Medical University Vienna Research Articles

Ventriculo-arterial coupling in children with Still's murmur.

Still's murmur is the most common innocent heart murmur in children and considered flow related; however, so far the cause of the murmur has not yet been fully explained. Assessment of the hemodynamic ventriculo‐arterial interaction and the proportional anatomical dimensions of the left ventricle and the aortic root were the objective for this study. This case–control study was conducted at the Division of Pediatric Cardiology, Vienna Medical University, including healthy children with and without Still's murmur. To assess ventriculo‐arterial interaction, the model of ventriculo‐arterial coupling (VAC) was applied. The model describes the interaction between the left ventricle (left ventricular contractility, ELV) and the arterial system (effective arterial elastance, EA) by the VAC ratio EA/ELV. The parameters EA and ELV can be derived from M‐mode echocardiography thereby allowing a noninvasive pressure–volume analysis. Outcomes comprised VAC ratio and diameters of both the aortic root (AOD) and the left ventricle in end diastole (LVED) and end systole (LVES) as well as their relative proportions, ejection fraction (EF), stroke volume (SV), blood pressure (BP), and heart rate (HR). Forty‐three healthy children with Still's murmur (mean age 5.2 years) and 42 healthy children without murmur (mean age 5.8 years) participated in this study. Children with Still's murmur had a significantly lower VAC ratio EA/ELV (0.5 ± 0.13 vs. 0.59 ± 0.15; P < 0.005), a significantly higher EF% (67.1 ± 5.8 vs. 63.3 ± 5.6; P < 0.005, P < 0.01), and a larger SV per kg bodyweight (1.84 ± 0.33 vs. 1.68 ± 0.38; P < 0.05) than controls. BP, HR, and diameters of AOD, LVED, and LVES as well as their relative anatomic proportions did not differ between children with Still's murmur and controls. Still's murmur seems to be generated by a subtle alteration in ventriculo‐arterial coupling in healthy children. This result can be translated to parents, as they may be informed that their child's innocent murmur is caused by a more “lively interplay between the heart and the aorta.”

Impact of the newly implemented human feedback in contrast to Q-CPR® feedback and standard BLS on the “Effective Compression Ratio” outcome

Tanja Muschnig1,∗, Christoph Schriefl1, Matthias Muller1, Christoph Dibiasi1, Erich Pawelka1, Dominik Stumpf2, Franz Josef Nierscher3, Robert Greif4, Henrik Fischer5 1 Medical University Vienna, Vienna, Austria 2 Hospital of the Sisters of Charity Linz, Linz, Austria 3 Department of Anaesthesia, General Intensive Care and Pain Medicine, Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care, Medical University Vienna, Vienna, Austria 4 Department of Anaesthesiology and Pain Medicine, University Hospital Bern and University of Bern, Bern, Switzerland 5 Federal Ministry of the Interior, Vienna, Austria

Geometric morphometric evaluations of a randomized prospective split‐mouth study on modes of ligation and reverse‐curve mechanics

To evaluate tooth position after six and 9 months of orthodontics with conventional brackets on one side of the dentition and ligature-less brackets on the other. Orthodontic Division, Vienna Medical University. Twenty patients aged 22.5 ± 5.7 years, symmetrical malocclusion and arch form, no premolar extraction. Prospective split-mouth study, 0.022-inch SmartClip self-ligating brackets assigned randomly to the left or right dentition, conventional 0.018-inch brackets on the other side. 52 dental landmarks, digitized on plaster casts, represented dental arches at baseline (t0), 6 months and 9 months (t1, t2). During t0-t1, we used 0.016 and 0.014 x 0.025 inch superelastic wires, during t1-t2 connected reverse-curve hemiarch wires: 0.017 x 0.025 inch ß-titanium on the ligature-less side, and 0.016 x 0.022 inch Elgiloy multiloop wires on conventional brackets. Morphometric analyses were used to assess differences in dental arch shapes. Neither initial alignment nor the reverse-curve phase showed statistically significant differences between ligature-less and conventional brackets in moving teeth. Morphometric shape analyses corroborated current evidence that self-ligating brackets were no more effective than conventional brackets with steel ligatures after 6-month initial alignment. From months 6-9 treatment with ß-titanium reverse-curve wires on 0.022-inch ligature-less brackets resulted in similar tooth positions as accomplished by Elgiloy multiloop wires on 0.018-inch steel-ligature-tied brackets.

