High CO2 levels drive the TCA cycle backwards towards autotrophy.

It has recently been shown that in anaerobic microorganisms the tricarboxylic acid (TCA) cycle, including the seemingly irreversible citrate synthase reaction, can be reversed and used for autotrophic fixation of carbon1,2. This reversed oxidative TCA cycle requires ferredoxin-dependent 2-oxoglutarate synthase instead of the NAD-dependent dehydrogenase as well as extremely high levels of citrate synthase (more than 7% of the proteins in the cell). In this pathway, citrate synthase replaces ATP-citrate lyase of the reductive TCA cycle, which leads to the spending of one ATP-equivalent less per one turn of the cycle. Here we show, using the thermophilic sulfur-reducing deltaproteobacterium Hippea maritima, that this route is driven by high partial pressures of CO2. These high partial pressures are especially important for the removal of the product acetyl coenzyme A (acetyl-CoA) through reductive carboxylation to pyruvate, which is catalysed by pyruvate synthase. The reversed oxidative TCA cycle may have been functioning in autotrophic CO2 fixation in a primordial atmosphere that is assumed to have been rich in CO2.

Test-retest reliability of ski-specific aerobic, sprint, and neuromuscular performance tests in highly trained cross-country skiers.

PURPOSE: Laboratory tests are commonly performed by cross-country (XC) skiers due to the challenges of obtaining reliable performance indicators on snow. However, only a few studies have reported reliability data for ski-specific test protocols. Therefore, this study examined the test-retest reliability of ski-specific aerobic, sprint, and neuromuscular performance tests. METHODS: Thirty-nine highly trained XC skiers (26 men and 13 women, age: 22 ± 4 years, V̇O2max : 70.1 ± 4.5 and 58.8 ± 4.4 mL·kg-1 ·min-1 , respectively) performed two test trials within 6 days of a diagonal V̇O2max test, n = 27; skating graded exercise test to assess the second lactate threshold (LT2 ), n = 27; 24-min double poling time trial (24-min DP, n = 25), double poling sprint test (SprintDP1 , n = 27), and 1-min self-paced skating sprint test (Sprint1-min , n = 26) using roller skis on a treadmill, and an upper-body strength test (UB-ST, n = 27) to assess peak power (Ppeak ) with light, medium, and heavy loads. For each test, the coefficient of variation (CV), intraclass correlation coefficient (ICC), and minimal detectable change (MDC) were calculated. RESULTS: V̇O2max demonstrated good-to-excellent reliability (CV = 1.4%; ICC = 0.99; MDC = 112 mL·min-1 ), whereas moderate-to-excellent reliability was found for LT2 (CV = 3.1%; ICC = 0.95). Performance during 24-min DP, SprintDP1 , and Sprint1-min showed good-to-excellent reliability (CV = 1.0%-2.3%; ICC = 0.96-0.99). Absolute reliability for UB-ST Ppeak was poor (CV = 4.9%-7.8%), while relative reliability was excellent (ICC = 0.93-0.97) across the loads. CONCLUSION: In highly trained XC skiers, sport-specific aerobic and sprint performance tests demonstrated high test-retest reliability, while neuromuscular performance for the upper body was less reliable. Using the presented protocols, practitioners can assess within- and between-season changes in relevant performance indicators.

Substrate usage determines carbon flux via the citrate cycle in Helicobacter pylori.

Helicobacter pylori displays a worldwide infection rate of about 50%. The Gram-negative bacterium is the main reason for gastric cancer and other severe diseases. Despite considerable knowledge about the metabolic inventory of H. pylori, carbon fluxes through the citrate cycle (TCA cycle) remained enigmatic. In this study, different 13 C-labeled substrates were supplied as carbon sources to H. pylori during microaerophilic growth in a complex medium. After growth, 13 C-excess and 13 C-distribution were determined in multiple metabolites using GC-MS analysis. [U-13 C6 ]Glucose was efficiently converted into glyceraldehyde but only less into TCA cycle-related metabolites. In contrast, [U-13 C5 ]glutamate, [U-13 C4 ]succinate, and [U-13 C4 ]aspartate were incorporated at high levels into intermediates of the TCA cycle. The comparative analysis of the 13 C-distributions indicated an adaptive TCA cycle fully operating in the closed oxidative direction with rapid equilibrium fluxes between oxaloacetate-succinate and α-ketoglutarate-citrate. 13 C-Profiles of the four-carbon intermediates in the TCA cycle, especially of malate, together with the observation of an isocitrate lyase activity by in vitro assays, suggested carbon fluxes via a glyoxylate bypass. In conjunction with the lack of enzymes for anaplerotic CO2 fixation, the glyoxylate bypass could be relevant to fill up the TCA cycle with carbon atoms derived from acetyl-CoA.

