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.

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.

Is ad-hoc plan adaptation based on 2-Step IMRT feasible?

BACKGROUND: The ability of a geometry-based method to expeditiously adapt a "2-Step" step and shoot IMRT plan was explored. Both changes of the geometry of target and organ at risk have to be balanced. A retrospective prostate planning study was performed to investigate the relative benefits of beam segment adaptation to the changes in target and organ at risk coverage. METHODS: Four patients with six planning cases with extraordinarily large deformations of rectum and prostate were chosen for the study. A 9-field IMRT plan (A) using 2-Step IMRT segments was planned on an initial CT study. The plan had to fulfil all the requirements of a conventional high-quality step and shoot IMRT plan. To adapt to changes of the anatomy in a further CT data set, three approaches were considered: the original plan with optimized isocentre position (B), a newly optimized plan (C) and the original plan, adapted using the 2-Step IMRT optimization rules (D). DVH parameters were utilized for quantification of plan quality: D(99) for the CTV and the central planning target volume (PTV), D(95) for an outer PTV, V(95), V(80) and V(50) for rectum and bladder. RESULTS: The adapted plan (D) achieved almost the same target coverage as the newly optimized plan (C). Target coverage for plan B was poor and for the organs at risk, the rectum V(80) was slightly increased. The volume with more than 95% of the target dose (V(95)) was 1.5+/-1.5 cm(3) for the newly optimized plan (C), compared to 2.2+/-1.3 cm(3) for the original plan (A) and 7.2+/-4.8 cm(3) (B) on the first and the second CT, respectively. The adapted plan resulted in 4.3+/-2.1 cm(3) (D), an intermediate dose load to the rectum. All other parameters were comparable for the newly optimized and the adapted plan. CONCLUSIONS: The first results for adaptation of interfractional changes using the 2-Step IMRT algorithm are encouraging. The plans were superior to plans with optimized isocentre position and only marginally inferior to a newly optimized plan.

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.

An interlaced IMRT technique for elongated tumor volumes.

Treatment of large target volumes with intensity modulated radiotherapy (IMRT) can be restricted by the maximum field size of the multileaf collimator (MLC). In this work, a straightforward technique for MLC-based IMRT is presented, which is generally applicable and does not depend on the capabilities of the linear accelerator's IMRT delivery system. A dual isocenter technique was developed that maximizes beam overlap. The beams at the first isocenter are arranged such that they interlace with the beams at the second isocenter. All beams contribute to the overlap region, whereas only some contribute to the superior and some to the inferior part of the target. The interlaced technique (9 beams) was compared with an alternative more complex approach (14 beams) for a head-and-neck case with simultaneous integrated boost and 3 different dose levels. The plans were compared in terms of complexity, dosimetry, and the effect of inaccurate translation between the isocenters. The interlaced and the more complex IMRT technique resulted in nearly identical dose distributions without clinically relevant differences. The total number of monitor units (MUs) was comparable with more MUs per segment for the interlaced technique. For the interlaced technique, the number of segments

A decision aid for intensity-modulated radiation-therapy plan selection in prostate cancer based on a prognostic Bayesian network and a Markov model.

OBJECTIVE: The prognosis of cancer patients treated with intensity-modulated radiation-therapy (IMRT) is inherently uncertain, depends on many decision variables, and requires that a physician balance competing objectives: maximum tumor control with minimal treatment complications. METHODS: In order to better deal with the complex and multiple objective nature of the problem we have combined a prognostic probabilistic model with multi-attribute decision theory which incorporates patient preferences for outcomes. RESULTS: The response to IMRT for prostate cancer was modeled. A Bayesian network was used for prognosis for each treatment plan. Prognoses included predicting local tumor control, regional spread, distant metastases, and normal tissue complications resulting from treatment. A Markov model was constructed and used to calculate a quality-adjusted life-expectancy which aids in the multi-attribute decision process. CONCLUSIONS: Our method makes explicit the tradeoffs patients face between quality and quantity of life. This approach has advantages over current approaches because with our approach risks of health outcomes and patient preferences determine treatment decisions.

Pre-segmented 2-Step IMRT with subsequent direct machine parameter optimisation - a planning study.

