RNA editing of Filamin A pre-mRNA regulates vascular contraction and diastolic blood pressure.

Epitranscriptomic events such as adenosine-to-inosine (A-to-I) RNA editing by ADAR can recode mRNAs to translate novel proteins. Editing of the mRNA that encodes actin crosslinking protein Filamin A (FLNA) mediates a Q-to-R transition in the interactive C-terminal region. While FLNA editing is conserved among vertebrates, its physiological function remains unclear. Here, we show that cardiovascular tissues in humans and mice show massive editing and that FLNA RNA is the most prominent substrate. Patient-derived RNA-Seq data demonstrate a significant drop in FLNA editing associated with cardiovascular diseases. Using mice with only impaired FLNA editing, we observed increased vascular contraction and diastolic hypertension accompanied by increased myosin light chain phosphorylation, arterial remodeling, and left ventricular wall thickening, which eventually causes cardiac remodeling and reduced systolic output. These results demonstrate a causal relationship between RNA editing and the development of cardiovascular disease indicating that a single epitranscriptomic RNA modification can maintain cardiovascular health.

A Randomized Trial of Parenteral Nutrition Using a Mixed Lipid Emulsion Containing Fish Oil in Infants of Extremely Low Birth Weight: Neurodevelopmental Outcome at 12 and 24 Months Corrected Age, A Secondary Outcome Analysis.

OBJECTIVE: To examine whether parenteral nutrition using a mixed lipid emulsion containing fish oil improves the neurodevelopmental outcomes of extremely low birth weight infants. STUDY DESIGN: The study is a secondary outcome analysis of a double-blind randomized trial of 230 extremely low birth weight infants performed at a single level IV neonatal care unit (Medical University Vienna; June 2012 to June 2015). Participants received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil, or a soybean oil-based lipid emulsion for parenteral nutrition. Neurodevelopment of study participants was assessed at 12 and 24 months corrected age (August 2013 to October 2017) using the Bayley Scales of Infant-Toddler Development, third edition. RESULTS: At discharge, 206 of the 230 study participants were eligible. At 12 and 24 months corrected age, 174 of 206 (85%) and 164 of 206 (80%) infants were evaluated. At 12 months, there was no significant difference in cognitive (mixed lipid: median, 95 [IQR, 85-101]; soybean oil: median, 95 [IQR, 85-100]; P = .71), language (mixed lipid: median, 86 [IQR, 77-94], soybean oil: median, 89 [IQR, 79-94]; P = .48), or motor scores (mixed lipid: median, 88 [IQR, 76-94], soybean oil: median, 88 [IQR, 79-94]; P = .69). At 24 months, there was again no significant difference in cognitive (mixed lipid: median, 95 [IQR, 80-105], soybean oil: median, 95 [IQR, 90-105]; P = .17), language (mixed lipid: median, 89 [IQR, 75-97], soybean oil 89 [IQR, 77-100]; P = .54), and motor scores (mixed lipid: median, 94 [IQR, 82-103], soybean oil: median, 94 [IQR, 85-103]; P = .53). CONCLUSIONS: Parenteral nutrition using a mixed lipid emulsion containing fish oil did not improve neurodevelopment of extremely low birth weight infants at 12 and 24 months corrected age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585935.

PRESENCE OF PERIPHERAL LESIONS AND CORRELATION TO MACULAR PERFUSION, OXYGENATION AND NEURODEGENERATION IN EARLY TYPE II DIABETIC RETINAL DISEASE.

