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A 40-year-old woman in whom the mitral valve had to be replaced with a prosthetic one (St. Jude's) had to be reoperated 8 months later because of endocarditis on the second prosthetic valve (Carbo-Medics). Four months later her general condition deteriorated progressively with cough and dyspnoea, requiring hospitalization. Auscultation revealed moist rales over both lung bases; heart sounds were distant but otherwise normal. The "international normalized ratio" was 2.5, while erythrocyte sedimentation rate, white cell count and C-reactive protein were normal. Transthoracic echocardiography demonstrated a hardly moving mitral valve prosthesis with an opening area of 0.8 cm. Subsequently this decreased further and measurement of the anticardiolipin antibody titre revealed an IgG fraction of 37.9 U/ml (normal up to 12 U/ml). Within 48 hours thrombolysis with streptokinase had increased the valve's opening area to 1.8 cm. The patient made an uneventful recovery under strict anticoagulation. This case illustrates that the anticardiolipin syndrome can be a cause of an otherwise unclear genesis.

From June 1988 to September 1989, a prospective survey comprising a total of 1183 patients in a university hospital was carried out to ascertain the additional length of stay in intensive care units because of nosocomial pneumonia associated with artificial ventilation (418 patients, 296 men, 122 women, mean age 48.8 +/- 21 years, ventilated for more than 24 h) or by postoperative wound infections (765 patients, 501 men, 264 women, mean age 60 +/- 11 years, after operations on the large bowel, heart or biliary tract). Each patient with a nosocomial infection was matched against a variable number of control patients (for cases of pneumonia a maximum of 6, for wound infections a maximum of 10) without nosocomial infection. Pneumonia developed in 100 (23.9%) of artificially ventilated patients, and 46 of these patients together with 101 controls were entered into the matching procedure. 24 patients with pneumonia had to be excluded from analysis because no controls could be found for them, and also 30 patients who died while in the intensive care unit. 49 (6.4%) of the surgical patients contracted postoperative wound infections. 43 of them, together with 210 controls, were entered into the matching procedure. Among patients with pneumonia the average additional duration of stay was 11.5 days, and among patients with post-operative wound infections it was 13.9 days. The results confirm that nosocomial infections contribute substantially to prolongation of hospital stay and hence to the costs.

OBJECTIVE To determine the prevalence rate of nosocomial infections in different parts of Germany. PATIENTS AND METHODS The study involved 14,966 patients (45.9% medical, 35.9% surgical, 14.7% obstetrical/gynaecological and 3.5% intensive care) in 72 randomly chosen German hospitals (59 in the old [i.e. previously West German] and 13 in the new [i.e. East German] Federal Lands). Using the CDC criteria for the diagnosis of nosocomial infections specially trained doctors determined whether the infection was in fact nosocomial. RESULTS There was a 3.5% prevalence rate of nosocomial infections in the entire population (95% confidence interval 3.1-3.9%). In view of the chosen methods and the in part incorrect indication of microbiological diagnosis in the included hospital, this rate of nosocomial infection is likely to be a minimum number. The prevalence rate for the most important nosocomial infections was lower in the new Lands of Federal Germany than the older ones (total prevalence of 2.7 vs 3.6%). The difference is mainly due to the less frequent employment of various devices (e.g. peripheral vascular catheters), rather than different hygienic standards in their use. CONCLUSION The lower prevalence rate of nosocomial infections in the new Lands, because fewer devices are employed, underlines the need constantly to test the indications for their use.

OBJECTIVE To find out whether in patients with dilated cardiomyopathy (DCM) there is a correlation between subjective reduction in physical capacity and the transmitral Doppler profile as a measure of left ventricular (LV) filling. PATIENTS AND METHODS 30 consecutive patients (24 men, six women; average age 55 +/- 2 years) with chronic primary DCM were examined by Doppler echocardiography to determine possible differences in LV filling pattern, in correlation with subjective impairment of physical capacity graded according to the New York Heart Association (NYHA) classification. RESULTS Mean LV ejection fraction was 34 +/- 1%. All patients were in sinus rhythm. Eight patients, in NYHA class I had nearly normal LV filling (E wave 79 m/s, A wave 0.76 m/s); 11 patients in class II had impaired relaxation (E wave 0.77 m/s. A wave 0.82 m/s) and 11 in class III/V had a restricted filling pattern (E wave 0.98 m/s. A wave 0.57 m/s). There was a significant difference between class II and class III/IV patients with regard to E wave deceleration time (0.15 and 0.11 s, respectively; P < 0.05), as well as between class I and class III/IV patients (0.18 and 0.11 s, respectively; P < 0.05). The A wave deceleration time was clearly shorter in class III/IV than class II (0.08 s and 0.11 s; P < 0.05) and class I patients (0.08 s and 0.10 s; P < 0.05). CONCLUSIONS The extent of LV diastolic dysfunction correlated with subjective physical capacity. The more the LV filling pattern had changed from normal towards restricted, the greater the patient's symptoms.

When analyzing clinical studies where the survival time of the patients or, more generally, the time to a certain event in the patients' clinical course is the main endpoint, several problems have to be taken into account. Most of these problems, e.g. incomplete data and follow-up of the patients, arise specifically from the factor time which plays the central role in these studies. How such problems should be incorporated into a statistical analysis and into a sensible interpretation of the results is demonstrated by means of the estimation of survival rates with the Kaplan-Meier-method.

