Outcomes With Belatacept Exposure During Pregnancy in Kidney Transplant Recipients: A Case Series.

BACKGROUND: Posttransplant fertility returns quickly, and female recipients of child-bearing age may conceive while on immunosuppression. However, pregnancy after transplantation confers risks to the recipient, transplant, and fetus, including gestational hypertension, preeclampsia, gestational diabetes, transplant dysfunction, preterm labor, and low birthweight infants. Additionally, mycophenolic acid (MPA) products are teratogenic. Literature evidence regarding belatacept, a selective T-cell costimulation blocker, during pregnancy and while breastfeeding is extremely limited. When female transplant recipients on a belatacept-based regimen are desirous of pregnancy or at the time of conception, transplant providers manage the immunosuppression regimen in 1 of 2 ways: (1) switch both belatacept and MPA to a calcineurin inhibitor-based regimen with or without azathioprine, which is the more common practice but requires several modifications, having potential negative outcomes; or (2) only switch MPA to azathioprine while continuing belatacept. METHODS: This case series includes 16 pregnancies in 12 recipients with exposure to belatacept throughout pregnancy and while breastfeeding. Patient information was obtained from several sources, including Transplant Pregnancy Registry International, providers at Emory University, and Columbia University, as well as literature review. RESULTS: Pregnancy outcomes included 13 live births and 3 miscarriages. No birth defects or fetal deaths were reported in any of the live births. Seven infants were breastfed while their mothers continued belatacept. Outcomes appear comparable to those documented with the administration of calcineurin inhibitors. CONCLUSIONS: This case series provides data supporting the continued administration of belatacept during pregnancy. Additional research will assist in developing better guidelines to counsel female transplant recipients on belatacept desiring to pursue pregnancy.

UV-chlorine advanced oxidation for potable water reuse: A review of the current state of the art and research needs.

This paper reports conclusions from a recent study completed for the Water Research Foundation and the State of California to offer guidance on UV-chlorine advanced oxidation for potable water reuse. The fundamentals of UV-chlorine advanced oxidation are discussed, and lessons learned from some of the early adopters of this technology are presented. Important highlights include the significant impact of ammonia and chloramines on UV-chlorine treatment, challenges associated with predicting UV-chlorine performance due to complex photochemistry, and an ongoing need to monitor potential byproducts and transformation products when employing any form of advanced oxidation for potable reuse.

Poor long-term prognosis in patients admitted with strong suspicion of acute myocardial infarction but discharged with another diagnosis.

BACKGROUND: Characteristics and prognosis of patients admitted with strong suspicion of myocardial infarction (MI) but discharged without an MI diagnosis are not well-described. OBJECTIVES: To compare background characteristics and cardiovascular outcomes in patients discharged with or without MI diagnosis. METHODS: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial compared 6629 patients with strong suspicion of MI randomized to oxygen or ambient air. The main composite end-point of this subgroup analysis was the incidence of all-cause death, rehospitalization with MI, heart failure (HF) or stroke during a follow-up of 2.1 years (median; range: 1-3.7 years) irrespective of randomized treatment. RESULTS: 1619 (24%) received a non-MI discharge diagnosis, and 5010 patients (76%) were diagnosed with MI. Groups were similar in age, but non-MI patients were more commonly female and had more comorbidities. At thirty days, the incidence of the composite end-point was 2.8% (45 of 1619) in non-MI patients, compared to 5.0% (250 of 5010) in MI patients with lower incidences in all individual end-points. However, for the long-term follow-up, the incidence of the composite end-point increased in the non-MI patients to 17.7% (286 of 1619) as compared to 16.0% (804 of 5010) in MI patients, mainly driven by a higher incidence of all-cause death, stroke and HF. CONCLUSIONS: Patients admitted with a strong suspicion of MI but discharged with another diagnosis had more favourable outcomes in the short-term perspective, but from one year onwards, cardiovascular outcomes and death deteriorated to a worse long-term prognosis.

Pedigree analysis of pre-breeding efforts in Trifolium spp. germplasm in New Zealand.