PURPOSE: The impact of peripheral retinal lesions (PL) visualized with ultra-wide-field imaging on diabetic retinopathy (DR) remains unclear. The purpose of this study was to assess the presence of PL and their association with macular microvasculopathy, metabolic dysfunction, and neurodegeneration in patients with Type II diabetes and early retinal disease. METHODS: Forty-five degree color fundus (Topcon) and 200° ultra-wide-field images (Optos) were assessed for the presence and severity of DR. Lesions anterior to the 45° were considered peripheral. The foveal avascular zone area, perimeter and acircularity index, and foveal full-retina and parafoveal superficial/deep complex vessel density were evaluated with RTVue optical coherence tomography angiography. Vessel oxygen saturation was measured with oximetry. Peripapillary retinal nerve fiber and individual macular retinal layer thicknesses were measured with Spectralis optical coherence tomography. RESULTS: Among the 161 eyes (80 left eyes) of 81 patients (34 female), 64 (39.8%) showed higher levels of DR on ultra-wide-field than on 45° fundus images (P < 0.0001). PL were identified in 97 eyes (60.3%) and in 59 among 115 eyes without central signs of DR. No significant correlation to biomarkers of central microvascular disease (foveal avascular zone/vessel density variables), oxygen saturation, and retinal layer thickness was found. CONCLUSION: Ultra-wide-field imaging helps to detect more eyes with early DR due to the detection of PL, which appear independently of biomarkers of macular microvascular impairment, metabolic function, and neuropathy in eyes without central signs of DR. These results suggest that the evaluation of the retinal periphery may become crucial in DR screening if PL are proven to influence disease outcomes.

TOPOGRAPHIC ANALYSIS OF PHOTORECEPTOR LOSS CORRELATED WITH DISEASE MORPHOLOGY IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To quantify morphologic photoreceptor integrity during anti-vascular endothelial growth factor (anti-VEGF) therapy of neovascular age-related macular degeneration and correlate these findings with disease morphology and function. METHODS: This presents a post hoc analysis on spectral-domain optical coherence tomography data of 185 patients, acquired at baseline, Month 3, and Month 12 in a multicenter, prospective trial. Loss of the ellipsoid zone (EZ) was manually quantified in all optical coherence tomography volumes. Intraretinal cystoid fluid, subretinal fluid (SRF), and pigment epithelial detachments were automatically segmented in the full volumes using validated deep learning methods. Spatiotemporal correlation of fluid markers with EZ integrity as well as bivariate analysis between EZ integrity and best-corrected visual acuity was performed. RESULTS: At baseline, EZ integrity was predominantly impaired in the fovea, showing progressive recovery during anti-vascular endothelial growth factor therapy. Topographic analysis at baseline revealed EZ integrity to be more likely intact in areas with SRF and vice versa. Moreover, we observed a correlation between EZ integrity and resolution of SRF. Foveal EZ integrity correlated with best-corrected visual acuity at all timepoints. CONCLUSION: Improvement of EZ integrity during anti-VEGF therapy of neovascular age-related macular degeneration occurred predominantly in the fovea. Photoreceptor integrity correlated with best-corrected visual acuity. Ellipsoid zone integrity was preserved in areas of SRF and showed deterioration upon SRF resolution.

There are no safe areas for avoiding the perforating arteries along the proximal part of the femur: A word of caution.

Knowledge about the variable course of the perforating arteries near the body of the femur is essential during surgical procedures (e.g., percutaneous cerclage wiring, plate osteosynthesis, Ilizarov technique). Our aims were to determine the number of perforating arteries, and to identify safe zones along the body of the femur within which perforating arteries are unlikely to pass toward the back of the thigh. The number of perforating arteries was determined in both legs of 100 formalin-fixed anatomic specimens of both sexes. The level of passage of perforating arteries near the body of the femur was measured in reference to a line from the anterior superior iliac spine to the medial femoral condyle. In each leg, two to seven perforating arteries were present. In 64% of legs, at least one artery divided into two to four branches before entering the back of the thigh. Thus, the total number of branches passing near the body of the femur varied between two to nine. Perforating arteries passed to the back of the thigh at every level between 14.0 and 36.5 cm from the anterior superior iliac spine (16-39% of the leg length). Within this distance, no safe zones along the body of the femur could be identified. The present study shows the high variability regarding number and course of the perforating arteries. Surgeons can be faced with an artery at every level on the posteromedial aspect of the body of the femur between 14.0 and 36.5 cm distally to the anterior superior iliac spine. Clin. Anat. 33:507-515, 2020. © 2019 Wiley Periodicals, Inc.

