Detailed Stratification Research Articles

The Role of Therapeutic Apheresis in High Immunologic Risk Renal Transplantation: A Review of Current Trends

Immunologic sensitization, defined by the presence of antibodies directed against donor human leukocyte antigen (or so called donor-specific antibodies [DSA]), is common among those awaiting kidney transplantation, and is associated with worse outcomes following transplant. Existing DSA have historically been screened for pretransplant using complement-dependent cytotoxic crossmatching and their risk circumnavigated through policies that prohibit transplants between incompatible donor-recipient pairs. This risk avoidance strategy maximizes outcomes following transplant, but at the expense of limiting access to transplant for sensitized individuals. Over the last decade, the field of kidney transplantation has moved to actively modify the risks posed by DSA, rather than to simply avoid them. More sensitive detection methods have provided detailed immunologic risk stratification of potential donor-recipient pairs. Desensitization protocols, in which therapeutic aphaeresis plays a central role, have been used to reduce the potential harms posed by DSA. More recently, desensitization and paired donor exchange programs have been used in combination to expand transplantation to highly sensitized patients with incompatible living donors. It is likely that this combination of risk mitigation and avoidance strategies will be used together more often to both maximize individuals' access to transplant, and optimize patient and graft outcomes.

FMS-Like Tyrosine Kinase 3 Internal Tandem Duplication and the Patterns of Its Gene Sequence in 207 Chinese Patients With De Novo Acute Myeloid Leukemia

Constitutive activation of the FMS-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase by internal tandem duplication (ITD) has been researched in patients with de novo acute myeloid leukemia (AML). To study the patterns of FLT3-ITD in Chinese patients with AML. A total of 207 patients with de novo AML were enrolled in the study. Genomic DNA was extracted from peripheral blood and polymerase chain reaction was performed. GeneScan was used to analyze the mutant to wild-type ratio. The sequencing of mutated genes was performed to confirm the mutation types and exclude false positives. A total of 42 cases (20.3%) were associated with mutations. FLT3-ITD was found equally in AML subtypes M1 to M6. The level of the ITD allele was heterogeneous. GeneScan showed that the mutant to wild-type ratio ranged from 0.03 to 3.78 (median, 0.43). Patients with a high ratio had significantly lower cancer remission rates and shorter survival. They also showed distinct clinical features including higher white blood cell counts and higher CD7 and CD56 expression. The length of the duplicated fragment was 26 to 57 bp (median, 43 bp). Twenty-two cases (52%) had simple tandem duplications, while 20 other cases (48%) had an extra interval of 12 to 30 bp before the tandem duplications. A hexanucleotide consisting of GAAAAG was found exclusively in the intervals. Patients with this GAAAAG interval showed better survival. The ITD to wild-type ratio, gene pattern, and CD7 expression status appear to be independent prognostic indices for patients with AML. Detection of FLT3 mutation is fast, easy, and inexpensive. The mutant to wild-type ratio is helpful for performing detailed risk stratification. DNA sequence analysis is more precise for confirming and evaluating the mutation pattern.

Postoperative Transarterial Chemoembolization Benefits Patients with High γ-Glutamyl Transferase Levels after Curative Hepatectomy for Hepatocellular Carcinoma: A Survival Stratification Analysis

Hepatocellular carcinoma (HCC) is the most common liver tumor in Asian countries, and hepatectomy is currently regarded as the optimal curative treatment for HCC; however, the postoperative outcome remains unsatisfactory. Aiming at further clarification of prognostic factors after hepatectomy, we adopted a detailed stratification on survival periods. A total of 428 HCC patients undergoing curative hepatectomy were firstly divided into two groups using 2-year survival as cutoff point. Multivariate analysis showed that tumor-related factors, including vascular invasion (P < 0.001), high Edmondson grade (P < 0.001), large tumor size (P < 0.001) and high serum alpha-fetoprotein level (P = 0.001), were significant determinants for early death within 2 years, while postoperative transarterial chemoembolization (TACE) was demonstrated a protective factor (P = 0.013). Then the 281 patients with survival > 2 years were divided into two subgroups according to survival or death during follow-up to examine the late death related factors. We found that high serum γ-glutamyl transpeptidase (GGT), indicating severity of underlying liver disease, was significantly linked to death in this stage (P = 0.006). In further comparison of survival rates between subgroups stratified by early- and late-death indictors, we found the long-term outcomes of patients with high serum GGT were poor, regardless of the factors related with primary tumor. Furthermore, postoperative TACE decreased late death rate of patients with high GGT levels. In conclusion, despite the overwhelmed effects of primary tumor in the early stage after hepatectomy, postoperative TACE is beneficial for HCC patients with poor liver status.

