Publications by authors named "Irene Steiner"

26 Publications

  • Page 1 of 1

The influence of retinal oxygen saturation and choroidal volume on postoperative outcomes in patients with epiretinal membrane.

Acta Ophthalmol 2021 Aug 15. Epub 2021 Aug 15.

Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.

Purpose: To investigate the effects of vitrectomy (Vy) with or without same time cataract surgery and membrane plus internal limiting membrane peeling (MP+ILMP) on retinal oxygenation and choroidal volume and their role on postoperative outcome.

Methods: Thirty-two eyes were included in this prospective clinical study. All patients received 23 gauge Vy+MP+ILMP. Additional cataract surgery was performed in 14 patients. Follow-up visits were scheduled at day 1, week 1, month 1 and month 3. At each visit, best corrected visual acuity (BCVA) using ETDRS charts, oxygenation of retinal vessels using the Oxymap T1, and optical coherence tomography (OCT, Heidelberg Spectralis) was performed.

Results: Mean BCVA increased significantly from 73 ± 11 letters to 77 ± 7 letters at month 3 (p = 0.02). Mean central retinal thickness (CRT) decreased from 456 ± 84 µm at baseline to 418±58µm (p = 0.01 baseline versus month 3). In the cataract surgery group, CRT was higher at month 3 than in the group without (400 ± 58 µm versus 441 ± 51 µm; p = 0.007). There was no statistically significant difference in choroidal volume or oxygenation of retinal vessels between groups (additional cataract surgery versus vitrectomy alone). Oxygenation of retinal arteries tended to decrease at day 1 followed by an increase, but the changes did not reach the level of significance (p = 0.29 baseline versus month 3). Oxygenation of retinal veins increased significantly (p = 0.02 baseline versus month 1; p = 0.04 baseline versus month 3, accordingly). There was a significant negative correlation (Spearman correlation coefficient rs = -0.35, p = 0.047) between visual acuity and oxygenation of retinal veins at month 3. No statistically significant correlation was found between CRT and oxygenation of neither retinal arteries nor veins. Choroidal volume (CV) of the central mm did not change significantly during the study period (baseline: 0.203 ± 0.04 mm , median: 0.206, month 3: 0.205 ± 0.04 mm , p = 0.54). There was no statistically significant effect of choroidal volume at baseline on postoperative clinical outcomes (change in BCVA estimate [95% CI]: 7 [-76; 90], p = 0.86; change in CRT: 147 [-577; 871], p = 0.68).

Conclusion: Oxygen saturation may affect the visual acuity outcome but not the CRT in patients after vitrectomy for epiretinal membrane. Choroidal thickness had no statistically significant influence on the study outcomes. Further studies are needed to evaluate if the measurement of retinal oxygenation may be helpful in the decision for surgery.
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http://dx.doi.org/10.1111/aos.14966DOI Listing
August 2021

Impact of large choroidal vessels on choriocapillaris flow deficit analyses in optical coherence tomography angiography.

PLoS One 2021 3;16(8):e0254955. Epub 2021 Aug 3.

Vienna Clinical Trial Center (VTC), Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.

Purpose: To investigate the impact of large choroidal vessels (LCV) on Choriocapillaris (CC) flow deficit (FD) analyses with swept-source optical coherence tomography angiography (SS-OCTA).

Design: Prospective, cross-sectional study.

Methods: Macular 6x6mm SS-OCTA scans were obtained from intermediate age-related macular degeneration (iAMD) and healthy eyes. Images were captured and processed according to most common standards and analyzed for percentage of flow-deficits (FD%) within four 1x1mm squares at the corners of each image. Choroidal thickness (CT), iris color and refraction error were considered as potential influential factors for LCV visibility. A linear mixed model and logistic regression models were calculated for statistical evaluation.

Results: Sixty-nine iAMD and 49 age-matched healthy eyes were enrolled. LCV were visible in at least one sector in 52% of iAMD and 47% of healthy eyes. Within the iAMD group FD% were significantly lower in areas containing LCV (p = 0.0029). Increasing CT resulted in an odds ratio decrease of LCV (OR: 0.94, p<0.0001). Below a CT value of ≤118μm LCV could be expected with a sensitivity of 86% and a specificity of 85%.

Conclusions: LCV can significantly affect CC FD analyses of SS-OCTA images. Their visibility is negatively associated with CT. The impact of LCV should be taken into account when performing CC FD assessments, especially in patients where reduced CT is to be expected and inclusion of affected areas should be considered carefully.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254955PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330935PMC
August 2021

Rotational Stability of Intraocular Lenses: A Standardized Method for More Accurate Measurements in Future Studies.

Am J Ophthalmol 2021 Jun 8. Epub 2021 Jun 8.

Department of Ophthalmology and Optometry of the Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address:

Purpose: To assess the reliability and reproducibility of a new semi automated evaluation method Rotix for intraocular lens rotation (IOL) and to define a standardized evaluation method for future toric IOL studies.

Design: Reliability and reproducibility study SETTING: Department of Ophthalmology, Medical University of Vienna PATIENT POPULATION: A dataset of 25 patients with 2 consecutive follow-up visits was created to test the intra- and inter-rater reliability. A datatest set of 10 patients including 30 pictures taken 5 minutes apart was created to test the short-term reproducibility.

Intervention: Evaluation of IOLs rotational stability using non-toric implants in 25 × 2 consecutive follow-up visits. Two experienced graders performed axis evaluation 3 times in a randomized order. One experienced grader performed axis evaluation for the short-term reproducibility study. Reference landmarks at the end of operation were used to assess the IOL axis.

Main Outcome Measures: Intra-, inter-rater reliability and short-term reproducibility of axis measurements.

Results: Mean standard deviation for intra-rater reliability was 0.16 degrees. The intra-class correlation coefficients (ICC) were 0.97 for grader 1 and 0.96 for grader 2, respectively. A very high inter-rater correlation of 0.95 was found. The mean individual difference between grader 1 and grader 2 was 0.061± 0.28 degrees. Short-term reproducibility showed a mean standard deviation of 0.22±0.14 degrees.