A Mixed Lipid Emulsion for Prevention of Parenteral Nutrition Associated Cholestasis in Extremely Low Birth Weight Infants: A Randomized Clinical Trial.

OBJECTIVES: To examine whether a mixed lipid emulsion reduces the incidence of parenteral nutrition associated cholestasis (PNAC) in extremely low birth weight (ELBW, <1000 g) infants. STUDY DESIGN: This double-blind randomized trial of 230 ELBW infants (June 2012-October 2015) was performed at a single level IV neonatal intensive care unit. Patients received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil-(intervention) or a soybean oil-based lipid emulsion (control) for parenteral nutrition. The primary outcome measure was PNAC (conjugated bilirubin >1.5 mg/dL [25 µmol/L] at 2 consecutive measurements). The study was powered to detect a reduction of PNAC from 25% to 10%. RESULTS: Reasons for noneligibility of 274 infants screened were refusal to participate (n = 16), death (n = 10), withdrawal of treatment (n = 5), higher order multiples (n = 9), and parents not available for consent (n = 4). Intention to treat analysis was carried out in 223 infants (7 infants excluded after randomization). Parenteral nutrition associated cholestasis was 11 of 110 (10.1%) in the intervention and 18 of 113 (15.9%) in the control group (P = .20). Multivariable analyses showed no statistically significant difference in the intention to treat (aOR 0.428, 95% CI 0.155-1.187; P = .10) or per protocol population (aOR 0.457, 95% CI 0.155-1.347; P = .16). There was no statistically significant effect on any other neonatal morbidity. CONCLUSIONS: The incidence of parenteral nutrition associated cholestasis was not significantly reduced using a mixed lipid emulsion in ELBW infants. TRIAL REGISTRATION: ClinicalTrials.govNCT01585935.

Surveillance colonoscopy in Austria: Are we following the guidelines?

BACKGROUND AND STUDY AIM: The European guidelines for quality assurance in colorectal cancer screening and diagnosis contain postpolypectomy surveillance recommendations. They recommend follow-up intervals depending on the findings at index colonoscopy, and divide patients into a low-, intermediate- or high-risk group. The aim of this study was to assess the adherence of Austrian endoscopists to the European guidelines and to determine whether sending a reminder letter resulted in better adherence. METHODS: A single reminder letter containing the guidelines was sent to all endoscopists who participated in the Certificate of Quality for Screening Colonoscopy program in Austria. Adherence was assessed before and after the letter had been sent. Factors associated with adherence were investigated. RESULTS: We found poor baseline adherence to the guidelines. After the reminder letter, the adherence slightly improved in the low-risk group, but did not change in the intermediate-risk or high-risk groups. An adenoma detection rate of at least 20 % was associated with higher adherence rates. Generally, internists and hospitals showed better adherence compared with surgeons and private practices, respectively, both before and after the reminder letter. CONCLUSION: A single reminder letter was not enough to improve the poor adherence to the European postpolypectomy surveillance guidelines. Thus, future studies are required to identify and eliminate all factors responsible for nonadherence to postpolypectomy guidelines in order to reach the goal of a safe, effective, and cost-effective colorectal cancer prevention tool in the near future.

COMPARISON OF GANGLION CELL INNER PLEXIFORM LAYER THICKNESS BY CIRRUS AND SPECTRALIS OPTICAL COHERENCE TOMOGRAPHY IN DIABETIC MACULAR EDEMA.