This report describes the infrequent case of the occurrence of eight aneurysms of the facial artery in association with hereditary hemorrhagic teleangiectasia (HHT, Rendu–Osler–Weber disease, ROW). The aneurysms and the teleangiectatic nodules of the tongue were successfully treated by endovascular embolization in a combined technique using particles (polyvinyl alcohol, PVA) and fibred platinum coils. Endothelial cell degeneration, fragmentation of the elastic lamina and loss of muscularis in the vessel wall may be causal and give rise to multiple aneurysms of the intracranial and extracranial circulation in hereditary hemorrhagic teleangiectasias. This case and a review of the literature are presented because in the literature neither combined occurrence of ROW with a single aneurysm nor with multiple aneurysms of extracranial vessels are described.

Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN), are rare but life-threatening cutaneous adverse reactions to drugs, especially to allopurinol, carbamazepine, lamotrigine, phenobarbital, phenytoine, sulfamethoxazole, oxicam and nevirapine. Recently, a strong association between carbamazepine and allopurinol induced SJS or TEN has been described with respectively, HLA-B*1502 and HLA-B*5801 in a Han Chinese population from Taiwan and other Asian countries.The objective is to further investigate the relationship between SJS/TEN and HLA-B in a large number of patients in a European population.HLA-B genotyping was performed on 150 patients included in a European study (RegiSCAR) of SJS and TEN. We focused on patients related to 'high-risk' drugs including: 31 cases related to allopurinol, 28 to sulfamethoxazole, 19 to lamotrigine and 14 to oxicam.Sixty-one percent of 31 allopurinol-induced SJS/TEN patients carried the HLA-B*5801 allele and the figure was 55% for 27 patients of European ancestry [odds ratio=80 (34-187)], (P10(-6)) as previously observed in Han Chinese. For other drugs, two rare alleles showed a weaker association with SJS/TEN in a limited number of patients: B*38 for sulfamethoxazole or lamotrigine-related patients, and B*73 for oxicam.At variance with prior results in Asia, this study shows that even when HLA-B alleles behave as strong risk factors, as for allopurinol, they are neither sufficient nor necessary to explain the disease. Further investigations are necessary to delineate the exact role of the HLA region in SJS/TEN, and to look for other associations in other regions of the genome.

The signs and values of the two-photon couplings $F_{M\gamma\gamma}$ of mesons $(M)$ and their couplings $g_{MNN}$ to the nucleon as entering into the $t$-channel parts of the difference of the electromagnetic polarizabilities $(\alpha-\beta)$ and the backward angle spin polarizabilities $\gamma_\pi$ are determined. The excellent agreement achieved with the experimental polarizabilities of the proton makes it possible to make reliable predictions for the neutron. The results obtained are $\alpha_n=13.4\pm 1.0$, $\beta_n=1.8\mp 1.0$ ($10^{-4}$ fm$^3$), and $\gamma^{(n)}_\pi=57.6\pm 1.8$ ($10^{-4}$ fm$^4$). New empirical information on the flavor wave functions of the $f_0(980)$ and the $a_0(980)$ meson is obtained.

Objective Problems arising with the estimation of sensitivity and specificity when two imperfect diagnostic tests are applied are widely discussed. Effects on the estimation of prevalence may be of importance as well. Different methods of dealing with two or more imperfect tests and unknown reference standard are contrasted with regard to their implications on prevalence estimation: discrepant analysis, composite reference standards, and latent class models. Study Design and Setting Prospective epidemiological multicenter study to determine the prevalence of respiratory syncytial virus in children with lower respiratory tract infections. A subsample of 1,003 patients from a hospital population and from a practice population is considered. Virus isolation, polymerase chain reaction, and rapid antigen test had been applied. Results Prevalence estimates obtained under various assumptions ranged from 0.263 to 0.386 in the hospital population and from 0.214 to 0.277 in the practice population. Conclusion Estimation procedures involving a resolver test applied to some but not all cells are at risk of introducing a serious bias in prevalence estimation as well as in the estimation of test accuracy parameters. Estimation via latent class modeling may be more useful, but care should be taken regarding the underlying assumptions.

OBJECTIVE To determine the long-term oncological outcome of patients with primary transitional cell carcinoma (TCC) of the distal ureter electively treated with either kidney-sparing surgery (KSS) or radical nephroureterectomy (RNU) in a retrospective, non-randomized, single-centre study. PATIENTS AND METHODS Of 43 consecutive patients with a primary solitary distal ureter TCC, 19 had KSS, consisting of distal ureter resection with bladder cuff excision and ureter reimplantation, and 24 had RNU with bladder cuff excision. RESULTS The median (range) age at surgery was 69 (31–86) years for the KSS group and 73 (59–87) years for the RNU group, patients in the latter having worse hydronephrotic kidneys. The median (range) follow-up was 58 (3–260) months. A recurrent bladder tumour was diagnosed after a median of 15 months in five of the 19 patients treated by KSS and after a median of 5.5 months in eight of the 24 treated by RNU. Five of the 19 patients treated by KSS and six of the 24 treated by RNU died from metastatic disease despite chemotherapy. Recurrence-free, cancer-specific and overall survival were comparable in the two groups. In two patients (11%) treated by KSS an ipsilateral upper urinary tract TCC recurred after 42 and 105 months, respectively. CONCLUSION Treatment by distal ureteric resection is feasible in patients with primary TCC of the distal ureter. The long-term oncological outcome seems to be comparable with that of patients treated by RNU. Furthermore, kidney preservation is advantageous if adjuvant or salvage chemotherapy is required.

