New dynamic diamond anvil cell for time-resolved radial x-ray diffraction.

The dynamic diamond anvil cell (dDAC) is a recently developed experimental platform that has shown promise for studying the behavior of materials at strain rates ranging from intermediate to quasi-static and shock compression regimes. Combining dDAC with time-resolved x-ray diffraction (XRD) in the radial geometry (i.e., with incident x-rays perpendicular to the axis of compression) enables the study of material properties such as strength, texture evolution, and deformation mechanisms. This work describes a radial XRD dDAC setup at beamline P02.2 (Extreme Conditions Beamline) at DESY's PETRA III synchrotron. Time-resolved radial XRD data are collected for titanium, zirconium, and zircon samples, demonstrating the ability to study the strength and texture of materials at compression rates above 300 GPa/s. In addition, the simultaneous optical imaging of the DAC sample chamber is demonstrated. The ability to conduct simultaneous radial XRD and optical imaging provides the opportunity to characterize plastic strain and deviatoric strain rates in the DAC at intermediate rates, exploring the strength and deformation mechanisms of materials in this regime.

Are biters sick? Health status of tail biters in comparison to control pigs.

BACKGROUND: Tail biting is a multifactorial problem. As the health status is one of the factors commonly linked to tail biting, this study focuses on the health of identified biters. 30 (obsessive) biters are compared to 30 control animals by clinical and pathological examination as well as blood and cerebrospinal fluid samples. In that way, altogether 174 variables are compared between the groups. Moreover, connections between the variables are analysed. RESULTS: In the clinical examination, 6 biters, but only 2 controls (P = 0.019) were noticeably agitated in the evaluation of general behaviour, while 8 controls were noticeably calmer (2 biters, P = 0.02). Biters had a lower body weight (P = 0.0007) and 13 biters had overlong bristles (4 controls, P = 0.008). In the pathological examination, 5 biters, but none of the controls had a hyperceratosis or inflammation of the pars proventricularis of the stomach (P = 0.018). However, 7 controls and only 3 biters were affected by gut inflammation (P = 0.03). In the blood sample, protein and albumin levels were below normal range for biters (protein: 51.6 g/l, albumin: 25.4 g/l), but not for controls (protein: 53.7 g/l, albumin: 27.4 g/l), (protein: P = 0.05, albumin: P = 0.02). Moreover, 14 biters, but only 8 controls had poikilocytosis (P = 0.05). Although not statistically different between groups, many animals (36/60) were affected by hypoproteinemia and hyponatremia as well as by hypokalemia (53/60) and almost all animals (58/60) had hypomagnesemia. For hypomagnesemia, significant connections with variables linked to tail damage and ear necrosis were detected (rs/V/ρ ≥ 0.4, P ≤ 0.05). CONCLUSION: The results suggest that behavioural tests might be helpful in identifying biters. Moreover, cornification and inflammation of the pars proventricularis is linked to becoming a biter. Furthermore, the results highlight the need for appropriate and adjusted nutrient and mineral supply, especially with regard to magnesium.

Development of a new grading system to assess the foster performance of lactating sows.

Increasing litter size has created the need for more sophisticated, accurate, and welfare-oriented systems for assessing the foster performance of lactating sows. The estimation of milk yield alone is not sufficient for meeting these requirements. Therefore, the aim of the current study was to develop a grading system for assessing the foster performance of lactating sows that can be easily applied in commercial farm practice. Data were collected in two German conventional farrow-to-feeder farms with a total sample size of 639 sows (4.05 ± 2.86 parities) and 1 728 litters. Besides general performance data, the piglets were weighed individually within the first 24 hours after birth and at the peak of lactation (day 18.22 ± 2.48). Based on these data, we proposed a new score referring to the milk score (MS). This score was compared with the commonly used formula for estimating milk yield (est. MY), which solely involves litter weight gain and litter size. The improvement of the developed MS allowed us to distinguish between the birth and foster performances of the lactating sows through considering cross-fostering, litter size, individual piglet weights, and piglet mortality during lactation. Both scores showed a similar progression across parities. It was found that litter size had a significant impact on the performance of lactating sows. A high est. MY was found to be associated with a significantly higher number of piglets per litter (15.79 ± 2.20), lower weight gain per piglet, and increased piglet mortality during lactation compared with sows with high MS, which showed a smaller litter size (13.51 ± 2.18) (P < 0.05). The focus on smaller litter size indicates a performance limitation, which seems to be related to the average teat number of 13-15 teats per sow. We recommend the consideration of the number of functional teats, because a litter size above it will not result in a sow having higher foster performance. In conclusion, as an extension of the common est. MY calculation, the MS considers cross-fostering as current farm-management practice when dealing with larger litters. Our recommendations emphasise the importance of an MS which indicates smaller litter size, higher piglet weight gain, and lower piglet mortality during lactation; these factors are related to an improvement in animal welfare for sows and piglets. Moreover, the presented MS could be used to develop a management tool for farmers to assess the foster performance of lactating sows, considering individual farm-management practices.

