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In May/June 2011, the new Shiga-like toxin-producing Escherichia coli (STEC) strain O104:H4 caused the severest outbreak ever recorded of hemorrhagic enterocolitis in 3842 patients in Germany.As bacterial enterocolitis is an established risk factor of subsequent irritable bowel syndrome (IBS), we aimed to estimate prevalence and incidence of post-infectious (PI)-IBS after six and 12 months in a cohort of STEC O104:H4 patients and to prospectively identify associated somatic and psychometric risk factors.A total of 389 patients were studied prospectively at baseline and at six and 12 months after STEC infection using STEC disease-related questionnaires and validated instruments for IBS (Rome III) and psychological factors. Frequencies and logistic regression models using multiple imputations were applied to assess predictor variables.Prevalence of IBS increased from 9.8% prior to STEC infection to 23.6% at six and 25.3% at 12 months after STEC infection. In patients without IBS symptoms prior to STEC infection, incidence of new IBS was 16.9%. Logistic regression models indicated higher somatization and anxiety scores as risk factors for, and mesalazine treatment during, STEC infection as the only significant protective factor against IBS. No other factor analyzed, including disease severity, showed an association.PI-IBS rates following this unusually severe STEC outbreak were similar to what has been observed after other infectious gastroenteritis outbreaks. Our findings suggest that mesalazine may have reduced the risk of subsequent PI-IBS. As altered mucosal immune activity is a pivotal pathogenic factor in PI-IBS, our observation of a potential protective effect of mesalazine might be explained by its known modulatory action on mucosal immunity, and may warrant further investigation.

Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 ± 9.8 years, 83% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) ≥40% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823, 81.7%) and myocardial infarction (n = 545, 54.1%) with a mean LVEF of 59.9% ± 9.3%. The mean left ventricular mass index (LVMI) was 52.1 ± 21.2 g/m2.7 and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI (95% CI: 1%–12%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition.

Background and Purpose— Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) has been used to estimate diffusion-weighted imaging (DWI) lesion volume in acute stroke. We aimed to assess correlations of DWI-ASPECTS with lesion volume in different middle cerebral artery (MCA) subregions and reproduce existing ASPECTS thresholds of a malignant profile defined by lesion volume ≥100 mL. Methods— We analyzed data of patients with MCA stroke from a prospective observational study of DWI and fluid-attenuated inversion recovery in acute stroke. DWI-ASPECTS and lesion volume were calculated. The population was divided into subgroups based on lesion localization (superficial MCA territory, deep MCA territory, or both). Correlation of ASPECTS and infarct volume was calculated, and receiver-operating characteristics curve analysis was performed to identify the optimal ASPECTS threshold for ≥100-mL lesion volume. Results— A total of 496 patients were included. There was a significant negative correlation between ASPECTS and DWI lesion volume ( r =–0.78; P r =–0.19; P =0.038) when compared with superficial ( r =–0.72; P r =–0.72; P Conclusions— ASPECTS has limitations when lesion location is not considered. Identification of patients with malignant profile by DWI-ASPECTS may be unreliable. ASPECTS may be a useful tool for the evaluation of noncontrast computed tomography. However, if MRI is used, ASPECTS seems dispensable because lesion volume can easily be quantified on DWI maps.

Uveal melanoma (UM) is the most common primary intraocular malignancy with a very poor prognosis. The most frequent chromosome aberration in UM is the monosomy of chromosome 3. Previously, we demonstrated that ~50% of UMs express type-I receptor for luteinizing hormone‑releasing hormone (LH-RH-R). The gene encoding LH-RH-R is located in chromosome 4 (location: 4q21.2); however, the occurrence of numerical aberrations of chromosome 4 have never been studied in UM. In the present study, we investigated the abnormalities of chromosome 3 and 4, and the possible correlation between them, as well as with LH-RH-R expression. Forty-six specimens of UM were obtained after enucleation. Numerical aberrations of chromosome 3 and 4 were studied by fluorescence in situ hybridization (FISH). Chromosome 4 was detected in normal biparental disomy only in 14 (30%) samples; however, 32 cases (70%) showed more than 2 signals/nucleus. Monosomy of chromosome 3 could be found in 16 (35%) samples. In 6 specimens (13%), more than 2 copies of chromosome 3 were found, while normal biparental disomy was detected in 24 (52%) samples. Statistical analysis indicated a statistically significant (p

Background & Aims From May through July 2011 in northern Germany, there was a large outbreak of hemolytic uremic syndrome and bloody diarrhea, which was related to infections from Shiga toxin–producing Escherichia coli O104 (STEC). We investigated the depression, posttraumatic symptoms, fatigue, and health-related quality of life among patients within the first 6 months after STEC infection and aimed to identify factors associated with poor outcome. Methods In a cohort study, we performed baseline assessments of 389 patients (69% female) 3 months after STEC infection (82 ± 36 days) and follow-up assessments of 308 of the patients 6 months afterward (199 ± 17 days). Data were collected at 13 hospitals in northern Germany. Patients completed validated self-report scales and a diagnostic interview. Results At baseline, hemolytic uremic syndrome was diagnosed in 31% of the patients. Six months after the infection, mean self-reported severity of depression and posttraumatic symptoms and fatigue were significantly greater than in the general population, and the mean score from the mental component of health-related quality of life survey was significantly lower than average. Posttraumatic stress disorder had recently developed in 3% of patients (95% confidence interval, 1%–5%), and 43% of patients had clinically relevant fatigue (95% confidence interval, 41%–45%). The most important baseline factors associated with poor psychological health 6 months after STEC infection were previous traumatic events, neuroticism, and low social support (all P Conclusions Six months after the major outbreak of STEC infection in northern Germany, a substantial number of patients had poor psychological health, persistent fatigue, and impaired quality of life. For future outbreaks, patients' premorbid risk factors should be considered, which might minimize the long-term effects of infections on mental health.