Comparison of the automatised and the optimised carbon monoxide rebreathing methods.

Recently, a new automated carbon monoxide (CO) rebreathing method (aCO) to estimate haemoglobin mass (Hbmass) was introduced. The aCO method uses the same CO dilution principle as the widely used optimised CO rebreathing method (oCO). The two methods differ in terms of CO administration, body position, and rebreathing time. Whereas with aCO, CO is administered automatically by the system in a supine position of the subject, with oCO, CO is administered manually by an experienced operator with the subject sitting. Therefore, the aim of this study was to quantify possible differences in Hbmass estimated with the two methods. Hbmass was estimated in 18 subjects (9 females, 9 males) with oCO using capillary blood samples (oCOc) and aCO taking simultaneously venous blood samples (aCOv) and capillary blood samples (aCOc). Overall, Hbmass was different between the three measurement procedures (F = 57.55, p < .001). Hbmass was lower (p < .001) for oCOc (737 g ± 179 g) than for both aCOv (825 g ± 189 g, -9.3%) and aCOc (835 g ± 189 g, -10.6%). There was no difference in Hbmass estimated with aCOv and aCOc procedures (p = .12). Three factors can likely explain the 10% difference in Hbmass: differences in calculations (including a factor for myoglobin flux), body position (distribution of CO in blood circulation) during rebreathing, and time of blood sampling. Moreover, the determination of Hbmass with aCO is possible with capillary blood sampling instead of venous blood sampling.

Metabolic adaption of Legionella pneumophila during intracellular growth in Acanthamoeba castellanii.

The metabolism of Legionella pneumophila strain Paris was elucidated during different time intervals of growth within its natural host Acanthamoeba castellanii. For this purpose, the amoebae were supplied after bacterial infection (t =0 h) with 11 mM [U-13C6]glucose or 3 mM [U-13C3]serine, respectively, during 0-17 h, 17-25 h, or 25-27 h of incubation. At the end of these time intervals, bacterial and amoebal fractions were separated. Each of these fractions was hydrolyzed under acidic conditions. 13C-Enrichments and isotopologue distributions of resulting amino acids and 3-hydroxybutyrate were determined by gas chromatography - mass spectrometry. Comparative analysis of the labelling patterns revealed the substrate preferences, metabolic pathways, and relative carbon fluxes of the intracellular bacteria and their amoebal host during the time course of the infection cycle. Generally, the bacterial infection increased the usage of exogenous glucose via glycolysis by A. castellanii. In contrast, carbon fluxes via the amoebal citrate cycle were not affected. During the whole infection cycle, intracellular L. pneumophila incorporated amino acids from their host into the bacterial proteins. However, partial bacterial de novo biosynthesis from exogenous 13C-Ser and, at minor rates, from 13C-glucose could be shown for bacterial Ala, Asp, Glu, and Gly. More specifically, the catabolic usage of Ser increased during the post-exponential phase of intracellular growth, whereas glucose was utilized by the bacteria throughout the infection cycle and not only late during infection as assumed on the basis of earlier in vitro experiments. The early usage of 13C-glucose by the intracellular bacteria suggests that glucose availability could serve as a trigger for replication of L. pneumophila inside the vacuoles of host cells.

Determinants of self-reported functional status (EPIC-26) in prostate cancer patients prior to treatment.