PURPOSE: Reduced thickness of the ganglion cell inner plexiform layer indicates diabetic neurodegeneration and can be assessed by spectral domain optical coherence tomography. The authors investigated the comparability of ganglion cell inner plexiform layer measurements from two spectral domain optical coherence tomography devices in patients with diabetic macular edema (DME). METHODS: Analysis of optical coherence tomography data sets of eyes with and fellow eyes without DME. Macular cube scans of sufficient signal strength on Cirrus (Carl Zeiss Meditec) were compared with correlating scans on Spectralis (Heidelberg Engineering, Germany) being acquired within 1 hour. RESULTS: Eighty-one equivalent data sets for 20 eyes with DME (20 patients; 6 female) and 33 for 9 fellow eyes without DME (9 patients; 2 female) were included from each device. In DME eyes, mean ganglion cell inner plexiform layer thicknesses were 62.5 ± 20.4 µm on Cirrus and 91.2 ± 9.3 µm on Spectralis. Ganglion cell inner plexiform layer was significantly thicker on Spectralis analyzing eyes with and without signs of DME (P < 0.001). The ganglion cell inner plexiform layer variance (54.2%) related to device differences decreased to 34.8% in eyes without DME. CONCLUSION: Ganglion cell inner plexiform layer data from different devices vary considerably and cannot be used interchangeably. As spectral domain optical coherence tomography is indispensable for identifying ganglion cell loss associated with diabetic neurodegeneration, clinicians should be aware of the difference when monitoring patients.

In vivo Tube Assay: An Optimised Protocol of the Directed in vivo Angiogenesis Assay by Implementing Immunohistochemistry.

BACKGROUND: Angiogenesis, the formation of new blood vessels, is an essential process under physiological and pathological conditions. METHOD: Here, we improved the directed in vivo angiogenesis assay (DIVAA®) test, which is based on the usage of small Matrigel-filled tubes that are implanted into mice subcutaneously for a period of up to 15 days. The subsequent ex vivo assessment of neoangiogenesis within the silicon tubes is then achieved by fluorometry. RESULTS: We showed that the immunohistochemical quantification of the ingrowth of endothelial cells, based on CD31, was superior to the fluorometric quantification advised in the manufacturer's instructions. We optimised the explantation procedure, ensuring the complete recovery of the ingrown vessels. Using this modified protocol, we investigated the effect of the length of stay of the implanted tubes as well as of the concentration of the growth factors VEGF and FGF on the assay. CONCLUSION: Our improved protocol offered an effective and reliable alternative to the original assay, which is expected to facilitate in vivo research on angiogenesis and, thus, might drive the development of novel therapeutic agents.

Depressive symptoms predict the quality of sleep in patients with partial epilepsy--A combined retrospective and prospective study.

INTRODUCTION: Epilepsy is one of the most common neurological diseases and has many detrimental effects on the patients' well-being as well as sleep quality. The aim of this study was to assess the subjective quality of sleep and influencing factors on subjective sleep quality in patients with partial epilepsy using a combined retrospective and prospective study design. METHODS: We conducted a combined retrospective and prospective study in patients with partial epilepsy and analyzed subjective ratings of sleep quality in 32 patients (17 female, 15 male; mean age: 40.41 ± 12.67 years, range: 20-64) with partial epilepsy (mean duration of epilepsy diagnosis: 18.31 ± 13.26 years) and 32 healthy gender-matched and age-matched controls. All patients filled out a seizure diary for 90 days, which included the number, duration, and type (partial vs. secondary generalized) of epileptic seizures and intake of antiepileptic and sleep medications. At baseline, all participants completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Beck's Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Poor sleepers were defined by a PSQI score of ≥ 5. RESULTS: Twenty-three patients (72%) reported 15.17 ± 25.54 seizures in the previous three months, and nine (28%) patients reported being seizure-free. During the 90-day diary period, twenty-two patients (69%) documented a total of 319 epileptic seizures, while ten patients (31%) reported that they were seizure-free. The mean PSQI score of all patients was 4.88 ± 2.92 (range: 1-14) and the mean ESS score was 5.25 ± 2.98 (range: 0-10). The mean PSQI score of the control group was 3.25 ± 1.57 (range: 1-6), and their mean ESS score was 6.72 ± 3.48 (range: 0-14). The comparison of the two groups showed a significantly higher PSQI score in the patient group (t = 2.778, p = 0.008), but no statistically significant difference regarding their ESS score (t = -1.811, p = 0.075). Sixteen (50%) patients were poor sleepers. Good sleepers showed a significantly lower PSQI (2.69 ± 1.08 vs. 7.06 ± 2.49; p < 0.001) and BDI scores (2.38 ± 2.50 vs. 9.63 ± 7.63; p < 0.002) than poor sleepers. Linear regression analysis showed that the BDI score was the significant predictor for the PSQI score (estimate: 0.2019; p = 0.00819) and for the ESS score (estimate: 0.2251; p = 0.0321). CONCLUSION: In patients with partial epilepsy, a higher depression score was the best predictor for a poor subjective sleep quality and increased daytime sleepiness.