Validation of the Prostate Cancer Risk Index (PRIX): A Simple Scoring System to Predict Risk of Biochemical Relapse after Radical Prostatectomy for Prostate Cancer

The Prostate Cancer Risk Index (PRIX) is a simple scoring system for risk stratification of clinically localized prostate cancer that relies on three variables: prostate-specific antigen level at diagnosis, Gleason score at biopsy and clinical T stage. The aim of this study was validation of the ability of the PRIX score to predict biochemical relapse after radical prostatectomy in a series of patients from a single Japanese center. From 1995 to 2008, 519 patients who underwent radical prostatectomy for clinically localized prostate cancer with no adjuvant therapies were included in the validation cohort. The biochemical relapse-free rate was estimated using the Kaplan-Meier method. The performance of the PRIX score was assessed with Cox proportional hazards regression model, concordance index and a calibration plot. For comparison, the performance of the D'Amico classification was also assessed. Biochemical relapse-free rate continuously decreased as the PRIX score increased. Each 1-point increment in the PRIX score led to an increase in hazard ratio for biochemical relapse. The concordance index of the PRIX score and the D'Amico classification to predict biochemical relapse was 0.719 and 0.730, respectively. The Kaplan-Meier plots and the calibration plots demonstrated the possibility that the PRIX score could present more detailed stratification than the D'Amico classification. The results of our investigation showed that in Japanese patients treated at a single center, the PRIX score can accurately predict biochemical relapse after radical prostatectomy and demonstrates reasonable calibration. The PRIX score may be one option as a prediction model for biochemical relapse after radical prostatectomy.

294 IN HIGH-RISK PROSTATE CANCER, 3 OR MORE POSITIVE NODES AT RADICAL PROSTATECTOMY REPRESENT AN INDEPENDENT PREDICTOR OF WORSE CSS, WHILE 1 OR 2 POSITIVE NODES DO NOT INFLUENCE CSS

294 IN HIGH-RISK PROSTATE CANCER, 3 OR MORE POSITIVE NODES AT RADICAL PROSTATECTOMY REPRESENT AN INDEPENDENT PREDICTOR OF WORSE CSS, WHILE 1 OR 2 POSITIVE NODES DO NOT INFLUENCE CSS

Twenty Years of Cardiac Surgery in Patients Aged 80 Years and Older: Risks and Benefits

Patients aged 80 years and older who require cardiac surgical procedures are an increasing population and usually present with considerable comorbidity. Detailed operative risk stratification versus long-term survival and quality of life after surgery is mandatory. A retrospective analysis was performed on 1,003 patients aged 82.3 years (range, 80 to 94 years) who underwent aortic valve replacement (n = 303), coronary artery bypass grafting (n = 403), or aortic valve replacement with coronary artery bypass grafting (n = 297) between 1987 and 2006. Preoperative data, operative outcome, long-term survival, and predictors for early and late mortality were analyzed. Furthermore, the Short Form 36 Health Status questionnaire was used to evaluate the quality of life. Overall in-hospital mortality was 7.1%. Overall actuarial survival at 1, 5, and 10 years was 81.6% ± 1.2%, 60.4% ± 1.9%, and 23.3% ± 2.6% (mean survival time, 6.25 ± 0.2 years) and showed no significant difference compared with an age- and sex-matched general population. Multivariate analysis showed that preoperative creatinine concentration greater than 1.3 mg/dL (p < 0.001), preoperative atrial fibrillation (p < 0.005), and postoperative prolonged ventilation (p < 0.001) were independent predictors for poor long-term survival. The physical health summarized score of the Short Form 36 Health Status questionnaire was significantly increased in the study population compared with a German standard population aged 80 years and older (p < 0.05). Despite an increased operative mortality, octogenarians showed a considerable quality of life and an excellent long-term survival. To further improve surgical outcome in octogenarians, patient selection should be done with consideration of the identified independent preoperative risk factors.