Sub-micrometer focusing setup for high-pressure crystallography at the Extreme Conditions beamline at PETRA†III.

Scientific tasks aimed at decoding and characterizing complex systems and processes at high pressures set new challenges for modern X-ray diffraction instrumentation in terms of X-ray flux, focal spot size and sample positioning. Presented here are new developments at the Extreme Conditions beamline (P02.2, PETRA III, DESY, Germany) that enable considerable improvements in data collection at very high pressures and small scattering volumes. In particular, the focusing of the X-ray beam to the sub-micrometer level is described, and control of the aberrations of the focusing compound refractive lenses is made possible with the implementation of a correcting phase plate. This device provides a significant enhancement of the signal-to-noise ratio by conditioning the beam shape profile at the focal spot. A new sample alignment system with a small sphere of confusion enables single-crystal data collection from grains of micrometer to sub-micrometer dimensions subjected to pressures as high as 200 GPa. The combination of the technical development of the optical path and the sample alignment system contributes to research and gives benefits on various levels, including rapid and accurate diffraction mapping of samples with sub-micrometer resolution at multimegabar pressures.

Differences in human and minipig platelet number, volume and activation induced by borosilicate glass beads in a modified chandler loop-system.

The pig is the most widely used large animal model in Europe, with cardiovascular research being one of the main areas of application. Adequate refinement of interventional studies in this field, meeting the requirements of Russel and Burchs' 3 R concept, can only be performed if blood-contacting medical devices are hemocompatible. Because most medical devices for cardiovascular interventional procedures are developed for humans they are tested mostly for compatibility with human blood. The aim of this study was therefore to determine whether there are differences in behavior of porcine and human platelets when they come into contact with glass, which was used as an exemplary thrombogenic material. For this purpose changes of platelet count, platelet volume and platelet expression of the activation markers CD61, CD62P and CD63 were measured using a modified chandler loop-system simulating the fluidic effects of the blood flow. Minipig and human platelets showed significant differences in number and volume, but not in activation after 4-8 min exposure to glass.

New dynamic diamond anvil cells for tera-pascal per second fast compression x-ray diffraction experiments.

Fast compression experiments performed using dynamic diamond anvil cells (dDACs) employing piezoactuators offer the opportunity to study compression-rate dependent phenomena. In this paper, we describe an experimental setup which allows us to perform time-resolved x-ray diffraction during the fast compression of materials using improved dDACs. The combination of the high flux available using a 25.6 keV x-ray beam focused with a linear array of compound refractive lenses and the two fast GaAs LAMBDA detectors available at the Extreme Conditions Beamline (P02.2) at PETRA III enables the collection of x-ray diffraction patterns at an effective repetition rate of up to 4 kHz. Compression rates of up to 160 TPa/s have been achieved during the compression of gold in a 2.5 ms fast compression using improved dDAC configurations with more powerful piezoactuators. The application of this setup to low-Z compounds at lower compression rates is described, and the high temporal resolution of the setup is demonstrated. The possibility of applying finely tuned pressure profiles opens opportunities for future research, such as using oscillations of the piezoactuator to mimic propagation of seismic waves in the Earth.

4G versus 3G-enabled telemedicine in prehospital acute stroke care.

BACKGROUND: Time to reperfusion treatment is closely related to outcome in ischemic stroke. Prehospital stroke work-up in CT-equipped mobile stroke units is effective in reducing time to thrombolytic treatment. Current evidence predominantly comes from mobile stroke units staffed with neurologists but telemedicine-guided management may be acceptable for providing neurological expertise in ambulances. With unsatisfactory experiences in third-generation (3G)-based approaches, fourth-generation (4G) networks may provide adequate audio-visual quality but systematic comparisons of technological parameters and decision-making are lacking. METHODS: Trained actors presented stroke symptoms and paramedics assisted the remotely guided extended National Institutes of Health Stroke Scale (eNIHSS) assessment on the mobile stroke unit in Berlin, Germany. We compared technical parameters of 4G and 3G connections, assessed audio-visual quality of examination, and analyzed reliability of neurological assessment and treatment decisions made by the remote neurologist versus the mobile stroke unit neurologist. RESULTS: 4G and 3G connections were evaluated in 40 scenarios each. Connectivity was not available in 17% of 4G- and 15% of 3G-attempts with 6% simultaneous unavailability of both networks. The remote examiners graded audio and video quality in 4G better than in 3G with slightly shorter assessment duration in 4G (mean: 9 (SD:5) vs. mean 11 (SD:3) min, p = 0.10). Reliability of the eNIHSS sum scores was high with intraclass correlation coefficients of 0.99 (95% CI: 0.987-1.00) for 4G and 0.98 (95% CI: 0.96-0.99) for 3G. None of the remote treatment decisions differed from onsite decisions. CONCLUSIONS: 4G mobile communications provided higher quality of video-examination and allowed reliable remote assessment of stroke symptoms but coverage was still incomplete in both networks.

