephone follow-up of class III obesity patients reached a rate of 85% after median 3.4 years. There were no additional complications or problems during sexual intercourse. The satisfaction with the cosmetic and the overall result was very high. CONCLUSIONS: Although the results of existing studies including normal-weight or merely moderately obese patients can hardly be applied to morbidly obese patients, especially regarding procedural time and the number of percutaneous trocars, obesity should not be an exclusion criterion for TVC, regardless of its magnitude.

Transvaginal hybrid-NOTES vs. traditional laparoscopic sigmoid resection for diverticulitis: a short-term comparative study.

The aim was to compare short-term results of transvaginal hybrid-NOTES (NSR) with traditional laparoscopic technique in sigmoid resection (LSR) in cases of diverticulitis. Natural Orifice Transluminal Endoscopic Surgery has been evolved as a minimally invasive procedure to reduce the operative trauma due to the absence of specimen extraction through the abdominal wall causing less postoperative pain, and shorter hospital stay. Despite the increasing use and published case series of NSR for diverticulitis as a laparoscopic procedure with transvaginal stapling and specimen extraction, there are no studies comparing this procedure with LSR. Twenty NSR patients operated at the Cologne-Merheim Medical Center have been documented and compared with 20 female LSR patients matched for body mass index, American Society of Anesthesiologists-classification (ASA), Hansen/Stock classification, and age. To ensure comparability regarding peri- and postoperative care, only procedures performed by the same surgeon were included. Procedural time, intra- and postoperative complications, conversion rate, postoperative pain, the duration of an epidural catheter, analgesic consumption, and postoperative length of hospital stay were analyzed. There were no significant differences in the sum of pain levels (p = 0.930), length of procedure (p = 0.079), intra- and postoperative complications, as well as duration of an epidural catheter. On the contrary, there were significant positive effects for NSR on morphine requirement at day seven and eight (p = 0.019 and p = 0.035 respectively) as well as the postoperative length of hospital stay (p = 0.031). This retrospective study reveals significant positive effects for NSR compared to LSR regarding length of hospital stay as well as morphine consumption after removal of the epidural catheter, whereas there were no significant differences in complication rate and procedural time. In summary, NSR is an adequate alternative to traditional laparoscopic sigmoid resection considering the surgeons experience and the patient's personal preferences.

Steep dose gradients for simultaneous integrated boost IMRT.

Steep dose gradients between two planning target volumes (PTVs) as may be required for simultaneous integrated boosts (SIB) should be an option provided by IMRT algorithms. The aim was to analyse the geometry of the SIB problem and to implement the results in an algorithm for IMRT segment generation denoted two-step intensity modulated radiotherapy (2-Step IMRT). It was hypothesized that a gap between segments directed to the inner and the outer PTV would steepen the dose gradient. The mathematical relationships were derived from the individual dose levels and the geometry (diameters) of the PTVs. The results generated by means of 2-Step IMRT segments were equivalent or better than the segment generation using a commercial IMRT planning system. The dose to both the inner and the outer PTV was clearly more homogeneous and the composite objective value was the lowest. The segment numbers were lower or equal--with better sparing of the surrounding tissue. In summary, it was demonstrated that 2-Step IMRT was able to achieve steep dose gradients for SIB constellations.

Tumor tracking and motion compensation with an adaptive tumor tracking system (ATTS): system description and prototype testing.

A novel system for real-time tumor tracking and motion compensation with a robotic HexaPOD treatment couch is described. The approach is based on continuous tracking of the tumor motion in portal images without implanted fiducial markers, using the therapeutic megavoltage beam, and tracking of abdominal breathing motion with optical markers. Based on the two independently acquired data sets the table movements for motion compensation are calculated. The principle of operation of the entire prototype system is detailed first. In the second part the performance of the HexaPOD couch was investigated with a robotic four-dimensional-phantom capable of simulating real patient tumor trajectories in three-dimensional space. The performance and limitations of the HexaPOD table and the control system were characterized in terms of its dynamic behavior. The maximum speed and acceleration of the HexaPOD were 8 mm/s and 34.5 mm/s2 in the lateral direction, and 9.5 mm/s and 29.5 mm/s2 in longitudinal and anterior-posterior direction, respectively. Base line drifts of the mean tumor position of realistic lung tumor trajectories could be fully compensated. For continuous tumor tracking and motion compensation a reduction of tumor motion up to 68% of the original amplitude was achieved. In conclusion, this study demonstrated that it is technically feasible to compensate breathing induced tumor motion in the lung with the adaptive tumor tracking system.

Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease.

BACKGROUND: Cellular antioxidant enzymes such as glutathione peroxidase 1 and superoxide dismutase have a central role in the control of reactive oxygen species. In vitro data and studies in animal models suggest that these enzymes may protect against atherosclerosis, but little is known about their relevance to human disease. METHODS: We conducted a prospective study among 636 patients with suspected coronary artery disease, with a median follow-up period of 4.7 years (maximum, 5.4) to assess the risk of cardiovascular events associated with base-line erythrocyte glutathione peroxidase 1 and superoxide dismutase activity. RESULTS: Glutathione peroxidase 1 activity was among the strongest univariate predictors of the risk of cardiovascular events, whereas superoxide dismutase activity had no association with risk. The risk of cardiovascular events was inversely associated with increasing quartiles of glutathione peroxidase 1 activity (P for trend <0.001); patients in the highest quartile of glutathione peroxidase 1 activity had a hazard ratio of 0.29 (95 percent confidence interval, 0.15 to 0.58; P<0.001), as compared with those in the lowest quartile. Glutathione peroxidase 1 activity was affected by sex and smoking status but retained its predictive power in these subgroups. After adjustment for these and other cardiovascular risk factors, the inverse association between glutathione peroxidase 1 activity and cardiovascular events remained nearly unchanged. CONCLUSIONS: In patients with coronary artery disease, a low level of activity of red-cell glutathione peroxidase 1 is independently associated with an increased risk of cardiovascular events. Glutathione peroxidase 1 activity may have prognostic value in addition to that of traditional risk factors. Furthermore, increasing glutathione peroxidase 1 activity might lower the risk of cardiovascular events.

Positioning accuracy of cone-beam computed tomography in combination with a HexaPOD robot treatment table.

PURPOSE: To scrutinize the positioning accuracy and reproducibility of a commercial hexapod robot treatment table (HRTT) in combination with a commercial cone-beam computed tomography system for image-guided radiotherapy (IGRT). METHODS AND MATERIALS: The mechanical stability of the X-ray volume imaging (XVI) system was tested in terms of reproducibility and with a focus on the moveable parts, i.e., the influence of kV panel and the source arm on the reproducibility and accuracy of both bone and gray value registration using a head-and-neck phantom. In consecutive measurements the accuracy of the HRTT for translational, rotational, and a combination of translational and rotational corrections was investigated. The operational range of the HRTT was also determined and analyzed. RESULTS: The system performance of the XVI system alone was very stable with mean translational and rotational errors of below 0.2 mm and below 0.2 degrees , respectively. The mean positioning accuracy of the HRTT in combination with the XVI system summarized over all measurements was below 0.3 mm and below 0.3 degrees for translational and rotational corrections, respectively. The gray value match was more accurate than the bone match. CONCLUSION: The XVI image acquisition and registration procedure were highly reproducible. Both translational and rotational positioning errors can be corrected very precisely with the HRTT. The HRTT is therefore well suited to complement cone-beam computed tomography to take full advantage of position correction in six degrees of freedom for IGRT. The combination of XVI and the HRTT has the potential to improve the accuracy of high-precision treatments.

A comparison between 2-Step IMRT and conventional IMRT planning.

BACKGROUND AND PURPOSE: 2-Step intensity modulated radiation therapy (2-Step IMRT) is an IMRT segmentation procedure based on analytical approximations [Bratengeier K. 2-Step IMAT and 2-Step IMRT: a geometrical approach. Med Phys 2005;32:777-785; Bratengeier K. 2-Step IMAT and 2-Step IMRT in three dimensions. Med Phys 2005;32:3849-3861]. The aim was to benchmark it with other IMRT algorithms and to establish it as planning tool for fast IMRT application with a reduced number of segments. MATERIALS AND METHODS: 2-Step IMRT plans were compared with IMRT-solutions obtained with methods from a commercial planning system (Pinnacletrade mark TPS). The four clinical cases chosen were: paraspinal tumour, carcinoma of the prostate, head and neck carcinoma and breast carcinoma. In addition the "Quasimodo" phantom study was used to compare the quality of the 2-Step IMRT method with respect to other planning procedures in the ESTRO study. RESULTS: The number of segments (and - to a minor degree - the monitor units per dose) of the majority of 2-Step IMRT plans was lower than for the commercial algorithms. The quality of the 2-Step IMRT-plan was comparable. In the Quasimodo comparison 2-Step IMRT plans with nine beams would place in the mid-range of all participants, whereas the 15-beam arrangements could compete with the best results. CONCLUSIONS: 2-Step IMRT is a valuable IMRT segmentation method, especially if the number of segments is to be limited (e.g. for reasons of precision, speed and leakage radiation).

Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina.

BACKGROUND: Interleukin (IL)-18 plays a central role in orchestrating the cytokine cascade and accelerates atherosclerosis and plaque vulnerability in animal models. However, epidemiological data evaluating the role of IL-18 levels in atherosclerosis are lacking. METHODS AND RESULTS: In a prospective study of 1229 patients with documented coronary artery disease, we measured baseline serum concentrations of IL-18 and other markers of inflammation. During the follow-up period (median, 3.9 years), 95 patients died of cardiovascular causes. Median serum concentrations of IL-18 were significantly higher among patients who had a fatal cardiovascular event than among those who did not (68.4 versus 58.7 pg/mL; P<0.0001). The hazard risk ratio of future cardiovascular death increased with increasing quartiles of IL-18 (hazard risk ratio, 1.46; 95% CI 1.21 to 1.76; P for trend <0.0001). After adjustment for most potential confounders, including the strong predictor ejection fraction as well as the inflammatory variables IL-6, high-sensitive C-reactive protein, and fibrinogen, this relation remained almost unchanged, such that patients within the highest quartile of IL-18 had a 3.3-fold increase in hazard risk compared with those in the first quartile (95% CI, 1.3 to 8.4, P=0.01). This relation was observed in patients with stable angina and patients with unstable angina at baseline. CONCLUSIONS: Serum IL-18 level was identified as a strong independent predictor of death from cardiovascular causes in patients with coronary artery disease regardless of the clinical status at admission. This result strongly supports recent experimental evidence of IL-18-mediated inflammation leading to acceleration and vulnerability of atherosclerotic plaques.

Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease.

BACKGROUND: Matrix metalloproteinase (MMP)-9 secretion by macrophages and other inflammatory cells accelerates atherosclerotic progression and destabilizes vulnerable plaque in animal models. However, epidemiological data evaluating the prognostic impact of circulating concentrations and functional genetic variations of MMP-9 are lacking. METHODS AND RESULTS: In a prospective study of 1127 patients with documented coronary artery disease, we measured baseline plasma MMP-9 levels and determined the MMP-9/C-1562T and MMP-9/R279Q genotypes. During the follow-up period (mean of 4.1 years), 97 patients died from cardiovascular (CV) causes. Median concentrations of MMP-9 were significantly higher among patients who experienced a fatal CV event than among those who did not (62.2 versus 47.8 ng/mL; P<0.0001). The crude hazard risk ratio of CV death associated with increasing quartiles of MMP-9 was 1.4 (95% CI, 1.2 to 1.8; P<0.0001), and after adjustment for clinical and therapeutic confounders, it was 1.3 (95% CI, 1.1 to 1.6; P=0.005). Additional adjustment for highly sensitive CRP, interleukin-6, fibrinogen, and interleukin-18 revealed a hazard risk ratio to 1.2 (95% CI, 0.9 to 1.6; P=0.15). The T allele of the C-1562T polymorphism was associated with increased MMP-9 levels in a fairly codominant fashion (P=0.004). Although none of the polymorphisms was significantly related with future CV death, there was a significant association (P=0.02) between the R279Q polymorphism and CV events in patients with stable angina. CONCLUSIONS: Plasma MMP-9 concentration was identified as a novel predictor of CV mortality in patients with coronary artery disease. Whether it provides independent prognostic information compared with other inflammatory markers will have to be additionally assessed.

Proarrhythmic effect of pacemaker stimulation in patients with implanted cardioverter-defibrillators.