Conclusion: The novel semi automated evaluation method showed an accurate inter- and intra-rater reliability. Short-term reproducibility was below 0.25 degrees. The method of using non-movable reference landmarks showed reliable results and should be used as a standard in future toric IOL studies.
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http://dx.doi.org/10.1016/j.ajo.2021.06.006DOI Listing
June 2021

Early Identification of Retinal Neuropathy in Subclinical Diabetic Eyes by Reduced Birefringence of the Peripapillary Retinal Nerve Fiber Layer.

Invest Ophthalmol Vis Sci 2021 04;62(4):24

Department of Ophthalmology and Optometry, Medical University Vienna, Vienna, Austria.

Purpose: To study birefringence of the peripapillary retinal nerve fiber layer (RNFL) of diabetic eyes with no clinical signs of diabetic retinopathy (DR) or mild to moderate DR stages using spectral-domain polarization-sensitive (PS) optical coherence tomography (OCT).

Methods: In this observational pilot study, circular PS-OCT scans centered on the optic nerve head were recorded in prospectively recruited diabetic and age-matched healthy eyes. From averaged circumpapillary intensity and retardation tomograms plots of RNFL birefringence were obtained by a linear fit of retardation versus depth within the RNFL tissue for each A-scan position and mean birefringence values for RNFL calculated. Spectral-domain OCT imaging (Heidelberg Engineering) was performed to assess peripapillary RNFL thickness and macular ganglion cell complex (GCC).

Results: Out of 70 eyes of 43 diabetic patients (mean ± SD age: 50.86 ± 15.71) 36 showed no signs of DR, 17 mild and 17 moderate nonproliferative DR with no diabetic macular edema. Thirty-four eyes of 34 healthy subjects (53.21 ± 13.88 years) served as controls. Compared with healthy controls (0.143° ± 0.014°/µm) mean total birefringence of peripapillary RNFL was significantly reduced in subclinical diabetic eyes (0.131° ± 0.014°/µm; P = 0.0033), as well as in mild to moderate DR stages (0.125° ± 0.018°/µm, P < 0.0001) with borderline statistically significant differences between diabetic patients (P = 0.0049). Mean birefringence values were significantly lower in inferior compared with superior RNFL sectors (P < 0.0001) of diabetic eyes with no such difference detected in the healthy control group.

Conclusions: We identified evidence of early neuroretinal alteration in diabetic eyes through reduced peripapillary RNFL birefringence assessed by PS-OCT occurring before appearance of clinical microvascular lesions or GCC alterations.
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http://dx.doi.org/10.1167/iovs.62.4.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083066PMC
April 2021

Comparison of safety and effectiveness between 23-gauge and 25-gauge vitrectomy surgery in common vitreoretinal diseases.

PLoS One 2021 5;16(3):e0248164. Epub 2021 Mar 5.

Department of Ophthalmology and Optometry, Medical University Vienna, Vienna, Austria.

Purpose: To assess and compare safety and effectiveness between 23-gauge and 25-gauge vitrectomy systems for the treatment of common vitreoretinal diseases in non-vitrectomized eyes.

Methods: Retrospective evaluation of patients who underwent pars plana vitrectomy from April 2018 to December 2019 at the Department of Ophthalmology and Optometry at the Medical University of Vienna (MUV) for the following indications: macular epiretinal membrane, macular hole, macular lamellar hole, vitreous hemorrhage, vitreous opacities, vitreomacular traction syndrome and macular edema.

Results: 201 eyes of 195 patients that underwent 23-gauge (n = 105 eyes) or 25-gauge (n = 96 eyes) vitrectomy were included in this study. The mean best-corrected visual acuity (BCVA) improved at 1-3 months postoperatively and beyond 3 months in both gauge groups. Risk of any complication within 1 month postoperatively was lower in the 25-gauge group, but the difference was statistically not significant (HR [95% CI]: 0.95 [0.53; 1.70], p = 0.85). Intraocular pressure less than 5 mmHg was observed in 2 eyes (2%) in the 23-gauge group at the first postoperative day. Intraocular pressure elevation over 25 mmHg occurred in 5 eyes (2 eyes, 2%, in 23-gauge and 3 eyes, 3%, in 25-gauge group) at postoperative day 1, between 7 and 28 days in 5 cases (2 eyes, 2%, in 23-gauge and 3 eyes, 3%, in 25-gauge group), and in 2 eyes (2%) of the 23-gauge group at postoperative day 145 and 61, respectively. Retinal detachment occurred in 1 eye (1%) in the 23-gauge and in 3 eyes (3%) in the 25-gauge group. We did not observe any cases of endophthalmitis.

Conclusion: Results in terms of safety, surgical success and visual outcomes for the treatment of common vitreoretinal surgery indications seem to be comparable between 23-gauge and 25-gauge vitrectomy systems, indicating that the two gauge systems can be used equally in the clinical routine.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248164PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935274PMC
March 2021

HIV infection as a risk factor for vaginal dysbiosis, bacterial vaginosis, and candidosis in pregnancy: A matched case-control study.

Birth 2021 03 18;48(1):139-146. Epub 2021 Jan 18.

Department of Obstetrics and Gynecology, Division of Obstetrics and Feto-maternal Medicine, Medical University of Vienna, Vienna, Austria.

Background: This study aimed to evaluate the vaginal microbiota of HIV-positive pregnant women relative to HIV-negative controls, and to compare their risk of vaginal dysbiosis, bacterial vaginosis, and vulvovaginal candidosis (VVC).

Methods: This is a nested matched case-control study that analyzed data from women who received pregnancy care at our center from 2003 to 2014. Women routinely underwent screening for asymptomatic vaginal infections using phase microscopy on Gram-stained smears. HIV-positive women were assigned to the case group, and HIV-negative women were assigned to the control group. Cases and controls were matched in a 1:4 ratio. Logistic regression was used to test whether HIV infection was associated with vaginal dysbiosis (Nugent score 4-6), BV (Nugent score 7-10), or VVC.

Results: One hundred and twenty-seven women were assigned to the case group, and 4290 were assigned to the control group (including 508 matched controls). Dysbiosis or BV was found in 29.9% of the cases and 17.6% of the controls. Women in the case group had increased risk of vaginal dysbiosis or BV (odds ratio [OR] 2.09, 95% confidence interval [CI], 1.30-3.32, P = .002). The risk of VVC was also higher in the case group (OR 2.14, 95% CI, 1.22-3.77, P = .008). The incidence of preterm birth did not differ significantly between the groups (cases: 8.7%; controls: 10%, P = .887).