Glioblastoma (GB) is the most frequent brain tumor. Despite recent improvement in therapeutic strategies, the prognosis of GB remains poor. Growth hormone-releasing hormone (GHRH) may act as a growth factor; antagonists of GHRH have been successfully applied for experimental treatment of different types of tumors. The expression profile of GHRH receptor, its main splice variant SV1 and GHRH have not been investigated in human GB tissue samples. We examined the expression of GHRH, full-length pituitary-type GHRH receptor (pGHRHR), its functional splice variant SV1 and non-functional SV2 by RT-PCR in 23 human GB specimens. Epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog gene (PTEN) expression levels were also evaluated by quantitative RT-PCR. Correlations between clinico-pathological parameters and gene expressions were analyzed. Expression of GHRH was found to be positive in 61.9 % of samples. pGHRH receptor was not expressed in our sample set, while SV1 could be detected in 17.4 % and SV2 in 8.6 % of the GB tissues. In 65.2 and 78.3 % of samples, significant EGFR over-expression or PTEN under-representation could be detected, respectively. In 47.8 % of cases, EGFR up-regulation and PTEN down-regulation occurred together. Survival was significantly poorer in tumors lacking GHRH expression. This worse prognosis in GHRH negative group remained significant even if SV1 was also expressed. Our study shows that GHRH and SV1 genes expressed in human GB samples and their expression patterns are associated with poorer prognosis.