BACKGROUND: Prebreeding in plants is the activity designed to identify useful characteristics from wild germplasm and its integration in breeding programs. Prebreeding aims to introduce new variation into the populations of a species of interest. Pedigree analysis is a valuable tool for evaluation of variation in genebanks where pedigree maps are used to visualize and describe population structure and variation within these populations. Margot Forde Germplasm Centre (MFGC) is New Zealand's national forage genebank and holds a collection of ~ 75 species of the genus Trifolium, of which only a dozen have been taken through prebreeding programs. The main objective of this study was to construct pedigree maps and analyse patterns of relatedness for seven minor Trifolium species accessions contained at the MFGC. These species are Trifolium ambiguum, Trifolium arvense, Trifolium dubium, Trifolium hybridum, Trifolium medium, Trifolium subterraneum and the Trifolium repens x Trifolium occidentale interspecific hybrids. We present a history of Trifolium spp. prebreeding in New Zealand and inform breeders of possible alternative forage species to use. RESULTS: Pedigree data from accessions introduced between 1950 and 2016 were used and filtered based on breeding activity. Kinship levels among Trifolium spp. remained below 8% and no inbreeding was found. Influential ancestors that contributed largely to populations structure were identified. The Australian cultivar 'Monaro' had a strong influence over the whole population of accessions in T. ambiguum. T. subterraneum and T. repens x T. occidentale had the largest number of generations (3). T. ambiguum and T. medium had the highest cumulative kinship across the decades. CONCLUSIONS: We conclude that there are high levels of diversity in the seven Trifolium spp. studied. However, collection and prebreeding efforts must be strengthened to maximize utilization and bring useful genetic variation.

Biowastes to augment the essential oil production of Leptospermum scoparium and Kunzea robusta in low-fertility soil.

Biowastes are unwanted materials of biological origin. They include biosolids, dairy shed effluent, and sawdust. When applied to soil, biowastes can provide plant nutrients, but also introduce heavy metals, pathogens, or xenobiotics. Biowastes could improve degraded or low-fertility soils and generate revenue through the production of non-food products such as essential oils. We grew New Zealand native plants, manuka (Leptospermum scoparium J.R. Forst & G. Forst) and kanuka (Kunzea robusta de Lange & Toelken) in series of greenhouse experiments in low-to-medium-fertility soils (Bideford clay loam, Lismore stony silt loam, and Pawson silt loam) amended with either biosolids (up to 13500 kg N ha-1 equiv.), biosolids + sawdust (1:0.5-1250 kg N ha-1 equiv.) and dairy shed effluent (200 kg N ha-1 equiv.). Two types of biosolids from Kaikoura (KB) and Christchurch City Council (CB) were used in the experiments. CB (1500 kg N ha-1 equiv.) and dairy shed effluent (200 kg N ha-1 equiv.) increased the biomass of L. scoparium by up to 120% and 31%, and K. robusta by up to 170% and 34%, respectively. Adding sawdust to KB increased the biomass of L. scoparium and K. robusta although it offset the L. scoparium growth increase in the KB-only treatment. The growth response of K. robusta to biowastes was greater than L. scoparium with oil production in K. robusta increasing by up to 211% when 1500 kg N ha-1 equiv. of CB was applied to Lismore stony silt loam. Generally, the treatments had a negligible effect on oil concentration in all the soil types, except for the KB + sawdust treatment, which increased the oil concentration by 82%. Most of the EOs' major components were unaffected by biowaste addition in the soils, although some components increased in the Bideford clay loam following KB and KB + sawdust application. Biosolids increased foliar concentrations of Zn, Cu, and Cd, but these were below risk-threshold concentrations. Applying CB (up to 1500 kg N ha-1 equiv.) to low-fertility soils is recommended to establish ecosystems dominated by L. scoparium and K. robusta that annually would produce ca. 100 kg ha-1 of EOs worth US$ 26k and 24k, respectively. Adding sawdust to CB could have environmental benefits through reduction of N leaching. Field trials are warranted to elucidate critical ecological variables and production economics in biowaste management.

Belatacept during pregnancy in renal transplant recipients: Two case reports.

Impaired fertility is common among patients with chronic organ failure, including end-stage renal disease (ESRD). Women of childbearing age undergoing transplantation may experience rapid return of fertility. Pregnancy posttransplant presents numerous risks for the patient, fetus, and allograft. Maternal risks include hypertension and preeclampsia. Allograft risks include acute rejection and failure of the organ, and fetal risks include miscarriage, birth defects from immunosuppressants, premature delivery, and low birth weight. Belatacept, a selective T cell costimulation blocker, was approved for use in kidney transplant recipients in the United States in 2011. Little is known about the safety of belatacept during pregnancy in humans. We describe 2 cases of successful pregnancy and delivery with the use of belatacept-based immunosuppression. The Transplant Pregnancy Registry International (TPR) is a voluntary registry for transplant recipients who have had pregnancies or fathered a pregnancy posttransplant. To date, these 2 cases are the only known exposures to belatacept that have been reported to the TPR.