Conclusions: HIV-positive women are at risk of vaginal dysbiosis, BV, and VVC during pregnancy. As imbalances of the vaginal microbiota can lead to preterm birth, screening and treatment of HIV-positive pregnant women are warranted.
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http://dx.doi.org/10.1111/birt.12526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247846PMC
March 2021

Association of macular perfusion status with microvascular parameters up to the far periphery in diabetic retinopathy using multimodal imaging.

Int J Retina Vitreous 2020 Nov 4;6(1):50. Epub 2020 Nov 4.

Department of Ophthalmology and Optometry, Vienna Clinical Trial Centre (VTC), Medical University of Vienna, Waehringer Guertel 18-20, E8i, 1090, Vienna, Austria.

Background: The aim of our study was to investigate a possible association between macular perfusion status and retinal ischemia and leakage up to far peripheral retinal areas in eyes with early to advanced stages of diabetic retinopathy (DR).

Methods: In a retrospective, cross sectional analysis ultrawide field (UWF) color fundus photos (Optos, Optomap California) were graded for DR severity. Foveal avascular zone (FAZ) and vessel density from the superficial (SCP) and deep capillary plexus (DCP) were assessed on optical coherence tomography angiography (OCTA) scans (Topcon, DRI-OCT Triton). UWF angiography images were used to quantify leakage/ischemic index and number of microaneurysms (MA). Age, gender, disease duration, type of diabetes, HbA1C, hypertension, complications of diabetes and ocular history were recorded. Univariate mixed models and Spearman correlation analysis were used for statistical testing.

Results: 24 eyes of 17 laser-naive diabetic patients with different stages of DR were analyzed. The mean age was 59.56 ± 8.46 years and the mean disease duration 19.65 ± 12.25 years. No statistically significant associations between FAZ size, macular vessel density of SCP/DCP and peripheral retinal ischemia, leakage and MA number were demonstrated. Higher stages of DR were associated with ischemic index (estimate [95% CI]: 13.04 [1.5; 24.5], p = 0.033) and MA count (estimate [95% CI]: 43.7 [15.6; 71.8], p = 0.01), but no association with leakage index was observed. Only weak correlations between DR severity and anamnestic data were found.

Conclusion: Retinal ischemic index and the amount of MAs assessed on UWFA up to peripheral areas are indicators of DR severity but not related to microvascular perfusion status in the macular region. Significance and timely sequence of macular vessel density in DR progression may need to be re-evaluated in future studies.
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http://dx.doi.org/10.1186/s40942-020-00253-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640640PMC
November 2020

Retinal vessel architecture in retinopathy of prematurity and healthy controls using swept-source optical coherence tomography angiography.

Acta Ophthalmol 2021 Mar 4;99(2):e232-e239. Epub 2020 Aug 4.

Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.

Purpose: To determine microvascular changes in children with a history of retinopathy of prematurity (ROP) and in a control group of full-term children.

Methods: In a cross-sectional study, 30 eyes of 15 children aged 6-8 years with a history of ROP were evaluated with swept-source optical coherence tomography angiography (SS-OCTA). Twenty-eight eyes of 22 age-matched full-term children served as a healthy control group. The foveal avascular zone (FAZ), vessel density (VD) and choroidal vascular flow area (VFA) were evaluated on OCTA and correlated with central retinal thickness (CRT), visual acuity (VA), birth weight (BW), gestational age (GA) and ROP stages.

Results: Twenty-two eyes of 14 children with a history of ROP (stage 1-3) and 25 eyes of 19 full-term children were available for evaluation. In the ROP group, the gestational age was 27 ± 2 weeks and birth weight was 781 ± 164 g. In the ROP group, CRT was higher in the central ETDRS segment (mean difference [95% CI]: 32.8 µm [18.7; 47.0], p = 0.0002) compared to the controls. Smaller mean FAZ area (-0.12 [-0.19; -0.04], p = 0.004) and perimeter (-662 [-1228; -96], p = 0.03) was found in comparison to the control group. An oval shape of the FAZ was observed among patients with a history of ROP. The mean central VD of the superficial plexus was 28 ± 8/23 ± 8% and of the deep plexus 7 ± 7/3 ± 5% (ROP group/control group; p > 0.05). No statistically significant difference was found regarding the choroidal VFA. Only weak correlation of FAZ and VD with function was observed.

Conclusions: Swept-source optical coherence tomography angiography imaging revealed significant microvascular anomalies in children with a history of ROP indicating disturbance of early morphological development of the central retina.
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http://dx.doi.org/10.1111/aos.14557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984179PMC
March 2021

Dupilumab for the Treatment of Atopic Dermatitis in an Austrian Cohort-Real-Life Data Shows Rosacea-Like Folliculitis.

J Clin Med 2020 Apr 24;9(4). Epub 2020 Apr 24.

Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria.

Dupilumab is the first biological treatment approved for moderate-to-severe atopic dermatitis (AD). Efficacy and safety have been demonstrated in clinical trials, but real-life data is still limited. The objective of this study was to retrospectively evaluate Dupilumab treatment in AD patients in a real-life clinical setting. Effectiveness and safety outcomes were collected at baseline and after 2, 6, 10, 24, 39, and 52 weeks by using clinical scores for disease activity, as well as serological markers. Ninety-four patients from five dermatological hospitals were included. After 24 weeks of treatment, the median Investigator Global Assessment (IGA) and Eczema Area and Severity Index (EASI) showed a significant reduction compared to baseline (3.9 ± 0.7 vs. 1.4 ± 0.8 and 26.5 ± 12.5 vs. 6.4 ± 6.5). Interestingly, we observed rosacea-like folliculitis as an unexpected side effect in 6.4% of patients. Dupilumab proves to be an effective and well-tolerated treatment under real-life conditions. The occurrence of rosacea-like folliculitis warrants further mechanistic investigation.
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http://dx.doi.org/10.3390/jcm9041241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230957PMC
April 2020

Cerebrospinal fluid disturbances after transcallosal surgery: incidence and predictive factors.