BACKGROUND: We sought to determine the potential of right ventricular VVI backup pacing to induce ventricular tachyarrhythmias in patients with implanted cardioverter-defibrillators. METHODS AND RESULTS: All consecutive patients presenting exclusively with pacemaker-induced tachycardias (PITs) were included in a prospective study using a crossover protocol. Patients were randomized to either group 1 (augmentation of the baseline frequency of the pacemaker to 60 bpm) or group 2 (pacemaker turned off) and were followed up for 1 year and then crossed over to the other programming, looking for reoccurrence of PIT. Of 150 consecutive patients, 39 (26%) had PIT, 13 of them exclusively (8.6%). Forty of 1063 analyzed tachyarrhythmias of all the patients were PIT (3%). Before inclusion in the study, the patients had 2.7+/-0.9 PITs in 11+/-6.5 months with their pacemakers programmed empirically at 42.3 bpm. During the study phase, no PIT occurred while the pacemaker was turned off, whereas programming to 60 bpm led to the recurrence of PIT in 5 of 6 patients (1.4+/-0.6 per patient). At the end of the study, 9 patients underwent a prolonged follow-up with their pacemakers turned off, resulting in spontaneous episodes of ventricular tachycardia/fibrillation in 5 patients, but PITs were no longer observed. CONCLUSIONS: This crossover protocol proves the potential proarrhythmic effect of pacemaker stimulation in implantable cardioverter-defibrillator patients. Resulting PITs led to clinical symptoms and antitachycardia therapy by the implantable cardioverter-defibrillator. Thus, in patients presenting with PIT but without a pacemaker indication, the pacemaker feature should be turned off, or, alternatively, the longest possible escape interval should be programmed.

Simvastatin inhibits inflammatory properties of Staphylococcus aureus alpha-toxin.

BACKGROUND: Simvastatin, a 3-hydroxy-methylglutaryl coenzyme A reductase inhibitor, has been shown to lower serum cholesterol levels in clinical use. Moreover, statins exert beneficial effects in vascular diseases by inhibition of leukocyte rolling, adherence, and transmigration. The aim of this study was to determine if pretreatment with simvastatin attenuates Staphylococcus aureus alpha-toxin-induced increase in leukocyte-endothelial interactions during exotoxemia. METHODS AND RESULTS: The effects of simvastatin on leukocyte-endothelial cell interactions were observed by intravital microscopy in the rat mesenteric microcirculation. Simvastatin (50 or 100 microg/kg) was administered 18 hours before the study. Activation of microcirculation was induced by bolus administration of 40 microg/kg S aureus alpha-toxin. Exotoxemia resulted in a significant and time-dependent increase in leukocyte rolling, adherence, and transmigration of leukocytes as well as P-selectin expression on the intestinal vascular endothelium. Pretreatment with simvastatin significantly inhibited exotoxin-induced leukocyte rolling from 71+/-10 to 14+/-4.7 cells/min (P<0.01) and adherence from 14+/-3.5 to 0.4+/-0.2 cells (P<0.01). In addition, simvastatin pretreatment significantly inhibited transmigration of leukocytes from 10.5+/-1.2 to 4.2+/-0.9 (P<0.05) cells. Immunohistochemical detection of endothelial cell adhesion molecule P-selectin showed a 50% decrease in endothelial cell surface expression after simvastatin treatment. Furthermore, simvastatin treatment resulted in enhanced expression of endothelial cell NO synthase III in the intestinal microcirculation. CONCLUSIONS: These results demonstrate that simvastatin interferes with exotoxin-induced leukocyte-endothelial cell interactions, which may be relevant in various infectious diseases. Statin treatment may offer a new therapeutic strategy for these clinical conditions.

Impact of infectious burden on extent and long-term prognosis of atherosclerosis.

BACKGROUND: Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. In hypothesizing an association between infectious agents and the development of atherosclerosis, we would expect a correlation to the extent of atherosclerosis. Moreover, this effect could be multiplied by the number of pathogens to which an individual had been exposed. METHODS AND RESULTS: In 572 patients, IgG or IgA antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, Hemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori were measured. The extent of atherosclerosis was determined by coronary angiography, carotid duplex sonography, and evaluation of the ankle-arm index. Elevated IgA antibodies against C pneumoniae (P<0.04) and IgG antibodies against H pylori (P<0.02), cytomegalovirus (P<0.05), and herpes simplex virus 2 (P<0.01) were associated with advanced atherosclerosis (> or =2 vascular regions), adjusted for age, sex, cardiovascular risk factors, and highly sensitive C-reactive protein. Infectious burden divided into 0 to 3, 4 to 5, and 6 to 8 seropositivities was significantly associated with advanced atherosclerosis, with an odds ratio (95% CI) of 1.8 (1.2 to 2.6) for 4 to 5 (P<0.01) and 2.5 (1.2 to 5.1) for 6 to 8 seropositivities (P<0.02) (adjusted). After a mean follow-up of 3.2 years, cardiovascular mortality rate was 7.0% in patients with advanced atherosclerosis and seropositive for 0 to 3 pathogens compared with 20.0% in those seropositive for 6 to 8 pathogens. CONCLUSIONS: Our results support the hypothesis that infectious agents are involved in the development of atherosclerosis. We showed a significant association between infectious burden and the extent of atherosclerosis. Moreover, the risk for future death was increased by the number of infectious pathogens, especially in patients with advanced atherosclerosis.