Bortezomib in late antibody-mediated kidney transplant rejection (BORTEJECT Study): study protocol for a randomized controlled trial

BackgroundDespite major advances in transplant medicine, improvements in long-term kidney allograft survival have not been commensurate with those observed shortly after transplantation. The formation of donor-specific antibodies (DSA) and ongoing antibody-mediated rejection (AMR) processes may critically contribute to late graft loss. However, appropriate treatment for late AMR has not yet been defined. There is accumulating evidence that the proteasome inhibitor bortezomib may substantially affect the function and integrity of alloantibody-secreting plasma cells. The impact of this agent on the course of late AMR has not so far been systematically investigated.Methods/designThe BORTEJECT Study is a randomized controlled trial designed to clarify the impact of intravenous bortezomib on the course of late AMR. In this single-center study (nephrological outpatient service, Medical University Vienna) we plan an initial cross-sectional DSA screening of 1,000 kidney transplant recipients (functioning graft at ≥180 days; estimated glomerular filtration rate (eGFR) >20 ml/minute/1.73 m2). DSA-positive recipients will be subjected to kidney allograft biopsy to detect morphological features consistent with AMR. Forty-four patients with biopsy-proven AMR will then be included in a double-blind placebo-controlled intervention trial (1:1 randomization stratified for eGFR and the presence of T-cell-mediated rejection). Patients in the active group will receive two cycles of bortezomib (4 × 1.3 mg/m2 over 2 weeks; 3-month interval between cycles). The primary end point will be the course of eGFR over 24 months (intention-to-treat analysis). The sample size was calculated according to the assumption of a 5 ml/minute/1.73 m2 difference in eGFR slope (per year) between the two groups (alpha: 0.05; power: 0.8). Secondary endpoints will be DSA levels, protein excretion, measured glomerular filtration rate, transplant and patient survival, and the development of acute and chronic morphological lesions in 24-month protocol biopsies.DiscussionThe impact of anti-humoral treatment on the course of late AMR has not yet been systematically investigated. Based on the hypothesis that proteasome inhibition improves the outcome of DSA-positive late AMR, we suggest that our trial has the potential to provide solid evidence towards the treatment of this type of rejection.Trial registrationClinicaltrials.gov: NCT01873157.

P1038 NEW QUALITY CRITERIA FOR TRANSIENT ELASTROGRAPHY CAN INCREASE THE PROPORTION OF VALID MEASUREMENTS WITH HIGH ACCURACY FOR DETECTION OF LIVER CIRRHOSIS AND PORTAL HYPERTENSION

P1038 NEW QUALITY CRITERIA FOR TRANSIENT ELASTROGRAPHY CAN INCREASE THE PROPORTION OF VALID MEASUREMENTS WITH HIGH ACCURACY FOR DETECTION OF LIVER CIRRHOSIS AND PORTAL HYPERTENSION P. Schwabl, S. Bota, P. Salzl, M. Mandorfer, B.-A. Payer, A. Ferlitsch, J. Stift, F. Wrba, M. Trauner, M. Peck-Radosavljevic, T. Reiberger, Vienna Hepatic Hemodynamic Lab. Dept. of Internal Medicine III, Div. of Gastroenterology & Hepatology, Medical University Vienna, Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria E-mail: philipp.schwabl@meduniwien.ac.at Background and Aims: Recently, new quality criteria for transient elastography (TE) measurements have been proposed (Boursier et. al. Hepatology 2013): very reliable: IQR/M 0.3 if TE 0.3 if TE >7.1 kPa. We evaluated the diagnostic power and accuracy of TE measurements according to these new quality criteria (accurate = very reliable + reliable) for non-invasive assessment of liver fibrosis (liver biopsy) and portal hypertension (HVPG). Methods: Patients undergoing TE, HVPG measurement and liver biopsy within 3 months at a tertiary care were retrospectively identified. Results: Among 278 patients (48.7±13.1 years, 74.7% male, 75.7% viral etiology, 57% F3/F4), traditional TE quality criteria identified 71.6% reliable measurements, while new criteria yielded in 83.2% accurate LS measurements (23.1% very reliable, 60.1% reliable). Reliable TE values according to traditional or new criteria were all significantly and similarly strong correlated with fibrosis stage (R =0.648 vs. R = 0.636) and HVPG (R=0.836 vs. R = 0.846). The accuracy for diagnosing liver cirrhosis (F4, cut-off: 14.5 kPa) was 76.5% and 75.0% for traditional and new TE criteria, respectively. The positive (PPV) and negative (NPV) values for new criteria at the 14.5 kPa cut-off were 83% and 70%. For predicting HVPG ≥10mmHg (cut-off: 16.1 kPa), the accuracies were 88.9% and 89.8% using traditional or new criteria, respectively. Both criteria resulted in AUCs for diagnosis of HVPG ≥10mmHg of over 0.95 with a PPV and NPV of 76% and 97%, respectively. Conclusions: Applying new quality criteria for TE measurements significantly increases the number of valid TE measurements without affecting accuracy of TE for diagnosis of liver cirrhosis and portal hypertension.