J Neurosurg 2019 Sep 27:1-9. Epub 2019 Sep 27.

1Department of Neurosurgery, Medical University of Vienna.

Objective: CSF dynamics after transcallosal resection of intraventricular lesions can be altered, and the need for shunt implantation complicates the management of these patients. Because the pathophysiological mechanism and contributing factors are poorly understood and the incidence has largely not been described, the authors conducted a study to elucidate these factors.

Methods: The authors retrospectively reviewed data from patients who had been operated on at their institution via a transcallosal approach between March 2002 and December 2016. They evaluated the need for a shunt implantation up to 3 months after surgery by assessing clinical variables. These variables were age at surgery, the need for perioperative external CSF drainage, histology of the lesion, and the following radiological parameters: pre- and postoperative Evans index, maximal postoperative extension of subdural effusions (SDEs) measured on axial images, and maximal interhemispheric fissure (IHF) width measured on coronal images assessed at 4 different points in time (preoperatively, day 1, days 2-4, and days 4-8 after surgery). To identify potential risk factors, univariate and multivariate regression models were constructed. Receiver operating characteristic (ROC) curves for significant predictors, as well as the area under the curve (AUC), were calculated.

Results: Seventy-four patients (40 female and 34 male) were identified; their median age at surgery was 17.6 years (range 4 months to 76 years). Shunt implantation was necessary in 13 patients (ventriculoperitoneal [VP] shunt, n = 7; subdural peritoneal [SDP] shunt, n = 6) after a median interval of 24 days (range 10 days to 3 months). Univariate logistic regression models revealed a significant effect of IHF width on days 4-8 (OR 1.31, 95% CI 1.03-1.66; p = 0.027), extension of SDE on days 2-4 (OR 1.33, 95% CI 1.11-1 0.60; p = 0.003), and age (OR 0.932, 95% CI 0.88-0.99; p = 0.02). In the multiple regression model, the effect of the independent variable extension of the SDE remained significant. ROC curves for the predictors IHF width on days 4-8 and extension of SDE on days 2-4 revealed an AUC equal to 0.732 and 0.752, respectively. Before shunt implantation, the ventricles were smaller compared to the preoperative size in 9 of the 13 patients (SDP shunt, n = 5; VP shunt, n = 4).

Conclusions: The rate of shunt-dependent hydrocephalus 3 months after surgery in this heterogeneous group of patients was 17.6% (95% CI 9.7%-28.2%). The authors identified as predictive factors the variables extension of the convexity space, IHF 1 week after surgery, and younger age.
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http://dx.doi.org/10.3171/2019.6.JNS19290DOI Listing
September 2019

Semi-automated quantification of geographic atrophy with blue-light autofluorescence and spectral-domain optical coherence tomography: a comparison between the region finder and the advanced retinal pigment epithelium tool in the clinical setting.

Acta Ophthalmol 2019 Sep 24;97(6):e887-e895. Epub 2019 Mar 24.

Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.

Purpose: To compare inter- and intraobserver reliability and intermodality agreement on quantification of geographic atrophy, using two routinely available quantification tools, based on blue-light fundus autofluorescence (BAF) and spectral-domain optical coherence tomography (SD-OCT).

Methods: Quantifications of atrophic lesions within the central 5 mm of 30 eyes from 30 patients (mean age: 76.1 years) were independently performed by two clinicians on BAF images using the region finder (RF; Heidelberg Engineering) and on SD-OCT using the advanced retinal pigment epithelium tool (ARPET; Carl Zeiss Meditec) at baseline and follow-up (mean interval: 336 days). Inter- and intraobserver reliability was determined by intraclass correlation coefficients (ICC) and Bland-Altmann plots. Additionally, graders rated the experienced difficulty of each measurement.

Results: Intraclass correlation coefficients (ICC) showed excellent inter- and intraobserver reliability with values between 0.994 and 0.998 for RF and slightly higher values for ARPET of 0.997 and 0.999. Bland-Altman plots showed smaller variability for ARPET. Mean interobserver differences (95% CI) for size measurements were -0.11 (-0.27; 0.05) (baseline) and -0.05 mm² (-0.18; 0.08) (follow-up) for RF and -0.04 (-0.14; 0.06) and -0.06 mm² (-0.14; 0.02) for ARPET. Measurements of lesions were on average 0.57 mm² (0.35; 0.79) or 7.6% larger in ARPET. Lesion size between graders did not differ significantly. There was no statistically significant difference in relative enlargement rates between methods. There was poor to moderate agreement between graders when rating the experienced difficulty of each measurement.

Conclusion: Semi-automated analysis of geographic atrophy with RF and ARPET is equally reliable and reproducible in clinical settings, despite both algorithms require frequent adjustment by users. The ARPET restricts size measurements to the central 5 mm, which limits its ability to fully track GA progression. Results of both tools are not interchangeable as measurements with ARPET result in larger lesion sizes.
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http://dx.doi.org/10.1111/aos.14085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767530PMC
September 2019

DNA methylation of microRNA-coding genes in non-small-cell lung cancer patients.

J Pathol 2018 08 20;245(4):387-398. Epub 2018 Jun 20.

Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria.

Deregulated DNA methylation leading to transcriptional inactivation of certain genes occurs frequently in non-small-cell lung cancers (NSCLCs). As well as protein-coding genes, microRNA (miRNA)-coding genes may be targets for methylation in NSCLCs; however, the number of known methylated miRNA genes is still small. Thus, we investigated methylation of miRNA genes in primary tumour (TU) samples and corresponding non-malignant lung tissue (NL) samples of 50 NSCLC patients by using methylated DNA immunoprecipitation followed by custom-designed tiling microarray analyses (MeDIP-chip), and 252 differentially methylated probes between TU samples and NL samples were identified. These probes were annotated, which resulted in the identification of 34 miRNA genes with increased methylation in TU samples. Some of these miRNA genes were already known to be methylated in NSCLCs (e.g. those encoding miR-9-3 and miR-124), but methylation of the vast majority of them was previously unknown. We selected six miRNA genes (those encoding miR-10b, miR-1179, miR-137, miR-572, miR-3150b, and miR-129-2) for gene-specific methylation analyses in TU samples and corresponding NL samples of 104 NSCLC patients, and observed a statistically significant increase in methylation of these genes in TU samples (p < 0.0001). In silico target prediction of the six miRNAs identified several oncogenic/cell proliferation-promoting factors (e.g. CCNE1 as an miR-1179 target). To investigate whether miR-1179 indeed targets CCNE1, we transfected miR-1179 gene mimics into CCNE1-expressing NSCLC cells, and observed downregulated CCNE1 mRNA expression in these cells as compared with control cells. Similar effects on cyclin E1 expression were seen in western blot analyses. In addition, we found a statistically significant reduction in the growth of NSCLC cells transfected with miR-1179 mimics as compared with control cells. In conclusion, we identified many methylated miRNA genes in NSCLC patients, and found that the miR-1179 gene is a potential tumour cell growth suppressor in NSCLCs. Overall, our findings emphasize the impact of miRNA gene methylation on the pathogenesis of NSCLCs. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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http://dx.doi.org/10.1002/path.5079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055722PMC
August 2018