Common genetic variation of the cholesteryl ester transfer protein gene strongly predicts future cardiovascular death in patients with coronary artery disease.

OBJECTIVES: We sought to evaluate the association between cholesteryl ester transfer protein (CETP) genotypes and the risk of future cardiovascular mortality in patients with coronary artery disease (CAD). BACKGROUND: Polymorphisms of the CETP gene influence CETP activity and high-density lipoprotein (HDL) cholesterol concentration and might affect the long-term prognosis and response to statin therapy in patients with CAD. METHODS: We used serum samples and deoxyribonucleic acid collected at baseline from a prospective cohort of 1,211 patients with CAD prospectively followed up (median follow-up of 4.1 years), 82 of whom experienced a fatal cardiovascular event. The CETP/C-629A and I405V polymorphisms, CETP activity, and HDL cholesterol were determined. RESULTS: Patients carrying the -629A allele had significantly lower CETP activity and higher HDL cholesterol levels. There was a significant association between this polymorphism and the risk of future cardiovascular death. Mortality decreased from 10.8% in CC homozygotes to 4.6% in CA heterozygotes and 4.0% in AA homozygotes (p < 0.0001). This association was independent of potential confounders, particularly HDL cholesterol and CETP activity levels. The clinical benefit of statin therapy was restricted to CC homozygotes, in whom cardiovascular mortality was divided by half (p = 0.01 for treatment x genotype interaction). Similar trends were observed with the CETP/I405V polymorphism, but these effects seemed to be mainly the consequence of linkage disequilibrium with the CETP/C-629A polymorphism. CONCLUSIONS: In patients with CAD, the CETP/-629A allele had a strong protective effect on future mortality from cardiovascular causes, independent of its role on HDL cholesterol and CETP activity levels. Additionally, this common polymorphism appeared to predict which patients with CAD will experience a survival benefit from statin therapy.

Outcome of urgent and elective percutaneous coronary interventions after pharmacologic reperfusion with tenecteplase combined with unfractionated heparin, enoxaparin, or abciximab.

OBJECTIVES: The aim of this study was to evaluate percutaneous coronary intervention (PCI) in the Assessment of the Safety and Efficacy of New Thrombolytic Regimens (ASSENT-3) trial. BACKGROUND: In the ASSENT-3 trial, co-therapy with abciximab (ABC) or enoxaparin (ENOX) reduced ischemic complications after ST-elevation acute myocardial infarction treated with tenecteplase when compared with unfractionated heparin (UFH). The effect of these new co-therapies on the results of PCI is unknown. METHODS: Clinical outcomes in patients who received co-therapy with ABC, ENOX, or UFH and subsequently underwent an elective (n = 1,064) or urgent (n = 716) PCI in the ASSENT-3 trial were compared. RESULTS: No significant differences in clinical end points were observed in patients who underwent an elective PCI. A non-significant trend toward fewer in-hospital myocardial re-infarctions was seen with ABC and ENOX when compared with UFH (0.5% vs. 0.6% vs. 1.5%, respectively). The incidence of bleeding complications was similar in the three treatment arms. Significantly fewer ABC- and ENOX-treated patients needed urgent PCI compared with UFH (9.1% vs. 11.9% vs. 14.3%; p < 0.0001), but outcomes in these patients were in general less favorable (30-day mortality: 8.2% vs. 5.4% vs. 4.5%; 1-year mortality: 11.0% vs. 8.5% vs. 5.6%; in-hospital re-infarction: 3.9% vs. 2.5% vs. 2.7%; major bleeding complications: 8.8% vs. 7.0% vs. 3.4%). In pairwise comparisons with UFH, the higher one-year mortality and major bleeding rates after ABC were statistically significant (p = 0.045 and p = 0.012, respectively). CONCLUSIONS: Clinical outcomes after elective PCI were similar with the three antithrombotic co-therapies studied in ASSENT-3. Although fewer patients needed urgent PCI with ABC and ENOX, clinical outcomes were less favorable in this selected population, especially with ABC.