P1039 APPLICABILITY (APP) CRITERIA FOR REAL-TIME SHEAR WAVE ELASTOGRAPHY (RT-SWE) BY AIXPLORER COMPARED TO TRANSIENT ELASTOGRAPHY (TE) BY FIBROSCAN AND TO FIBROTEST

P1038 NEW QUALITY CRITERIA FOR TRANSIENT ELASTROGRAPHY CAN INCREASE THE PROPORTION OF VALID MEASUREMENTS WITH HIGH ACCURACY FOR DETECTION OF LIVER CIRRHOSIS AND PORTAL HYPERTENSION P. Schwabl, S. Bota, P. Salzl, M. Mandorfer, B.-A. Payer, A. Ferlitsch, J. Stift, F. Wrba, M. Trauner, M. Peck-Radosavljevic, T. Reiberger, Vienna Hepatic Hemodynamic Lab. Dept. of Internal Medicine III, Div. of Gastroenterology & Hepatology, Medical University Vienna, Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria E-mail: philipp.schwabl@meduniwien.ac.at Background and Aims: Recently, new quality criteria for transient elastography (TE) measurements have been proposed (Boursier et. al. Hepatology 2013): very reliable: IQR/M 0.3 if TE 0.3 if TE >7.1 kPa. We evaluated the diagnostic power and accuracy of TE measurements according to these new quality criteria (accurate = very reliable + reliable) for non-invasive assessment of liver fibrosis (liver biopsy) and portal hypertension (HVPG). Methods: Patients undergoing TE, HVPG measurement and liver biopsy within 3 months at a tertiary care were retrospectively identified. Results: Among 278 patients (48.7±13.1 years, 74.7% male, 75.7% viral etiology, 57% F3/F4), traditional TE quality criteria identified 71.6% reliable measurements, while new criteria yielded in 83.2% accurate LS measurements (23.1% very reliable, 60.1% reliable). Reliable TE values according to traditional or new criteria were all significantly and similarly strong correlated with fibrosis stage (R =0.648 vs. R = 0.636) and HVPG (R=0.836 vs. R = 0.846). The accuracy for diagnosing liver cirrhosis (F4, cut-off: 14.5 kPa) was 76.5% and 75.0% for traditional and new TE criteria, respectively. The positive (PPV) and negative (NPV) values for new criteria at the 14.5 kPa cut-off were 83% and 70%. For predicting HVPG ≥10mmHg (cut-off: 16.1 kPa), the accuracies were 88.9% and 89.8% using traditional or new criteria, respectively. Both criteria resulted in AUCs for diagnosis of HVPG ≥10mmHg of over 0.95 with a PPV and NPV of 76% and 97%, respectively. Conclusions: Applying new quality criteria for TE measurements significantly increases the number of valid TE measurements without affecting accuracy of TE for diagnosis of liver cirrhosis and portal hypertension.

Lack of donor and recipient age interaction in cardiac transplantation

The proportion of older donors and recipients is constantly rising in heart transplantation (HTX). The impact of age on different outcomes after HTX has been studied; however, effects of interaction between donor and recipient age remain elusive. This retrospective cohort study comprised 1,190 patients who underwent HTX between 1984 and 2011 at the Medical University Vienna. Multivariable models consisted of a basic set that included donor age, recipient age, and transplant eras and were adjusted for 2 sets of 6 possible confounders and 3 mediator variables. Cox models were used to estimate the risk of death. To search for age-related effects on the development of cardiac allograft vasculopathy (CAV), we applied cause-specific Cox models and proportional sub-distribution hazard models for competing risk data. Survival was 80%, 77%, 69%, and 56% after 1, 2, 5, and 10 years, respectively. Donor age (hazard ratio [HR], 1.1; 95% confidence interval [CI], 1.0-1.2), recipient age (HR, 1.1; 95% CI, 1.0-1.2), admission from intensive care unit to HTX (HR, 1.5; 95% CI, 1.2-1.9), and diabetes (HR, 1.4; 95% CI, 1.1-1.7) were identified as significant independent risk factors for death. Significant risk factors for CAV were donor age (HR, 1.4; 95% CI, 1.3-1.5) and male recipient sex (HR, 1.5; 95% CI, 1.0-2.2). Recipient age was inversely associated with initiation of CAV (HR, 0.8; 95% CI, 0.8-1.0). Analysis of the interaction between donor and recipient age was not significant for death (p = 0.8) or CAV (p = 0.6). We found no interaction between donor and recipient age negatively affecting mortality and CAV. The identified independent risk factors may have implications for allocation strategies in elderly recipients.