Can hypothermic oxygenated perfusion (HOPE) rescue futile DCD liver grafts?

BACKGROUND: The new UK-DCD-Risk-Score has been recently developed to predict graft loss in DCD liver transplantation. Donor-recipient combinations with a cumulative risk of >10 points were classified as futile and achieved an impaired one-year graft survival of <40%. The aim of this study was to show, if hypothermic oxygenated perfusion (HOPE) can rescue such extended DCD livers and improve outcomes. METHODS: "Futile"-classified donor-recipient combinations were selected from our HOPE-treated human DCD liver cohort (01/2012-5/2017), with a minimum follow-up of one year. Main risk factors, which contribute to the classification "futile" include: elderly donors>60years, prolonged functional donor warm ischemia time (fDWIT > 30min), long cold ischemia time>6hrs, donor BMI>25 kg/m2, advanced recipient age (>60years), MELD-score>25points and retransplantation status. Endpoints included all outcome measures during and after DCD LT. RESULTS: Twenty-one donor-recipient combinations were classified futile (median UK-DCD-Risk-Score:11 points). The median donor age and fDWIT were 62 years and 36 min, respectively. After cold storage, livers underwent routine HOPE-treatment for 120 min. All grafts showed immediate function. One-year and 5-year tumor death censored graft survival was 86%. CONCLUSION: HOPE-treatment achieved excellent outcomes, despite high-risk donor and recipient combinations. Such easy, endischemic perfusion approach may open the door for an increased utilization of futile DCD livers in other countries.

Author Correction: Nearly all the sky is covered by Lyman-α emission around high-redshift galaxies.

Change history: In this Letter, author M. Akhlaghi should be associated with affiliation (2) rather than (3). This error has been corrected online.

Nearly all the sky is covered by Lyman-α emission around high-redshift galaxies.

Galaxies are surrounded by large reservoirs of gas, mostly hydrogen, that are fed by inflows from the intergalactic medium and by outflows from galactic winds. Absorption-line measurements along the lines of sight to bright and rare background quasars indicate that this circumgalactic medium extends far beyond the starlight seen in galaxies, but very little is known about its spatial distribution. The Lyman-α transition of atomic hydrogen at a wavelength of 121.6 nanometres is an important tracer of warm (about 104 kelvin) gas in and around galaxies, especially at cosmological redshifts greater than about 1.6 at which the spectral line becomes observable from the ground. Tracing cosmic hydrogen through its Lyman-α emission has been a long-standing goal of observational astrophysics1-3, but the extremely low surface brightness of the spatially extended emission is a formidable obstacle. A new window into circumgalactic environments was recently opened by the discovery of ubiquitous extended Lyman-α emission from hydrogen around high-redshift galaxies4,5. Such measurements were previously limited to especially favourable systems6-8 or to the use of massive statistical averaging9,10 because of the faintness of this emission. Here we report observations of low-surface-brightness Lyman-α emission surrounding faint galaxies at redshifts between 3 and 6. We find that the projected sky coverage approaches 100 per cent. The corresponding rate of incidence (the mean number of Lyman-α emitters penetrated by any arbitrary line of sight) is well above unity and similar to the incidence rate of high-column-density absorbers frequently detected in the spectra of distant quasars11-14. This similarity suggests that most circumgalactic atomic hydrogen at these redshifts has now been detected in emission.

Ordnung muss sein: heteroelement order and disorder in polyoxovanadates.

