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Calcineurin inhibitor (CNI)-induced nephrotoxicity and chronic graft dysfunction with deteriorating glomerular filtration rate (GFR) are common problems of kidney transplant recipients. The aim of this study was to analyze the role of belatacept as a rescue therapy in these patients. In this retrospective, observational study we investigated 20 patients (10 females, 10 males) who were switched from a CNI (tacrolimus) to a belatacept-based immunosuppression because of CNI intolerance or marginal transplant function. Patient follow-up was 12 months. Patients were converted to belatacept in mean 28.8 months after transplantation. Reasons for conversion were CNI intolerance (14 patients) or marginal transplant function (6 patients). Mean estimated GFR (eGFR) before conversion was 22.2 ± 9.4 ml/min at baseline and improved significantly to 28.3 ± 10.1 ml/min at 4 weeks and to 32.1 ± 12.6 ml/min at 12 months after conversion. Serum bicarbonate significantly increased from 24.4 ± 3.2 mmol/l at baseline to 28.7 ± 2.6 mmol/l after 12 months. Conversion to belatacept decreased parathyroid hormone and phosphate concentrations significantly, whereas albumin levels significantly increased. In 6 cases an acute rejection preceded clinically relevant CNI toxicity; only two patients suffered from an acute rejection after conversion. Belatacept was well tolerated and there was no increase in infectious or malignant side effects. A late conversion from a tacrolimus-based immunosuppression to belatacept is safe, effective and significantly improves renal function in kidney transplant recipients. Additionally, the conversion to belatacept has a beneficial impact on acid-base balance, mineral-bone and protein metabolism, independently of eGFR.

Rotating wire brushes are used, e.g., for rust removal. Detaching fragments can cause severe eye injuries. The purpose of this study was to investigate mechanism, severity, clinical outcome, validity of Ocular Trauma Score (OTS) and to assess the likelihood of final visual acuity. Twenty patients with traumatic ocular injuries by rotating wire brushes were included. Location and type of injury, grade of injury according to OTS, surgical procedure, and development of visual acuity were evaluated. Eleven accidents (55%) happened at work, nine at home (45%). Eighteen injuries (90%) were penetrating, one (5%) was perforating. In one case (5%), an intraocular foreign body was present. One case each was classified OTS 1 and 2 (5%), six cases OTS 3 (30%), four cases OTS 4 (20%), and eight cases OTS 5 (40%). None of the patients was wearing safety goggles. Fourteen patients (70%) were surgically treated. Of these, five were treated at the anterior segment only, nine additionally underwent pars-plana vitrectomy. Nine patients received phacoemulsification. Mean best corrected visual acuity was logMAR 1.0 (2/20) at admission and 0.3 (10/20) at last follow-up. Our results were similar to those in the OTS study, except for OTS 1 (p = 0.046). Comparing the categorical distribution of final visual acuity in all OTS categories, no statistically significant difference was found (p = 0.119) between our results and the OTS study group. OTS may provide prognostic information in traumatic ocular injuries by rotating wire brushes. The injuries could have been avoided by wearing safety goggles.

BACKGROUND The influenza vaccination rate among older and chronically ill patients in Germany has declined in the past decade in spite of vaccination campaigns. METHODS The influenza vaccination rate among persons with chronic renal disease was studied with the aid of billing data from various Associations of Statutory Health Insurance Physicians (Kassenarztliche Vereinigungen, ASHIPs) in Germany. It was tested in a randomized controlled trial whether a written vaccination appeal, sent by physicians to patients, led to an increase in the vaccination rate. It was tested in a further such trial whether the vaccination rate among patients with renal disease could be improved by an appeal for vaccination that was sent by the ASHIPs to the treating nephrologists. Finally, it was also tested in a prospective interventional study whether the vaccination rate could be improved by an appeal for vaccination sent by a health- insurance carrier directly to the patients. RESULTS In 2012-2017, the vaccination rate among persons with chronically impaired renal function ranged from 41.1% to 46.9%; it ranged from 31.7% to 33.7% in kidney transplant recipients and from 42.7% to 44.7% in dialysis patients. An appeal for vaccination that was sent from physicians to patients raised the vaccination rate by 8.3% in the intervention group compared to the control group (p = 0.03; number needed to treat [NNT]: 13). On the other hand, an appeal for vaccination that was sent to the nephrologists lowered the vaccination rate by 0.8% in the intervention group compared to the control group. Finally, an appeal for vaccination that was sent by the health-insurance fund to the patients raised the vaccination rate by 3.2% (p