Can Early Rehabilitation on the General Ward After an Intensive Care Unit Stay Reduce Hospital Length of Stay in Survivors of Critical Illness?: A Randomized Controlled Trial.

Am J Phys Med Rehabil 2017 Sep;96(9):607-615

From the Department of Physical Medicine and Rehabilitation, Medical University of Vienna, General Hospital Vienna (WG, KP, CH, TP-S); Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Medical Statistics, Medical University of Vienna (IS); Department of Anaesthesia and Intensive Care, Medical University of Vienna, General Hospital Vienna (JMH); and Department of Physical Medicine and Rehabilitation, Danube Hospital Vienna, Vienna Hospital Association (TP-S), Vienna, Austria.

Objective: The aim of this study was to evaluate if an early rehabilitation program for survivors of critical illness improves functional recovery, reduces length of stay, and reduces hospital costs.

Design: This was a prospective randomized controlled trial. Fifty-three consecutive survivors of critical illness were included in the study. After discharge from the intensive care unit, the intervention group received an early rehabilitation program, and the standard-care group received physical therapy as ordered by the primary care team. Length of stay at the general ward after transfer from the intensive care unit was recorded. In addition, Early Rehabilitation Barthel Index, visual analog scale for pain, 3-minute walk test, Beck Depression Inventory, State-Trait Anxiety Inventory, and Medical Research Council scale were used.

Results: In the per-protocol analysis, length of stay at the general ward was a median 14 days (interquartile range [IQR], 12-20 days) in the early rehabilitation and 21 days [IQR, 13-34 days) in the standard-care group. This significant result could not be confirmed by the intention-to-treat analysis (16 days [IQR, 13-23 days] vs. 21 days [IQR, 13-34 days]). Secondary outcomes were similar between the groups. Hospital costs were lower in the intervention group. No adverse effects were detected.

Conclusions: An early rehabilitation program in survivors of critical illness led to an earlier discharge from the hospital, improved functional recovery, and was also cost-effective and safe.

To Claim Cme Credits: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to (1) delineate the benefits of early rehabilitation on a general medicine ward after an intensive care unit stay, (2) recognize the safety of appropriately implemented early rehabilitation, and (3) incorporate early rehabilitation on the general medical ward as applicable.

Level: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
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http://dx.doi.org/10.1097/PHM.0000000000000718DOI Listing
September 2017

Supraclavicular Approach to the Subclavian Vein as an Alternative Venous Access Site for ECMO Cannulae? A Retrospective Comparison.

ASAIO J 2017 Sep/Oct;63(5):679-683

From the *Department of Medicine I, Intensive Care Unit 13i2, Medical University of Vienna, General Hospital of Vienna, Vienna, Austria; and †Section for Medical Statistics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.

Venous reperfusion and double-lumen cannulae for extracorporeal membrane oxygenation (ECMO) are usually inserted via the right internal jugular vein. The supraclavicular approach to the right or left subclavian vein could serve as a possible alternative. The aim of this analysis was to compare feasibility, complications, and performance of supraclavicular and jugular cannulation. We retrospectively analyzed charts and registry data of patients undergoing venovenous ECMO. Twenty-four patients underwent jugular cannulation, and 11 patients underwent supraclavicular cannulation. Ten patients underwent femoro-jugular, and five patients underwent femoro-supraclavicular ECMO. Double-lumen cannulae were inserted via the jugular approach in 14 patients and via the supraclavicular approach in 6 patients. No cannulation-associated complications but for a single minor bleeding from the insertion site of a supraclavicular double-lumen cannula were recorded. Performance of the extracorporeal circuit was comparable between jugular and supraclavicular groups but for a more pronounced oxygenation effect in the supraclavicular double-lumen group caused by higher blood flows via larger (24 F) cannulae. The supraclavicular approach seems safe and equivalent to jugular cannulation and could serve as a valid alternative.
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http://dx.doi.org/10.1097/MAT.0000000000000529DOI Listing
April 2018

Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post-transplant CDT monitoring for alcohol relapse assessment - a retrospective study.

Transpl Int 2016 May 1;29(5):559-67. Epub 2016 Mar 1.

Department of Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria.

Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post-LT long-term observation is challenging, and biomarkers as carbohydrate-deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow-up was 73 months (0-213). One- and five-year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post-transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single-center analysis showed good post-transplant long-term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post-LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse.
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http://dx.doi.org/10.1111/tri.12756DOI Listing
May 2016

Effect of photodynamic therapy on short-wavelength fundus autofluorescence in eyes with acute central serous chorioretinopathy.

Retina 2015 Feb;35(2):223-30

*The Ludwig Boltzmann Institute for Retinology and Biomicroscopic Laser Surgery, Vienna, Austria; †Department of Ophthalmology, Rudolf Foundation Clinic, Vienna, Austria; ‡Department of Ophthalmology, Medical University of Graz, Graz, Austria; §Retina Center Vienna, Vienna, Austria; and ¶Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Medical Statistics, Medical University of Vienna, Vienna, Austria.

Purpose: To evaluate short-wavelength FAF as a parameter of retinal pigment epithelium function in eyes with acute symptomatic central serous chorioretinopathy after indocyanine green angiography-guided verteporfin photodynamic therapy with half-fluence rate.