Fast image acquisition and processing on a TV camera-based portal imaging system.

The present paper describes the fast acquisition and processing of portal images directly from a TV camera-based portal imaging device (Siemens Beamview Plus). This approach employs not only hard- and software included in the standard package installed by the manufacturer (in particular the frame grabber card and the Matrox Intellicam interpreter software), but also a software tool developed in-house for further processing and analysis of the images. The technical details are presented, including the source code for the Matrox interpreter script that enables the image capturing process. With this method it is possible to obtain raw images directly from the frame grabber card at an acquisition rate of 15 images per second. The original configuration by the manufacturer allows the acquisition of only a few images over the course of a treatment session. The approach has a wide range of applications, such as quality assurance (QA) of the radiation beam, real-time imaging, real-time verification of intensity-modulated radiation therapy (IMRT) fields, and generation of movies of the radiation field (fluoroscopy mode).

Impact of infectious burden on progression of carotid atherosclerosis.

BACKGROUND AND PURPOSE: Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. The extent of atherosclerosis and the prognosis of patients with atherosclerosis seem to be increased by the number of infections to which an individual has been exposed. In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the progression of carotid atherosclerosis. METHODS: In 504 patients (74.9% men; age, 62.9+/-10 years), we measured intima-media thickness and prevalence of carotid artery stenosis. Follow-up measurements after a mean of 2.5 years were available in 427 patients (85%). Blood samples were taken, and IgG or IgA antibodies to Chlamydia pneumoniae, Helicobacter pylori, Haemophilus influenzae, Mycoplasma pneumoniae, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus types 1 and 2 were measured. Statistical evaluation was performed with logistic regression procedures. RESULTS: Elevated IgA antibodies against C pneumoniae (P<0.04) and IgG antibodies against Epstein-Barr virus (P<0.01) and herpes simplex virus type 2 (P<0.04) were associated with progression of atherosclerosis (increase of intima-media thickness > or =0.1 mm/y or progression of carotid stenosis) after adjustment for age, sex, cardiovascular risk factors, highly sensitive C-reactive protein, and statin intake. Infectious burden, divided into 0 to 3, 4 to 5, and 6 to 8 seropositivities, was significantly associated with progression of atherosclerosis, with odds ratios of 1.8 (95% confidence interval, 1.1 to 2.9) for 4 to 5 and 3.8 (95% CI, 1.6 to 8.8) for 6 to 8 compared with 0 to 3 seropositivities after adjustment. CONCLUSIONS: Our results support the hypothesis that the number of infectious pathogens to which an individual has been exposed independently contributes to the progression of carotid atherosclerosis.

Nickel release after implantation of the Amplatzer occluder.

BACKGROUND: Transcatheter closure of atrial septal defects is a new and less traumatic technique than open heart surgery. In recent years, patients with a patent foramen ovale sustaining potential paradoxical embolism have also become candidates for interventional closure devices. One of the more popular occluding devices is the Amplatzer septal occluder, which, like many other occluders, is made of nitinol. Nitinol-based alloys are widely used in medical products, for example, in orthopedics and orthodontics. However, the clinical use of nitinol, which contains 55% nickel, is still controversial because of concerns about its biocompatibility. Therefore, we examined the systemic nickel release after implantation of the Amplatzer occluder. METHODS AND RESULTS: In 67 patients with no history of nickel sensitivity, blood samples were taken 24 hours before and 24 hours, 1, 3, and 12 months after occluder implantation. Nickel serum concentrations were measured by atomic absorption spectrometry; a value of <2 ng/mL of nickel was considered to be normal. A rise in mean serum levels of nickel was observed, from 0.47 ng/mL before implantation to 1.27 ng/mL (24 hours after), to a maximum of 1.50 ng/mL 1 month after implantation, which was statistically significant (P =.008 and P = 0.022, Wilcoxon Test). During follow-up, the values decreased to those measured before implantation. CONCLUSIONS: Nickel seems to be released from the device, causing a systemic rise in serum levels of nickel, possibly until a calcium-phosphate layer has formed on the passive oxide film of the device or until endothelialization is complete. Possible biological effects should be considered, particularly in young patients or patients with nickel hypersensitivity.

Impact of pathogen burden in patients with coronary artery disease in relation to systemic inflammation and variation in genes encoding cytokines.