PURPOSE: The self-reported functional status (sr-FS) of prostate cancer (PCa) patients varies substantially between patients and health-care providers before treatment. Information about this issue is important for evaluating comparisons between health-care providers and to assist in treatment decision-making. There have been few reports on correlates of pretherapeutic sr-FS. The objective of the article, therefore, is to describe clinical and sociodemographic correlates of pretherapeutic sr-FS, based on a subset of the TrueNTH Global Registry, a prospective cohort study. METHODS: A total of 3094 PCa patients receiving local treatment in 44 PCa centers in Germany were recruited between July 2016 and April 2018. Multilevel regression models were applied to predict five pretherapeutic sr-FS (EPIC-26) scores based on clinical characteristics (standard set suggested by the International Consortium for Health Outcomes Measurement), sociodemographic characteristics, and center characteristics. RESULTS: Impaired pretherapeutic sr-FS tended to be associated with lower educational level and poorer disease characteristics-except for "urinary incontinence" which was only associated with age. Notably, age was a risk factor ("urinary incontinence," "urinary irritative/obstructive," "sexual") as well as a protective factor ("hormonal") for pretherapeutic sr-FS. Pretherapeutic sr-FS varies little across centers. CONCLUSIONS: Pretherapeutic sr-FS varies by clinical patient characteristics and age as well as by socioeconomic status. The findings point out the benefit of collecting and considering socioeconomic information in addition to clinical and demographic patient characteristics for treatment decision-making and fair comparisons between health-care providers.

Psychometric validation of the German version of the EPIC-26 questionnaire for patients with localized and locally advanced prostate cancer.

PURPOSE: For patients with prostate cancer, validated and reliable instruments are essential for measuring patient-reported outcomes. The aim of this study was to validate the German version of the widely established Expanded Prostate Cancer Index Composite with 26 items (EPIC-26). METHODS: A German translation of the original questionnaire was tested in 3094 patients with localized or locally advanced (any T, any N and M0) prostate cancer with treatment intent (including radical prostatectomy, brachytherapy, active surveillance, watchful waiting). They completed the EPIC-26 questionnaire before treatment. A total of 521 of them also completed a questionnaire 12 months afterward. Internal consistency, sensitivity to change, and construct validity were assessed. RESULTS: The internal consistency of all domains was sufficient (Cronbach's alpha between 0.64 and 0.93). Item-to-scale correlation coefficients showed acceptable associations between items and their domain score (all > 0.30), with the lowest scores for "bloody stools" (r = 0.37) and "breast problems" (r = 0.32). Confirmatory and exploratory factor analysis confirmed the five-dimension structure of the EPIC-26 (comparative fit index 0.95). CONCLUSIONS: Psychometric evaluation suggests that the German version of the EPIC-26 is a well-constructed instrument for measuring patient-reported health-related symptoms in patients with prostate cancer.

A high frequency, power, and efficiency diaphragm acoustic-to-electric transducer for thermoacoustic engines and refrigerators.

A high frequency, power, and efficiency diaphragm transducer is described for use with thermoacoustic engines and refrigerators. It uses a tube acting in compression and extension as the primary spring so that the mechanical resonant frequency is around 500 Hz. A high-frequency transducer results in more compact and higher power density thermoacoustic engines, refrigerators, and heat pumps. The tube spring furthermore constitutes a part of the pressure vessel so that the alternator is outside the pressure vessel, thereby simplifying transducer construction and reducing mass. The hermetically sealed transducer operates entirely without wear or lubricants, leading to a long maintenance-free lifetime. We present in situ efficiency measurement results at the full power operating frequency and temperature of the transducer. Despite the high operating frequency, the transducer efficiency is better than that of other transducers previously used in thermoacoustic systems. Accelerated fatigue test results on tube spring coupons justify the long-life claims. The exceptional stiffness of the primary spring in this transducer leads to the unusual need to consider stretch in additional transducer structural components. We present a multi-mass, lumped-element, coupled oscillator model of the transducer and discuss thermoacoustic system design using this model.

Influence of wheel rim width on rolling resistance and off-road speed in cross-country mountain biking.