Estimates of the prediction error play an important role in the development of statistical methods and models, and in their applications. We adapt the resampling tools of Efron and Tibshirani (1997, Journal of the American Statistical Association92, 548-560) to survival analysis with right-censored event times. We find that flexible rules, like artificial neural nets, classification and regression trees, or regression splines can be assessed, and compared to less flexible rules in the same data where they are developed. The methods are illustrated with data from a breast cancer trial.

A noninvasive treatment of an occipital dural AV fistula by external compression of the carotid artery and jugular vein is documented. The late successful occlusion of the malformation after almost 19 months and a total of 13,216 single manual compressions shows that fistula occlusion can be achieved late and is dependent on careful performance of the maneuver.

Data analysis was performed in a multicenter study to evaluate magnetic resonance (MR) imaging for classification of brain tumors, prognosis, and prediction of tumor histological diagnosis.The clinical, MR imaging, and histological findings obtained in 142 pediatric cases of brainstem disease were assessed in a multicenter study performed as a blinded review. Clinical data were available in 142 cases, histopathological findings in 126, and MR images in 131. The subgroup of cases involving brainstem gliomas (78 cases) was analyzed separately. Images that met criteria for evaluation were reviewed in random order by three experienced observers who were initially blinded to clinical data as well as histopathological diagnoses. Subsequently, the images were randomized again and provided to the observers for review together with the clinical symptoms of the specific patients. The three observers were able to correctly identify lesions as tumors or nontumorous disease on MR images in 99, 96, and 95% of cases, resulting in an overall sensitivity of 0.94, a specificity of 0.43, a positive predictive value of 0.96, and a negative predictive value of 0.45. Awareness of clinical symptoms did not change the results.Based on 14 imaging criteria together with the patient's clinical history and symptoms, laboratory data (results of cerebrospinal fluid analysis as well as infectious and immunological parameters), and imaging follow up, a diagnosis of brainstem tumor, as opposed to demyelination, encephalitis, or granuloma, could generally be made. Given these findings, there is only rarely a need for biopsy, and in those patients in whom it is considered, the potential costs and benefits must be carefully assessed on a case-by-case basis.

The purpose of this study was to analyse risk factors for blood stream infection (BSI) and pneumonia in neutropenic patients who have undergone peripheral blood stem-cell transplantation (PBSCT). Data were taken from the ONKO-KISS multicenter surveillance project. Infections were identified using CDC definitions (laboratory-confirmed BSI) and modified criteria for pneumonia in neutropenic patients. The multivariate analysis was performed using the Fine-Gray regression model for the cumulative incidences of the competing events 'infection', 'death' and 'end of neutropenia'. The risk factors investigated were: sex, age, underlying disease and type of transplant. From January 2000 to June 2004, a total of 1699 patients in 20 hospitals were investigated. In the multivariate analysis, male patients had a significantly higher risk of acquiring BSI than female patients (P=0.002). The risk of acquiring BSI is highest in patients with advanced acute myeloid leukaemia (AML). In the univariate and multivariate analysis, unrelated donor allogeneic transplantation constituted a risk factor for pneumonia (P=0.012). ONKO-KISS provides reference data on the incidence of pneumonia and BSI. The increased risk for BSI in males and patients with advanced AML, and the increased risk for pneumonia in unrelated donor allogeneic PBSCT patients should be targeted to prevent infections in these higher risk groups.

Summary Objectives: The log-binomial model is recommended for calculating the prevalence ratio in cross-sectional studies with binary outcomes. However, convergence problems may occur as this model is numerically unstable. If this happens, the Poisson model should be used, but the Poisson model variance needsto be adjusted. Here, we compare different adjustments. Methods: Using simulation we evaluated the performance of Poisson models with i) a robust variance, ii) the scale parameter adjusted by Pearson’s chi-square, and iii) the scale parameter adjusted by the deviance. These models were compared with the log-binomial model with respectto hypothesis testing. Confounding and effect modification are considered. Results: All adjustment models improved the variance estimation. The Poisson model with a robust variance performed best. When the log-binomial model is numerically stable as well as unstable, this model yields reasonable power and type I error values. But the Poisson model with the scale parameter adjusted by Pearson’s chi-square also showed good results. Conclusions: When estimating prevalence ratios, if the log-binomial fails to converge, we recommend the Poisson modelwith a robust estimate of variance.

After peripheral blood stem-cell transplantation, patients treated for severe haematologic diseases enter a critical phase (neutropenia). Analysis of bloodstream infection during neutropenia has to account for competing risks. Separate Cox analyses of all cause-specific hazards are the standard technique of choice, but are hard to interpret when the overall effects of covariates on the cumulative incidence function (CIF) are of interest. Proportional subdistribution hazards modelling of the subdistribution of the CIF is establishing itself as an interpretation-friendly alternative. We apply both methods and discuss their relative merits.