The first mixed antimonato-germanato polyoxovanadates were synthesized using two different strategies, highlighting the critical role of the precursors. Following the traditional route using multiple single sources as precursors the polyanions [V15Sb2Ge4O42(OH)4(H2O)]6- (1) and [V15Sb3Ge3O42(OH)3(H2O)]6- (2) are obtained, which display disorder of their Sb/Ge positions, indicating that clusters of different compositions are in equilibrium in solution. In contrast, if the water-soluble single-source precursor {Ni(en)3}3[V15Sb6O42(H2O)]·ca. 15H2O is reacted with GeO2, {Ni(en)3}3[V15Sb3Ge3O42(OH)3(H2O)]·≈9H2O (3) forms, in which Sb and Ge occupy distinct positions that might have been formed via partial substitution reactions in the {V15Sb6} precursor.

In situ ligand exchange-mediated 0D/1D transformation of a polyoxovanadate.

The antimonato-polyoxovanadate {NiII(en)3}3[VSbO42(H2O)]·ca.15H2O was utilized as a synthon for the solvothermal in situ generation of the new compound {NiII(phen)3}2[{NiII(en)2}VSbO42(H2O)]·19H2O, a rearrangement induced by ligand metathesis. While in the precursor structure cations and anions are isolated, the solid-state structure of the product is characterized by 1D chains consisting of alternating [V15Sb6O42(H2O)]6- cluster shells and [Ni(en)2]2+ units covalently linked to neighboring clusters via terminal oxygen atoms. Water clusters composed of sixteen hydrogen-bonded H2O molecules are located in void spaces of the structure. The magnetic properties indicate weak antiferromagnetic interactions of the bridging Ni2+ center and adjacent polyoxovanadate anions, as well as small magnetic anisotropy of the individual Ni2+ centers.

The Extreme Conditions Beamline P02.2 and the Extreme Conditions Science Infrastructure at PETRA III.

A detailed description is presented of the Extreme Conditions Beamline P02.2 for micro X-ray diffraction studies of matter at simultaneous high pressure and high/low temperatures at PETRA III, in Hamburg, Germany. This includes performance of the X-ray optics and instrumental resolution as well as an overview of the different sample environments available for high-pressure studies in the diamond anvil cell. Particularly emphasized are the high-brilliance and high-energy X-ray diffraction capabilities of the beamline in conjunction with the use of fast area detectors to conduct time-resolved compression studies in the millisecond time regime. Finally, the current capability of the Extreme Conditions Science Infrastructure to support high-pressure research at the Extreme Conditions Beamline and other PETRA III beamlines is described.

[Comparison of novel infrared heating plates and conventional warm water plates for piglets' creep areas in farrowing pens]. / Vergleich neuartiger Infrarotwärmeplatten mit konventionellen Warmwasserplatten als Ausrüstung für Ferkelnester im Abferkelstall.

OBJECTIVE: On a conventionally managed piglet-producing farm, novel infrared (IR) heating plates for piglets in the farrowing pens were tested for their suitability and compared with common warm-water (WW) heating plates. MATERIAL AND METHODS: In total, 134 litters (summer n = 82, winter n = 52) were investigated, which were housed on IR or WW heating plates, respectively, with or without an extra cover plate (groups 1-4). To determine the influence of the different heat sources, the wound healing after castration and tail docking, the umbilical regression and the weight gain of the piglets were investigated. Additionally, the lying behavior of the piglets and the position of the sows' udder at the time of farrowing were examined with regard to the heating plates. Furthermore, the energy consumption and costs were compared. RESULTS: The piglets housed on IR heating plates displayed better wound healing after castration and tail docking than the piglets housed on WW plates. The best results were obtained in piglets kept on IR heating plates with an extra cover plate. In addition, significant benefits were demonstrated for the usage of IR heating plates regarding umbilical regression. The piglets kept on IR heating plates had a slightly better weight gain in summer, whereas there were no differences between groups during winter. The lying behavior in the creep areas was similar in all groups. In general, with increasing age the percentage of time piglets spent in the lying position on the plates decreased. The percentage of time lying on the plates was higher in winter than in summer. At farrowing, 74.6% of all investigated sows directed their udder towards the heating plates. With the IR heating plates, this behavior occurred significantly more often. The energy consumption (kWh) per litter was significantly lower for the IR heating plates (electric power) both in winter and summer in comparison with the WW plates (gas). The energy costs were comparable in summer, but were higher for the IR heating plates in winter. CONCLUSION AND CLINICAL RELEVANCE: IR radiation of heating plates has a positive influence on wound healing after castration and tail docking as well as on umbilical regression. In addition, the lying behavior of sows at farrowing is influenced by the IR radiation. Despite the lower energy consumption of the IR heating plates, the most profitable system has to be determined individually for each farm.

[Manifestation of Dupuytren nodules following fracture of the distal radius]. / Dupuytrenknotenbildung nach Operation einer distalen Radiusfraktur.