Methods: A retrospective review over a period of 1 year of short-wavelength FAF images of 15 consecutive patients treated with half-fluence rate (25 J/cm) indocyanine green angiography-guided verteporfin photodynamic therapy due to acute symptomatic central serous chorioretinopathy was performed. Short-wavelength (488 nm) FAF gray values were evaluated with a confocal scanning laser ophthalmoscope at a 350-μm diameter and a 1,200-μm diameter circle centered on the fovea. The change in short-wavelength (488 nm) FAF gray values for the 2 circles was evaluated by calculating the differences of respective values between the first month after treatment and the 3, 6, 9, and 12 months follow-up.

Results: Mean differences (95% confidence interval) in short-wavelength (488 nm) FAF gray values of the 350-μm and 1,200-μm diameter circle between the 1-month and the 3-month (n = 15) follow-up were -0.03 (-0.11 to 0.05) (P = 0.46) and -0.03 (-0.17 to 0.10) (P = 0.6). Respective differences between the 1 month and the 6 (n = 15), 9 (n = 14), and 12 months (n = 13) of follow-up were -0.03 (-0.11 to 0.05) (P = 0.42) and -0.04 (-0.16 to 0.08) (P = 0.5); -0.05 (-0.12 to 0.03) (P = 0.23) and -0.06 (-0.18 to 0.07) (P = 0.33); -0.03 (-0.12 to 0.07) (P = 0.57) and -0.07 (-0.20 to 0.05) (P = 0.22).

Conclusion: Half-fluence rate (25 J/cm) indocyanine green angiography-guided verteporfin photodynamic therapy did not significantly affect short-wavelength FAF at a 350-μm diameter and a 1,200-μm diameter circle in eyes with resolved acute symptomatic central serous chorioretinopathy throughout 12 months of follow-up.
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http://dx.doi.org/10.1097/IAE.0000000000000280DOI Listing
February 2015

Identification of International Classification of Functioning, Disability and Health categories for patients with peripheral arterial disease.

Am J Phys Med Rehabil 2014 Jul;93(7):570-8

From the Department of Physical Medicine and Rehabilitation (EV, WG, OS) and Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Medical Statistics (IS), Medical University Vienna, Vienna, Austria.

Objective: Disease-specific categories of the International Classification of Functioning, Disability and Health have not yet been described for patients with chronic peripheral arterial obstructive disease (PAD). The authors examined the relationship between the categories of the Brief Core Sets for ischemic heart diseases with the Peripheral Artery Questionnaire and the ankle-brachial index to determine which International Classification of Functioning, Disability and Health categories are most relevant for patients with PAD.

Design: This is a retrospective cohort study including 77 patients with verified PAD. Statistical analyses of the relationship between International Classification of Functioning, Disability and Health categories as independent variables and the endpoints Peripheral Artery Questionnaire or ankle-brachial index were carried out by simple and stepwise linear regression models adjusting for age, sex, and leg (left vs. right).

Results: The stepwise linear regression model with the ankle-brachial index as dependent variable revealed a significant effect of the variables blood vessel functions and muscle endurance functions. Calculating a stepwise linear regression model with the Peripheral Artery Questionnaire as dependent variable, a significant effect of age, emotional functions, energy and drive functions, carrying out daily routine, as well as walking could be observed.

Conclusions: This study identifies International Classification of Functioning, Disability and Health categories in the Brief Core Sets for ischemic heart diseases that show a significant effect on the ankle-brachial index and the Peripheral Artery Questionnaire score in patients with PAD. These categories provide fundamental information on functioning of patients with PAD and patient-centered outcomes for rehabilitation interventions.
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http://dx.doi.org/10.1097/PHM.0000000000000063DOI Listing
July 2014

Non-responders to treatment with antagonists of vascular endothelial growth factor in age-related macular degeneration.

Br J Ophthalmol 2013 Nov 21;97(11):1443-6. Epub 2013 Aug 21.

The Ludwig Boltzmann Institute for Retinology and Biomicroscopic Laser Surgery, Vienna, Austria.

Purpose: Most of the publications on modern therapy of neovascular age-related macular degeneration focus on the effect of the treatment. The purpose of this study is to determine the frequency of non-responders to anti-vascular endothelial growth factor (anti-VEGF) treatment and find possible reasons for their failure to respond.

Methods: The records of patients treated until the end of 2008 the first time with either bevacizumab or ranibizumab were reviewed. Based on the availability of measurable results and according to prior publications showing the effect of the therapy, loss of three lines of distance acuity, increase of retinal thickness or lesion size were identified as indicators of non-responders. Two of these three signs had to be present.

Results: 334 eyes of 283 patients were included; 74.55% received bevacizumab and 25.45% received ranibizumab. Overall 14.37% of the eyes were identified as non-responders (14.06% in the bevacizumab group and 15.29% in the ranibizumab group). Baseline distance acuity and vitreo-retinal adhesions were significantly correlated with non-responders. Correlations with age, gender, lesion type, other morphologic features, and the kind of anti-VEGF agent failed to be significant. 10.4% of the non-responders showed a delayed but good response to anti-VEGF treatment.

Conclusions: About 15% did not sufficiently respond to anti-VEGF treatment. Vitreo-retinal adherences were the only ophthalmologic factor which could be identified to be significantly correlated with insufficient response.
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http://dx.doi.org/10.1136/bjophthalmol-2013-303513DOI Listing
November 2013

Systematic correlation of morphologic alterations and retinal function in eyes with uveitis-associated cystoid macular oedema during development, resolution and relapse.

Br J Ophthalmol 2013 Oct 2;97(10):1289-96. Epub 2013 Aug 2.

Department of Ophthalmology, Medical University of Vienna, , Vienna, Austria.

Purpose: To evaluate morphological changes due to uveitis-associated cystoid macular oedema (uvCME) and their impact on central retinal sensitivity (CRS) before and after intravitreal triamcinolone-acetonide (IVTA).

Methods: 28 eyes with uvCME were examined with microperimetry and spectral-domain optical-coherence-tomography (SD-OCT) before and after IVTA. Microperimetry-maps were superimposed on SD-OCT and morphological-alterations were correlated point to point with CRS and followed-up for 3 months. The effects of morphological-alterations on CRS over time were evaluated with a linear mixed-model.