Background Since 2010, the number of organ donations in Germany has decreased by one third, mostly due to undetected organ donors. It is unclear, how the undetected potential donor pool is distributed among the different German hospital categories (A = university hospital, B = hospitals with neurosurgery, C = hospitals without neurosurgery) and region types. Methods We performed a nationwide secondary data analysis of all German inpatient cases of the year 2016 (n = 20,063,689). All fatalities were regarded as potential organ donors, in which primary or secondary brain damage was encoded and organ donation was not excluded by a contraindication or a lack of ventilation therapy. Results In 2016, 28,087 potential organ donors were identified. Thereof 21% were found in category A, 28% in category B and 42% in category C hospitals. The contact rate (= organ donation related contacts/ potential organ donors) and realization rate (= realized organ donations/ potential organ donors) of category A, B and C hospitals was 10.6% and 4.6%, 10.9% and 4.8% and 6.0% and 1.7%, respectively. 58.2% of the donor potential of category C hospitals was found in the largest quartile of category C hospitals. 51% (n = 14,436) of the potential organ donors were treated in hospitals in agglomeration areas, 28% (n = 7,909) in urban areas and 21% (n = 5,742) in rural areas. The contact- and realization rate did not significantly differ between these areas. Conclusions The largest proportion of potential organ donors and the lowest realization rate are found in category C hospitals. Reporting and donation practice do not differ between urban and rural regions.

Background Outcome predictions in patients with acute severe neurologic disorders are difficult and influenced by multiple factors. Since the decision for and the extent of life-sustaining therapies are based on the estimated prognosis, it is vital to understand which factors influence such estimates. This study examined whether previous professional experience with rehabilitation medicine influences physician decision-making. Methods A case vignette presenting a typical patient with an extensive brain stem infarction was developed and distributed online to clinical neurologists. Questions focused on prognosis, interpretation of an advanced directive, whether to withdraw life-sustaining treatments and information on prior rehabilitation experience from the survey respondent. Results Of the participating neurologists, 77% opted for the withdrawal of life-sustaining therapies (n = 70; response rate: 14.8%). This decision was not affected by age, gender, or length of clinical experience. Neurologists with experience in rehabilitation medicine tended to estimate a more positive prognosis than neurologists without, but this result was not significant (p = .13). There was an association between the intervention chosen and previous experience in rehabilitation; neurologists with experience in rehabilitation medicine opted significantly more often (31.8%) for continuing life-sustaining treatments than neurologists without such experience (8.7%, p = .04). Conclusion Our results indicate that there are subjective factors influencing decisions to limit life-sustaining treatments that are based on previous professional experience. This finding emphasizes the variability and cognitive bias of such decision processes and should be integrated into future guidelines for specialist training on end-of-life decision-making.

Upon ligand binding, plasma membrane-located TNF-related apoptosis-inducing ligand (TRAIL)-receptors 1 and 2 induce apoptosis as well as cancer-promoting signaling in cancer cells. TRAIL-R3 and TRAIL-R4 are believed to negatively regulate TRAIL-mediated apoptosis. Intracellular localization of TRAIL-receptors, as observed in many tumor cells, has been associated with oncogenic features, which are distinct from membrane-associated TRAIL-R signaling. Here, analyzing a panel of 354 breast cancer specimens, we found that an unfavorable outcome correlating with cancer-promoting properties of TRAIL-R1, TRAIL-R2, and TRAIL-R4 was most significantly defined by their intracellular distribution and mutual co-expression. A nuclear or cytoplasmic heterogeneous expression pattern correlated with markedly decreased overall survival and discriminated high-risk breast cancer patients from low-risk patients with a homogeneous distribution of expression, i.e., nuclear and cytoplasmic expression. The homogeneous TRAIL-R expression was associated with favorable breast cancer surrogate markers corresponding with excellent survival prognoses at 5 years after diagnosis (hazard ratio, 0.043) and over the complete course of follow-up (hazard ratio, 0.098; both p 0.001). No associations with specific intrinsic breast cancer subtypes were found. Our data suggest that the determination of intracellular co-expression patterns of TRAIL-R1, TRAIL-R2, and TRAIL-R4 provides an innovative and robust method for risk stratification in breast cancer patients beyond conventional prognostic markers. KEY MESSAGES: A total of 70% of breast cancer specimens show comparably high levels of intracellular TRAIL-Rs. Nuclear or cytoplasmic TRAIL-R co-expression occurs in the majority of tumors. A total of 25% of tumors show a heterogeneous expression of cytoplasmic or nuclear TRAIL-Rs. Patients with a heterogeneous TRAIL-R expression present with poor prognoses. Additive TRAIL-R-based risk stratification comprises different breast cancer subtypes.