New Risk Stratification Markers in Brugada Syndrome

Although spontaneous type 1 ECG has been reported as a predictor of the Brugada syndrome, many patients without documented ventricular fibrillation (VF) have this ECG type and detailed risk stratification will be required. Recently, we proposed new two ECG markers to predict patients’ risk: fragmented QRS (fQRS) and spontaneous ECG alterations (ECG-alt). The fQRS is defined as multiple spikes within QRS complex in leads V1–V3 (≥4 spikes in one lead). The ECG-alt is defined as day-by-day spontaneous ECG type change or changes in ST level ≥0.2 mV. Both fQRS and ECG-alt were frequent in patients with VF, but less frequent in patients without any symptoms (fQRS: asymptomatic patients 34%, VF patients 95%, p<0.01; ECG-alt: asymptomatic patient 44%, patients with VF 97%, p<0.01). Multivariate analysis showed both fQRS and ECG-alt were associated with occurrence of VF. Experimental studies using canine wedge preparation model of Brugada syndrome showed that the fQRS and the ECG-alt represented delayed conduction and unstable repolarization at right ventricular epicardium, respectively. Existence of both repolarization and depolarization abnormalities will be associated with initiation of the VF. Because new onset of VF is less frequent in asymptomatic patients with Brugada syndrome, these two markers should be verified by future prospective study. A recent prospective study in Italy (PRELUDE) that was reported in HRS2011 showed QRS fragmentation as significant and independent predictors of arrhythmic events (hazard ratio: 4.94).

Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium.

Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, P(trend) = 2 x 10(-26)), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, P(trend) = 1 x 10(-10)) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, P(trend) = 5 x 10(-8)) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, P(trend) = 2 x 10(-5); rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, P(trend) = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.

Architecture of a nascent viral fusion pore

Enveloped viruses use specialized protein machinery to fuse the viral membrane with that of the host cell during cell invasion. In influenza virus, hundreds of copies of the haemagglutinin (HA) fusion glycoprotein project from the virus surface. Despite intensive study of HA and its fusion activity, the protein's modus operandi in manipulating viral and target membranes to catalyse their fusion is poorly understood. Here, the three-dimensional architecture of influenza virus–liposome complexes at pH 5.5 was investigated by electron cryo-tomography. Tomographic reconstructions show that early stages of membrane remodeling take place in a target membrane-centric manner, progressing from punctate dimples, to the formation of a pinched liposomal funnel that may impinge on the apparently unperturbed viral envelope. The results suggest that the M1 matrix layer serves as an endoskeleton for the virus and a foundation for HA during membrane fusion. Fluorescence spectroscopy monitoring fusion between liposomes and virions shows that leakage of liposome contents takes place more rapidly than lipid mixing at pH 5.5. The relation of ‘leaky' fusion to the observed prefusion structures is discussed.

STRATIGRAPHIC STRUCTURE OF CENOZOIC SEDIMENTS OF PREKERCH SHELF AND EAST BALCK SEA BASIN

The model of stratigraphic structure has been developed and the regional stratigraphic chart of Cenozoic sediments of the Prekerch shelf andEastBlack SeaBasinhas been proposed. It is based on the analysis of the biostratigraphic, lithologic, geomorphologic, structural-tectonic, formation, facial, sediment-paleographical, seismographic factors and the tectonic-geodynamic peculiarities of the region. Characteristics were subjected to biolithofacial space-time zonality, cycles of the Cenozoic complexes, in particular to Paleogene (Eocene, Maikop), Neogene and Quaternary complexes. The detailed stratification of the Cenozoic sediments of the Subotin structure and Miocene-Quaternary structure of theEastBlack SeaBasinbased on the complex of methods is presented. Geodynamics and sedimentological stages of the Cenozoic evolution have been described. The existence of the biolithofacial and sedimentological analogy was proved together with similarities in the development of the Carpathian, Karkinit, Sorokin, Indolo-Cuban boundary deeps. The similarity and cycles of the terrigenous complexes of the schists, carbonate-terrigenous facies of the Cenozoic different stratigraphic levels (Menilite geosyncline deposits of the Precarpathian deep, Planorbel, Kerleut and Tarchan thin-layered black-colored facies of the external shelf and continental slope of the Western and Eastern Black Sea basin) are essential features of the hydrocarbon perspectives on the Prekerch shelf and continental slope of the Western and Eastern Black Sea basin.