Additive homeopathy in cancer patients: Retrospective survival data from a homeopathic outpatient unit at the Medical University of Vienna

Current literature suggests a positive influence of additive classical homeopathy on global health and well-being in cancer patients. Besides encouraging case reports, there is little if any research on long-term survival of patients who obtain homeopathic care during cancer treatment. Data from cancer patients who had undergone homeopathic treatment complementary to conventional anti-cancer treatment at the Outpatient Unit for Homeopathy in Malignant Diseases, Medical University Vienna, Department of Medicine I, Vienna, Austria, were collected, described and a retrospective subgroup-analysis with regard to survival time was performed. Patient inclusion criteria were at least three homeopathic consultations, fatal prognosis of disease, quantitative and qualitative description of patient characteristics, and survival time. In four years, a total of 538 patients were recorded to have visited the Outpatient Unit Homeopathy in Malignant Diseases, Medical University Vienna, Department of Medicine I, Vienna, Austria. 62.8% of them were women, and nearly 20% had breast cancer. From the 53.7% (n=287) who had undergone at least three homeopathic consultations within four years, 18.7% (n=54) fulfilled inclusion criteria for survival analysis. The surveyed neoplasms were glioblastoma, lung, cholangiocellular and pancreatic carcinomas, metastasized sarcoma, and renal cell carcinoma. Median overall survival was compared to expert expectations of survival outcomes by specific cancer type and was prolonged across observed cancer entities (p<0.001). Extended survival time in this sample of cancer patients with fatal prognosis but additive homeopathic treatment is interesting. However, findings are based on a small sample, and with only limited data available about patient and treatment characteristics. The relationship between homeopathic treatment and survival time requires prospective investigation in larger samples possibly using matched-pair control analysis or randomized trials.

Is There a Contribution of Both Cav1.4 and Cav1.3 L-Type Calcium Channels to Retinal Synaptic Transmission?

Cav1.3 and Cav1.4 L-type calcium channels were previously both shown to be expressed in the retina. Whereas Cav1.4 channels are predominantly expressed in the outer plexiform layer (OPL) at photoreceptor ribbon synapses, reports on the distribution pattern of Cav1.3 channels in the retina are controversial. One study reported the uniform expression across all retinal cell layers, and others showed accumulation in photoreceptor inner segments or the OPL or the inner nuclear layer or the ganglion cell (GC) layer of the retina. Mutations in the pore-forming α1-subunit, found in patients diagnosed with Congenital Stationary Night Blindness type 2 (CSNB2), result in impaired signaling between photoreceptor cells and second-order neurons. Exemplary, we report the functional consequences of the novel CaV1.4 mutation GV found in an Austrian family. Biophysical analysis of GV channels in whole-cell patch-clamp experiments revealed a reduced current density ([pA/pF]: wt: 12.8±1.4, n=18; GV: 3.7±1.0, n=7; p<0.001, 15 mM Ca2+ used as charge carrier) due to decreased surface expression of functional channels, expected to lead to impaired retinal signaling. In contrast, the contribution of Cav1.3 channels to synaptic transmission is rather ambiguous. We therefore performed multi electrode (MEA) analyses of light-dark evoked GC activity in Cav1.3-/- mice retinas. Retinas were excised from adult wildtype (wt) and Cav1.3-/- mice (red-light, carbogen-equilibrated Ames) and mounted ganglion-cell-side-down (via nitrocellulose-menbrane) on a MEA array. Preliminary data showed a prolongation of GC response latencies in Cav1.3-/- compared to wt supporting the idea that Cav1.3 channels also contribute to synaptic transmission. However qRT-PCR analysis of Cav1.4-/- retinas showed a significant upregulation of Cav1.3-mRNA, thus an alternative role for signal transduction might also be suggested. Support: Austrian Science Funds (FWF), P22526:AK; SFB F44 (F44020): JS, AK, (F44060): GJO, Medical University Vienna.