Supplemental oxygen therapy does not affect the systemic inflammatory response to acute myocardial infarction.

BACKGROUND: Oxygen therapy has been used routinely in normoxemic patients with suspected acute myocardial infarction (AMI) despite limited evidence supporting a beneficial effect. AMI is associated with a systemic inflammation. Here, we hypothesized that the inflammatory response to AMI is potentiated by oxygen therapy. METHODS: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) multicentre trial randomized patients with suspected AMI to receive oxygen at 6 L min-1 for 6-12 h or ambient air. For this prespecified subgroup analysis, we recruited patients with confirmed AMI from two sites for evaluation of inflammatory biomarkers at randomization and 5-7 h later. Ninety-two inflammatory biomarkers were analysed using proximity extension assay technology, to evaluate the effect of oxygen on the systemic inflammatory response to AMI. RESULTS: Plasma from 144 AMI patients was analysed whereof 76 (53%) were randomized to oxygen and 68 (47%) to air. Eight biomarkers showed a significant increase, whereas 13 were decreased 5-7 h after randomization. The inflammatory response did not differ between the two treatment groups neither did plasma troponin T levels. After adjustment for increase in troponin T over time, age and sex, the release of inflammation-related biomarkers was still similar in the groups. CONCLUSIONS: In a randomized controlled setting of normoxemic patients with AMI, the use of supplemental oxygen did not have any significant impact on the early release of systemic inflammatory markers.

Fresnel diffractograms from pure-phase wave fields under perfect spatio-temporal coherence: Non-linear/non-local aspects and far-field behavior.

Recently, the diffractogram, that is, the Fourier transform of the intensity contrast induced by Fresnel free-space propagation of a given (exit) wave field, was investigated non-perturbatively in the phase-scaling factor S (controlling the strength of phase variation) for the special case of a Gaussian phase of width [Formula: see text]. Surprisingly, an additional low-frequency zero σ* = σ*(S, F) >0 emerges critically at small Fresnel number F (σ proportional to square of 2D spatial frequency). Here, we study the S-scaling behavior of the entire diffractogram. We identify a valley of maximum S-scaling linearity in the F - σ plane corresponding to a nearly universal physical frequency ξml = (0:143 ± 0.001)w -1/2. Large values of F (near field) are shown to imply S-scaling linearity for low σ but nowhere else (overdamped non-oscillatory). In contrast, small F values (far field) entail distinct, sizable s-bands of good S-scaling linearity (damped oscillatory). These bands also occur in simulated diffractograms induced by a complex phase map (Lena). The transition from damped oscillatory to overdamped non-oscillatory diffractograms is shown to be a critical phenomenon for the Gaussian case. We also give evidence for the occurrence of this transition in an X-ray imaging experiment. Finally, we show that the extreme far-field limit generates a σ-universal diffractogram under certain requirements on the phase map: information on phase shape then is solely encoded in S-scaling behavior.

Ocular Manifestations of Obstructive Sleep Apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) incurs a host of systemic side effects. The eyes are particularly susceptible to both mechanical and vascular sequelae of the disease. This paper outlines the ocular manifestations of sleep apnea. The authors hope to increase awareness of the ocular complications of this common disorder and increase communication and co-management between eye-care providers and sleep specialists alike. METHODS: Data were collected from PubMed and the Brown University Library Collection. RESULTS: Twenty-two papers were included in this review to address floppy eyelid syndrome, nonarteritic anterior ischemic optic neuropathy, central serous retinopathy, retinal vein occlusion, and glaucoma. We used three meta-analyses and several cross-sectional cohort and case-control studies that investigate the aforementioned conditions and their associations with OSA. CONCLUSIONS: Hypoxia induced by nightly cessation of breathing increases patients' risk of coronary artery disease, heart failure, stroke, and other conditions. As with many maladies detrimental to vascular health, obstructive sleep apnea affects the eye and ocular adnexa. This paper summarizes the current evidence implicating OSA in these ocular maladies and highlights their proposed mechanisms. The authors describe ocular pathology which sleep specialists may encounter. We encourage more aggressive attention to ocular symptoms in patients with sleep apnea to prevent vision-threatening complications. Further research should investigate how sleep apnea treatment affects these ocular findings and identify which sleep apnea patients are most prone to developing ocular pathology.