The rim width of cross-country mountain bike wheel sets has increased in recent years, but the effect of this increase on performance remains unknown. The aim of this study was to analyse the influence of rim width on rolling resistance and off-road speed. We compared 3 tubeless wheel sets: 25 mm inner width as baseline, 30 mm width with the same tyre stiffness, and 30 mm width with the same tyre pressure. Three riders conducted 75 rolling resistance tests for each wheel set on a cross-country course. We determined rolling resistance using the virtual elevation method and calculated off-road speeds for flat and uphill conditions using a mathematical model. Baseline rolling resistance (Cr) was 0.0298, 90% CI [0.0286, 0.0310], which decreased by 1.4%, [0.7, 2.2] with the wider rim and the same tyre stiffness and increased by 0.9%, [0.1, 1.6] with the wider rim and the same tyre pressure. The corresponding effects on off-road speed were most likely trivial (0.0% to 0.7% faster and 0.1% to 0.6% slower, respectively). Because the effect of rim width on off-road speed seems negligible, athletes should choose the rim width that offers the best bike handling and should experiment with low tyre pressures.

Do male athletes with already high initial haemoglobin mass benefit from 'live high-train low' altitude training?

NEW FINDINGS: What is the central question of this study? It has been assumed that athletes embarking on an 'live high-train low' (LHTL) camp with already high initial haemoglobin mass (Hbmass ) have a limited ability to increase their Hbmass further post-intervention. Therefore, the relationship between initial Hbmass and post-intervention increase was tested with duplicate Hbmass measures and comparable hypoxic doses in male athletes. What is the main finding and its importance? There were trivial to moderate inverse relationships between initial Hbmass and percentage Hbmass increase in endurance and team-sport athletes after the LHTL camp, indicating that even athletes with higher initial Hbmass can reasonably expect Hbmass gains post-LHTL. It has been proposed that athletes with high initial values of haemoglobin mass (Hbmass ) will have a smaller Hbmass increase in response to 'live high-train low' (LHTL) altitude training. To verify this assumption, the relationship between initial absolute and relative Hbmass values and their respective Hbmass increase following LHTL in male endurance and team-sport athletes was investigated. Overall, 58 male athletes (35 well-trained endurance athletes and 23 elite male field hockey players) undertook an LHTL training camp with similar hypoxic doses (200-230 h). The Hbmass was measured in duplicate pre- and post-LHTL by the carbon monoxide rebreathing method. Although there was no relationship (r = 0.02, P = 0.91) between initial absolute Hbmass (in grams) and the percentage increase in absolute Hbmass , a moderate relationship (r = -0.31, P = 0.02) between initial relative Hbmass (in grams per kilogram) and the percentage increase in relative Hbmass was detected. Mean absolute and relative Hbmass increased to a similar extent (P ≥ 0.81) in endurance (from 916 ± 88 to 951 ± 96 g, +3.8%, P < 0.001 and from 13.1 ± 1.2 to 13.6 ± 1.1 g kg-1 , +4.1%, P < 0.001, respectively) and team-sport athletes (from 920 ± 120 to 957 ± 127 g, +4.0%, P < 0.001 and from 11.9 ± 0.9 to 12.3 ± 0.9 g kg-1 , +4.0%, P < 0.001, respectively) after LHTL. The direct comparison study using individual data of male endurance and team-sport athletes and strict methodological control (duplicate Hbmass measures and matched hypoxic dose) indicated that even athletes with higher initial Hbmass can reasonably expect Hbmass gain post-LHTL.

The Overall Survival Benefit for Patients with T1 Renal Cell Carcinoma after Nephron-Sparing Surgery Depends on Gender and Age.

Due to the recommendations in the urological guidelines to perform nephron-sparing surgery in patients with organ-confined renal cell carcinoma (RCC), the customary therapy regimen changed, but it is not well studied yet whether partial nephrectomy (PN) especially in the elderly is beneficial. From 2000 to 2015, 3,592 patients from 7 clinics undergoing surgery in RCC were identified; 2,323 had T1 tumours. We retrospectively compared the overall survival benefit of patients with T1 RCC who underwent either PN or radical nephrectomy (RN) and studied effects of age and gender. RESULTS: In T1 RCC, PN was beneficial in male patients (p = 0.0006) independent of age, especially in those men ≤75 years of age (p = 0.0005); but PN was not beneficial for female patients (p = 0.0629) regardless of age and male patients older than 75 years (p = 0.736). The OS of female patients after RN and male patients after PN is the same, regardless of age. A life expectancy of more than 45 months at least is necessary to experience an overall survival benefit after PN. CONCLUSIONS: There should be harder proven indications for PN in female patients and especially in all patients older than 75 years, particularly with regard to perioperative risk factors.