Lead Transfer during Breastfeeding: A Start toward Filling in the Data Gaps

Adverse health effects of lead have been detected at ever decreasing blood concentrations.1 Yet there is still a degree of mystery around the toxicokinetics of lead in the body—that is, the processes controlling a chemical’s uptake, biotransformation, distribution, and elimination, which ultimately determine how toxic it is.2 A new study in EHP provides insight into lead transfer from mothers to their children via breast milk.3 Lead is stored primarily in bone. Women’s blood lead levels rise during pregnancy and lactation due to increased bone turnover, which releases previously stored lead. Human milk is a proven route of lead exposure for breastfeeding infants, although the lack of information about lead toxicokinetics has made it impossible to clearly define any risk. Lead exposure in utero and during breastfeeding can cause adverse effects in children independent of any later exposure, so prevention is critical.4 Clinicians are generally advised that women with blood lead levels below 40 µg/dL can breastfeed without clinical harm to their children.5 The rationale is that only a tiny fraction of the lead in blood is bioavailable (i.e., biologically active).6 Human milk is low in protein, the molecular carrier of lead.3 Lead is therefore not expected to transfer heavily from blood into milk, and the milk-to-plasma (M/P) ratio for humans has been reported at less than 1.0.5 (A ratio of 1.0 would indicate equal concentrations of lead in milk and plasma.) Given that human milk can be an important source of lead for nursing infants, early testing may be prudent for babies of highly exposed women. But the authors of the current study could find no clear justification for that number in humans. To validate the ratio, they used samples that had been collected in Mexico City in the late 1990s during a longitudinal study of lead biomarkers and reproduction. In that study 463 pregnant women provided blood and plasma samples during pregnancy and the first year postpartum. Breastfeeding mothers also provided milk samples 1 month postpartum. The current study focused on blood, plasma, and milk samples from 81 women; for a subsample of 60 mother–infant pairs, 3-month infant blood samples were available. Lead concentrations were measured in all samples and were found to vary widely: 1.7–28.7 µg/dL, 0.03–0.5 µg/L, and 0.04–3.2 µg/L for maternal blood, plasma, and milk, respectively, and 0.5–14.5 µg/dL for infant blood. M/P ratios ranged from 0.6 to 39.8, averaging 7.7, with 97% of the ratios exceeding 1.0. According to Claudia Gundacker, an associate professor at the Institute of Medical Genetics, Medical University Vienna, who was not involved with the study, further work is needed to substantiate the findings on the higher M/P ratio and determine what they might mean for advising pregnant and nursing women. “In general,” she says, “there is a gap of knowledge on lead cellular toxicokinetics and on transport of lead across membranes.” She says the major strength of the study is that breast milk lead was analyzed in relation to maternal plasma lead and whole blood lead, “which provides valuable information on the distribution of lead in the various compartments.” Lead author Adrienne Ettinger, an assistant professor at the Yale Center for Perinatal, Pediatric and Environmental Epidemiology, stresses that the findings should not discourage women from breastfeeding. “However, if a woman is known to have lead exposure, … the infant’s blood lead levels should be checked earlier than they normally would be,” she says. That way, steps can be taken to reduce or eliminate exposure. Children typically aren’t checked until they’re 9–12 months old. “In certain places,” Ettinger says, “they’re not being checked at all because they are considered ‘low risk’ [for lead exposure].” Gundacker notes that the study raises many questions regarding the factors contributing to the huge variability in the observed M/P ratios, including genetic variation. Although the cross-sectional design of the study limits the conclusions that can be drawn, the variability of lead transfer from mothers to their children via breast milk may provide an impetus to reexamine current advice, she says.

Posterior capsule opacification and neodymium:YAG rates with 2 single-piece hydrophobic acrylic intraocular lenses: Three-year results

To compare the incidence and intensity of posterior capsule opacification (PCO) between 2 similar 1-piece foldable hydrophobic acrylic intraocular lenses (IOLs) over 3 years. Department of Ophthalmology, Medical University Vienna, Vienna, Austria. Randomized prospective patient- and examiner-masked clinical trial with intraindividual comparison. Patients with bilateral age-related cataract had cataract surgery and implantation of a Tecnis ZCB00 continuous-optic-edge IOL in 1 eye and an Acrysof SA60AT interrupted-optic-edge IOL in the other eye. Postoperative examinations were performed at 6 months and 3 years. Digital retroillumination images were taken of each eye. The amount of PCO (score 0 to 10) was assessed subjectively at the slitlamp and objectively using automated image-analysis software. The study comprised 54 patients (108 eyes). The mean objective PCO score was 1.3 ± 1.7 (SD) for the continuous-optic-edge IOLs and 0.9 ± 1.3 for the interrupted-optic-edge IOLs (P=.10). Three years postoperatively, a neodymium:YAG (Nd:YAG) capsulotomy was performed in 26.1% of eyes with the continuous-optic-edge IOL and 21.7% with the interrupted-optic-edge IOL (P=.56). There was no significant difference in corrected distance visual acuity, capsulorhexis–IOL overlap, capsule folds, or anterior capsule opacification 3 years after surgery. Both IOLs had comparable PCO and Nd:YAG rates 3 years postoperatively. The optimized barrier function of the continuous-optic-edge IOL and the material properties of the interrupted-optic-edge IOL seemingly outbalanced the effect on lens epithelial cell migration and proliferation beneath the optic.