Optimizing structural and mechanical properties of cryogel scaffolds for use in prostate cancer cell culturing.

Prostate cancer (PCa) currently is the second most diagnosed cancer in men and the second most cause of cancer death after lung cancer in Western societies. This sets the necessity of modelling prostatic disorders to optimize a therapy against them. The conventional approach to investigating prostatic diseases is based on two-dimensional (2D) cell culturing. This method, however, does not provide a three-dimensional (3D) environment, therefore impeding a satisfying simulation of the prostate gland in which the PCa cells proliferate. Cryogel scaffolds represent a valid alternative to 2D culturing systems for studying the normal and pathological behavior of the prostate cells thanks to their 3D pore architecture that reflects more closely the physiological environment in which PCa cells develop. In this work the 3D morphology of three potential scaffolds for PCa cell culturing was investigated by means of synchrotron X-ray computed micro tomography (SXCµT) fitting the according requirements of high spatial resolution, 3D imaging capability and low dose requirements very well. In combination with mechanical tests, the results allowed identifying an optimal cryogel architecture, meeting the needs for a well-suited scaffold to be used for 3D PCa cell culture applications. The selected cryogel was then used for culturing prostatic lymph node metastasis (LNCaP) cells and subsequently, the presence of multi-cellular tumor spheroids inside the matrix was demonstrated again by using SXCµT.

Production of Biomass Crops Using Biowastes on Low-Fertility Soil: 1. Influence of Biowastes on Plant and Soil Quality.

Land application of biosolids to low-fertility soil can improve soil quality by increasing concentrations of macronutrients and trace elements. Mixing biosolids with sawdust could reduce the risks of contaminant accumulation posed by rebuilding soils using biosolids alone. We aimed to determine the effects of biosolids and biosolids-sawdust on the plant quality and chemical composition of sorghum, rapeseed, and ryegrass. Plants were grown in a greenhouse over a 5-mo period in a low-fertility soil amended with biosolids (1250 kg N ha), biosolids-sawdust (0.5:1), or urea (200 kg N ha). Biosolids application increased the biomass of sorghum, rapeseed, and ryegrass up to 14.0, 11.9, and 4.1 t ha eq, respectively. Mixing sawdust with biosolids resulted in a growth response similar to biosolids treatments in rapeseed but nullified the effect of biosolids in sorghum. Urea fertilization provided insufficient nutrients to promote rapeseed growth and seed production, whereas seed yields after biosolids application were 2.5 t ha. Biosolids and biosolids-sawdust application enhanced plant quality by increasing element concentrations, especially Zn, and potentially toxic elements (Cd, Cr, Ni) did not exceed food safety standards. An application of 50 t ha of biosolids, equivalent to 1250 kg N ha, did not exceed current soil limits of Cu, Zn, and Cd and hence was effective in rebuilding soil without accumulating contaminants. The effect of mixing sawdust with biosolids varies with plant species but can further enhance plant nutrient quality in biomass and seeds, especially P, Cu, Zn, Mn, Fe, S, and Na.

Rooting depth and root depth distribution of Trifolium repens × T. uniflorum interspecific hybrids.

Background and aims Traits related to root depth distribution were examined in Trifolium repens × T. uniflorum backcross 1 (BC1) hybrids to determine whether root characteristics of white clover could be improved by interspecific hybridization. Methods Two white clover cultivars, two T. uniflorum accessions and two BC1 populations were grown in 1 -m deep tubes of sand culture. Maximum rooting depth and root mass distribution were measured at four harvests over time, and root distribution data were fitted with a regression model to provide measures of root system shape. Morphological traits were measured at two depths at harvest 3. Key Results Root system shape of the hybrids was more similar to T. uniflorum than to white clover. The hybrids and T. uniflorum had a higher rate of decrease in root mass with depth than white clover, which would result in higher proportions of root mass in the upper profile. Percentage total root mass at 100-200 mm depth was higher for T. uniflorum than white clover, and for Crusader BC1 than 'Crusader'. Roots of the hybrids and T. uniflorum also penetrated deeper than those of white clover. T. uniflorum had thicker roots at 50-100 mm deep than the other entries, and more of its fine root mass at 400-500 mm. The hybrids and white clover had more of their fine root mass higher in the profile. Consequently, T. uniflorum had a higher root length density at 400-500 mm than most entries, and a smaller decrease in root length density with depth. Conclusions These results demonstrate that rooting characteristics of white clover can be altered by hybridization with T. uniflorum, potentially improving water and nutrient acquisition and drought resistance. Root traits of T. uniflorum are likely to be adaptations to soil moisture and fertility in its natural environment.