BACKGROUND The annual number of post-mortem organ donations in Germany has declined by more than 30% since 2010. The causes of this development have not yet been adequately determined. METHODS All patients hospitalized in Germany between 2010 and 2015 (112 172 869 hospitalizations in total) were included in this nationwide secondary analysis. Among the deceased patients we identified those who had died in the presence of a brain damage and for whom organ donation was not excluded either by a medical contraindication or by the patient's not having been artificially ventilated. The analysis was also conducted separately for six German university hospitals. RESULTS Over the period 2010-2015, the number of potential organ donors per year in Germany rose by 13.9%, from 23 937 to 27 258. This development was due to an increase in the number of deaths with severe brain damage as well as an increase in the percentage of patients who were treated with invasive ventilation before death. The contact quotient, i.e., the percentage of potential donors for whom contact was made with the German Foundation for Organ Transplantation (Deutsche Stiftung Organtransplantation, DSO) fell over this period from 11.4% to 8.2%. At the same time, the realization quotient (the percentage of potential donors who became actual donors) fell from 5.4% to 3.2%, and the conversion quotient (the percentage of potential donors for whom contact was made who became actual donors) fell from 47% to 39.1%. From 2010 to 2012, the falling realization quotient was accounted for mainly by the falling conversion quotient; from 2012 to 2015, it was accounted for mainly by the falling contact quotient. The contact and realization quotients among the six university hospitals studied differed markedly (by factors of 17.5 and 23.3, respectively), while the conversion quotients differed only minimally (by a factor of 1.3). CONCLUSION The decline in post-mortem organ donation is due to a deficiency in the recognition and reporting of potential organ donors in hospital. If this process were better supported on the organizational and political level, far more organs could be transplanted.

Background Since 2014, expected graft and recipient survival are matched by the U.S. kidney allocation system to improve organ utility. This mechanism is based on the kidney donor profile index (KDPI) and the estimated posttransplant survival score (EPTS). Here we analyzed 1. the transferability of these scores into the Eurotransplant (ET) region and 2. the extent to which the ET kidney allocation algorithm promotes utility. Methods We studied data of 262 kidney transplantations performed at the University Hospital Kiel between 2000 and 2009 (median follow-up, 9.94 years). Results Multivariable Cox regression analysis revealed that only the variables donor age of the KDPI and recipient's age of the EPTS have a significant value as predictors of posttransplant graft and recipient survival. The other variables showed no additional predictive value. Analyzing all kidneys allocated in the ET kidney allocation system and the European Senior Program, we found that donor and recipient's age and KDPI and EPTS were weakly correlated (rage-age = 0.5, P Conclusion The ET kidney allocation algorithm poorly matched predicted graft and recipient survival at our center. A better age-matching may improve organ utility.