Thirty-six years of research on oral surgery and implantology in Vienna

At the end of 2012 Professor Georg Watzek retired as head of the Department of Oral Surgery at the Bernhard Gottlieb School of Dentistry, Vienna Medical University. This gives the opportunity to look back on 36 years of publication history since his first research article was published in 1976. Professor Georg Watzek was affiliated to the Department of Oral and Maxillofacial Surgery (Vienna Medical University, Austria, head: Univ. Prof. Dr. Siegfried Wunderer) from 1973 and published his first papers there. After his habilitation in 1980 he became head of the Department of Oral Surgery (University Dental Clinic, Vienna Medical University, Austria) and in 1987 head of the Dental Clinic. From 1983 to 1993 he was editor of the journal Stomatologie, president of the Austrian Society for Oral Surgery and Implantology (1983–2002) and president of the Austrian Dental Association (1989–1993). Professor Georg Watzek is an honorary member of the Hungarian Dental Association (1991) and the German and Czech Society for Implantology (2003). From 1994 to 1997 he was visiting professor at the University of Pennsylvania and in 2003 he served as president of the European Association for Osseointegration (EAO). He is a founding member of the scientific board of the Osteology Foundation in 2004 and became associate editor for the International Journal of Oral & Maxillofacial Implants (JOMI) in 2006. This special issue of The International Journal of Stomatology and Occlusion Medicine gives a survey of all PubMed listed scientific articles published by Watzek and coworkers from 1976 to 2012 structured into four time periods. We hope you enjoy this 36th anniversary compilation of research on oral surgery and implantology in Vienna. J. Stomat. Occ. Med. (2013) 6:1 DOI 10.1007/s12548-013-0085-8

Authors’ Reply

The number of lung transplants (LTx) performed to treat bronchiolitis obliterans in patients with end-stage lung disease caused by chronic graft-versus-host disease (cGvHD) is small, limiting comparison of outcome between centers. Holm et al. (1) report 13 patients with LTx for bronchiolitis obliterans after allogeneic stem cell transplantation (SCT) with a much lower mortality rate (15%) compared with our patients (57%). However, Koenecke et al. published 12 patients in a multicenter study with a case fatality rate of 33% (2). When we focus on the patient characteristics, there is a remarkable difference in the extensiveness of cGvHD. Nearly half of the patients reported by Holm et al. (1) did not have any other organ involvement with cGvHD. This is an interestingly high incidence rate of solitary cGvHD of the lung. All of our patients presented with at least two other organs involved with cGvHD (3). Therefore, the intensity and number of immunosuppressants in our patient series are much higher (median of four treatment lines). One could speculate that this results in a higher rate of infectious complications and secondary malignancies, which limits the prognosis after LTx. Another unresolved question is the ideal time point of LTx after allogeneic SCT. Our patients were considered for LTx if, despite multiple lines of immunosuppressants for at least 6 months, patients were immobilized and oxygen dependent with severe respiratory distress. Depending on the onset and progression of cGvHD, patients received the first available matching lung. The guidelines of the International Society of Heart and Lung Transplantation that recommend an interval of 5 years between LTx and previous malignancy are not applicable for SCT after hematologic malignancies. The time and the interval of listing is dependent on the clinical presentation of the patient and the worsening of lung function tests. In summary, the differing survival rates clearly derive from a center-dependent patient selection for LTx. The outcome of LTx patients after allogeneic SCT is at least similar to patients whose underlying disease is other than cGvHD. Due to the limitation of systemic immunosuppressants for disease stabilization, LTx is still a good treatment option that should be offered to selected patients with cGvHD of the lung. Ursula M. Vogl 1 Kazuhiro Nagayama2,3 Werner Rabitsch1 1 Department of Internal Medicine I Bone Marrow Transplantation Medical University Vienna Vienna, Austria 2 Department of Thoracic Surgery Vienna, Austria 3 Department of Thoracic Surgery The University of Tokyo Graduate School of Medicine Tokyo, Japan

Chronic hepatitis E infection in lung transplant recipients

Hepatitis E virus (HEV) genotype 3 has been identified in patients with autochthonous HEV infections in developed countries and is currently being recognized as an emerging zoonotic pathogen. HEV infection may lead to a chronic hepatitis in immune-compromised patients. We studied the incidence of HEV in adult lung transplant recipients at the Medical University Vienna and the University Medical Center Groningen. These recipients presented with elevated liver test results during the post-transplant follow-up period. The time of infection was investigated using stored specimens, and the HEV genotype was determined by sequence analysis of the open reading frame (ORF)1 and ORF2 region. The study included 468 adult lung transplant recipients. Ten patients (2.1%) tested positive for HEV RNA. At the time of HEV detection, all patients had elevated liver test results, with median alanine aminotransferase levels of 77 U/liter and showed a mild hepatitis. A chronic HEV infection was diagnosed in the 8 lung transplant recipients who survived longer than 6 months after transplantation. Viral genotyping revealed only genotype 3 strains. In 2 of the lung transplant recipients treated with oral ribavirin monotherapy, HEV RNA was cleared from the plasma within 2 months with simultaneous normalization of alanine aminotransferase levels. Chronic HEV is an important cause of liver test abnormalities after lung transplantation; therefore, routine screening for HEV RNA is strongly recommended in lung transplant recipients. Oral ribavirin appears to be a safe and effective treatment for chronic HEV infection in lung transplant recipients.

