Three-year results from a preclinical implantation study of a long-term resorbable surgical mesh with time-dependent mechanical characteristics.

PURPOSE: The purpose of this study was to evaluate the biocompatibility, local tissue effects and performance of a synthetic long-term resorbable test mesh (TIGR(®) Matrix Surgical Mesh) compared to a non-resorbable polypropylene control mesh following implantation in a sheep model. METHODS: Full-thickness abdominal wall defects were created in 14 sheep and subsequently repaired using test or control meshes. Sacrifices were made at 4, 9, 15, 24 and 36 months and results in terms of macroscopic observations, histology and collagen analysis are described for 4, 9, 15, 24 and 36 months. RESULTS: The overall biocompatibility was good, and equivalent in the test and control meshes while the resorbable mesh was characterized by a collagen deposition more similar to native connective tissue and an increased thickness of the integrating tissue. The control polypropylene mesh provoked a typical chronic inflammation persistent over the 36-month study period. As the resorbable test mesh gradually degraded it was replaced by a newly formed collagen matrix with an increasing ratio of collagen type I/III, indicating a continuous remodeling of the collagen towards a strong connective tissue. After 36 months, the test mesh was fully resorbed and only microscopic implant residues could be found in the tissue. CONCLUSIONS: This study suggests that the concept of a long-term resorbable mesh with time-dependent mechanical characteristics offers new possibilities for soft tissue repair and reinforcement.

[Cellular injury associated with extracorporeal circulation]. / Atteintes cellulaires associées à une circulation extracorporelle.

Circulation of blood extracorporeally through plastic tubing causes severe shear stresses to blood cells and activates several regulatory cascades. These various pathways include the cytokine cascades, complement and coagulation. Interleukine-1, -6, -8, tumor necrosis factor-alpha have been implicated. Among various mediators of tissue injury released by activated neutrophils, elastase and metalloproteinases have been considered to be relevant in postoperative organ dysfunction in cardiac operations. Endothelial cells are extremely sensitive to insults that occur during cardiopulmonary bypass (CPB). These insults lead to disruption of barrier function and leukocyte adhesion. Immunoglobulins such as ICAM-1 and VCAM-1 are expressed on endothelium cells and act as ligands for integrins. It is also important to remember that during cardiac operations, the interest on the metabolism of in free radicals has focused on the heart and the lungs because they are exposed to ischemia and subsequent reperfusion. Increased production of free radicals during CPB is associated with myocardial and pulmonary dysfunctions. Now it is well recognized that the whole body inflammatory response induced by CPB is mainly responsible for postoperative organ dysfunctions.

Epidemiology of neonatal respiratory failure in the United States: projections from California and New York.

We wanted to determine the incidence, cost, outcome, and patterns of care for neonates requiring mechanical ventilation (MV) in the United States. Using 1994 state hospital discharge data from California and New York, we conducted an observational study of all neonatal hospitalizations (n = 16,405) with MV, comparing outcomes at centers of different technological capability, and generating national projections using census and natality reports. The MV rate was 18 per 1,000 live births. Although the incidence was much higher in lower birth weight (BW) babies, one-third had normal BW. The incidence was higher in boys (20 versus 15.6 per 1,000) and in blacks (29 per 1,000). Hospital mortality was 11.1%, higher in minority groups, and associated with low BW, congenital anomalies, and major hemorrhage. Mean hospital length of stay and costs were 31.1 d and $51,700. Half of all deaths occurred at lower level centers. There are 80,000 cases per year in the United States with 8,500 deaths and total hospital costs of $4.4 billion. We conclude neonatal respiratory failure is common, expensive, and frequently fatal. There are a surprisingly large number of normal BW cases and there are large racial differences.

Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients.

The high incidence of cardiovascular disease in hemodialyzed (HD) patients is well established and oxidative stress has been involved in this phenomenon. The aim of our study was to evaluate if a vitamin E-coated dialyzer could offer protection to HD patients against oxidative stress. Sixteen HD patients were successively assessed for one month (i) on a high biocompatible synthetic dialyzer (AN) and (ii) on a vitamin E-coated dialyzer (VE). Blood samples were taken before and after the dialysis session at the end of each treatment period. HD session conducted with the AN dialyzer was responsible for acute oxidative stress, significantly assessed after HD by a decreased plasma vitamin C level and an increased ascorbyl free radical (AFR)/vitamin C ratio used as an index of oxidative stress. Plasma elastase activity, reflecting neutrophil activation, was also increased; soluble P-selectin, reflecting platelet activation, did not show any variation. The use of the VE dialyzer was associated with a less extended oxidative stress compared with the AN membrane: basal vitamin C level was higher, and after the HD session AFR/vitamin C ratio and elastase activity were not significantly increased. Plasma vitamin E levels were not affected. Our study demonstrates that HD is associated with oxidative stress, which can be partially prevented by the use of a vitamin E-coated dialyzer. Our data suggest that this dialyzer may exert a site-specific scavenging effect on free radical species in synergy with a reduced activation of neutrophils.

Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.

OBJECTIVE: To determine the incidence, cost, and outcome of severe sepsis in the United States. DESIGN: Observational cohort study. SETTING: All nonfederal hospitals (n = 847) in seven U.S. states. PATIENTS: All patients (n = 192,980) meeting criteria for severe sepsis based on the International Classification of Diseases, Ninth Revision, Clinical Modification. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We linked all 1995 state hospital discharge records (n = 6,621,559) from seven large states with population and hospital data from the U.S. Census, the Centers for Disease Control, the Health Care Financing Administration, and the American Hospital Association. We defined severe sepsis as documented infection and acute organ dysfunction using criteria based on the International Classification of Diseases, Ninth Revision, Clinical Modification. We validated these criteria against prospective clinical and physiologic criteria in a subset of five hospitals. We generated national age- and gender-adjusted estimates of incidence, cost, and outcome. We identified 192,980 cases, yielding national estimates of 751,000 cases (3.0 cases per 1,000 population and 2.26 cases per 100 hospital discharges), of whom 383,000 (51.1%) received intensive care and an additional 130,000 (17.3%) were ventilated in an intermediate care unit or cared for in a coronary care unit. Incidence increased >100-fold with age (0.2/1,000 in children to 26.2/1,000 in those >85 yrs old). Mortality was 28.6%, or 215,000 deaths nationally, and also increased with age, from 10% in children to 38.4% in those >85 yrs old. Women had lower age-specific incidence and mortality, but the difference in mortality was explained by differences in underlying disease and the site of infection. The average costs per case were $22,100, with annual total costs of $16.7 billion nationally. Costs were higher in infants, nonsurvivors, intensive care unit patients, surgical patients, and patients with more organ failure. The incidence was projected to increase by 1.5% per annum. CONCLUSIONS: Severe sepsis is a common, expensive, and frequently fatal condition, with as many deaths annually as those from acute myocardial infarction. It is especially common in the elderly and is likely to increase substantially as the U.S. population ages.

Quality-adjusted survival in the first year after the acute respiratory distress syndrome.

There is little information on long-term outcome after acute respiratory distress syndrome (ARDS). We measured quality-adjusted survival in the first year after ARDS in a prospective cohort (n = 200). All patients met traditional criteria for ARDS. Patients with sepsis and acute nonpulmonary organ dysfunction at presentation were excluded. The cohort was healthy before onset of ARDS as evidenced by high functional status (mean Karnofsky Performance Status index: 82.2/100 where >/= 80 = able to perform normal activities independently) and minimal comorbid illness (mean Charlson-Deyo comorbidity score: 0.32/17 where 0 = absence of chronic illness). We determined quality-adjusted life-years (QALYs) using the Quality of Well-being (QWB) scale (0 to 1 scale where 1 = optimal well-being), measured at 6 and 12 mo. Survival was 69.5 +/- 5.0% at 1 month, fell to 55.7 +/- 3.7% at 6 mo, and did not change at 12 mo, yielding a survival of 59 life-years in the first year per 100 patients with ARDS. QWB was low at 6 and 12 mo (0.59 +/- 0.015 and 0.60 +/- 0.015), yielding a quality-adjusted survival of 36 QALYs per 100 patients (sensitivity range: 21 to 46 QALYs). We conclude that ARDS developing in previously healthy patients is associated with poor quality-adjusted survival. These data are important for cost-effectiveness analyses and long-term care.

Predicting hospital mortality for patients in the intensive care unit: a comparison of artificial neural networks with logistic regression models.

OBJECTIVE: Logistic regression (LR), commonly used for hospital mortality prediction, has limitations. Artificial neural networks (ANNs) have been proposed as an alternative. We compared the performance of these approaches by using stepwise reductions in sample size. DESIGN: Prospective cohort study. SETTING: Seven intensive care units (ICU) at one tertiary care center. PATIENTS: Patients were 1,647 ICU admissions for whom first-day Acute Physiology and Chronic Health Evaluation III variables were collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We constructed LR and ANN models on a random set of 1,200 admissions (development set) and used the remaining 447 as the validation set. We repeated model construction on progressively smaller development sets (800, 400, and 200 admissions) and retested on the original validation set (n = 447). For each development set, we constructed models from two LR and two ANN architectures, organizing the independent variables differently. With the 1,200-admission development set, all models had good fit and discrimination on the validation set, where fit was assessed by the Hosmer-Lemeshow C statistic (range, 10.6-15.3; p > or = .05) and standardized mortality ratio (SMR) (range, 0.93 [95% confidence interval, 0.79-1.15] to 1.09 [95% confidence interval, 0.89-1.38]), and discrimination was assessed by the area under the receiver operating characteristic curve (range, 0.80-0.84). As development set sample size decreased, model performance on the validation set deteriorated rapidly, although the ANNs retained marginally better fit at 800 (best C statistic was 26.3 [p = .0009] and 13.1 [p = .11] for the LR and ANN models). Below 800, fit was poor with both approaches, with high C statistics (ranging from 22.8 [p <.004] to 633 [p <.0001]) and highly biased SMRs (seven of the eight models below 800 had SMRs of <0.85, with an upper confidence interval of <1). Discrimination ranged from 0.74 to 0.84 below 800. CONCLUSIONS: When sample size is adequate, LR and ANN models have similar performance. However, development sets of < or = 800 were generally inadequate. This is concerning, given typical sample sizes used for individual ICU mortality prediction.