Background High-throughput technology allows for genome-wide measurements at different molecular levels for the same patient, e.g. single nucleotide polymorphisms (SNPs) and gene expression. Correspondingly, it might be beneficial to also integrate complementary information from different molecular levels when building multivariable risk prediction models for a clinical endpoint, such as treatment response or survival. Unfortunately, such a high-dimensional modeling task will often be complicated by a limited overlap of molecular measurements at different levels between patients, i.e. measurements from all molecular levels are available only for a smaller proportion of patients. Results We propose a sequential strategy for building clinical risk prediction models that integrate genome-wide measurements from two molecular levels in a complementary way. To deal with partial overlap, we develop an imputation approach that allows us to use all available data. This approach is investigated in two acute myeloid leukemia applications combining gene expression with either SNP or DNA methylation data. After obtaining a sparse risk prediction signature e.g. from SNP data, an automatically selected set of prognostic SNPs, by componentwise likelihood-based boosting, imputation is performed for the corresponding linear predictor by a linking model that incorporates e.g. gene expression measurements. The imputed linear predictor is then used for adjustment when building a prognostic signature from the gene expression data. For evaluation, we consider stability, as quantified by inclusion frequencies across resampling data sets. Despite an extremely small overlap in the application example with gene expression and SNPs, several genes are seen to be more stably identified when taking the (imputed) linear predictor from the SNP data into account. In the application with gene expression and DNA methylation, prediction performance with respect to survival also indicates that the proposed approach might work well. Conclusions We consider imputation of linear predictor values to be a feasible and sensible approach for dealing with partial overlap in complementary integrative analysis of molecular measurements at different levels. More generally, these results indicate that a complementary strategy for integrating different molecular levels can result in more stable risk prediction signatures, potentially providing a more reliable insight into the underlying biology. Electronic supplementary material The online version of this article (doi:10.1186/s12859-016-1183-6) contains supplementary material, which is available to authorized users.

In clinical and epidemiological studies information on the primary outcome of interest, that is, the disease status, is usually collected at a limited number of follow-up visits. The disease status can often only be retrieved retrospectively in individuals who are alive at follow-up, but will be missing for those who died before. Right-censoring the death cases at the last visit (ad-hoc analysis) yields biased hazard ratio estimates of a potential risk factor, and the bias can be substantial and occur in either direction. In this work, we investigate three different approaches that use the same likelihood contributions derived from an illness-death multistate model in order to more adequately estimate the hazard ratio by including the death cases into the analysis: a parametric approach, a penalized likelihood approach, and an imputation-based approach. We investigate to which extent these approaches allow for an unbiased regression analysis by evaluating their performance in simulation studies and on a real data example. In doing so, we use the full cohort with complete illness-death data as reference and artificially induce missing information due to death by setting discrete follow-up visits. Compared to an ad-hoc analysis, all considered approaches provide less biased or even unbiased results, depending on the situation studied. In the real data example, the parametric approach is seen to be too restrictive, whereas the imputation-based approach could almost reconstruct the original event history information.

The Higgs boson, recently discovered with a mass of 125.09$\pm$0.24 GeV is known to mediate the masses of elementary particles, but only 2% of the mass of the nucleon. Extending a previous investigation [1] and including the strange-quark sector, hadron masses are derived from the quark condensate of the QCD vacuum and from the effects of the Higgs boson. These calculations include the $\pi$ meson, the nucleon and the scalar mesons $\sigma(600)$, $\kappa(800)$, $a_0(980)$ $f_0(980)$ and $f_0(1370)$. The predicted second $\sigma$ meson $\sigma'(1344)=|s\bar{s}\rangle$, is investigated and identified with the $f_0(1370)$ meson. An outlook is given on the hyperons $\Lambda$, $\Sigma^{0,\pm}$ and $\Xi^{0,-}$., Comment: 18 pages, 2 figures

Guidelines on hypertension management recommend adjusting therapeutic efforts in accordance with global cardiovascular risk (CVR) rather than by blood pressure levels alone. However, this paradigm change has not yet arrived in German General Practice. We have evaluated the effect of an educational outreach visit with general practitioners (GPs), encouraging them to consider CVR in treatment decisions for patients with hypertension. Prospective cluster-randomised trial comprising 3443 patients with known hypertension treated by 87 GPs. Practices were randomly assigned to complex (A) or simple (B) intervention. Both groups received a guideline by mail; group A also received complex peer intervention promoting the concept of global CVR. Clinical data were collected at baseline and 6-9 months after intervention. Main outcome was improvement of calculated CVR in the predefined subpopulation of patients with a high CVR (10-year mortality ≥5%), but no manifest cardiovascular disease. Adjusted for baseline the follow-up CVR were 13.1% (95% CI 12.6%-13.6%) (A) and 12.6% (95% CI 12.2%-13.1%) (B) with a group difference (A vs. B) of 0.5% (-0.2%-1.1%), p = 0.179. The group difference was -0.05% in patients of GPs familiar with global CVR and 1.1% in patients of GPs not familiar with with global CVR. However, this effect modification was not significant (p = 0.165). Pooled over groups, the absolute CVR reduction from baseline was 1.0%, p