Reliability, validity, sensitivity and internal consistency of the ICF based Basic Mobility Scale for measuring the mobility of patients with musculoskeletal problems in the acute hospital setting: a prospective study.

BACKGROUND: The assessment of mobility is important in the acute care setting. Existing tests suffer from limitations. The aim of the study was to examine the inter-rater reliability, the validity, the sensitivity to change, and the internal consistency of an ICF based scale. METHODS: In a prospective study inpatients in the acute care setting with restricted mobility aged above 50 years assigned to rehabilitative treatment were included. Assessment of subscales of the Functional Independence Measure (FIM) and the ICF based Basic Mobility Scale (BMS) were performed at admission and before discharge. Furthermore pain, length of stay in hospital, and post-discharge residential status were recorded. Inter-rater reliability, criterion-concurrent validity, sensitivity to change, and internal consistency were calculated. Furthermore, floor and ceiling effects were determined. RESULTS: One hundred twenty-five patients (79 women/46 men) were included. The BMS showed an excellent inter-rater reliability for the total BMS (ICC BMS: 0.85 (95 % CI: 0.81-0.88). The criterion-concurrent validity was high to excellent (Spearman correlation coefficient: -0.91 in correlation to FIM) and the internal consistency was good (Cronbach's alpha 0.88). The BMS proved to be sensitive to improvements in mobility (Wilcoxon's signed rank test: p < 0.0001; The effect size for the BMS was 1.075 and the standardized response mean 1.10. At admission, the BMS was less vulnerable to floor effects. CONCLUSIONS: The BMS may be used as a reliable and valid tool for the assessment of mobility in the acute care setting. It is easy to apply, sensitive to change during the hospital stay and not vulnerable to floor and ceiling effects.

Fibrinogen reduction and bleeding complications in plasma exchange, immunoadsorption and a combination of the two.

BACKGROUND: Immunoadsorption (IAS) and therapeutic plasma exchange (TPE) are considered safe although fibrinogen is removed. To date no comparison of fibrinogen reduction and associated risk of bleeding in apheresis exists. METHODS: Retrospective analysis of TPE, three IAS adsorbers, and combined TPE/IAS regarding fibrinogen reduction and bleeding incidence in 67 patients (1,032 treatments). RESULTS: TPE and TPE/IAS reduced fibrinogen by 64 ± 11% and 58 ± 9%, leading to concentrations <100 mg/dl in 20 and 17% of treatments, respectively. IAS decreased fibrinogen less than TPE (26 ± 6%, p < 0.0001), resulting in fibrinogen concentrations <100 mg/dl in 1% of treatments. The processed volume correlated with reduction in TPE (r = 0.64, p < 0.01), but not in IAS. Bleeding occurred in 1.3% (IAS), 2.3% (TPE) and 3.1% (TPE/IAS) of treatments. CONCLUSION: Hypofibrinogenemia occurs in 20% of patients after TPE and TPE/IAS, but rarely after IAS. IAS removes fibrinogen independently of volume processed. Overall, bleeding is rare in apheresis.

Effects of alcohol mixed with energy drink and alcohol alone on subjective intoxication.