Predicting ICU mortality: a comparison of stationary and nonstationary temporal models.

OBJECTIVE: This study evaluates the effectiveness of the stationarity assumption in predicting the mortality of intensive care unit (ICU) patients at the ICU discharge. DESIGN: This is a comparative study. A stationary temporal Bayesian network learned from data was compared to a set of (33) nonstationary temporal Bayesian networks learned from data. A process observed as a sequence of events is stationary if its stochastic properties stay the same when the sequence is shifted in a positive or negative direction by a constant time parameter. The temporal Bayesian networks forecast mortalities of patients, where each patient has one record per day. The predictive performance of the stationary model is compared with nonstationary models using the area under the receiver operating characteristics (ROC) curves. RESULTS: The stationary model usually performed best. However, one nonstationary model using large data sets performed significantly better than the stationary model. CONCLUSION: Results suggest that using a combination of stationary and nonstationary models may predict better than using either alone.

Alteration in plasma antioxidant capacities in chronic renal failure and hemodialysis patients: a possible explanation for the increased cardiovascular risk in these patients.

OBJECTIVE: The high incidence of cardiovascular diseases in chronic renal failure (CRF) and hemodialyzed (HD) patients is now well established and the involvement of oxidative stress has been hypothesized in these phenomena. The aim of our study was to evaluate the level of oxidative stress in healthy controls (CTL) compared with CRF and HD patients before (pre-HD) and after (post-HD) the dialysis session, carried out on a high biocompatible polyacrylonitrile membrane AN69. METHODS: Several indicators of the extracellular redox status were evaluated in plasma. The ascorbyl free radical (AFR) was directly measured using electron spin resonance spectroscopy (ESR) and expressed with respect to the vitamin C level to obtain a direct index of oxidative stress. Indirect plasma parameters such as vitamin E, thiol and uric acid levels were also quantified. The plasma antioxidant status (PAS) was evaluated by the allophycocyanin test. Nitric oxide (NO) stable-end metabolites: nitrites and nitrates (NO(x)), were measured in plasma. RESULTS: In CRF patients, vitamin C and thiol levels were low, and the AFR/vitamin C ratio high compared with the CTL. On the other hand, PAS and uric acid levels were shown to be higher in CRF patients. After the dialysis session, vitamin C level decreased and AFR/vitamin C ratio increased. The thiol levels were shown to be increased, in return PAS and uric acid levels were significantly lower after the dialysis session. NO(x) levels rose during CRF, but were significantly decreased after the dialysis procedure. No differences in vitamin E status were observed between CTL, CRF and HD patients. CONCLUSION: Our study demonstrates that profound disturbances in the extracellular redox system occur during the course of chronic renal failure and hemodialysis, and may provide an explanation for the cardiovascular complications in these patients.

Short-term and long-term outcome prediction with the Acute Physiology and Chronic Health Evaluation II system after orthotopic liver transplantation.

OBJECTIVE: To evaluate the relationship between the postoperative Acute Physiology and Chronic Health Evaluation (APACHE) II score and mortality at hospital discharge and at 1 yr in liver transplant recipients. POPULATION: Adult orthotopic liver transplant (OLTX) recipients (n = 599) admitted to the intensive care unit postoperatively at a university hospital. METHODS: The cohort was split randomly into development and validation sets. Three models were compared for each end point: a) the original APACHE II slope with the original APACHE II postgastrointestinal surgery intercept; b) the original APACHE II slope with an OLTX-specific intercept generated from the development set; and c) an OLTX-specific slope and intercept generated from the development set. Goodness-of-fit and calibration were assessed by the Hosmer-Lemeshow C statistic (where p>.05 suggests good fit) and standardized mortality ratios. Discrimination was assessed by receiver operator characteristic area under the curve analysis. MEASUREMENTS AND MAIN RESULTS: Hospital and 1-yr mortality rates were 9.9% and 15.9%, respectively. The APACHE II score was strongly associated with mortality (chi-square, p<.0001), but when used with the original equation, it significantly overestimated hospital mortality (standardized mortality ratio, 0.73 [confidence interval, 0.58-0.99]). Using the OLTX-specific approaches, goodness-of-fit for both hospital and 1-yr mortality was good (p = .2-.57) but discrimination was only moderate (receiver operator characteristic area under the curve, 0.675-0.723). CONCLUSIONS: APACHE II is a good predictor of short- and long-term mortality after liver transplantation, especially when using OLTX-specific coefficients. Because fit and calibration were better than discrimination, APACHE II will be most useful in the prediction of risk for groups of patients (e.g., in clinical trials or institutional comparisons) rather than for individuals. This study raises the possibility that APACHE II may be useful for long-term mortality prediction in other critically ill populations. The overestimation of mortality using the original equation suggests that orthotopic liver transplantation, by reversing the underlying pathophysiology, may modify risk.