BACKGROUND: Modern intensity modulated radiotherapy (IMRT) mostly uses iterative optimisation methods. The integration of machine parameters into the optimisation process of step and shoot leaf positions has been shown to be successful. For IMRT segmentation algorithms based on the analysis of the geometrical structure of the planning target volumes (PTV) and the organs at risk (OAR), the potential of such procedures has not yet been fully explored. In this work, 2-Step IMRT was combined with subsequent direct machine parameter optimisation (DMPO-Raysearch Laboratories, Sweden) to investigate this potential. METHODS: In a planning study DMPO on a commercial planning system was compared with manual primary 2-Step IMRT segment generation followed by DMPO optimisation. 15 clinical cases and the ESTRO Quasimodo phantom were employed. Both the same number of optimisation steps and the same set of objective values were used. The plans were compared with a clinical DMPO reference plan and a traditional IMRT plan based on fluence optimisation and consequent segmentation. The composite objective value (the weighted sum of quadratic deviations of the objective values and the related points in the dose volume histogram) was used as a measure for the plan quality. Additionally, a more extended set of parameters was used for the breast cases to compare the plans. RESULTS: The plans with segments pre-defined with 2-Step IMRT were slightly superior to DMPO alone in the majority of cases. The composite objective value tended to be even lower for a smaller number of segments. The total number of monitor units was slightly higher than for the DMPO-plans. Traditional IMRT fluence optimisation with subsequent segmentation could not compete. CONCLUSION: 2-Step IMRT segmentation is suitable as starting point for further DMPO optimisation and, in general, results in less complex plans which are equal or superior to plans generated by DMPO alone.

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.

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).

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.

Three-dimensional spatial modelling of the correlation between abdominal motion and lung tumour motion with breathing.

The aim of this research was to investigate whether a spatial correlation could be found between an external 3-D respiratory signal and the tumour trajectory. The respiratory signal was obtained by tracking the abdominal movement and the tumour trajectory was obtained by automatically determining the tumour position in a series of portal images. Three different models, based on Systems Identification, are presented to model the correlation using a 1-D respiratory signal, a 3-D respiratory signal and a 3-D respiratory signal together with previously determined tumour positions. Adequate correlation was found for all models in the direction of the tumour movement with standard deviations of 0.89 mm, 0.72 mm and 0.75 mm, respectively, and model fit of Rt2 = 0.19, 0.63 and 0.82, respectively. Increasing the frame rate for the acquisition of portal images from 3 to 15 frames per second improved the standard deviation and model fit. In summary, it is possible to spatially correlate a 3-D respiratory signal with the tumour trajectory using this approach. The models presented provide a framework that can be extended to include more information if required. A 3-D respiratory signal is preferable to a 1-D signal in modelling the tumour motion that is not along the main axis of tumour movement.

Distinct effects of rectum delineation methods in 3D-conformal vs. IMRT treatment planning of prostate cancer.

BACKGROUND: The dose distribution to the rectum, delineated as solid organ, rectal wall and rectal surface, in 3D conformal (3D-CRT) and intensity-modulated radiotherapy treatment (IMRT) planning for localized prostate cancer was evaluated. MATERIALS AND METHODS: In a retrospective planning study 3-field, 4-field and IMRT treatment plans were analyzed for ten patients with localized prostate cancer. The dose to the rectum was evaluated based on dose-volume histograms of 1) the entire rectal volume (DVH) 2) manually delineated rectal wall (DWH) 3) rectal wall with 3 mm wall thickness (DWH(3)) 4) and the rectal surface (DSH). The influence of the rectal filling and of the seminal vesicles' anatomy on these dose parameters was investigated. A literature review of the dose-volume relationship for late rectal toxicity was conducted. RESULTS: In 3D-CRT (3-field and 4-field) the dose parameters differed most in the mid-dose region: the DWH showed significantly lower doses to the rectum (8.7% +/- 4.2%) compared to the DWH(3) and the DSH. In IMRT the differences between dose parameters were larger in comparison with 3D-CRT. Differences were statistically significant between DVH and all other dose parameters and between DWH and DSH. Mean doses were increased by 23.6% +/- 8.7% in the DSH compared to the DVH in the mid-dose region. Furthermore, both the rectal filling and the anatomy of the seminal vesicles influenced the relationship between the dose parameters: a significant correlation of the difference between DVH and DWH and the rectal volume was seen in IMRT treatment. DISCUSSION: The method of delineating the rectum significantly influenced the dose representation in the dose-volume histogram. This effect was pronounced in IMRT treatment planning compared to 3D-CRT. For integration of dose-volume parameters from the literature into clinical practice these results have to be considered.

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).

Assessment of the tricuspid valve morphology by transthoracic real-time-3D-echocardiography.