Introduction: Surgical procedures require informed patient consent, which is mandatory prior to any procedure. These requirements apply in particular to elective surgical procedures. The communication with the patient about the procedure has to be comprehensive and based on mutual understanding. Furthermore, the informed consent has to take into account whether a patient is of legal age. As a result of large-scale migration, there are eventually patients planned for medical procedures, whose chronological age can’t be assessed reliably by physical inspection alone. Age determination based on assessing wisdom tooth development stages can be used to help determining whether individuals involved in medical procedures are of legal age, i.e., responsible and accountable. At present, the assessment of wisdom tooth developmental stages barely allows a crude estimate of an individual’s age. This study explores possibilities for more precise predictions of the age of individuals with emphasis on the legal age threshold of 18 years. Material and Methods: 1,900 dental orthopantomograms (female 938, male 962, age: 15–24 years), taken between the years 2000 and 2013 for diagnosis and treatment of diseases of the jaws, were evaluated. 1,895 orthopantomograms (female 935, male 960) of 1,804 patients (female 872, male 932) met the inclusion criteria. The archives of the Department of Diagnostic Radiology in Dentistry, University Medical Center Hamburg-Eppendorf, and of an oral and maxillofacial office in Rostock, Germany, were used to collect a sufficient number of radiographs. An effort was made to achieve almost equal distribution of age categories in this study group; ‘age’ was given on a particular day. The radiological criteria of lower third molar investigation were: presence and extension of periodontal space, alveolar bone loss, emergence of tooth, and stage of tooth mineralization (according to Demirjian). Univariate and multivariate general linear models were calculated. Using hierarchical multivariate analyses a formula was derived quantifying the development of the four parameters of wisdom tooth over time. This model took repeated measurements of the same persons into account and is only applicable when a person is assessed a second time. The second approach investigates a linear regression model in order to predict the age. In a third approach, a classification and regression tree (CART) was developed to derive cut-off values for the four parameters, resulting in a classification with estimates for sensitivity and specificity. Results: No statistically significant differences were found between parameters related to wisdom tooth localization (right or left side). In univariate analyses being of legal age was associated with consecutive stages of wisdom tooth development, the obliteration of the periodontal space, and tooth emergence, as well with alveolar bone loss; no association was found with tooth mineralization. Multivariate models without repeated measurements revealed imprecise estimates because of the unknown individual-related variability. The precision of these models is thus not very good, although it improves with advancing age. When calculating a CART-analysis and a receiver operating characteristics – area under the curve of 78% was achieved; when maximizing both specificity and sensitivity, a Youden’s index of 47% was achieved (with 73% specificity and 74% sensitivity). Discussion: This study provides a basis to help determine whether a person is 18 years or older in individuals who are assumed to be between 15 and 24 years old. From repeated measurements, we found a linear effect of age on the four parameters in the individuals. However, this information can't be used for prognosis, because of the large intra-individual variability. Thus, although the development of the four parameters can be estimated over time, a direct conclusion with regard to age can’t be drawn from the parameters without previous biographic information about a person. While a single parameter is of limited value for calculating the target age of 18 years, combining several findings, that can be determined on a standard radiography, may potentially be a more reliable diagnostic tool for estimating the target age in both sexes. However, a high degree of precision can’t be achieved. The reason for persistent uncertainty lies in the wide chronological range of wisdom tooth development, which stretches from well below to above the 18th life year. The regression approach thus seems not optimal. Although sensitivity and specificity of the CART-model are moderately high, this model is still not reliable as a diagnostic tool. Our findings could have impact, e.g. on elective surgeries for young individuals with unknown biography. However, these results cannot replace social engagement, in particular thorough physical examination of patients and careful registration of their histories. Further studies on the use of this calculation method in different ethnic groups would be desirable., Einleitung: Die Durchführung operativer Eingriffe bedarf der rechtsgültigen Aufklärung. Diese hat insbesondere bei geplanten elektiven Eingriffen umfassend und verständlich zu erfolgen. Darüber hinaus hat sich die ärztliche Aufklärung hinsichtlich der Einwilligungserklärung an der juristisch definierten Volljährigkeit zu orientieren. Infolge der großen transnationalen Migrationen gibt es einen Anteil an Patienten, deren Lebensalter unbekannt ist und deren ärztliche Alterseinschätzung das Erreichen des 18. Lebensjahres ausschließlich anhand des äußeren Erscheinungsbildes nur unsicher vermuten lässt. In dieser Situation kann die aus der forensischen Odontostomatologie bekannte Altersschätzung nach den radiologisch bestimmten Entwicklungsphasen der Weisheitszahnentwicklung die juristisch relevante Entscheidung unterstützen, ob die ärztliche Aufklärung einem Heranwachsenden oder Erwachsenen gilt. Da die Beurteilung der Zahnwurzelentwicklungsstadien der Weisheitszähne lediglich einen Zeitkorridor des wahrscheinlichen Lebensalters vorgibt, war es das Anliegen dieser Untersuchung, mit zusätzlichen Parametern der Radiomorphologie des unteren Weisheitszahns die Altersschätzung für das Erreichen des 18. Lebensjahres zu präzisieren. Material und Methoden: Es wurden 1.900 Orthopantomogramme der Kiefer von Patienten mit bekanntem Geburtsdatum untersucht, 5 Orthopantomogramme entsprachen nicht den Einschlusskriterien. Das Lebensalter lag zwischen 15 und 24 Jahren. Es wurde eine Gleichverteilung der Untersuchungsgruppe nach Alter (je Lebensjahr) und Geschlecht bei der Auswahl der Röntgenbilder angestrebt und hinreichend eingehalten. Die Röntgenaufnahmen wurden in den Jahren 2000 bis 2013 in der Abteilung Zahnärztliche Radiologie des Universitätsklinikums Hamburg-Eppendorf oder in einer mund-kiefer-gesichtschirurgischen Praxis in Rostock angefertigt. Eine mehrfache Untersuchung von Patienten (n=1.804, mit 1.895 auswertbaren Orthopantomogrammen) war nicht ausgeschlossen und wurde ggf. bei den Analysen berücksichtigt. An den unteren Weisheitszähnen wurden vier Parameter bestimmt: Nachweis und Ausdehnung des Parodontalspaltes bzw. der periradikulären Sklerose, vertikaler Knochenverlust des Alveolarfortsatzes im Bereich des Zahnes, Durchbruchsstadium des Zahnes in die Mundhöhle und das Wurzelentwicklungsstadium (nach Demirjian). Nach einer Überprüfung, ob bereits die Erhebung eines Parameters ausreicht und hinreichend gute Erkenntnisse über die Volljährigkeit des Untersuchten liefert, wurden die erhobenen Parameter in drei Ansätzen kombiniert; hier wurde das Augenmerk auf unterschiedliche Aspekte, Anwendungen und Aussagen gerichtet. Die erste Analyse betrachtet die Entwicklung der vier Parameter im jeweiligen Patienten über die Zeit. Der zweite Ansatz untersucht die Vorhersage des Lebensalters basierend auf allen vier erhobenen Parametern unter Berücksichtigung der Messwiederholungen mittels eines gemischten linearen Modells, und schließlich wurden ein Gesamtmodell und geschlechtsspezifische Entscheidungsbäume erstellt, mit deren Hilfe bei Vorliegen der vier erhobenen Parameter eine Abschätzung der Wahrscheinlichkeit für das Erreichen bzw. Nicht-Erreichen der Volljährigkeit abgeleitet werden kann. Ergebnisse: Es ließen sich keine signifikanten Unterschiede hinsichtlich der Lokalisation der Weisheitszähne (rechts/links) nachweisen. In den univariaten ROC-AUC-Analysen zeigten die Parameter Zahndurchbruchsstadium, Parodontalspalt und der Knochenschwund des den Weisheitszahn umgebenden Alveolarfortsatzes einen klaren signifikanten prognostischen Wert hinsichtlich der Volljährigkeit in der Untersuchungsgruppe. Das Mineralisationsstadium zeigte sich nicht als geeigneter Parameter zur direkten Bestimmung der Volljährigkeit. Für die Prognose scheinen drei der vier Parameter somit geeignet. Betrachtet man die Entwicklung der Zähne in Individuen anhand der vier Parameter mit wachsendem Lebensalter, konnte eine Veränderung der vier Zahnparameter nachgewiesen werden. Eine Umkehr der Kausalität und die Vorhersage des Lebensalters durch die vier Zahnparameter erscheint jedoch problematisch. Eine erhebliche individuelle Komponente ist bei den untersuchten Personen zu beobachten. Dies liegt u.a. daran, dass eine Entwicklung der Weisheitszähne durchaus vor und nach dem Erreichen des 18. Lebensjahres stattfinden kann. In multivariaten Analysen konnte gezeigt werden, dass durch die Kombination der Parameter mit wesentlich größerer Wahrscheinlichkeit ein Lebensalter von 18 Jahren und höher korrekt vorausgesagt werden kann und somit eine Formel die Kalkulation des Alters ermöglicht. Eine Trennung zwischen Heranwachsenden und Volljährigen ist mit einer Formel jedoch bei weitem nicht so perfekt, wie man es sich eigentlich wünschen würde. Ein Entscheidungsbaum, der nach geeigneten, aufeinander abgestimmten Cut-off-Werten sucht, verspricht eine leicht handhabbare Lösung zu liefern. Der Gesamtentscheidungsbaum hatte eine Fläche unter der Kurve (AUC) von 78%. Die Wahl der Entscheidungsregel setzt jedoch eine Abwägung der Priorisierung von Sensitivität oder Spezifität voraus. Ausgehend von der Annahme, dass beide Kriterien gleichwertig sind, lässt sich eine angestrebte Maximierung der Summe der beiden Maßzahlen anstreben. Die Ableitung eines Entscheidungsbaumes führte bei geeigneter Wahl der Knoten zu einer Sensitivität von 74% und einer Spezifität von 73% (hieraus folgt ein Youden-Index von 47%). Eine vollständig sichere Unterscheidung forensisch relevanter Lebensalter ist mit den vorgestellten Methoden somit nicht zu treffen. Diskussion: In der ärztlichen Aufklärung ist besondere Sorgfalt auf die alters- und entwicklungsangepasste Kommunikation mit dem Patienten zu achten. Ein wesentlicher Pfeiler der juristischen Personeneinschätzung ist das Erreichen der Volljährigkeit, die in Deutschland im Grundsatz mit dem 18. Lebensjahr erreicht ist. Für Personen mit unbekanntem Geburtsdatum können gelegentlich Schwierigkeiten entstehen, auf welcher Grundlage die ärztliche Aufklärung zu erfolgen hat, wenn es sich dem Anschein nach um eine Person im fortgeschrittenen Heranwachsenden-Alter handelt. Unter der Voraussetzung, dass die ärztliche Einschätzung für einen geplanten Eingriff von einem einverständnisfähigen Patienten ausgeht, kann die hier vorgestellte Methode die Bestimmung des 18. Lebensjahres anhand einer radiologischen Standarduntersuchung der Kiefer mit Wahrscheinlichkeit leisten. Die biologische Breite der Weisheitszahnentwicklung liegt jedoch beidseits des 18ten Lebensjahres. Die Fehlerbreite nimmt mit zunehmendem Alter ab, insbesondere bei der Abschätzung der Volljährigkeit von tatsächlich bereits 21-Jährigen, erreicht aber auch hier keine vollständige Sicherheit der Abschätzung der Volljährigkeit. Die vorgelegten Untersuchungsergebnisse sind geeignet, die forensische Altersschätzung in mehreren Bereichen ärztlicher Tätigkeit fundiert zu unterstützen. Die Untersuchungsmethoden sind für den Behandler jedoch ungeeignet, anhand dieser Berechnungen sich der genauen Kenntnis der individuellen Lebensumstände des jeweiligen Patienten zu entziehen. Insbesondere die sorgfältig erhobene Lebensgeschichte und körperliche Untersuchung bleiben vorrangig zu bestimmende Werte der Personeneinschätzung. Die Erweiterung des Berechnungsansatzes durch Anwendung in anderen Populationen ist anzustreben., GMS Interdisciplinary Plastic and Reconstructive Surgery DGPW; 5:Doc23