Severity scoring systems in the modern intensive care unit.

In recent years, several factors have led to increasing focus on the meaning of appropriateness of care and clinical performance in the intensive care unit (ICU). The emergence of new and expensive treatment modalities, a deeper reflection on what constitutes a desirable outcome, increasing financial pressure from cost containment efforts, and new attitudes regarding end-of-life decisions are reshaping the delivery of intensive care worldwide. This quest for a measure of ICU performance has led to the development of severity adjustment systems that will allow standardised comparisons of outcome and resource use across ICUs. These systems, for many years used only in the research setting, have evolved to become sophisticated, computer-based decision-support tools, in some instances commercially developed, and capable of predicting a diverse set of outcomes. Their application has broadened to include ICU performance assessment, individual patient decision-making, and pre- and post-hoc risk stratification in randomised trials. In this paper, we review the popular scoring systems currently in use; design issues in the development and evaluation of new scoring systems; current applications of scoring systems; and future directions.

Measuring resource use in the ICU with computerized therapeutic intervention scoring system-based data.

BACKGROUND AND OBJECTIVE: In this era of health-care reform, there is increasing need to monitor and control health-care resource consumption. This requires the development of measurement tools that are practical, uniform, reproducible, and of sufficient detail to allow comparison among institutions, among select groups of patients, and among individual patients. We explored the feasibility of generating an index of resource use based on the Therapeutic Intervention Scoring System (TISS) from hospital electronic billing data. Such an index is potentially comparable across institutions, allows assessment of care at many levels, is well understood by clinicians, and captures many of the resources relevant to the ICU. DESIGN: We developed an automated mapping of the hospital billing database into the different items of TISS and generated computerized active TISS scores on 1,372 ICU days. The computerized score was then validated by comparison to prospectively gathered active TISS scores by trained data collectors. SETTING: Eight ICUs within a university teaching institution. PATIENTS: We studied 1,229 general medical and surgical ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Active TISS scores ranged from 0 to 31 points. The two scores were well correlated (R2=0.53) and highly calibrated (as assessed by regression of active TISS on mean computerized active TISS [R2=0.85]). The scores were identical on 756 days (55.6%) and differed by < or = 3 TISS points on an additional 387 (28.2%) days. Interreliability assessment suggested substantial agreement (kappa statistic=0.71). The discriminatory power of the computerized score to identify different levels of ICU resource use was excellent as assessed by area under the receiver operating characteristics curves at four threshold points (0.91, 0.87, 0.89, and 0.88). Performance of the computerized score was similar across medical, coronary, and surgical ICU patient groups. CONCLUSION: An automated algorithm can reproduce valid TISS scores from standard hospital billing data, allowing comparison of patients and groups of patients in order to better understand ICU resource use.

International comparisons of critical care outcome and resource consumption.

Though there are reasonable data to suggest that certain countries, such as the United States, spend considerably more money on the provision of critical care services than others, there is little information regarding the added benefits accrued with this additional expense. Studies to date have suggested little if no difference in outcome but have been limited in their size, design, and choice of outcome measures. Furthermore, significant underlying societal priorities and philosophy may dictate that the optimal critical care delivery system is different for different countries. With the increasing availability of large patient databases, however, it will be more feasible in the future to design and conduct assessments of critical care delivery systems between countries taking appropriate account of the choice of study design, definition of at-risk populations, and choice of valuable measures of output and cost. The results of such assessments will hopefully drive wiser decision making in the design and management of critical care delivery systems worldwide.

[Phlebography versus Doppler sonography for follow-up of venous thromboses of the legs]. / Phlebographie versus Doppler-Sonographie bei Kontrollen von Beinvenenthrombosen.

The authors demonstrate on the basis of a case that in known thrombosis follow-up of the course of the disease via Doppler sonography will not suffice to determine the success of the treatment. Attention is drawn to the importance of detailed examination in respect of completion or continuation of treatment.