The number of infectious pathogens to which an individual has been exposed (pathogen burden) has been linked to the development and the prognosis of coronary artery disease (CAD). The interaction among infection, genetic host susceptibility, and CAD remains unclear. This study was aimed at evaluating the modulation of the association between CAD and pathogen burden, by serum levels of inflammatory markers and polymorphisms of the interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha genes. Immmunoglobulin (Ig) G or IgA antibodies to 8 pathogens were determined in 991 patients with CAD and 333 control subjects. Serum levels of high-sensitivity C-reactive protein, fibrinogen, IL-6, and TNF-alpha were also measured. All subjects were genotyped for the IL-6/G-174C, the TNF/C-851T, and the TNF/G-308A polymorphisms. Analysis of single pathogens demonstrated a positive relation to the presence of CAD for some (Chlamydia pneumoniae, cytomegalovirus, Helicobacter pylori, and herpes virus simplex type 1), but not all pathogens. A strong association between increasing pathogen burden and CAD was confirmed, even after adjustment for risk factors. The prevalence of a high pathogen burden (>/=4 pathogens) was 50% in patients and 21% in controls (p <0.0001). A high pathogen burden was associated with decreased high-density lipoprotein cholesterol levels (p <0.001). The association between CAD and pathogen burden was modulated by the IL6/G-174C polymorphism, the odds ratio being higher in heterozygotes than in both types of homozygotes (p <0.05). This interaction appeared to be mediated by variations in serum IL-6 levels. No such interaction was detected with any of the 2 TNF-alpha polymorphisms.

Serum uric acid as an independent predictor of mortality in patients with angiographically proven coronary artery disease.

It is a matter of controversy as to whether uric acid is an independent predictor of mortality in patients with coronary artery disease (CAD) or whether it represents only an indirect marker of adverse outcome by reflecting the association between uric acid and other cardiovascular risk factors. Therefore, we studied the influence of uric acid levels on mortality in patients with CAD. In 1,017 patients with angiographically proven CAD, classic risk factors and uric acid levels were determined at enrollment. A follow-up over a median of 2.2 years (maximum 3.1) was performed. Death from all causes was defined as an end point of the study. In CAD patients with uric acid levels <303 micromol/L (5.1 mg/dl) (lowest quartile) compared with those with uric acid levels >433 micromol/L (7.1 mg/dl) (highest quartile), the mortality rate increased from 3.4% to 17.1% (fivefold increase). After adjustment for age, both sexes demonstrated an increased risk for death with increasing uric acid levels (female patients: hazard ratio [HR] 1.30, 95% confidence intervals [CI] 1.14 to 1.49, p < or = 0.001; male patients: HR 1.39 [95% CI 1.21 to 1.59], p < or = 0.001). In multivariate Cox regression analysis performed with 12 variables that influence overall mortality-including diuretic use-elevated levels of uric acid demonstrated an independent, significant positive relation to overall mortality (HR 1.23 [95% CI 1.11 to 1.36], p <0.001) in patients with CAD. Thus, uric acid is an independent predictor of mortality in patients with CAD.

Relation of markers of inflammation (C-reactive protein, fibrinogen, von Willebrand factor, and leukocyte count) and statin therapy to long-term mortality in patients with angiographically proven coronary artery disease.

We evaluated a possible interaction between statins and inflammation in 1,246 patients with angiographically diagnosed coronary artery disease. Four different inflammatory markers were determined: high, sensitive C-reactive protein (hs-CRP) (p = 0.001), fibrinogen (p = 0.006), von Willebrand factor (p = 0.006), and leukocyte count (p = 0.03); these levels were significantly higher among the 88 patients who died of cardiac causes during follow-up (median 2.9 years) than among survivors. In a multivariate backward stepwise Cox regression mode, only hs-CRP was evaluated to be a significant predictor of death from coronary artery disease. This prediction was lost in statin-treated patients. Compared with patients receiving statin medication, patients without statins did not have increased cardiac mortality (even when low-density lipoprotein [LDL] levels were >125 mg/dl) when hs-CRP levels were not elevated. In contrast, patients without statins and elevated hs-CRP (top quartile) had a 2.3-fold increase in risk for fatal coronary events, independent of LDL levels. In conclusion, only elevated hs-CRP was selected as an independent predictor of death. Statin therapy is associated with elevated hs-CRP, with a risk reduction for fatal coronary events, independent of LDL levels; this, in part, may be explained by the anti-inflammatory effects on atherosclerosis.