The aim of this study was to research the impact of inpatient rehabilitation on work ability and health-related quality of life factors for healthcare personnel (HP) with chronic hepatitis B and C virus (HBV and HCV) infection. A prospective evaluation study with three data collection times without an external control group was conducted. HP (n = 163) with an occupational acquired chronic hepatitis B/C infection who participated in an inpatient rehabilitation program were surveyed. Information was collected on work ability (WAI&mdash, Work Ability Index), quality of life (SF-36&mdash, Short Form-36 Health Survey), and anxiety and depression-related symptoms (HADS-D&mdash, Hospital Anxiety and Depression Scale). The majority of participants had HCV infection. Work ability was poor, improved significantly until the end of treatment, and remained at a moderate level six months later. The SF-36 showed no change in physical health over the study period, the results regarding mental health were in the average range with a significant improvement directly after intervention. The HADS-D results indicate noteworthy anxiety and depression symptoms during the study period. The inpatient rehabilitation program proved to be effective in the short term regarding mental health (SF-36) and WAI. To ensure long lasting positive results, services aimed at enhancing physical and mental health should be provided as early as possible and on a recurring basis.

Background Restenosis remains an unresolved problem despite different treatment modalities and new stent technology in femoropopliteal arteries. No standard therapy has proven to provide acceptable outcome data for this entity. Directional atherectomy alone did not result in satisfactory long-term patency rates. The outcome might be improved in conjunction with drug-coated balloon angioplasty. Methods In this retrospective study, restenotic lesions of the femoropopliteal arteries were treated with directed atherectomy in 89 lesions of consecutive patients (58% male; mean age, 69 ± 11 years). All patients received adjunctive treatment with conventional balloon percutaneous angioplasty (PTA; n = 60) or drug-coated balloon angioplasty (DCB; n = 29). Results Lesion location was in the stent (DCB [n = 27] vs PTA [n = 36]) and in native restenotic vessels (DCB [n = 2] vs PTA [n = 25]). The 1-year Kaplan-Meier freedom from restenosis estimates (95% confidence intervals) in the DCB and PTA groups were 84.7% (70.9%-98.5%) and 43.8% (30.5%-57.1%), respectively. In a multivariable Cox model for restenosis, DCB treatment had a hazard ratio (95% confidence interval) of 0.28 (0.12-0.66; P = .0036) compared with the PTA group. In the multivariable model for procedural success, the effect of treatment did not differ between PTA and DCB ( P = .134). Conclusions The combination of directed atherectomy with adjunctive DCB is associated with a better event-free survival at 12 months of follow-up compared with PTA after directed atherectomy.