Significance of a Multiple Biomarkers Strategy Including Endothelial Dysfunction to Improve Risk Stratification for Cardiovascular Events in Patients at High Risk for Coronary Heart Disease

We investigated whether a multiple biomarkers strategy that includes plasma levels of endothelium-derived microparticles (EMP), reflecting endothelial dysfunction, can improve prediction of future cardiovascular events in patients at high risk for coronary heart disease (CHD). Detailed risk stratification using multiple biomarkers can provide clinical benefits in high-risk patients. Endothelial dysfunction has been described as a predictor of cardiovascular complications. We measured 3 biomarkers in 488 consecutive patients with various CHD risks: B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), and EMP. We followed 387 stable patients at high risk for CHD and examined future cardiovascular events. During a mean follow-up of 36 months, 55 patients developed cardiovascular events. Multivariate Cox proportional hazards analysis adjusted for established risk factors identified age, BNP, hsCRP, and EMP as significant and independent predictors of future cardiovascular events (age: hazard ratio [HR]: 1.042, 95% confidence interval [CI]: 1.007 to 1.080, p = 0.02; BNP: HR: 1.242, 95% CI: 1.004 to 1.536, p = 0.046; hsCRP: HR: 1.468, 95% CI: 1.150 to 1.875, p = 0.002; EMP: HR: 1.345, 95% CI: 1.094 to 1.652, p = 0.005). The C statistics for cardiovascular events increased when each biomarker or combinations of biomarkers were added to the Framingham risk model (C statistics: Framingham risk model alone 0.636, Framingham risk + BNP 0.695, Framingham risk + hsCRP 0.696, Framingham risk + EMP 0.682, and Framingham risk + BNP + hsCRP + EMP 0.763). The assessment of endothelial dysfunction by plasma levels of EMP can independently predict future cardiovascular events in patients at high risk for CHD. A multiple biomarkers strategy that includes endothelial dysfunction assessed by EMP can identify patients vulnerable to cardiovascular disease. (University Hospital Medical Information Network number: UMIN000000876).

Estimating Incidence of HIV Infection in Uganda

To the Editor: The study by Dr Mermin and colleagues provided data on recent HIV infection in Uganda by using theBED capture enzyme immunosorbent assay as a proxy for HIV incidence. It demonstrated that the weighted incidence of HIV infection in the region of north central Uganda was 4.7 per 100 person-years more than double any other part of the country. Although only given brief mention in the discussion this finding is extremely interesting and worth further attention because as the authors note north central Uganda (defined as the districts of Gulu Kitgum and Pader) has experienced war since 1986 unlike other parts of the country. The relationship between war and HIV transmission is disputed because certain conflict settings have appeared protective 2 likely through isolation of the population whereas in other settings war appears to increase risk of HIV infection. The lack of clarity regarding HIV transmission in conflict settings has been particularly true in north central Uganda. Data from the study by Mermin et al were collected between August 2004 and January 2005 a period of time in which active conflict still affected north central Uganda. Unfortunately the articles results do not present a more detailed stratification of the particular sampling locations of the household surveys (eg whether residing in an internally displaced peoples camp district of sampling sex education wealth index by location). It is not clear if data were collected evenly across north central Uganda or if the authors were limited in their data collection by war activity. Provision of more detailed information about the sampling locations for north central Uganda if available would offer a more useful interpretation of the geographic differences in the patterns of incident HIV infection observed in the study and further insight about the relationship between war and HIV transmission. (full text)