Background/Aims: The high complexity of pediatric reference ranges across age, sex, and units impairs clinical application and comparability of steroid hormone data, e.g., in congenital adrenal hyperplasia (CAH). We developed a multiples-of-median (MoM) normalization tool to overcome this major drawback in pediatric endocrinology. Methods: Liquid chromatography tandem mass spectrometry data comprising 10 steroid hormones representing 905 controls (555 males, 350 females, 0 to > 16 years) from 2 previous datasets were MoM transformed across age and sex. Twenty-three genetically proven CAH patients were included (21-hydroxylase deficiency [21OHD], n = 19; 11β-hydroxylase deficiency [11OHD], n = 4). MoM cutoffs for single steroids predicting 21OHD and 11OHD were computed and validated through new, independent patients (21OHD, n = 8; adrenal cortical carcinoma, n = 6; obesity, n = 40). Results: 21OHD and 11OHD patients showed disease-typical, easily recognizable MoM patterns independent of age, sex, and concentration units. Two single-steroid cutoffs indicated 21OHD: 3.87 MoM for 17-hydroxyprogesterone (100% sensitivity and 98.83% specificity) and 12.28 MoM for 21-deoxycortisol (94.74% sensitivity and 100% specificity). A cutoff of 13.18 MoM for 11-deoxycortisol indicated 11OHD (100% sensitivity and 100% specificity). Conclusions: Age- and sex-independent MoMs are straightforward for a clinically relevant display of multi-steroid patterns. In addition, defined single-steroid MoMs can serve alone as predictors of 21OHD and 11OHD. Finally, MoM transformation offers substantial enhancement of routine and scientific steroid hormone data exchange due to improved comparability.

Objectives Unilateral pulmonary oedema (UPE) is a rare but potentially life-threatening complication that has been described after minimally invasive mitral valve surgery (MICS). Over the last 8 years, we have witnessed, in our institution, several cases of severe UPE requiring immediate postoperative extracorporeal life support after MICS. Reviewing the available literature, data regarding this complication after MICS are rare. Consequently, we decided to retrospectively analyse patients scheduled for MICS in our institution. Methods After approval by our institutional review board, 256 MICS patients were analysed. As a primary end-point, we defined a newly developed UPE, radiographically evident within the first 24 h postoperatively. Secondary end-points were length of stay in the intensive care unit, length of stay in the hospital and in-hospital mortality. Chest radiographs were analysed by an independent consultant of radiology. Results Fifty-one (19.9%) patients showed increased right-sided pulmonary vascular congestion in the 1st postoperative chest radiography performed in the intensive care unit. Five (1.95%) patients immediately required extracorporeal life support after admission to the intensive care unit. Cardiopulmonary bypass time was significantly longer in the UPE group [UPE vs non-UPE 213 (49) vs 196 (43) min; P = 0.013]. More patients with UPE showed a preoperative increase of C-reactive protein >0.4265 mg/dl (P = 0.05). Logistic regression analysis identified a preoperative increase in C-reactive protein >0.4265 mg/dl as well as a prolonged cardiopulmonary bypass time (odds ratio 1.009, 95% confidence level 1.002-1.016; P = 0.014) independent risk factors, significantly associated with the development of UPE (odds ratio 2.583, 95% confidence interval 1.275-5.233; P = 0.008), a prolonged cardiopulmonary bypass time (odds ratio 1.009, 95% confidence interval 1.002-1.016; P = 0.014). The presence of pulmonary hypertension (odds ratio 0.273, 95% confidence interval 0.08-0.84; P = 0.02) seemed to be a protective factor regarding the genesis of UPE. Conclusions In accordance with the rarely available literature regarding UPE after MICS, our analysis led us to hypothesize the possibility of an inflammatory disposition for UPE. The role of pulmonary hypertension remains unclear in our patient population. Clinical trials number NCT02655094.

Ears nose and throat (ENT) involvement is found on a substantial proportion of patients with granulomatosis with polyangiitis (GPA). Structured, reliable ENT assessment is essential in the management of GPA patients. It is the aim of this study to determine the repeatability (intra-rater reliability) and reproducibility (inter-rater reliability) of the ENT Assessment Score (ENTAS 2).The ENTAS 2 built the fundament of the prospective randomized trial. Anamnestic, video endoscopic and diagnostic data of 47 patients were used. A single assessor reference was created. GPA/ENT activity and damage were evaluated by three physicians at two time points (T1/T2). GPA/ENT activity was evaluated in dichotomy (yes/no) and grading (none/mild/moderate/high) and GPA/ ENT damage in dichotomy.ENTAS 2 activity evaluations intra-rater reliability was 80.7% (κ=0.56) in dichotomy and 72.8% (κ=0.41) in grading. ENTAS 2 damage evaluations showed 87.8% (κ=0.74) intra-rater reliability. ENTAS 2 activity inter-rater reliability at T1 was 62.2% (κ=0.43) in dichotomy and 51.1% (κ=0.29) in grading, at T2 it was 68.2% (κ=0.48) in dichotomy and 55.32% (κ=0.33) in grading. Inter-rater reliability of ENTAS 2 damage evaluation was 84.4% (κ=0.79) at T1 and 72.5% (κ=0.64) at T2.ENTAS 2 intra-rater reliability was high in dichotomous and graded GPA/ENT activity and damage evaluations. Inter-rater reliability was high in dichotomous activity and damage evaluations, but low in graded activity evaluations. The data demonstrate that the ENTAS 2 is a reliable score-system considering GPA/ENT activity and damage evaluations.