Patients with lung failure who undergo prone positioning often receive extended hemodynamic monitoring. We investigated the influence of modified prone positioning (135°) on the accuracy of pulse contour-derived calibrated cardiac index (CIPC) and uncalibrated cardiac index (CIVIG) in this patient population with transpulmonary thermodilution (TPTD) as reference technique.We studied 16 critically ill and mechanically ventilated patients (11 men, 5 women, aged 20-71 years) with acute lung injury or acute respiratory distress syndrome. Patients were monitored by TPTD with an integrated calibrated pulse contour technique (PiCCO®) and by uncalibrated pulse contour analysis (FloTrac/Vigileo™). Before prone positioning, cardiac index (given in L·min(-1)·m(-2)) was measured by TPTD (CITPTD) and CIPC was calibrated. After positioning, CIPC and CIVIG were read from the monitor and CITPTD was measured. After 8 to 10 hours, prone positioning was completed and measurements were performed analogously. Bland-Altman analysis based on a random-effects model was used to calculate limits of agreement (LOA) and percentage errors. Polar plots were used for trend analysis.Supine CITPTD was 3.3 ± 0.9 (mean ± SD) and CIVIG was 3.1 ± 0.8. After proning, CIPC was 3.5 ± 0.8, CIVIG 3.3 ± 0.8, and CITPTD 3.6 ± 0.8. Before repositioning, CITPTD was 3.5 ± 0.7 and CIVIG 3.3 ± 1.0. After repositioning, CITPTD was 3.1 ± 0.7, CIPC 3.3 ± 0.7, and CIVIG 2.9 ± 0.6. Mean bias pooled for proning and repositioning was -0.1 (LOA -0.7 to 0.6) for CIPC (percentage error 19%) and 0.3 (LOA -1.3 to 1.9) for CIVIG (percentage error 48%). Changes in CI were too small for trending analysis.Although calibrated CI measurements are only marginally influenced by prone positioning, according to the criteria of Critchley and Critchley, uncalibrated CI values show a degree of error, too high to be considered clinically acceptable.

BACKGROUND AND PURPOSE: The mismatch between lesions identified in perfusion- and diffusion-weighted MR imaging is typically used to identify tissue at risk of infarction in acute stroke. The purpose of this study was to analyze the variability of mismatch volumes resulting from different time-to-peak or time-to-maximum estimation techniques used for hypoperfused tissue definition. MATERIALS AND METHODS: Data of 50 patients with middle cerebral artery stroke and intracranial vessel occlusion imaged within 6 hours of symptom onset were analyzed. Therefore, 10 different TTP/Tmax techniques and delay thresholds between +2 and +12 seconds were used for calculation of perfusion lesions. Diffusion lesions were semiautomatically segmented and used for mismatch quantification after registration. RESULTS: Mean volumetric differences up to 40 and 100 mL in individual patients were found between the mismatch volumes calculated by the 10 TTP/Tmax estimation techniques for typically used delay thresholds. The application of typical criteria for the identification of patients with a clinically relevant mismatch volume resulted in different mismatch classifications in ≤24% of all cases, depending on the TTP/Tmax estimation method used. CONCLUSIONS: High variations of tissue-at-risk volumes have to be expected when using different TTP/Tmax estimation techniques. An adaption of different techniques by using correction formulas may enable more comparable study results until a standard has been established by agreement.

Background Inappropriate activation of T lymphocytes plays an important role in perinatal complications. However, data on T lymphocyte activation markers of preterm infants is scarce. We investigated the association between gender, gestational and postnatal age, preeclampsia (PE), premature rupture of membranes (PROM) as well as prenatal steroid treatment (PS) and the frequency of activated T lymphocyte subsets (HLA-DR+, CD69+, CD25+, CD62L+) and major T lymphocyte subpopulations (CD4, CD8, Th1, Th2, naïve, memory) in peripheral blood during the first postnatal week in preterm infants. Results Cord blood and peripheral blood samples were collected from 43 preterm infants on the 1st, 3rd, and 7th days of life. We assessed the frequency of the above T lymphocyte subsets using flow cytometry. The ‘mixed effect model’ was used to analyze the effects of clinical parameters on T lymphocyte markers. The frequency of CD25+ T lymphocytes was higher in PROM. The frequency of CD4+ and CD8+ cells and the CD4+/CD8+ cell ratio was decreased in PE. The frequency of CD62L+ T lymphocytes was higher in male compared with female infants. PS did not affect the frequency of the investigated markers. CD4+ CD25+ cells had a lower frequency at birth than on day 7. Th2 lymphocytes had a lower frequency on postnatal days 1 and 3 when compared to day 7. Conclusions Our observations indicate that alterations affecting the expression of T lymphocyte activation markers are associated with the above factors and may play a role in the development of perinatal complications.

Background— Ablation of atrial fibrillation (AF) is an established treatment option for symptomatic patients. It is not known whether complete pulmonary vein isolation (PVI) is superior to incomplete PVI with regard to the patients’ clinical outcome. Methods and Results— Patients with drug-refractory, symptomatic paroxysmal AF were randomly assigned to either incomplete (group A) or complete PVI (group B). In group A, a persistent gap was intentionally left within the circumferential ablation line, whereas in group B, complete PVI without any gaps was intended. At 3 months, all patients underwent invasive reevaluation to assess the rate of persistent PVI. Clinical follow-up was based on daily 30-s transtelephonic ECG transmissions. Primary study end point was the time to first recurrence of (symptomatic or asymptomatic) AF. A total of 233 patients were enrolled (116 in group A and 117 in group B). AF recurrence within 3 months was observed in a total of 161 patients (136 [84.5%] with symptomatic and 25 [15.5%] with asymptomatic AF); AF recurred in 62.2% of group B patients and 79.2% of group A patients ( P Conclusions— This study proves the superiority of complete PVI over incomplete PVI with respect to AF recurrence within 3 months. However, the rate of electric reconduction 3 months after PVI is high in patients with initially isolated PVs. Clinical Trial Registration— URL: http://clinicaltrials.gov ; Unique identifier: NCT00293943.