Hypertension and Risk Stratification

Japan has become a super-aged society (the percentage of the elderly ≥20% of the population), and medicine is shifting to “preventive medicine” for the prevention of severe cardiovascular diseases to use limited medical resources effectively. In particular, the specific health checkup for Japanese aged 40– 74 years, which was initiated in April 2008, is considered to be a large-scale intervention study aiming at preventing cardiovascular diseases and has attracted global attention. The specific health checkup focuses on the early detection of metabolic syndrome. The diagnostic criteria of this syndrome (1) were proposed not only by introducing visceral obesity as a new concept, but also by paying attention to the clustering of cardiovascular risks before the development of disease. The blood pressure criterion for metabolic syndrome is equal to or more than 130/85 mmHg, which corresponds to a highnormal value according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004) (2). The cluster of blood pressure higher than this criterion, visceral obesity, and lipid metabolism abnormality synergistically increases the risk of cardiovascular disease. As shown in Fig. 1, the Seventh Report of the Joint National Committee on Prevention (JNC-7) (3) in the U.S. abolished risk stratification and simplified the criteria so that treatment principles could be determined based on blood pressure alone. In contrast, the European Society of Hypertension (ESH)/the European Society of Cardiology (ESC) Guidelines for the Management of Arterial Hypertension (4) classified the non-hypertensive group into two (normal, high-normal) groups, and proposed treatment based on detailed risk stratification. In the guidelines in Japan or China (5), the risk stratification in the hypertensive group is similar to that in the ESH/ESC guidelines, but risk assessment in the non-hypertensive group is described only in the text. The proposal of a risk stratification system for the development of strokes or transient ischemic attack (TIA) by Asayama et al. in this issue of Hypertension Research (6) showed a classification of blood pressure into 6 grades from optimal to Stage 3, that of risk factors into 3 strata, and that of severity assessment into 4 grades (no–high). The unique point in their proposal was the classification of non-hypertensive group into 3 grades. The risk stratification in their paper was similar to that of the ESH/ ESC guidelines, but differed in that a very high risk group was not established because clinical intervention methods are similar between high and very high risk groups, and an optimal blood pressure group was established. In Fig. 1, for the comparison of evaluation based on casual blood pressures as in other guidelines, we presented the table in Fig. 2C of Asayama et al. (6), showing relatively well-separated casual blood pressures after minor adjustments based on absolute risks. The unique point of Asayama et al.’s proposal that differs from other guidelines is that the Stage 2 group with 1–2 risk factors (* in the figure) was classified as high severity. If classification based on home blood pressures effective for predicting prognosis as a characteristic of this paper is adopted, the risk stratification shown in Fig. 2B of Asayama et al. (6) is excellent. In this stratification, this group (* in the figure) is classified as moderate severity, as is observed in other guidelines. The other important findings in Asayama et al. (6) were an increased stroke risk even in the high-normal and normal blood pressure groups compared with the optimal blood pressure group and a definite increase in the relative risk of the presence of multiple risk factors even in the same blood pressure group. The only difference between Fig. 2A and B of

Risk stratification of individual coronary lesions using local endothelial shear stress: a new paradigm for managing coronary artery disease

The purpose of this review is to summarize the role of endothelial shear stress in the natural history of coronary atherosclerosis, and to propose an individualized risk-stratification strategy of atherosclerotic lesions based on the in-vivo characterization of local endothelial shear stress and wall morphology. Low endothelial shear stress promotes the development of early fibroatheromas, which subsequently follow an individualized natural history of progression. This individual natural history is critically dependent on the magnitude of low endothelial shear stress, which subsequently regulates the severity of inflammation within the wall and ultimately the vascular remodeling response. Very low endothelial shear stress enhances plaque inflammation, leading to excessive expansive remodeling. Excessive expansive remodeling leads to perpetuation, or even exacerbation, of the local low endothelial shear stress environment, thereby setting up a self-perpetuating vicious cycle among low local endothelial shear stress, inflammation, and excessive expansive remodeling, which transforms an early fibroatheroma to a high-risk plaque. In-vivo assessment of the local endothelial shear stress environment, severity of inflammation and vascular remodeling response, all responsible for individual plaque behavior and natural history, in combination with systemic biomarkers of vulnerability, may allow for detailed risk stratification of individual early atherosclerotic plaques, thereby guiding both systemic and local, lesion-specific therapeutic strategies.