Reliability of the virtual elevation method to evaluate rolling resistance of different mountain bike cross-country tyres.

Although a low rolling resistance is advantageous in mountain bike cross-country racing, no studies have used the virtual elevation method to compare tyres from different manufacturers as used in international competitions so far. The aims of this study were to assess the reliability of this method, to compare the off-road rolling resistance between tyres and to calculate the influence on off-road speed. Nine 29-in. mountain bike cross-country tyres were tested on a course representing typical ground surface conditions 5 or 6 times. The coefficient of rolling resistance was estimated with the virtual elevation method by 3 investigators and corresponding off-road speeds were calculated. The virtual elevation method was highly reliable (typical error = 0.0006, 2.8%; limits of agreement <0.0005, r ≥ 0.98). The mean coefficient of rolling resistance was 0.0219 and differed from 0.0205 to 0.0237 (P < 0.001) between tyres. The calculated differences in off-road speed amounted to 2.9-3.2% (0% slope) and 2.3-2.4% (10% slope) between the slowest and the fastest tyre. The reliability of the method and the differences in rolling resistance between the tyres illustrate the value of testing tyres for important competitions on a representative ground surface using the virtual elevation method.

The PAZOREAL noninterventional study to assess effectiveness and safety of pazopanib and everolimus in the changing metastatic renal cell carcinoma treatment landscape.

VEGFR and mTOR inhibitors are broadly used in metastatic renal cell carcinoma (mRCC) therapy, and sequential first-line pazopanib (VEGFR inhibitor) and second-line everolimus (mTOR inhibitor) is a standard treatment option. Nivolumab and lenvatinib/everolimus combination was recently approved in Europe for use in mRCC after previous therapy. Prospective routine data on sequential therapy including nivolumab and/or lenvatinib are missing. This is a prospective, noninterventional study, which evaluates the effectiveness, tolerability, safety and quality of life following 450 patients with mRCC starting either on pazopanib as first-line therapy or third-line everolimus plus/minus lenvatinib following nivolumab. Adults with histologically confirmed mRCC of any subtype, who have a life expectancy of at least 6 months, are eligible.

Detection of blood volumes and haemoglobin mass by means of CO re-breathing and indocyanine green and sodium fluorescein injections.

The main aim of the present study was to quantify the magnitude of differences introduced when estimating a given blood volume compartment (e.g. plasma volume) through the direct determination of another compartment (e.g. red cell volume) by multiplication of venous haematocrit and/or haemoglobin concentration. However, since whole body haematocrit is higher than venous haematocrit such an approach might comprise certain errors. To test this experimentally, four different methods for detecting blood volumes and haemoglobin mass (Hbmass) were compared, namely the carbon monoxide (CO) re-breathing (for Hbmass), the indocyanine green (ICG; for plasma volume [PV]) and the sodium fluorescein (SoF; for red blood cell volume [RBCV]) methods. No difference between ICG and CO re-breathing derived PV could be established when a whole body/venous haematocrit correction factor of 0.91 was applied (p = 0.11, r = 0.43, mean difference -340 ± 612 mL). In contrast, when comparing RBCV derived by the CO re-breathing and the SoF method, the SoF method revealed lower RBCV values as compared to the CO re-breathing method (p < 0.05, r = 0.95, mean difference -728 ± 184 mL). However, compared to the ICG and the SoF methods, the typical error (%TE) and hence reliability of the CO re-breathing method was lower for all measured parameters. Therefore, estimating blood volume compartments by the direct assessment of another compartment can be considered a suitable approach. The CO re-breathing method proved accurate in determining the induced phlebotomy and is at the same time judged easier to perform than any of the other methods.

Accuracy of Cycling Power Meters against a Mathematical Model of Treadmill Cycling.