Impact of Her-2-Targeted Therapy on Overall Survival in Patients With Her-2 Positive Metastatic Breast Cancer

Upon disease progression on trastuzumab-based therapy, patients with HER-2 positive metastatic breast cancer (MBC) may switch to lapatinib or continue on trastuzumab. We aimed to assess the impact of both strategies on overall survival (OS) in all patients treated for HER-2 positive MBC at the Medical University Vienna from 1999 until 2009. A total of 201 patients were identified from a breast cancer data base. Of these 115 (57.2%) received multiple lines of trastuzumab-based therapy, whereas 58 (28.9%) were treated with a single line. A control group of 28 patients (13.9%) had never received trastuzumab as they were treated before 1999, when trastuzumab was registered. OS from diagnosis of metastatic disease was defined as primary study endpoint. Trastuzumab significantly prolonged OS in HER-2 positive MBC (41 versus 13months; p<0.001). Administration of multiple lines further improved OS; this, however, did not reach statistical significance (47 versus 28months; p=0.069). Positive estrogen receptor (ER) status (HR 1.6; 95% CI 1.13-2.27) was associated with better outcome compared to negative estrogen receptor status (p=0.02). Addition of lapatinib did not improve OS significantly in patients with prior trastuzumab-based therapy (62 versus 47months; p=n.s.). Patients receiving lapatinib after diagnosis of BM, however, experienced an improvement of OS (22 versus 5months; p=0.022). Trastuzumab improves OS in patients with HER-2 positive MBC with further nonsignificant improvement when administered in multiple lines. Lapatinib did not further improve OS in the entire population; however, lapatinib might improve OS in patients with BM.

Evaluation of process management of postpartum hemorrhage due to uterine atony

Objective: To evaluate the management process and the guidelines for management of postpartum hemorrhage due to uterine atony at the General Hospital Vienna, Medical University Vienna. Material and Methods: A retrospective analysis was carried out on all 24 cases of postpartum hemorrhage due to uterine atony with an estimated blood loss of more than 800 mL, in which standardized guidelines were obtained. We included all women who gave birth at the General Hospital of Vienna, the Medical University Vienna, during the period from January 1st 2003 and December 31st 2009 and who suffered blood loss 800 mL at minimum due to uterine atony. Results: The guidelines were in use for 14% - 71%. The average blood loss of the 24 cases with uterine atony was 1342 mL. Conclusion: The management process of postpartum hemorrhage due to uterine atony deviates from the hospital’s guidelines in many cases.

LAMP-2, a novel endocytic receptor on human monocytes derived dendritic cells (MDDC).

Event Abstract Back to Event LAMP-2, a novel endocytic receptor on human monocytes derived dendritic cells (MDDC). Dario Leone1* 1 Medical University Vienna, Clinical Institute of Pathology, Austria LAMP-2, a novel endocytic receptor on human monocytes derived dendritic cells (MDDC). Dario Leone* Renate Kain and Andrew Rees* Clinical Institute of Pathology, Medical University of Wien. Supported by Marie Curie action (Transvir network) Keyword (Human Dendritic Cell, novel endocytic receptor, LAMP-2, uptake, antigen presentation) Lysosome-associated membrane protein-2 (LAMP-2) is a type 2 membrane-protein that is commonly used as lysosome and late endosomal marker and with essential roles in chaperone mediated autophagy and antigen presentation. LAMP-2 is also present on the cell-surface although its role was never studied. We focus on the role of LAMP-2 as a receptor on freshly isolated monocytes and iDCs with possible implication in antigen presentation. LAMP-2 was detected on the surface of immature MDDC both by FACS and confocal microscopy, its expression increased after maturation with IFN-γ LPS. The monoclonal anti-LAMP-2 antibody (H4B4) bound to LAMP-2 on the surface of MDDC and was rapidly and specifically internalized when compared to control antibodies in the presence of Fc blockade. Also the Fab fragment alone is internalized as well. Uptake was absent in MDDC from an individual with genetic LAMP-2 deficiency, Danon-disease. As expected, MDDC LAMP-2 and HLA-DR localized to partially overlapping compartments in iDC but there was no co-localization with HLA-DM. However, confocal microscopy showed that H4B4 transits into a HLA-DM positive compartment 1 hour after ligating LAMP-2 on the cell surface. Co-localization is no longer detectable after 3 hours. Finally, stimulation of immature MDDCs with H4B4 promote activation in the presence of IFN-γ indicated by up-regulation of CD80/CD83. This data suggest that when LAMP-2 is on the membrane acts as a specific receptor for internalization of extracellular molecules. H4B4 mimics natural ligands and after internalization can be found into the MIIC causing as well the maturation of DCs up-regulating CD80/83. Keywords: human dendritic cell, Antigen Presentation, Lysosomes, endocytic receptor, autoan, MHCII compartment Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune receptors and signaling Citation: Leone D (2013). LAMP-2, a novel endocytic receptor on human monocytes derived dendritic cells (MDDC).. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00633 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Dario Leone, Medical University Vienna, Clinical Institute of Pathology, Vienna, 1090, Austria, bleons2.0@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Dario Leone Google Dario Leone Google Scholar Dario Leone PubMed Dario Leone Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Medizinbibliothekenbeta – Konstant im Wandel