Classical apparent motion stimuli exhibit an inherent ambiguity with respect to the onsets and offsets of the stimulus elements. Sigman and Rock (1974, Perception3 9 – 28) presented evidence suggesting that occlusion cues are used to resolve this ambiguity. We present results from experiments designed to further test predictions of this hypothesis. As expected, we found that the apparent motion of a target stimulus is suppressed when a ‘moving’ occluder is positioned such that it rationalises the onsets and offsets of the stimulus elements constituting the target. Somewhat unexpectedly, though, we also observed a slight tendency for motion suppression under conditions where the target was only partially occluded. The expected motion suppression occurred both with solid occluders and purely virtual Kanizsa-like occluders, although it was not always observed in the latter case. Motion suppression was found to occur over a wide range of stimulus onset asynchronies. Finally, we used binocular disparity cues to test the occlusion account of the motion suppression phenomenon against an alternative explanation in terms of attentional factors. The results are in clear favour of the occlusion account.

Introduction. Transcranial direct current stimulation (tDCS) is a non-invasive method of modulating brain activity. Previous studies with common tDCS montages have shown that there are positive effects on the left inferior dorsolateral prefrontal cortex (lDLPFC) for both healthy and clinical population like improvement of the working memory. Nevertheless, there is still lack of clear guidelines and safety instructions, probably due to not specific enough simulation montages, especially when focusing on pediatric population. This study aims to investigate behavioral outcome of multichannel tDCS over the lDLPFC in healthy children and adolescents. Therefore, tDCS was coupled with a memory task, especially focusing on accuracy and reaction time changes. Methods. The study was approved by the Ethic Committee of the Faculty of Medicine of Kiel University. The study was conducted in a double-blinded, randomized, sham-controlled design. 28 healthy children and adolescents (Age range: 10–17 years, mean age = 14,18, SD = 2,23) were included in the analysis. In four separate sessions, they received multichannel 2 mA anodal or sham tDCS for 20 minutes over the left DLPFC before or during working memory task (2 back task). At the behavioral level response time and accuracy for N-back task were evaluated. Additionally, safety and tolerability of multichannel tDCS has been investigated by written questionnaires. For multichannel 2 mA tDCS over DLPFC we used a 6-channel solution (3.14 cm2 circular electrodes; AF3 (897 μΑ), AF7 (284 μΑ), F3 (819 μΑ), Fp2 (−1000 μΑ) und T7 (−1000 μΑ)). Before, during and after stimulation 32 channel EEG was recorded in order to demonstrate neurophysiological changes. All materials required for the stimulations and EEG recording were obtained from Neuroelectrics (Barcelona, Spain). Results. All participants tolerated the stimulation well. Our preliminary behavioral results showed that there were no significant effects on accuracy (ACC) or reaction time (RT) compared tDCS to sham stimulation. There were also no significant effects on ACC and RT between online or offline stimulation and no significant effects in the interaction of these variables (p > 0.05). Conclusion. In summary, our study demonstrates that multichannel tDCS over DLPFC with 2 mA intensity over 20 min is well tolerated, and thus may be used as an experimental and treatment method in the pediatric population. Based on preliminary behavioral data, we could not show any stimulation effect. In accordance to literature though, stimulation often shows bigger effects on clinical population rather than healthy participants. Possible reasons for null findings could be ceiling effects (e.g. Suitability of the Paradigm depending on age). Furthermore, individual differences like baseline activity, may have had an impact on stimulation effectivity. Additional EEG analysis may provide more specific insights into developmental aspects of working memory processing on the neural level.