The aim of this study was to compare the accuracy among a high number of current mobile cycling power meters used by elite and recreational cyclists against a first principle-based mathematical model of treadmill cycling. 54 power meters from 9 manufacturers used by 32 cyclists were calibrated. While the cyclist coasted downhill on a motorised treadmill, a back-pulling system was adjusted to counter the downhill force. The system was then loaded 3 times with 4 different masses while the cyclist pedalled to keep his position. The mean deviation (trueness) to the model and coefficient of variation (precision) were analysed. The mean deviations of the power meters were -0.9±3.2% (mean±SD) with 6 power meters deviating by more than±5%. The coefficients of variation of the power meters were 1.2±0.9% (mean±SD), with Stages varying more than SRM (p<0.001) and PowerTap (p<0.001). In conclusion, current power meters used by elite and recreational cyclists vary considerably in their trueness; precision is generally high but differs between manufacturers. Calibrating and adjusting the trueness of every power meter against a first principle-based reference is advised for accurate measurements.

Performance differences when using 26- and 29-inch-wheel bikes in Swiss National Team cross-country mountain bikers.

The purpose of this study was to analyse the effect of bike type - the 26-inch-wheel bike (26" bike) and the 29-inch-wheel bike (29" bike) - on performance in elite mountain bikers. Ten Swiss National Team athletes (seven males, three females) completed six trials with individual start on a simulated cross-country course with 35 min of active recovery between trials (three trials on a 26" bike and three trials on a 29" bike, alternate order, randomised start-bike). The course consisted of two separate sections expected to favour either the 29" bike (section A) or the 26" bike (section B). For each trial performance, power output, cadence and heart rate were recorded and athletes' experiences were documented. Mean overall performance (time: 304 ± 27 s vs. 311 ± 29 s; P < 0.01) and performance in sections A (P < 0.001) and B (P < 0.05) were better when using the 29" bike. No significant differences were observed for power output, cadence or heart rate. Athletes rated the 29" bike as better for performance in general, passing obstacles and traction. The 29" bike supports superior performance for elite mountain bikers, even on sections supposed to favour the 26" bike.

Everolimus in metastatic renal cell carcinoma after failure of initial anti-VEGF therapy: final results of a noninterventional study.

BACKGROUND: Data are limited regarding routine use of everolimus after initial vascular endothelial growth factor (VEGF)-targeted therapy. The aim of this prospective, noninterventional, observational study was to assess efficacy and safety of everolimus after initial VEGF-targeted treatment in patients with metastatic renal cell carcinoma (mRCC) in routine clinical settings. METHODS: Everolimus was administered per routine clinical practice. Patients with mRCC of any histology from 116 active sites in Germany were included. The main objective was to determine everolimus efficacy in time to progression (TTP). Progression-free survival (PFS), treatment duration, tumor response, adherence to everolimus regimen, treatment after everolimus, and safety were also assessed. RESULTS: In the total population (N = 334), median follow-up was 5.2 months (range, 0-32 months). Median treatment duration (safety population, n = 318) was 6.5 months (95% confidence interval [CI], 5-8 months). Median TTP and median PFS were similar in populations investigated. In patients who received everolimus as second-line treatment (n = 211), median (95% CI) TTP was 7.1 months (5-9 months) and median PFS was 6.9 months (5-9 months). Commonly reported adverse events (safety population, n = 318) were dyspnea (17%), anemia (15%), and fatigue (12%). Limitations of the noninterventional design should be considered. CONCLUSIONS: This study reflects routine clinical use of everolimus in a large sample of patients with mRCC. Favorable efficacy and safety were seen for everolimus after previous therapy with one VEGF-targeted agent. Results of this study confirm everolimus as one of the standard options in second-line therapy for patients with mRCC. Novartis study code, CRAD001LD27: VFA registry for noninterventional studies ( http://www.vfa.de/de/forschung/nisdb/).

Urine protein profiling identified alpha-1-microglobulin and haptoglobin as biomarkers for early diagnosis of acute allograft rejection following kidney transplantation.