A comprehensive approach to the diagnosis of MDS after triage by morphology towards cytogenetics and other techniques

The myelodysplastic syndromes (MDS) are heterogeneous disorders ranging from rather stable conditions such as 5q- to advanced stages close to acute leukaemia. The variability of the clinical course, of cytomorphological phenotypes, and of genetic aberrations outlines MDS classification as a major challenge. However, therapeutic options became more differentiated e.g. due to lenalidomide or reduced intensity conditioning in allogeneic transplantation and require a more detailed risk stratification. Established classification systems as the FAB were mainly based on cytomorphological criteria implicating some problems e.g. of interobserver variability. The WHO proposal of 2001 which subdivided MDS into 10 subtypes focused as well mainly on cytomorphology, but took in addition cytogenetics with respect to the 5q- syndrome into account. Another important classification system is represented by the International Prognostic Scoring System (IPSS) of 1997 which offers an accurate biologically based classification and prognostication. Multiparameter flow cytometry (MFC) and molecular techniques may contribute increasingly by detection of aberrant antigen expression patterns and by the finding that some mutations e.g. the FLT3-LM/ITD or NRAS are associated with leukaemic transformation. In conclusion, a multimodal approach including cytomorphology, cytogenetics, fluorescence in situ hybridization (FISH), PCR, and MFC is possible to achieve a comprehensive characterization of MDS. Diagnostic algorithms providing a hierarchy of methods to guarantee an efficient work-flow, to provide all parameters necessary for classification and for minimal-residual-disease (MRD) strategies, and to guide new treatment strategies are needed.

Preoperative Risk Stratification With Myocardial Perfusion Imaging in Intermediate and Low-Risk Non-Cardiac Surgery

Perioperative cardiac risk in high risk surgery is often stratified with myocardial perfusion single-photon emission computed tomography (SPECT). However, little and no data are available about intermediate and low-risk surgery, respectively. A total of 1,220 consecutive patients underwent electrocardiography-gated dipyridamole stress SPECT to evaluate myocardial perfusion and cardiac function before intermediate or low risk non-cardiac surgery. Variables predictive of perioperative cardiac events were determined and the usefulness of combining pretest information and the incremental prognostic value of SPECT was estimated. The frequency of all cardiac events depended on clinical risk factors and type of surgical procedures. After sorting the patients with clinical risk factors and surgical risk, assessment of myocardial perfusion or cardiac function yielded significant risk stratification in intermediate, but not in low-risk surgery. Adding functional data to perfusion variables offered an incremental prognostic value for patients with an intermediate clinical risk and scheduled intermediate risk surgery. Integrating information about clinical risk factors, type of surgery, myocardial perfusion and cardiac function allows detailed preoperative risk stratification. Preoperative SPECT provides an incremental prognostic value in intermediate, but not in low-risk surgery.

Wilms-Tumor

Wilms tumor is the most frequent malignancy of the urogenital tract in children. Its treatment gives an excellent example of the efficacy of multimodal therapeutic strategies in oncological diseases. In particular, the performance of international, randomized multicenter studies has led to a continuous increase in disease-free survival among the affected patients in recent decades, thanks to increasingly detailed stratification of individual elements of the therapy. The pediatric urologist has a definite place in interdisciplinary teams treating Wilms tumor, being needed for the operative component of the treatment. For further improvement of the prognosis in this disease and to reduce the comorbidity caused by the treatment, the major challenge for pediatric urologists in coming years will be to make the surgery less traumatic and thus also to reduce the incidence and severity of perioperative complications.