The focus of the current issue 3/2013 of GMS Medizin – Bibliothek – Information is the annual conference 2013 of the German Medical Libraries Association in Berlin. The motto of the conference was “Medical librariesbeta – Change is the constant”. The authors in this issue are Michaele Adam (Open access publishing in medicine – in the focus of bibliometrics at the SLUB Dresden), Bruno Bauer, Helmut Dollfus & Daniel Formanek (The university library at the Medical University Vienna goes e-only. Change in the provision of literature from p+e to e-only on January 1st, 2013), Henriette Senst & Jens Erling (The teaching services of the Robert Koch-Institute’s library) and Martina Semmler-Schmetz & Jutta Matrisciano (Medical Librariesbeta – Change is the Constant. Annual meeting 2013 of the German MLA (AGMB), September 16th to 18th in Berlin). Furthermore this focus issue features articles from Oliver Obst & Verena Salewsky (How do today’s students learn? An e-book study of the branch library of medicine, University of Munster) and from Oliver Obst, Christiane Hofmann, Helge Knuttel & Petra Zoller (“Ask a question, get an answer, continue your work!” – Survey on the use of UpToDate at the universities of Freiburg, Leipzig, Munster and Regensburg).

Factor V Leiden Mutation Increases the Risk of Venous Thromboembolism in Cancer Patients – Results From the Vienna Cancer and Thrombosis Study (CATS).

AbstractAbstract 2253 Background:Patients with cancer are at an increased risk of venous thromboembolism (VTE). The risk varies markedly in different patient populations and improvement of the prediction of VTE would be of advantage for tailoring thrombosis prophylaxis. Factor V Leiden is the most common genetic risk factor for VTE and the impact of factor V Leiden on cancer-associated thrombosis is not yet fully elucidated. Objective:To study the impact of factor V Leiden on the risk of VTE in cancer patients. Patients and Methods:Nine-hundred-eighty-two patients with newly diagnosed cancer (n=745) or progression of disease after complete or partial remission (n=237) were included in the cancer and thrombosis study (CATS), a prospective observational single centre cohort study at the Medical University Vienna. Patients were followed for a maximum period of 2 years. Blood samples were collected at inclusion and factor V Leiden was determined by genotyping. The main outcome measure was symptomatic or lethal objectively confirmed VTE. All VTE events were adjudicated independently. Results:Of the 982 patients (median age 62 years, interquartile range (IQR) 52–68, 537 men, 445 women) factor V-Leiden was found in 72 (7.3%), 70 had a heterozygous and two a homozygous genotype. Ten of 72 (14%) patients with factor V-Leiden developed VTE, whereas this was the case in 69 of 910 (7.6%) patients without factor V-Leiden. Interestingly, both patients with homozygous factor V Leiden developed VTE. In multivariable analysis that included age, sex, different tumour types, newly diagnosed versus recurrence of disease and the treatment modalities (chemotherapy, radiotherapy and surgery) the hazard ratio (HR) for factor V Leiden was 2.04 (95% confidence interval (CI) 1.04–3.97)). In patients with newly diagnosed tumours the HR for factor V Leiden was 3.7 (95% CI 1.2–12.2) after 30 days. In Kaplan Meier analysis the probability for development of VTE after 6 months was 5.7% in those without and 13% in those with factor V Leiden, after one year the corresponding rates were 7.3% and 15%. Conclusions:Factor V Leiden is a genetically determined and thus disease-independent parameter, which is associated with VTE in cancer patients, especially shortly after cancer diagnosis, and could therefore be used for individual risk assignment. Disclosures:No relevant conflicts of interest to declare.

Involvement of epigenetic mechanisms in regulating expression of the calcium sensing receptor in colorectal cancer

Involvement of epigenetic mechanisms in regulating expression of the calcium sensing receptor in colorectal cancer