Rona Reibis,1,2 Andras Treszl,3 Karl Wegscheider,3 Kurt Bestehorn,4 Barbara Karmann,4 Heinz Völler1,51Department of Cardiology, Klinik am See, Rehabilitation Center of Cardiovascular Diseases, Rüdersdorf, 2Kardiologische Gemeinschaftspraxis am Park Sanssouci Potsdam, Potsdam, 3Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, 4Medical Department, MSD Sharp and Dohme GmbH, Haar, 5Center of Rehabilitation Research, University of Potsdam, Potsdam, GermanyBackground: There are few data available regarding the specificity and modifiability of major cardiovascular (CV) risk factors in patients with premature versus (vs) late-onset coronary artery disease (CAD). This study was designed to analyze and compare these risk factors.Patients and methods: Data from 15,381 consecutive patients (mean age, 62.3 ± 11.7 years; female, 33.8%) hospitalized with CAD were collected from a large-scale registry (Transparency Registry to Objectify Guideline-Oriented Risk Factor Management) and analyzed. The patients were divided into two groups, depending on age at inclusion: group 1 patients (n = 5725; mean age, 50.5 ± 7.2 years) were males aged < 55 years and females aged < 65 years; group 2 patients (n = 9656; mean age, 69.4 ± 7.4 years) were males aged > 55 years and females aged > 65 years and had a low-density lipoprotein cholesterol level of >100 mg/dL on admission to cardiac rehabilitation. Besides the conventional risk factors, lipoprotein(a) concentrations and glucose tolerance were measured facultatively. Univariate (chi-square test) and multivariate logistic regression models were used.Results: Cigarette smoking (group 1 at 31.5% vs group 2 at 9.4%; P < 0.001), family history of CAD (group 1 at 43.6% vs group 2 at 26.5%; P < 0.001), and dyslipidemia (group 1 at 92.7% vs group 2 at 91.8%; P < 0.001) were dominant risk factors in the younger group. Arterial hypertension (group 1 at 71.4% vs group 2 at 87.0%; P < 0.001) and diabetes (group 1 at 23.5% vs group 2 at 30.1%; P < 0.001) were dominant risk factors in the older group. Impaired glucose tolerance and diabetes were less frequent in the younger group (Ptrend = 0.038), and identical lipoprotein(a) concentration levels of >30 mg/dL were found in both groups (8.0%; P = 0.810). Modification of lipid profile and blood pressure was more effective in the younger group (low-density lipoprotein cholesterol < 100 mg/dL: group 1 at 66.3% vs group 2 at 61.1%; systolic blood pressure < 140 mmHg: group 1 at 91.7% vs group 2 at 83.0%; P < 0.001).Conclusion: CV risk factors differ markedly between premature and non-premature CAD. Cardiac rehabilitation provides an opportunity to reinforce secondary prevention after acute coronary syndrome.Keywords: acute coronary syndrome, premature manifestation, cardiovascular risk factors, diabetes, cholesterol

Summary This study was carried out to evaluate the association between 77C>G transversion (rs17612648) in exon A of the PTPRC gene and liver transplant rejection. No significant differences in genotype and allele frequencies of the 77C>G transversion were detected between recipients without rejection (n = 106) and recipients with rejection (n = 104). In conclusion, there was no evidence for the contribution of the 77C>G transversion in susceptibility to liver transplant rejection in a Caucasian population.

Telomere length has emerged as a biological correlate for ageing, which in turn is a risk factor for the manifestation of cardiovascular diseases. This study investigated the relation between leucocyte telomere length (LTL) and its genetic background to cardiac structure and function in patients with arterial hypertension. We analysed a cohort of 1,106 treated hypertensive patients (83.3% males; mean age, 57.9 ± 9.8 years) with an ejection fraction (EF) over 40% and documented cardiovascular disease or target organ damage. LTL and genotypes of single nucleotide polymorphisms (SNPs), previously implicated in LTL, were determined by real-time PCR. The mean left ventricular mass index (LVMI) and EF were 51.8 ± 21.0 g/H2.7 and 61.1 ± 9.6%, respectively. In multivariate adjusted analysis, a 1.5-fold LTL was positively related with a 2.2% increase of LVMI (CI = 0.1% to 4.2%, p = 0.044) and an absolute increase in EF of 0.6% (CI = 0.1% to 1.1%, p = 0.028). One SNP near TERC (rs16847897) showed a significant absolute difference in EF dependent on allele status (rs16847897, G allele 2.7%; CI = 0.7% to 4.6%; p raw = 0.008, p mt = 0.048, after adjustment for multiple testing). This applied also for two SNPs in BICD1 (rs2630578, C allele −1.8%; CI = −2.8% to −0.7%; p raw = 0.002, p mt = 0.018; rs1151026, G allele −1.9%, CI = −3.0% to −0.8%; p raw

Cytokine production in activated T lymphocytes of the term neonate is reduced compared with adults. We aimed to characterize the calcium influx kinetics of activated T lymphocytes in the neonate and to test the functionality and expression of Kv1.3 and IKCa1 lymphocyte potassium channels, important regulators of calcium influx. We isolated lymphocytes from the peripheral blood of nine adults and cord blood of nine term neonates. We measured the calcium influx kinetics with flow cytometry in the T(h)1, T(h)2, CD4 and CD8 T-lymphocyte subsets activated with PHA. We determined the sensitivity of calcium influx to specific inhibitors of the Kv1.3 and IKCa1 channels. We also measured Kv1.3 channel expression using specific antibody. With the exception of the CD4 subset, calcium influx kinetics was decreased upon activation in neonatal T lymphocytes compared with adults. Neonatal T lymphocytes were found to be less sensitive to the specific inhibition of Kv1.3 and IKCa1 channels. The expression of Kv1.3 channels was higher on major T-lymphocyte subsets of newborns except for T(h)1 lymphocytes. Our findings suggest that the characteristics of short-term activation of major neonatal T-lymphocyte subsets are altered compared with adults. The altered function of neonatal lymphocyte potassium channels may contribute to this phenomenon.