Clinical outcome estimates based on treatment target limits of laboratory tests: proposal for a plot visualizing effects and differences of medical target setting exemplified by glycemic control in diabetes

In modern medicine many laboratory measurements are used as a surrogate for clinical outcome. There is therefore a need for models to quantify this approach. The target plot presented here is based on the difference plot. The difference between two measurements is plotted against the initial measurement, of which the first measurement is the index measurement (Mindex) and the second the outcome measurement (Moutcome). A vertical line separates normal vs. increased Mindex concentrations according to a selected target concentration, and a horizontal line describes the situation of no change. A target line (Mtarget) with a slope equal to -1 and indicating the selected target concentration is drawn through the crossing point. The six outcome areas thus refer to the combined effect of Mindex and Moutcome. A target plot taking the biological and analytical variation in consideration is considered. MATERIALS AND MODEL: The target plot addresses sources of outcome categories, and calculates the percentage in each of these categories according to a defined target value. Hemoglobin A1c (HbA1c) in diabetes in patients from Vejle County, Denmark was taken as an example. Different strategies for target setting for HbA1c were investigated: the Danish Diabetes Association (DDA) target of 5.84% HbA1c, the target from the American Diabetes Association (ADA) of 7.0% HbA1c, and 6.62% HbA1c, which is the 99.9 centile of the Danish national reference interval. All three strategies can be validated from the target plot for differences in surrogate clinical outcome in spite of identical patient material. Use of the ADA target (the highest nominal value) reveals the lowest percentage of index values above the target, and of those the highest percentage outcome values of the surrogate measure reached the target. The target plot allows detailed stratification of outcome based on surrogate parameters and assessment of risk of disease based on the selected target. The need to standardize outcome targets in diabetes to allow comparison of quality of treatment is obvious.

A detailed receiver function image of the sedimentary structure in the Bohai Bay Basin

If the site at which receiver functions are constructed is filled by sediments, then the waveforms from these receiver functions are dominantly controlled by the sedimentary structures within the first few seconds after the direct P arrival. Based on this observation, waveform data collected at 44 temporary seismic stations have been used to image the sedimentary structure of the Bohai Bay Basin, a major continental petroliferous basin in Eastern China. An adapted hybrid global waveform inversion method was applied to the receiver functions to extract structural information beneath each of the stations. The derived S-velocity structure provides for the first time, a basin-scale seismic image of detailed sedimentary stratification. The sedimentary cover of the basin is about 2–12 km thick, consisting of Cenozoic, Mesozoic, and Paleozoic strata from top to bottom. The structural features presented in the S-velocity image coincide quite well with the depression–uplift type of tectonic system in the Bohai Bay Basin. The reconstructed morphology of the sedimentary layers provides seismological evidence for the two-stage evolution of the intracontinental basin that were caused by an intensive tectonic regime transition in late Mesozoic immediately following the lithospheric reforming of the Eastern China continent.

Impact of the Revised Criteria for Acute Myocardial Infarction Using Cardiac Troponins in a Japanese Population With Acute Coronary Syndromes

The clinical implications of applying the new criteria of acute myocardial infarction (AMI) with cardiac troponins in terms of their diagnostic and prognostic impact in patients with suspected acute coronary syndromes (ACS) have not been well evaluated. The study group comprised 973 consecutive patients who were diagnosed as having ACS with or without ST elevation (STE). They were divided into 3 groups: unstable angina (UA) group (n=195) representing patients with no significant elevations of creatine kinase (CK) and troponin T (TnT); TnT-myocardial infarction (MI) group (n=170) with TnT elevation and no CK elevation (additionally detected AMI by the new criteria); CK-MI group (n=608) with significant elevation of CK (AMI by the old criteria). In the TnT-MI group, 140 (76%) patients had non-STE ACS. In-hospital mortality rates for STE ACS were 0%, 2.5% and 9.7% in the UA, TnT-MI and CK-MI groups, respectively. The corresponding values for non-STE ACS were 1.8%, 4.6%, and 16.5%, respectively (p<0.0001), suggesting a pivotal role of TnT. In multiple logistic regression analysis, significant CK elevation was selected as an independent predictor of in-hospital death in concurrence with age > or =75 years, prior MI, shock and low left ventricular ejection fraction in non-STE ACS. The new criteria result in a substantial increase in the diagnosis of AMI from non-STE ACS in particular. They assist greatly in detailed risk stratification of ACS patients, notably in cooperation with the old CK criteria.