Obstructive thrombosis of bioprosthetic valves is considered rare but may have dramatic consequences for the individual patient including repeat valve replacement, thrombolysis, or long-term anticoagulation. Whether the risk of obstructive thrombosis is dependent on the type of bioprosthesis (porcine versus bovine pericardial) is uncertain.Between 2007 and 2012 a total of 1751 patients received a single stented bioprosthesis in the aortic valve position, 749 (43%) were porcine and 1002 (57%) bovine. During a mean follow-up of 3.4±1.9years, obstructive thrombosis (identified by an increase in mean pressure gradient≥20mm Hg or a decrease in velocity ratio≥0.05 and confirmed by either ECG-gated computer tomography, a return to baseline of stenosis parameters under treatment with a vitamin K antagonist, or histology in case of reoperation) was diagnosed in 17 patients with a porcine (2.3%) and none with a bovine valve (p0.001). The cumulative probability of developing an obstructive thrombosis was significantly higher in patients with a porcine valve (p0.001 log-rank test). Adjusting for differences in baseline variables and stratification by the estimated propensity score showed that strata with a high probability of receiving a bovine valve had the highest number of obstructive thrombosis in porcine valves. These findings were further confirmed in a Poisson model and a competing risk model including all-cause mortality. Treatment of obstructive thrombosis with a vitamin K antagonist was safe and effective in 15/17 patients.The porcine valve type is an independent predictor of obstructive thrombosis in bioprostheses in the aortic position.

Conditional survival (CS) is defined as the probability of surviving further t years, given that a patient has already survived s years after the diagnosis of a chronic disease. It is the simplest form of a dynamic prediction in which other events in the course of the disease or biomarker values measured up to time s can be incorporated. CS has attracted attention in recent years either in an absolute or relative form where the latter is based on a comparison with an age-adjusted normal population being highly relevant from a public health perspective. In its absolute form, CS constitutes the quantity of major interest in a clinical context. Given a clinical cohort of patients with a particular type of cancer, absolute CS can be estimated by conditional Kaplan–Meier estimates in strata defined, for example, by age and disease stage or by a conditional version of the Cox and other regression models for time-to-event data. CS can be displayed as a function of the prediction time s in parametric as well as nonparametric fashion. We illustrate the use of absolute CS in a large clinical cohort of patients with multiple myeloma. For investigating CS, it is necessary to ensure almost complete long-term follow-up of the patients enrolled in the clinical cohort and to consider potential age–stage migration as well as changing treatment modalities over time. CS provides valuable and relevant information on how prognosis develops over time. It also serves as a starting point for identifying factors related to long-term survival. Clin Cancer Res; 21(7); 1530–6. ©2015 AACR.

INTRODUCTION AND OBJECTIVES Data on the oncological outcomes in patients undergoing robot-assisted radical cystectomy (RARC) is limited. Globally extracorporeal urinary diversion following RARC remains the most common approach despite potential advantages of a completely minimally invasive approach. We report oncological outcomes and associated prognostic factors from a multi-institutional European database focusing on the centres performing totally intracorporeal RARC. METHODS In the ERUS scientific working group database, 467 patients underwent totally intracorporeal RARC for bladder cancer between 2003 and 2014. Clinical and pathological data at the time of the latest follow-up was reviewed. Recurrence free survival (RFS), cancer specific survival (CSS) and overall survival (OS) were the outcomes of interest and evaluated using the Kaplan Meier estimator. Multivariable Cox regression analysis was performed to identify factors associated with outcomes of interest. RESULTS Mean age was 67 years, 80% were men. 384 (82%) patients were alive at the time of the analysis. Median follow-up was 17.9 months (range 1-130 months). 87 patients (19%) had undergone surgery 3 or more years' ago. Median follow-up of patients alive was 16 months. 31% patients had pathological non organ-confined disease. Positive surgical margins were present in 5%; median lymph node yield was 18 with 19% of patients having positive lymph nodes. The 3-year RFS, CSS and OS were 73%, 75% and 73% respectively. On multivariable analysis, non-organ confined disease was found to impact RFS, CSS and OS (HR 4.0, 4.3 and 4.2 respectively) and LN positive disease was associated with poorer RFS (HR 2.1). Histopathology stage pT0 was a positive prognostic indicator associated with better RFS, CSS and OS (HR 0.15, 0.16 and 0.74 respectively). CONCLUSIONS This is the largest reported multi-institutional cohort of totally intracorporeal RARC showing acceptable medium term survival outcomes comparable to open radical cystectomy series. The ERUS scientific working group database indicates that a totally intracorporeal approach is replicable.