Results: Mean-CRS increased significantly after IVTA (p=0.009). Proportion of cysts correlated negatively with corresponding CRS (estimate/95% CI -3.8 dB/-6.6 to -0.9, p=0.011). Proportion of diffuse macular-oedema (DifME) had no significant effect on mean-CRS (-0.76 dB/-4.9 to 3.3, p=0.71). The proportion of serous retinal detachment (SRD) had a borderline significant effect on mean-CRS (-9.5 dB/-19.1 to 0.1, p=0.052), however the initial presence of SRD at baseline had no significant negative effect on mean-CRS (-1.3 dB/-4.9 to 2.3, p=0.46). Patients with epiretinal-membrane showed lower mean-CRS than patients without (-3.3 dB/-6.5 to -0.008, p=0.05). The lowest percentage of morphological-alterations was achieved 30 days post IVTA concordant to best visual-acuity (logMAR 0.16 ± 0.26), while best mean-CRS was achieved 90 days post IVTA (16.9 ± 1.8 dB). Fixation-stability showed no significant improvement.

Conclusions: UvCME Morphological-alterations were associated with specific CRS-decreases. DifME showed no significant- and SRD only a borderline effect on mean-CRS, which implicates that their presence should be considered when interpreting SD-OCT and making treatment-decisions.
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http://dx.doi.org/10.1136/bjophthalmol-2012-303052DOI Listing
October 2013

Endogenous erythroid colony formation in chronic myeloid leukemia: a recurrent finding associated with persistent minimal residual disease under imatinib.

Stem Cells Dev 2013 Dec 4;22(23):3043-51. Epub 2013 Sep 4.

1 Department of Laboratory Medicine, Medical University of Vienna , Vienna, Austria .

In vitro endogenous erythroid colony (EEC) formation is a common finding in BCR-ABL-negative myeloproliferative neoplasms. The aim of the present study was to determine the prevalence and the clinical significance of EEC growth in chronic myeloid leukemia (CML). Results of clonogeneic progenitor cell assays from 52 patients with newly diagnosed CML were correlated with disease characteristics at presentation and molecular response to imatinib. EECs (median 7 per dish, range 1-39) were detectable in 16 patients (31%). The proportion of patients with a high-risk Sokal score was lower in the EEC group (7% vs. 30%, respectively). The cumulative incidence of achieving a major molecular response after 2 years of imatinib was similar for both groups. However, patients with EECs were less likely to achieve a more profound decline of BCR-ABL transcripts. After 6 years of imatinib, the cumulative probability [95% CI] of reaching a ≥4 log reduction of BCR-ABL was 48% [16%; 92%] for patients of the EEC group and 84% [63%; 97%] for patients of the No EEC group. The probability [95% CI] of achieving a >4.5 log reduction of BCR-ABL after 7 years was 13% [2%; 61%] for patients with EECs and 52% [30%; 78%] for patients without EECs. In vitro EECs disappeared after achievement of a major molecular response in all evaluable patients. The data indicate that EEC formation is a recurrent finding in patients with CML which deserves further attention as a possible biomarker predicting the degree of molecular response to imatinib.
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http://dx.doi.org/10.1089/scd.2013.0096DOI Listing
December 2013

Natalizumab therapy for highly active pediatric multiple sclerosis.

JAMA Neurol 2013 Apr;70(4):469-75

Department ofNeurology, Medical University of Vienna, WaehringerGuertel 18-20, A-1090 Vienna, Austria.

Importance: Given the high frequency of failure of first-line therapies, there is an urgent need for second-line treatment strategies for pediatric patients with multiple sclerosis (MS).

Objective: To report the use of natalizumab in pediatric MS. Natalizumab, a humanized monoclonal antibody targeting α4 integrin, is effective against active relapsing-remitting MS in adults.

Design: Retrospective study.

Setting: Eleven centers for neurology and pediatric neurology in Germany and Austria.

Participants: A total of 20 pediatric patients with MS who started treatment with natalizumab prior to 18 years of age. These patients underwent magnetic resonance imaging as clinically indicated, despite the fact that 19 of these 20 patients were undergoing first-line disease-modifying therapy. The mean (SD) age at initiation of natalizumab therapy was 16.7 (1.1) years, and the mean (SD) pretreatment period was 18 (10) months.

Intervention: Natalizumab, 300 mg every 4 weeks.

Main Outcome Measures: Annualized relapse rates, Expanded Disability Status Scale scores, number of new T2/fluid-attenuated inversion recovery lesions and contrast-enhancing lesions on magnetic resonance imaging, number of adverse events, the prevalence of neutralizing antibodies against natalizumab, and serum JC virus-antibody status. RESULTS Treatment with natalizumab was associated with reductions in mean annualized relapse rates (3.7 without treatment vs 0.4 with treatment; P < .001), median Expanded Disability Status Scale scores (2 without treatment vs 1 with treatment; P < .02), and mean number of new T2/fluid-attenuated inversion recovery lesions per year (7.8 without treatment vs 0.5 with treatment; P < .001). Two patients developed high-titer neutralizing antibodies against natalizumab and had to stop therapy. Adverse events included headaches, asthenia, infections, and hypersensitivity. Abnormal laboratory results were found for 8 patients. JC virus antibodies were found in 5 of 13 patients. After the discontinuation of natalizumab therapy, relapse activity occurred in 6 of 8 patients within 6 months.

Conclusions And Relevance: Our data indicate that natalizumab may be safe and effective against MS in pediatric patients with breakthrough disease.
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http://dx.doi.org/10.1001/jamaneurol.2013.923DOI Listing
April 2013

Lysis matters: red cell lysis with FACS Lyse affects the flow cytometric enumeration of circulating leukemic blasts.

J Immunol Methods 2013 Apr 4;390(1-2):127-32. Epub 2013 Feb 4.

Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

The whole blood lysis method has become a standard procedure to remove red cells prior to immunophenotypic analysis of leukocytes. In the present study we investigated the influence of four different lysis protocols on the flow cytometric recovery of leukemic blasts. 32 blast cells containing blood samples were stained with anti-CD45 and anti-CD34 monoclonal antibody combinations. Red cell lysis was performed with FACS Lysing Solution and BD PharmLyse™ (Becton Dickinson and Company BD Biosciences, San Jose, CA; n=32) as well as Optilyse C and IOTest 3 (Immunotech SAS, Marseille; n=15 out of 32). Flow cytometric enumeration of blasts was performed on a FACS-Canto flow cytometer. The percentage of blasts after treatment with FACS Lyse was significantly smaller than after PharmLyse™ (p<0.0001), Optilyse C (p<0.0001), or IOTest 3 (p<0.0001), respectively. The difference between PharmLyse™ and Optilyse C (p=0.93), PharmLyse™ and IOTest 3 (p=0.31), and Optilyse C and IOTest 3 (p=0.34) was not significant. These results emphasize the importance of harmonization of red cell lysis protocols for the application of flow cytometry in hematological neoplasms.
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http://dx.doi.org/10.1016/j.jim.2013.01.013DOI Listing
April 2013

Factors influencing neurosensory disturbance after bilateral sagittal split osteotomy: retrospective analysis after 6 and 12 months.

Oral Surg Oral Med Oral Pathol Oral Radiol 2013 Apr 20;115(4):473-82. Epub 2012 Nov 20.

Department of Oral and Maxillofacial Surgery, Danube General Hospital, Vienna, Austria.

Objective: The aim of this study was to analyze several factors regarding their possible influence on neurosensory disturbance (NSD) of the inferior alveolar nerve (IAN) after bilateral sagittal split osteotomy (BSSO).

Study Design: We investigated the possible influence of sex, age at the time of surgery, total operating time, intraoperative nerve encounter, advancement versus setback, fixation method, additional genioplasty, side, and region (lower lip vs. chin) on subjective neurosensory outcome a half-year after surgery. Results of a battery of neurosensory testing methods are also presented; 103 out of the initial 128 patients were available for further follow-up 1 year after surgery.

Results: Normal subjective sensibility was found in 74.6% and 77.2% of the regions after 6 and 12 months, respectively. Multiple regression models revealed significant effects of age, region, and total operating time after 6 months, and significant effects of age, region, and sex after 12 months.

Conclusions: NSD of the IAN after BSSO is influenced by age, total operating time (at 6 months), and sex (at 12 months). Significantly higher rates of NSD were found in the chin region.
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http://dx.doi.org/10.1016/j.oooo.2012.08.454DOI Listing
April 2013

Genome-wide CpG island methylation analyses in non-small cell lung cancer patients.

Carcinogenesis 2013 Mar 19;34(3):513-21. Epub 2012 Nov 19.

Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna 1090, Austria.

DNA methylation is part of the epigenetic gene regulation complex, which is relevant for the pathogenesis of cancer. We performed a genome-wide search for methylated CpG islands in tumors and corresponding non-malignant lung tissue samples of 101 stages I-III non-small cell lung cancer (NSCLC) patients by combining methylated DNA immunoprecipitation and microarray analysis. Overall, we identified 2414 genomic positions differentially methylated between tumor and non-malignant lung tissue samples. Ninety-seven percent of them were found to be tumor-specifically methylated. Annotation of these genomic positions resulted in the identification of 477 tumor-specifically methylated genes of which many are involved in regulation of gene transcription and cell adhesion. Tumor-specific methylation was confirmed by a gene-specific approach. In the majority of tumors, methylation of certain genes was associated with loss of their protein expression determined by immunohistochemistry. Treatment of NSCLC cells with epigenetically active drugs resulted in upregulated expression of many tumor-specifically methylated genes analyzed by gene expression microarrays suggesting that about one-third of these genes are transcriptionally regulated by methylation. Moreover, comparison of methylation results with certain clinicopathological characteristics of the patients suggests that methylation of HOXA2 and HOXA10 may be of prognostic relevance in squamous cell carcinoma (SCC) patients. In conclusion, we identified a large number of tumor-specifically methylated genes in NSCLC patients. Expression of many of them is regulated by methylation. Moreover, HOXA2 and HOXA10 methylation may serve as prognostic parameters in SCC patients. Overall, our findings emphasize the impact of methylation on the pathogenesis of NSCLCs.
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http://dx.doi.org/10.1093/carcin/bgs363DOI Listing
March 2013

Non-surgical periodontal therapy influences salivary melatonin levels.

Clin Oral Investig 2013 May 31;17(4):1219-25. Epub 2012 Jul 31.

Division of Oral Surgery, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Austria, Vienna, Austria.

Objectives: Melatonin is a hormone, which is involved in the control of the circadian rhythm, but also acts as an antioxidant and immune modulator. Previous studies reported decreased salivary and serum melatonin levels in periodontitis. This prospective cohort trial assessed the effect of non-surgical periodontal therapy on melatonin levels.

Methods: Salivary and serum samples of 60 participants (30 patients suffering from a severe generalized form of periodontitis, 30 healthy controls) were collected at baseline and 19 samples of periodontitis patients after treatment. Salivary and serum melatonin levels were determined by a commercially available ELISA kit and serum C-reactive protein (CRP) by a routine laboratory test.

Results: At baseline, periodontitis patients showed significantly increased serum CRP values and significantly decreased salivary melatonin levels compared to the control group. Clinical periodontal parameters significantly correlated with salivary melatonin levels and serum CRP. Periodontal therapy resulted in a recovery of the decreased salivary melatonin levels and a negative correlation was detected for the changes of salivary melatonin and the inflammatory parameter bleeding on probing. Serum melatonin levels showed no significant differences.

Conclusions: Salivary melatonin levels recovered after periodontal therapy and correlated with a decrease of local periodontal inflammation. This may imply the local involvement of melatonin in the pathogenesis of periodontitis due to its antioxidant abilities. However, the exact role of melatonin in periodontal disease remains to be investigated in future trials.

Clinical Relevance: The present results suggest salivary melatonin as a risk indicator for the severity of periodontal disease.
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http://dx.doi.org/10.1007/s00784-012-0801-6DOI Listing
May 2013

Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine in anaplastic large cell lymphoma.

Biochimie 2012 Nov 9;94(11):2297-307. Epub 2012 Jun 9.

Clinical Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16(INK4A) after drug administration and senescence associated β-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use.
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http://dx.doi.org/10.1016/j.biochi.2012.05.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480637PMC
November 2012
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