[Big surprise in the lesser pelvis]. / Große Überraschung im kleinen Becken.

A 17-year-old young man presented at our clinic with asymptomatic microhematuria. Ultrasonography and computer tomography found an intraperitoneal lesion of unknown dignity located on top of the bladder. Surgical exploration and histological examination confirmed the diagnosis of a secondary pelvic spleen, a lien bipartitus.

[Operative interventions of urologic traumata in severe injured patients in the acute phase]. / Operative Interventionen urologischer Verletzungen beim schwerverletzten Patienten in der Akutphase.

INTRODUCTION: The frequency of urological traumata and the need for interventions in severely injured patients in Germany are unknown. The aim of this study was to determine the frequency of urological traumata in about 90,000 severely injured patients (Injury Severity Score, ISS ≥ 16). MATERIALS AND METHODS: Data of 90,000 patients from the TraumaRegister DGU® were retrospectively analyzed. All patients with an ISS of ≥ 16 were included. The kind of urological traumata and the need for urological intervention within 24 hours were assessed, as well as the kind of accident, additional traumata and the clinical course. RESULTS: 48,797 patients fulfilled the inclusion criteria. Urological trauma was existent in 7.1 %, especially in men (78 %). Kidneys were affected most frequently (4.8 %) compared to ureters (0.2 %), urinary bladder (1.2 %), urethra (0.5 %) and genitals (0.4 %). Traffic accidents and falls from higher levels represented the main cause for urological traumata (> 90 %). It was associated with additional pelvis, thorax and abdomen traumata (each 7.1 %) and showed a distinct increase dependent on the abbreviated injury scale (AIS). Ureter (10.6%) and urethra (6.3%) trauma was deferred diagnosed most, this was associated with a higher rate of urological operations. The general duration of hospital stay and that in the intensive care unit were prolonged by urological traumata. DISCUSSION: The data showed the prevalence of urological trauma in severely injured patients analyzed in a huge patient cohort of the TraumaRegister DGU®. For the first time the number, degree and medical care in the reality of urological traumata in severely injured patients were available.

Evaluation of flow hydrodynamics in a pilot-scale dissolved air flotation tank: a comparison between CFD and experimental measurements.

Computational fluid dynamics (CFD) models of dissolved air flotation (DAF) have shown formation of stratified flow (back and forth horizontal flow layers at the top of the separation zone) and its impact on improved DAF efficiency. However, there has been a lack of experimental validation of CFD predictions, especially in the presence of solid particles. In this work, for the first time, both two-phase (air-water) and three-phase (air-water-solid particles) CFD models were evaluated at pilot scale using measurements of residence time distribution, bubble layer position and bubble-particle contact efficiency. The pilot-scale results confirmed the accuracy of the CFD model for both two-phase and three-phase flows, but showed that the accuracy of the three-phase CFD model would partly depend on the estimation of bubble-particle attachment efficiency.

Does visualisation during urethrocystoscopy provide pain relief? Results of an observational study.

BACKGROUND: To measure the effects of real-time visualisation during urethrocystoscopy on pain in patients who underwent ambulatory urethrocystoscopy. METHODS: An observational study was designed. From June 2012 to June 2013 patients who had ambulatory urethrocystoscopy participated in the study. In order to measure pain perception we used a numeric rating scale (NRS) 0 to 10. Additional data was collected including gender, reason for intervention, use of a rigid or a flexible instrument and whether the patient had had urethrocystoscopy before. RESULTS: 185 patients were evaluated. 125 patients preferred to watch their urethrocystoscopy on a real-time video screen, 60 patients did not. There was no statistically relevant difference in pain perception between those patients who watched their urethrocystoscopy on a real-time video screen and those who did not (p = 0.063). However, men who were allowed to watch their flexible urethrocystoscopy experienced significantly less pain, than those who did not (p = 0.007). No such effects could be measured for rigid urethrocystoscopy (p = 0.317). Furthermore, women experienced significantly higher levels of pain during the urethrocystoscopy than men (p = 0.032). CONCLUSIONS: Visualisation during urethrocystoscopy procedures in general does not significantly decrease pain in patients. Nevertheless, men who undergo flexible urethrocystoscopy should be offered to watch their procedure in real-time on a video screen. To make urethrocystoscopy less painful for both genders, especially for women, should be subject to further research.