To analyze the underlying risk factors in patients with nonarteritic central retinal artery occlusion (CRAO) in a well-defined and homogenous group of patients enrolled in the European Assessment Group for Lysis in the Eye (EAGLE) study.Analysis of the cardiovascular risk factors in a prospective, randomized clinical trial.Seventy-seven EAGLE patients with nonarteritic CRAO.Analysis of vascular risk factors and underlying diseases detected by questionnaire and standardized physical examination within 1 month after occlusion.The standardized physical examination included carotid Doppler ultrasonography, echocardiography, electrocardiography, blood pressure monitoring, pulse rate, urine analysis, body mass index analysis, and laboratory tests.Seventy-seven of 84 patients had complete datasets for analysis. Fifty-two (67%) patients had cardiovascular risk factors in their medical history, and comprehensive phenotyping identified at least 1 new risk factor in 60 patients (78%; 95% confidence interval, 67%-87%). Thirty-one (40%) had carotid artery stenosis of at least 70%. Eleven patients experienced a stroke, 5 of those within 4 weeks after the CRAO occurred. Arterial hypertension was found in 56 (73%) patients and was newly diagnosed in 12 (16%) study participants. Cardiac diseases were also highly prevalent (22% coronary artery disease, 20% atrial fibrillation, and 17% valvular heart disease).Previously undiagnosed vascular risk factors were found in 78% of all CRAO patients. The most meaningful risk factor was ipsilateral carotid artery stenosis. A comprehensive and prompt diagnostic work-up is mandatory for all CRAO patients.

We report a rare case with a man who presented himself with hypacusis, vertigo and insecure gait. MRI revealed a tumor in the left cerebellopontine angle extending into the internal auditory canal. The tumor, preoperatively diagnosed as an acoustic schwannoma, was a large anaplastic B cell non-Hodgkins lymphoma. Although rare, the non-Hodgkins lymphoma should be included in the differential diagnoses of tumors in the cerebellopontine angle.

Background and Purpose— C-reactive protein (CRP) is an inflammatory marker known to be a risk factor for stroke. We examined the associations between CRP, carotid atherosclerosis, white matter lesions, and lacunes as manifestations of cerebral large- and small-vessel disease. Methods— In the community-based Austrian Stroke Prevention Study, CRP concentrations were measured by a highly sensitive assay in 700 participants at baseline. All underwent carotid duplex scanning, and a subset of 505 subjects underwent brain magnetic resonance imaging. Imaging was repeated after 3 and 6 years. We graded carotid atherosclerosis in both common and internal carotid arteries on a 5-point scale and calculated the sum of scores as an index of the severity of carotid atherosclerosis. The volume of white matter lesions and the number of lacunes were considered small vessel disease–related brain abnormalities. Results— After adjustment for vascular risk factors, the severity and progression of extracranial carotid atherosclerosis increased with increasing quintiles of CRP. Only study participants in the fourth and fifth quintile (>2.50 mg/L) had significantly more baseline atherosclerosis and greater progression when we used the first quintile ( Conclusions— We found evidence for differential effects of CRP in different beds of the arterial brain supply. CRP was a marker for active carotid atherosclerosis but not for small vessel disease–related brain lesions.

The status of Compton scattering by the nucleon at energies of the first and second resonance is summarized. In addition to a general test of dispersion theories and a precise determination of polarizabilities, the validities of four fundamental sum rules are explored. {\it Recommended} averages of experimental values for the electromagnetic polarizabilities and spin-polarizabilities of the nucleon are determined: $\alpha_p=12.0\pm 0.6$, $\beta_p=1.9\mp 0.6$, $\alpha_n= 12.5 \pm 1.7$, $\beta_n= 2.7 \mp 1.8$ (unit $10^{-4}$fm$^3$), $\gamma^{(p)}_\pi= -38.7 \pm 1.8$, $\gamma^{(n)}_\pi = 58.6 \pm 4.0$ (unit $10^{-4}$fm$^4$)., Comment: version appearing in the conference proceedings

Acute hemorrhagic leukoencephalitis (AHLE) is a rare fulminant demyelinating disorder. It is considered to be the most severe form of acute disseminated encephalomyelitis. It is associated with a high rate of mortality or severe neurological deficits, with only few reports of recovering patients. We report a 49-year-old female patient who presented with acute onset of neurological deficits, due to a right thalamic hemorrhage together with intraventricular bleeding. There was a continued clinical deterioration. In follow-up CT and MRI scans bilateral confluent white matter lesions were seen, together with T2 * hypointense lesions indicating microbleeds. A stereotactic biopsy was carried out and the diagnosis of AHLE was suggested. In acute post infectious encephalitides (and especially the severe form) early diagnosis, administration of treatment is of prime importance for outcome in a patient with Hurst encephalitis.

Over the past 20 years orthotopic urinary reconstruction with the techniques developed at Ulm and Bern has become a widely accepted form of urinary diversion. So far, both centers together have performed more than 1,300 orthotopic bladder substitutions with an overall rate of neobladder formation in 58% of all cystectomized patients. Today, the absolute contraindications for this procedure are urinary stress incontinence, damaged rhabdosphincter, severely impaired renal and liver function, severe intestinal diseases or an oncologic situation requiring urethrectomy. In patients treated for transitional cell carcinoma of the bladder, the rate of urethral recurrence in both centers was 1.5 and 5%, respectively, and the rate of upper urinary tract recurrence was 2-3%. Local tumor recurrence usually did not affect neobladder function. The rate of outlet obstruction by local recurrence was 2%, that of gross hematuria 1%, and of entero-reservoir fistulas 1-2%. Daytime continence at 12 months was 92%, while nighttime continence was lower around 80%. Transient or permanent urinary retention was seen in 11-12% of male patients. In both series, long-term upper urinary tract safety was good. The risk of stenoses of the uretero-intestinal anastomosis with consecutive loss of renal function decreased with the introduction of non-refluxing implantation techniques. The rate of long-term metabolic complications remains low when adequate substitution with sodium bicarbonate is guaranteed in patients with impaired renal function. Patient selection and meticulous postoperative follow-up contributed to achieve good long-term results after cystectomy and orthotopic ileal neobladder substitution of the two large series of patients from the Universities of Ulm and Bern.