Erythropoietin (EPO) protects the kidneys from ischemia/reperfusion (I/R) injury; however, the exact signalling mechanisms are not fully understood. The serum and glucocorticoid-regulated kinase 1 (SGK1) is an anti-apoptotic protein kinase regulated through the phosphatidylinositol 3-kinase (PI3-kinase) pathway by cellular stimuli, hormones and growth factors. The objective of the present study was to examine the role of SGK1 in the renoprotective effects of EPO in renal I/R injury. In vitro, cultures of HEK293 cells were exposed to 16h hypoxia. Incubation with EPO at a doses of 400U/ml exerted a protective effect on cell death assessed by LDH release and Annexin V FACS analysis. This was paralleled by up-regulation of SGK1 expression, as well as phosphorylation. Downregulation of SGK1 expression by small interfering RNA technique ameliorated the anti-apoptotic effect of EPO treatment. In an in vivo rat model of unilateral renal I/R injury, rats were treated with 500U/kg EPO 24h prior to ischemia. EPO resulted in less severe tissue injury and ameliorated the elevation in creatinine and urea nitrogen levels 24h after reperfusion. Furthermore, SGK1 expression and phosphorylation were higher in EPO compared to vehicle-treated rats as demonstrated by real-time PCR, Western blot and immunofluorescence technique. We conclude that EPO protects from renal I/R injury and SGK1 might contribute to the mediation of EPO effects under ischemic conditions.

Objective: To investigate the associations of blood glucose (BG) parameters and postoperative complications following paediatric cardiac surgery in the presence and absence of insulin treatment. Methods: Prospectively collected perioperative data on 810 consecutive patients who underwent surgery for congenital heart disease were retrospectively analysed. A combined outcome of death and multiple organ dysfunction (any two of the followings: infectious, cardiac, pulmonary, renal or neurological complications) was considered as the endpoint. Results: In total, 110 patients developed the combined endpoint and 32 of these patients died during the perioperative period. Patients treated with insulin were younger, smaller and underwent more complex procedures. They had higher peak BG levels and higher daily BG fluctuation, however, BG parameters were not associated with adverse outcome. In patients without insulin treatment, peak BG values higher than 250 mg/dl (OR, 7.65; 95% CI, 1.06–55.17; p=0.043) and BG fluctuation exceeding the level of 150 mg/dl (10.72; 1.74–65.90 p=0.010) on the first postoperative day were independently associated with the combined endpoint. Conclusions: Peak BG level and BG fluctuation on the first postoperative day were associated with the combined endpoint of complications and death but these results were only confined to patients without insulin treatment.

Previous reports have suggested that delivery is associated with the induction of inflammatory cytokines. The present study was designed to investigate whether increased cytokine production was present on postpartum day 3 after a normal pregnancy and whether any changes were associated with the mode of delivery. In total, 33 pregnant women were enrolled; 18 delivered vaginally and 15 underwent an elective caesarean section (C-section). The levels of 17 cytokines and growth hormones were measured at the beginning of delivery or before anaesthesia and on postpartum day 3. While interleukin (IL)-6 and IL-8 levels decreased significantly postpartum, other cytokine concentrations were comparable before and after delivery. Only IL-7 levels were significantly increased in the C-section patients compared with the vaginal birth patients postpartum. In conclusion, there was no risk of a prolonged maternal inflammatory reaction after an uncomplicated vaginal birth or elective C-section, so it is probably not necessary to consider this as an issue when making a decision on the mode of delivery following uncomplicated pregnancy.

Peptide analogues targeting various neuropeptide receptors have been used effectively in cancer therapy. A hallmark of adrenocortical tumor formation is the aberrant expression of peptide receptors relating to uncontrolled cell proliferation and hormone overproduction. Our microarray results have also demonstrated a differential expression of neuropeptide hormone receptors in tumor subtypes of human pheochromocytoma. In light of these findings, we performed a comprehensive analysis of relevant receptors in both human adrenomedullary and adrenocortical tumors and tested the antiproliferative effects of peptide analogues targeting these receptors. Specifically, we examined the receptor expression of somatostatin-type-2 receptor, growth hormone-releasing hormone (GHRH) receptor or GHRH receptor splice variant-1 (SV-1) and luteinizing hormone-releasing hormone (LHRH) receptor at the mRNA and protein levels in normal human adrenal tissues, adrenocortical and adrenomedullary tumors, and cell lines. Cytotoxic derivatives of somatostatin AN-238 and, to a lesser extent, AN-162, reduced cell numbers of uninduced and NGF-induced adrenomedullary pheochromocytoma cells and adrenocortical cancer cells. Both the splice variant of GHRH receptor SV-1 and the LHRH receptor were also expressed in adrenocortical cancer cell lines but not in the pheochromocytoma cell line. The GHRH receptor antagonist MZ-4–71 and LHRH antagonist Cetrorelix both significantly reduced cell growth in the adrenocortical cancer cell line. In conclusion, the expression of receptors for somatostatin, GHRH, and LHRH in the normal human adrenal and in adrenal tumors, combined with the growth-inhibitory effects of the antitumor peptide analogues, may make possible improved treatment approaches to adrenal tumors.