Recent studies suggest that the combination of caffeine-containing drinks together with alcohol might reduce the subjective feelings of alcohol intoxication-the so-called "masking effect". In this study, we aimed to review the effects of alcohol in combination with caffeine or energy drink with special focus on the "masking effect". Fifty-two healthy male volunteers were analysed concerning breath alcohol concentration and subjective sensations of intoxication using a 18 item Visual Analogue Scale in a randomised, double-blinded, controlled, four treatments cross-over trial after consumption of (A) placebo, (B) alcohol (vodka 37.5% at a dose of 46.5 g ethanol), (C) alcohol in combination with caffeine at a dose of 80 mg (equivalent to one 250 ml can of energy drink) and (D) alcohol in combination with energy drink at a dose of 250 ml (one can). Primary variables were headache, weakness, salivation and motor coordination. Out of four primary variables, weakness and motor coordination showed a statistically significant difference between alcohol and non-alcohol group, out of 14 secondary variables, five more variables (dizziness, alterations in sight, alterations in walking, agitation and alterations in speech) also showed significant differences due mainly to contrasts with the non-alcohol group. In none of these end points, could a statistically significant effect be found for the additional ingestion of energy drink or caffeine on the subjective feelings of alcohol intoxication. This within-subjects study does not confirm the presence of a "masking effect" when combining caffeine or energy drink with alcohol.

Longitudinal analysis of microvascular perfusion and neurodegenerative changes in early type 2 diabetic retinal disease.

AIM: To prospectively monitor subclinical changes in capillary perfusion and retinal layer thickness in patients with type 2 diabetes and early diabetic retinal disease over 2 years. METHODS: In this longitudinal study we performed biannual retinal vascular imaging using optical coherence tomography angiography (RTVue) to analyse the foveal avascular zone (FAZ) area, perimeter, acircularity index (AI) and parafoveal superficial/deep vessel density (VD). Spectral-domain optical coherence tomography (Spectralis) was used to measure the thickness of nine macular layers and the peripapillary nerve fibre layer. RESULTS: Among 117 eyes (58 left) of 59 patients (21 female), 105 had no diabetic retinopathy (DR), 6 mild and 6 moderate non-proliferative DR at baseline. We found DR progression in 13 eyes at year 2. The FAZ area (+0.008±0.002 mm2/year, p<0.0001), perimeter (+0.036±0.010 mm/year, p=0.006) and AI (+0.005±0.002/year, p=0.0280) increased significantly. A pronounced decrease was found in the superficial (-1.425±0.290%/year, p<0.0001) but not the deep VD. Inner neuroretinal loss was confined to the ganglion cell (-0.539±0.150 µm/year, p=0.0004) and the inner plexiform layer (-0.361±0.127 µm/year, p=0.0045). In the outer retina, we observed a statistically significant decrease in thickness in the outer plexiform, photoreceptor layer and pigment epithelium of -0.921±0.161 µm/year, -0.325±0.139 µm/year and -0.385±0.084 µm/year, respectively. CONCLUSION: Subclinical signs of microangiopathy and neurodegeneration appear in parallel and are highly progressive even in the earliest stages of diabetic retinal disease. Trial registration number EudraCT20156000239634.

Systematic ultrastructural comparison of swept-source and full-depth spectral domain optical coherence tomography imaging of diabetic macular oedema.

BACKGROUND/AIMS: Optical coherence tomography (OCT) is commonly used to diagnose and assess diabetic macular oedema (DME). Swept-source OCT (SS-OCT) promises improved imaging depth and more independence from media opacities. Heidelberg Spectralis full-depth imaging (FDI) combines details at different depths to one representation. The aim of this study was to determine the comparability of the imaging methods concerning DME ultrastructure. METHODS: Two graders assessed the presence of typical DME phenomena in eyes with centre-involving DME on Topcon Atlantis SS-OCT and Heidelberg Spectralis FDI spectral-domain OCT (SD-OCT) B-scans. Retinal layer segmentation was corrected and choroidal layers were manually segmented. Graders measured cyst and subretinal fluid (SRF) diameters and counted hyper-reflective foci (HRF). Findings were recorded and statistically analysed. RESULTS: Statistically significant systematic biases (Spectralis-Atlantis) were found for the HRF count (outside the central mm, -6.39, p=0.0338), chorioretinal thickness (central mm: -35.45 µm, p=0.00034), choroidal thickness (central mm: -60.97 µm, p=0.00004) and Sattler's layer thickness (-42.69 µm, p=0.0001). Intergrader agreement was excellent or very good for posterior vitreous detachment, vitreomacular attachment (central mm) and SRF presence in both devices. Manually delineated Sattler's layer thickness showed an intraclass correlation of 0.85 with FDI SD-OCT but 0.26 with SS-OCT (p=0.003). CONCLUSION: Prominent aspects such as cysts in the outer nuclear layer and SRF can be identified with comparable confidence, while a significant systematic bias underlies chorioretinal, choroidal and Sattler's layer thickness and HRF count. Specialists should use the same device at every examination during longitudinal clinical consideration or cross-sectional evaluation of these ultrastructural biomarkers.