PURPOSE: Early diagnosis of acute rejection and effective immunosuppressive therapy lead to improvement in graft survival following kidney transplantation. In this study, we aimed to establish a urinary protein profile suitable to distinguish between patients with rejection and stable graft function and to predict acute rejection based on postoperatively collected urine samples. A further objective was to identify candidate proteins for the use as biomarkers in clinical practice. METHODS: Urine samples of 116 kidney recipients were included. Rejection was proven by biopsy (n = 58), and stable transplant function was monitored for at least 2 years (n = 58). Postoperative urine samples were collected between 3rd and 10th day following transplantation. Urinary protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Protein identification and validation were performed using multiplex fluorescence 2DE, peptide mass fingerprinting and enzyme-linked immunosorbent assay. RESULTS: A protein profile including four mass peaks differentiated acute rejection from stable transplants at the time point of rejection and at the postoperative state with 73 % sensitivity and 88 % specificity. Alpha-1-microglobulin (A1MG) and Haptoglobin (Hp) were identified as putative rejection biomarkers. Protein levels were significantly higher in postoperative urine from patients with rejection (A1MG 29.13 vs. 22.06 µg/ml, p = 0.001; Hp 628.34 vs. 248.57 ng/ml, p = 0.003). The combination of both proteins enabled the diagnosis of early rejection with 85 % sensitivity and 80 % specificity. CONCLUSION: Protein profiling using mass spectrometry is suitable for noninvasive detection of rejection-specific changes following kidney transplantation. A specific protein profile enables the prediction of early acute allograft rejection in the immediate postoperative period. A1MG and Hp appear to be reliable rejection biomarkers.

Introduction of Unit-Dose Care in the 1,125 Bed Teaching Hospital: Practical Experience and Time Saving on Wards.

Purpose: The shortage of nursing staff as well as the slow progress in the German health care system's digitalisation has gained much attention due to COVID-19. Patient-specific medication management using the unit-dose dispensing system (UDDS) has the potential for a lasting and positive influence on both digitalisation and the relief of nursing staff. Methods: Nursing staff UDDS-acceptance was determined via a validated online survey. For the evaluation of stock keeping on the wards, the delivery quantities were determined for a comparative period before and after the introduction of the UDDS. The time required for on-ward medication-related processes on ward before and after the introduction of UDDS was recorded based on a survey form and the nursing relief in full-time equivalent (FTE) was calculated using the data obtained. Results: We show that nurses appreciate the UDDS and confirm a significant reduction in drug stocks on the wards. The UDDS reduces the time needed to dispense medications from 4.52 ± 0.35 min to 1.67 ± 0.15 min/day/patient. In relation to the entire medication process, this corresponds to a reduction of 50% per day and per patient. Based on 40,000 patients/year and a supply of 1,125 beds with unit-dose blisters, 7.36 FTE nursing staff can be relieved per year. In contrast, 6.5 FTE in the hospital pharmacy are required for supplying the hospitals. Conclusion: UDDS is well accepted by nurses, reduces stock levels on ward, and fulfils criteria as a nursing-relief measure.

Validation of a 3D-printed robot-assisted partial nephrectomy training model.

Objectives: Most renal tumours can be treated with a partial nephrectomy, with robot-assisted partial nephrectomy becoming the new gold standard. This procedure is challenging to learn in a live setting, especially the enucleation and renorraphy phases. In this study, we attempted to evaluate face, content, and preliminary construct validity of a 3D-printed silicone renal tumour model in robotic training for robot-assisted partial nephrectomy. Materials and Methods: We compared the operative results of three groups of surgeons with different experience levels (>20 partial nephrectomies, 1-20 partial nephrectomies and no experience at all) performing a robotic tumour excision of a newly developed silicone model with four embedded 3D-printed renal tumours. We evaluated the participants' performance using surgical margins, excision time, total preserved parenchyma, tumour injury and GEARS score (as assessed by two blinded experts) for construct validity. Postoperatively, the participants were asked to complete a survey to evaluate the usefulness, realism and difficulty of the model as a training and/or evaluation model. NASA-TLX scores were used to evaluate the operative workload. Results: Thirty-six participants were recruited, each group consisting of 10-14 participants. The operative performance was significantly better in the expert group as compared to the beginner group. NASA-TLX scores proved the model to be of an acceptable difficulty level.Expert group survey results showed an average score of 6.3/10 on realism of the model, 8.2/10 on the usefulness as training model and 6.9/10 score on the usefulness as an evaluation tool. GEARS scores showed a non-significant tendency to improve between trials, emphasizing its potential as a training model. Conclusion: Face and content validity of our 3D renal tumour model were demonstrated. The vast majority of participants found the model realistic and useful for training and for evaluation. To evaluate construct and predictive validity, we require further research, aiming to compare the results of 3D-model trained surgeons with those of untrained surgeons in real-life surgery.