Familial hypertrophic cardiomyopathy (FHC) is caused by mutations in genes encoding sarcomeric proteins. Incomplete penetrance suggests the existence of modifier genes. Calmodulin (CaM) could be of importance given the key role of Ca(2+) for cardiac contractile function and growth. Any variant that affects CaM expression and/or function may impact on FHC clinical expression.We screened the promoter region of human calmodulin III gene (CALM3) and identified a new -34TA polymorphism with a T-allele frequency of 0.70. The distribution of CALM3 genotypes differed in 180 unrelated FHC patients carrying a known FHC mutation compared with 134 controls, with higher TT-genotype frequency (0.73 vs. 0.51) and lower frequencies of AT- (0.24 vs. 0.37) and AA genotypes (0.03 vs. 0.11; P = 0.0005). To study whether the -34TA polymorphism could play a modifier role, patients' relatives including both affected and healthy carriers were added. Affected carriers had a 0.56 times higher odds of carrying a T allele than healthy carriers (P = 0.053). We then investigated whether the -34TA polymorphism affects the promoter activity using luciferase reporter vectors containing either CALM3-T or CALM3-A promoters. The activity of CALM3-T was lower than CALM3-A in HEK293 cells (1.00 +/- 0.19 vs. 2.31 +/- 0.13, P = 0.00001) and in cardiomyocytes (0.96 +/- 0.10 vs. 1.33 +/- 0.08, P = 0.00727).These data suggest that the -34TA CALM3 polymorphism is a modifier gene for FHC, potentially by affecting expression level of CALM3 and therefore Ca(2+)-handling and development of hypertrophy.

Studies have been performed to describe the significance of genetic polymorphisms in complications associated with disturbed perinatal adaptation. Due to the large number of interacting factors, the results of classic statistical methods are often inconsistent. The random forest technique (RFT) is a robust nonparametric statistical approach that overcomes this problem through the calculation of the importance of each factor. We used RFT to reanalyze the importance of 24 genetic polymorphisms in the classification of preterm infants (birth weight, 680-1460 g, n = 100) to affected and unaffected groups according to the presence of acute perinatal complications. The accuracy of classification was between 0.5 and 0.8 for each complication when only birth data were considered. However, when genetic polymorphisms with the highest importance scores (ISs) were included in the analysis, the accuracy of classification according overall morbidity, necrotizing enterocolitis (NEC), acute renal failure (ARF), infant respiratory distress syndrome (IRDS), cardiac failure (CF), and patent ductus arteriosus (PDA) improved from 0.69, 0.60, 0.70, 0.72, 0.68, and 0.57 to 0.77, 0.70, 0.76, 0.77, 0.76, and 0.64, respectively. Our findings suggest that genetic polymorphisms identified by RFT as predictors may improve the risk assessment of preterm infants. RFT is a suitable tool to develop risk factor patterns in this population.

The aim of our study was to determine, how severe calorie restriction in anorexia nervosa (AN) may influence regulatory T (Treg) cells and their cellular networks, that is, their main inducers (dendritic cells (DC) and monocytes) and their target cells, CD4+ lymphocytes.We measured the prevalence of Tregs, myeloid and plasmocytoid DC. The prevalence of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12-positive monocytes, IL-2, IL-4 and interferon (IFN)-gamma positive CD4+ cells was determined by intracellular staining after activation.In total, 21 AN patients and 19 healthy age-matched controls (body mass index values, median (range): 14.9 (11.1-17.4) vs 23.2 (19.5-27.4) kg/m(2)) have been recruited.Prevalence of Tregs, DCs, TNF-alpha and IL-12-positive monocytes, IL-4 and IFN-gamma-producing CD4+ cells were similar in AN and controls. The prevalence of IL-2-positive CD4+ cells was somewhat lower in AN (% value, median (range): 12.05 (7.50-16.70) vs 14.40 (12.00-22.00), P0.05). None of these parameters correlated with the patients' clinical characteristics.Our results suggest that the antigen presenting cell - regulatory T cell - CD4+ lymphocyte axis is not affected by calorie and nutritional deficiency.

Background Transcatheter aortic-valve implantation (TAVI) is an established alternative therapy in patients with severe aortic stenosis and a high surgical risk. Despite a rapid growth in its use, very few data exist about the efficacy of cardiac rehabilitation (CR) in these patients. We assessed the hypothesis that patients after TAVI benefit from CR, compared to patients after surgical aortic-valve replacement (sAVR). Methods From September 2009 to August 2011, 442 consecutive patients after TAVI (n=76) or sAVR (n=366) were referred to a 3-week CR. Data regarding patient characteristics as well as changes of functional (6-min walk test. 6-MWT), bicycle exercise test), and emotional status (Hospital Anxiety and Depression Scale) were retrospectively evaluated and compared between groups after propensity score adjustment. Results Patients after TAVI were significantly older (p

Invariant NKT (iNKT) cells are considered to be important in some autoimmune diseases including Type 1 diabetes mellitus (T1DM). So far, the published data are contradictory in regard to the role of iNKT cells in T1DM. We aimed to study iNKT cell frequency and the function of different iNKT cell subgroups in T1DM. We compared the results of four subject groups: healthy (H), long-term T2DM (ltT2DM; more than 1 year), newly diagnosed T1DM (ndT1DM; less than 3 months), and ltT1DM (more than 1 year) individuals. We measured the iNKT cell frequencies by costaining for the invariant TCR α-chain with 6B11-FITC and Vα24-PE. After sorting the Vα24+6B11+ cells, the generated iNKT clones were characterized. We tested CD4, CD8, and CD161 expression and IL-4 and IFN-γ production on TCR stimulation. The CD4+ population among the iNKT cells was decreased significantly in ltT1DM versus ndT1DM, ltT2DM, or H individuals. The T1DM iNKT cell cytokine profile markedly shifted to the Th1 direction. There was no difference in the frequency of iNKT cells in PBMC among the different patient groups. The decrease in the CD4+ population among the iNKT cells and their Th1 shift indicates dysfunction of these potentially important regulatory cells in T1DM.