Viennese risk prediction score for Advanced Gastroesophageal carcinoma based on Alarm Symptoms (VAGAS score): characterisation of alarm symptoms in advanced gastro-oesophageal cancer and its correlation with outcome.

INTRODUCTION: The prognostic value of symptoms at disease presentation of advanced gastro-oesophageal cancer is unknown. Thus, the aim of this study was to characterise these symptoms and correlate them with the outcome, so new prognostic markers can be defined. METHODS: We analysed clinical data including symptoms, therapies and survival of patients with stage IV gastro-oesophageal cancer treated between 2002 and 2018 at the Vienna General Hospital, Austria. Initial symptoms as well as stenosis in endoscopy and HER2 positivity were evaluated in a cross-validation model to ascertain the impact of each variable on patient survival. RESULTS: In total, 258 patients were evaluated. Five factors (stenosis in endoscopy, weight loss, HER2 positivity, dyspepsia, ulcer or active bleeding) have proven to be statistically relevant prognostic factors and were given a count of +1 and -1, if applicable. The resulting score ranges between -3 and +2. The survival probability for 180 days with a score of -3/-2, -1, 0, +1 and +2 is 90%, 80%, 73%, 72% and 42%, whereas for 2 years, it is 30%, 30%, 8%, 7% and 3%, respectively. The median overall survival of a score of -3/-2, -1, 0, +1 and +2 was 579 (95% CI 274 to not measurable), 481 (95% CI 358 to 637), 297 (95% CI 240 to 346), 284 (95% CI 205 to 371), 146 (95% CI 120 to 229) days, respectively. CONCLUSION: The data from this retrospective study indicate that the Viennese risk prediction score for Advanced Gastroesophageal carcinoma based on Alarm Symptoms score provides independent prognostic information that may support clinical decision making at diagnosis of advanced gastro-oesophageal cancer. Our findings should be evaluated in prospective studies.

Analysis of Running-Related Injuries: The Vienna Study.

BACKGROUND: This study aimed to provide an extensive and up-to-date analysis of running-related injuries (RRI) and analyze a broad range of contributing factors for a large heterogeneous and non-selected running population from Central Europe. METHODS: Anthropometric, training, footwear, anatomic malalignment, and injury data from 196 injured runners were assessed case-controlled and retrospectively. Univariate and multivariate regression models were developed to identify associated factors for specific injury locations and diagnoses. RESULTS: The majority of patients were female (56%). Three most frequently observed malalignments included varus knee alignment, pelvic obliquity, and patellar squinting. The most common injuries were the patellofemoral pain syndrome (PFPS), the iliotibial band friction syndrome (ITBFS), patellar tendinopathy, spinal overload, and ankle instability. A number of contributing factors were identified. Previous injury history was a contributing factor for knee injuries and ITBFS. Lower training load was reported with a higher incidence of PFPS, while a higher training load was positively associated with injuries of the lower leg. Runners with a higher body mass index (BMI) were at a significantly higher risk for lower back injuries. CONCLUSIONS: Running-related injuries are multifactorial associated with a combination of variables including personal data, training load, anatomic malalignments, and injury history. They can furthermore result from a lack of experience/training as well as from overuse. Suffering a specific RRI of high risk could be defined based on individual predispositions and help to induce appropriate training balance.