Background.Reliable data on the costs attributable to nosocomial infection (NI) are crucial to demonstrating the real cost-effectiveness of infection control measures. Several studies investigating this issue with regard to intensive care unit (ICU) patients have probably overestimated, as a result of inappropriate study methods, the part played by NIs in prolonging the length of stay.Methods.Data from a prospective study of the incidence of NI in 5 ICUs over a period of 18 months formed the basis of this analysis. For describing the temporal dynamics of the data, a multistate model was used. Thus, ICU patients were counted as case patients as soon as an NI was ascertained on any particular day. All patients were then regarded as control subjects as long as they remained free of NI (time-to-event data analysis technique).Results.Admitted patients (n = 1,876) were observed for the development of NI over a period of 28,498 patient-days. In total, 431 NIs were ascertained during the study period (incidence density, 15.1 NIs per 1,000 patient-days). The influence of NI as a time-dependent covariate in a proportional hazards model was highly significant (P< .0001, Wald test). NI significantly reduced the discharge hazard (hazard ratio, 0.72 [95% confidence interval, 0.63-0.82])—that is, it prolonged the ICU stay. The mean prolongation of ICU length of stay due to NI ( ± standard error) was estimated to be 5.3 ± 1.6 days.Conclusions.Further studies are required to enable comparison of data on prolongation of ICU length of stay with the results of various study methods.

Background and Purpose: Little is known about the incidence and treatment of ureteropelvic junction (UPJ) obstruction of renal grafts. We report on three cases treated by endopyelotomy. Patients and Methods: Graft function declined in three patients 98, 135, and 144 days after kidney transplantation. Acute rejection was excluded by renal biopsy. Ultrasonography revealed a dilated collecting system, and a percutaneous nephrostomy tube was placed. An antegrade nephrostogram showed UPJ obstruction. Percutaneous antegrade endopyelotomy was performed with the cold-knife technique, and the area was stented for 6 weeks using a 14F/8.2F Smith endopyelotomy stent. Results: No intraoperative or postoperative complications occurred. The endopyelotomies were successful, and the creatinine clearances returned to normal. Conclusion: Antegrade endopyelotomy in patients with UPJ obstruction of a renal graft is feasible and effective. Normal kidney function was restored after correction of the obstruction.

Die radikale Prostatektomie stellt bei Patienten mit klinisch lokalisiertem Prostatakarzinom eine mögliche Therapieform dar. Die Selektion der Patienten und die operative Technik der Prostatektomie haben in den letzten Jahren eine Reihe von wichtigen Veränderungen erfahren, welche sich in tieferen Morbiditätsraten und möglicherweise in einer besseren Tumorkontrolle äußern. Die funktionellen Ergebnisse, d.h. Kontinenz- und Potenzraten sind von zunehmender Wichtigkeit und beeinflussen nachhaltig die Lebensqualität der Patienten. Die radikale retropubische Prostatektomie gilt weiterhin als Goldstandard in der Behandlung des lokalisierten Prostatakarzinoms, insbesondere auf Grund ihrer guten onkologischen und funktionellen Langzeitergebnisse, wobei neuere operative Verfahren an Bedeutung gewinnen. Insbesondere der Stellenwert der laparoskopischen Prostatektomie und der roboterunterstützten Chirurgie wird weiterhin kontrovers diskutiert, weil bis heute Langzeitresultate fehlen, die operative Lernkurve lange sein kann und die funktionellen Ergebnisse eher unter denen der offenen radikalen retropubischen Prostatektomie liegen.

Several methods for estimating the functional form of the effect of one continuous covariate are investigated in the framework of the Cox proportional hazards model. In particular, prespecified as well as data-driven risk functions are considered: Using the former (e.g. restricted cubic splines, the categorisation of the continuous covariate by fixed cutpoints) the general functional form is given in advance, the data are used for estimating the parameters of these functions only. With data-driven risk functions (e.g. the categorisation by data-driven cutpoints, fractional polynomials) the functional form is estimated from the data, too. All methods are extended by adapting bootstrap aggregating (bagging). The approaches are illustrated with the data of a breast cancer study. Assessment is performed by a simulation study considering typical risk functions. Altogether fractional polynomials performed best. Furthermore, it could be shown that bagging is able to improve the estimation of risk functions, if the underlying method does not describe the true effect correctly in the original data.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug reactions, which can be caused by a certain number of specific drugs among which is carbamazepine, an antiepileptic agent. A very strong association of carbamazepine-induced SJS with HLA-B*1502 has recently been described in the Han Chinese population. Here in, we report preliminary results from a European study (RegiSCAR) of 12 carbamazepine-induced SJS/TEN cases (nine French and three German). Among these only four had a HLA-B*1502 allele. Remarkably, these four patients had an Asian ancestry, whereas the others did not as far as we have ascertained. This shows that although the HLA region may contain important genes for SJS, the HLA-B*1502 allele is not a universal marker for this disease and that ethnicity matters.