AIM: To demonstrate the feasibility of transthoracic three-dimensional real-time echocardiography (3D-TTE) supplemental to routine assessments of the tricuspid valve and to analyze interrater agreement. METHODS: Twenty healthy subjects and 74 patients with right ventricular failure were examined with conventional 2D and additionally 3D-TTE (SONOS 7500, Philips, Netherlands). The 3D exams were performed and recorded by one of two raters. The recordings were evaluated offline and independently by both raters for visualization of morphological and functional features of the tricuspid valve according to a subjective 3-point scale. Statistical analyses were performed for interrater agreement and for comparison of imaging quality between the two study groups. In addition, we present an illustrative case report. RESULTS: Visualization of the spatial relationship between the tricuspid valve and vicinal structures, of the commissures, the orifice, and entirety of valve depiction were better in the ventricular failure group as compared to the control group. Annular dimensions were equally assessable in both groups, leaflet thickness and mobility were not significantly different. Interrater agreement on assessability was slight for leaflet thickness, fair for leaflet mobility and orifice area, and good for the remaining features. The 3D-TTE exam including offline evaluation took 6.5 minutes on average and maximally 14 minutes. CONCLUSION: 3D-TTE of the tricuspid valve can be performed in addition to routine 2D echocardiography within a reasonable time and with high assessability of important features in patients with right ventricular failure. Interrater agreement was fair to good overall. Thus, its feasibility may encourage prospective studies on its potential for more detailed noninvasive diagnosis and preoperative planning.

Analysis of N-terminal-pro-brain natriuretic peptide and C-reactive protein for risk stratification in stable and unstable coronary artery disease: results from the AtheroGene study.

AIMS: N-terminal-pro-brain natriuretic peptide (Nt-proBNP) is a reliable risk predictor in acute coronary artery disease (CAD). Little is known about patients with stable angina pectoris (SAP). We aimed to investigate the prognostic impact of Nt-proBNP in a population with CAD especially focussing on patients with SAP. METHODS AND RESULTS: We obtained baseline samples from a prospective cohort of 904 consecutive patients with CAD. Cardiovascular events were registered during follow-up (median 2 years; maximum 3.7 years). Baseline Nt-proBNP was significantly higher among individuals with cardiovascular events compared with those without (711.5 vs. 238.8 pg/mL; P<0.0001). A similar association was found if the analysis was performed in patients who presented with stable angina (330 vs. 166.5 pg/mL; P=0.006) or acute coronary syndrome (990.9 vs. 527.7 pg/mL; P=0.03). In the SAP group, patients within the top quartile (>487.9 pg/mL) had a 3.7-fold (95% CI 1.2-9.1; P=0.01) increase in cardiovascular risk. After adjustment for most potential confounders including left ventricular ejection fraction, Nt-proBNP remained predictive for patients with serum concentrations in the upper quartile in comparison with patients in the lowest quartile (hazard ratio highest vs. lowest quartile: 4.0; P=0.03) (n=417). CONCLUSION: Baseline concentration of Nt-proBNP is independently related to future cardiovascular events in patients with stable angina.

Application of influence diagrams to prostate intensity-modulated radiation therapy plan selection.

The purpose is to incorporate clinically relevant factors such as patient-specific and dosimetric information as well as data from clinical trials in the decision-making process for the selection of prostate intensity-modulated radiation therapy (IMRT) plans. The approach is to incorporate the decision theoretic concept of an influence diagram into the solution of the multiobjective optimization inverse planning problem. A set of candidate IMRT plans was obtained by varying the importance factors for the planning target volume (PTV) and the organ-at-risk (OAR) in combination with simulated annealing to explore a large part of the solution space. The Pareto set for the PTV and OAR was analysed to demonstrate how the selection of the weighting factors influenced which part of the solution space was explored. An influence diagram based on a Bayesian network with 18 nodes was designed to model the decision process for plan selection. The model possessed nodes for clinical laboratory results, tumour grading, staging information, patient-specific information, dosimetric information, complications and survival statistics from clinical studies. A utility node was utilized for the decision-making process. The influence diagram successfully ranked the plans based on the available information. Sensitivity analyses were used to judge the reasonableness of the diagram and the results. In conclusion, influence diagrams lend themselves well to modelling the decision processes for IMRT plan selection. They provide an excellent means to incorporate the probabilistic nature of data and beliefs into one model. They also provide a means for introducing evidence-based medicine, in the form of results of clinical trials, into the decision-making process.

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.

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.

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.

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.