[Treatment of female stress urinary incontinence. Value of classical incontinence operations]. / Behandlung der weiblichen Belastungsinkontinenz. Stellenwert klassischer Inkontinenzoperationen.

BACKGROUND: Fascial sling and the colposuspension were considered standard operations in the therapy of female stress urinary incontinence until the mid-1990s. New surgical procedures were compared with these techniques in regard to cure rate and long-term results. RESULTS: Nowadays fascial slings are rarely performed. Colposuspension - despite comparable results - was replaced by tension-free tapes as the new gold standard. This is not due to lower efficacy, but predominantly due to reduced surgical trauma, simple use, and rapid convalescence. However, in cases of recurrence and the combined treatment of prolapse, colposuspension is still used.

A model of particle removal in a dissolved air flotation tank: importance of stratified flow and bubble size.

An analytical model and a computational fluid dynamic model of particle removal in dissolved air flotation were developed that included the effects of stratified flow and bubble-particle clustering. The models were applied to study the effect of operating conditions and formation of stratified flow on particle removal. Both modeling approaches demonstrated that the presence of stratified flow enhanced particle removal in the tank. A higher air fraction was shown to be needed at higher loading rates to achieve the same removal efficiency. The model predictions showed that an optimum bubble size was present that increased with an increase in particle size.

[Indications for nephron-sparing surgery. Analysis over a 13-year period in the context of changing guidelines]. / Indikationsstellung zur organerhaltenden Nierentumorchirurgie. Analyse eines 13-Jahres-Zeitraums vor dem Hintergrund sich wandelnder Leitlinien.

BACKGROUND: The indications for nephron-sparing surgery have been considerably extended by guideline recommendations in recent years. It remains unclear whether clinical practice still reflects these new guidelines. OBJECTIVE: In this retrospective, monocentric analysis at a tertiary referral center the indications for partial nephrectomy over a 13-year period were evaluated. METHODS: In a retrospective database analysis all cases of surgically treated renal masses from 2001 to 2013 were evaluated. Besides demographic, tumor-specific and perioperative variables the development of the surgical technique depending on the tumor stage was evaluated. RESULTS AND DISCUSSION: The proportion of nephron-sparing surgery cases increased from below 20 % in 2001 to 35 % in 2013 in the entire cohort. For stage T1a tumors, partial nephrectomy increased from approximately 50 % to over 90 % and for T1b tumors it rose from 10 % to 50 %. Logistic regression revealed stage 1 tumors to be predictive of partial nephrectomy over the complete evaluation period. Extending the indications for partial nephrectomy even to higher stages is under discussion but not yet supported by data from prospective, controlled studies.

[Metastasized renal cell carcinoma. Measurement of plasma levels of the tyrosine kinase inhibitors sunitinib, sorafenib and pazopanib]. / Metastasiertes Nierenzellkarzinom. Bestimmung der Plasmaspiegel der Tyrosinkinaseinhibitoren Sunitinib, Sorafenib und Pazopanib.

BACKGROUND: Several tyrosine kinase inhibitors (TKI) are used in the treatment of metastasized renal cell carcinoma (mRCC). This article presents a feasibility study for the measurement of plasma levels of sunitinib, sorafenib and pazopanib using liquid chromatography tandem mass spectrometry (LC-MS/MS). METHODS: A total of 23 patients suffering from mRCC under treatment with sunitinib (n=16), sorafenib (n=3) and pazopanib (n=4) were included. Plasma samples (100 µl) were separated by liquid chromatographic analysis and the plasma levels of the TKIs determined by tandem mass spectrometry. RESULTS: The plasma levels of sunitinib, sorafenib and pazopanib were measurable and the results reproducible. During storage of the plasma samples for 1 week at 4°C no significant decrease of the initial concentration was found. The highest plasma levels detected were 99 ng/ml for sunitinib, 9.8 µg/ml for sorafenib and 63 µg/ml for pazopanib. We could show variability in plasma levels according to changes in dosage of TKIs or during treatment-free intervals. CONCLUSION: Measurement of TKI plasma levels using LC-MS/MS is feasible. Further clinical studies have to be conducted to examine if there are any threshold levels for the incidence of adverse events or response to treatment.