Summary Objectives: Data collected within the German nosocomial infection surveillance system KISS are recommended as reference data for judging nosocomial infection rates in German intensive care units (ICUs). It is unknown whether the KISS data tend to under- or overestimate the true infection incidence rates. In this article, methodological aspects of the SIR1 study on the incidence of nosocomial infections are discussed, with the aim of estimating unbiased incidence rates of nosocomial infections in interdisciplinary German ICUs and examining whether the KISS data are representative. Methods: We discuss the following methodological issues: 1) Sample size estimation. 2) Stratified random sampling of German ICUs. 3) Investigation of seasonal effects. 4) Statistical modeling of incidence rates using a negative binomial regression model. 5) Comparison of weighted incidence rates with the standardized rate ratio (SRR). Results: Random sampling proved difficult to realize in practice since many ICUs refused to participate, particularly those in small hospitals. Analysis was adjusted for hospital size. No seasonal trends were found in the KISS data. Due to marked differences between ICUs, the number of infections is over-dispersed compared to a Poisson model, so negative binomial regression was used. Fifty ICUs were observed for two consecutive months each, corresponding to 21,832 patient days, during which 262 infections occurred. Infections were more frequent in large hospitals. The incidence rates provided by the SIR study are on average (SRR) 1.89 (1.63-2.20) times as large as those estimated by the KISS system. Conclusion: For estimating nosocomial infection incidence rates, random sampling and statistical modeling of over-dispersion were successfully performed. The study provides evidence that the KISS surveillance system tends to underestimate the true incidence rates of nosocomial infections in German ICUs.

We recently found that rat hepatocyte transplantation was efficient (liver repopulation: 2.4%) in a sublethal nude mouse model (less than 33% mortality) of repeated liver injury generated using Jo2, a mouse-specific anti-Fas antibody, at sublethal dose of 250 μg/kg for 3 weeks. Genomic analysis of the livers revealed cell cycle blockade and an antiproliferative status of circadian genes, suggesting a selective advantage. By contrast, in the present study, freshly isolated human hepatocyte transplantation performed in the same mouse model resulted in implantation of less than 6,000 cells per liver (about 0.006% repopulation) in all animals. Genomic analysis of nude mouse livers revealed a lack of P21 upregulation, while a signature of stimulation of liver regeneration was observed, including upregulation of early response genes and upregulation of circadian genes. When we translated this sublethal model to a lethal model (65% mortality) by increasing the Jo2 repeated doses to 375 μg/kg, human hepatocyte engraftment was still very low; however, animal mortality was corrected by transplantation (only 20% mortality). Genomic findings in livers from the mice of the lethal Jo2 transplanted group were similar to those of the sublethal Jo2 transplanted group, that is, no selective advantage genomic signature and signature of mouse liver regeneration. In conclusion, transplanted human hepatocytes acted as if they modified nude mouse liver responses to Jo2 by stimulating liver regeneration, leading to an increased survival rate.

The natural course of central retinal artery occlusion (CRAO) often leads to legal blindness in the affected eye. To date, none of the conservative therapies had proven effective in retrospective studies. In 1991, a new minimally invasive therapy was started in patients with an acute CRAO. This therapy, namely, local intra-arterial fibrinolysis, is comparable to the minimally invasive therapy in patients with an acute ischemic stroke. In pilot studies, it showed promising results in comparison with conservative treatments. The efficacy of this method is now being investigated in a randomized multicenter study. The European Assessment Group for Lysis in the Eye (EAGLE) started a prospective and randomized multicenter study in 2002 to evaluate therapeutic efficacy. Inclusion criteria are age between 18 and 75 years and a CRAO not older than 20 h with a visual acuity less than 0.32. The most important exclusion criteria are branch retinal artery occlusion (BRAO), cilioretinal arteries supplying the macula, and serious general disease. After randomization the patient is treated by conservative or local intra-arterial lysis therapy. The conservative regime included bulbus massage, lowering intraocular pressure with topical beta-blocker and acetazolamide, acetylsalicylic acid, heparin, and—depending on the hematocrit—isovolemic hemodilution. In case of local intra-arterial fibrinolysis, a maximum of 50 mg rtPA is injected into the ophthalmic artery by the neuroradiologist. During the following 5 days, all patients are treated with heparin. Primary study end point is visual acuity 1 month after therapy in comparison with visual acuity before therapy. The calculated sample size is 100 patients per subtrial (a total of 200 patients). The study was started in June 2002. To April 2005, 47 patients were included. The EAGLE Study is the first randomized prospective clinical trial to compare conservative medical treatment and local intra-arterial fibrinolysis in patients with CRAO. The results of this study should enable ophthalmologists and neuroradiologists to improve the therapy of patients with acute CRAO. To April 2005, treatment is only justified in randomized multicenter studies because of the limited therapeutical visual outcome. We welcome new study centers to join.