PURPOSE: The aim of this study is to evaluate the incidence of post-traumatic development of Dupuytren nodules in distal radius fractures treated operatively. PATIENTS AND METHODS: In 2 prospective randomised studies for operative treatment of distal radius fractures, the formation of Dupuytren nodules was registered. One of the exclusion criteria was a pre-existing Dupuytren's disease at the date of trauma. In addition to the notification of the development of Dupuytren nodules, signs of a complex regional pain syndrome were registered as well as the wrist function, level of pain and grip strength. The Castaing and the Gartland and Werley scores were assessed. The clinical outcomes of patients with and without Dupuytren nodules were compared. 239 of 275 (87%) of the patients could be examined 1 year after the operation, consisting of 32 men and 207 women with a median age of 64.2 years. The patients with Dupuytren nodules were re-evaluated after 16-60 months (median 41.8) for progression of the disease. RESULTS: 21 patients (8.7%) developed changes of the palmar aponeurosis. In 20 patients nodules were stated, one patient showed a cord at the fourth ray of the injured hand. 19 out of 21 patients were female (90.5%). At re-evaluation after 41.8 months (16-60) progression could not be noted nor could similar changes be seen on the contralateral side. Patients with Dupuytren nodules were not handicapped in their hand function. 3 patients (14.3%) revealed a positive family history for Dupuytren's disease. Abuse of alcohol or diabetes was not present in any of the patients with Dupuytren nodules, 7 (33%) were smokers. CONCLUSION: The occurrence of Dupyutren nodules can be triggered by a trauma or operation. It may be speculated that these nodules are an entity of their own as no progression of the contracture could be seen during the follow-up period.

TGF-ß stimulates Pyk2 expression as part of an epithelial-mesenchymal transition program required for metastatic outgrowth of breast cancer.

Epithelial-mesenchymal transition (EMT) programs are essential in promoting breast cancer invasion, systemic dissemination and in arousing proliferative programs in breast cancer micrometastases, a reaction that is partially dependent on focal adhesion kinase (FAK). Many functions of FAK are shared by its homolog, protein tyrosine kinase 2 (Pyk2), raising the question as to whether Pyk2 also participates in driving the metastatic outgrowth of disseminated breast cancer cells. In addressing this question, we observed Pyk2 expression to be (i) significantly upregulated in recurrent human breast cancers; (ii) differentially expressed across clonal isolates of human MDA-MB-231 breast cancer cells in a manner predictive for metastatic outgrowth, but not for invasiveness; and (iii) dramatically elevated in ex vivo cultures of breast cancer cells isolated from metastatic lesions as compared with cells that produced the primary tumor. We further show that metastatic human and murine breast cancer cells robustly upregulate their expression of Pyk2 during EMT programs stimulated by transforming growth factor-ß (TGF-ß). Genetic and pharmacological inhibition of Pyk2 demonstrated that the activity of this protein tyrosine kinase was dispensable for the ability of breast cancer cells to undergo invasion in response to TGF-ß, and to form orthotopic mammary tumors in mice. In stark contrast, Pyk2-deficiency prevented TGF-ß from stimulating the growth of breast cancer cells in 3D-organotypic cultures that recapitulated pulmonary microenvironments, as well as inhibited the metastatic outgrowth of disseminated breast cancer cells in the lungs of mice. Mechanistically, Pyk2 expression was inversely related to that of E-cadherin, such that elevated Pyk2 levels stabilized ß1 integrin expression necessary to initiate the metastatic outgrowth of breast cancer cells. Thus, we have delineated novel functions for Pyk2 in mediating distinct elements of the EMT program and metastatic cascade regulated by TGF-ß, particularly the initiation of secondary tumor outgrowth by disseminated cells.

Implementation of the quality management system improves postoperative pain treatment: a prospective pre-/post-interventional questionnaire study.

BACKGROUND: An organizational approach is proposed as an immediate solution for improving postoperative pain (POP) management. The aim was to evaluate the clinical effectiveness of a quality management system (QMS), based on procedure-specific, multimodal analgesic protocols, modified to meet the individual patients' requirements. METHODS: Patients from the orthopaedic, gynaecological, visceral, and trauma surgery departments of the university hospital were involved in two prospective surveys. Survey 1 was performed at baseline and survey 2 was performed after the implementation of QMS within an interval of 1 year. The patients were asked to report pain intensity on the visual rating scale, incidence of analgesia-related side-effects, and incidence of pain interference with the items of life quality and their satisfaction with the treatment of POP. RESULTS: Patients from Survey 2 (n=251) reported 25-30% less pain than those from Survey 1 (n=269) (P<0.0001). Nausea was reported by 40% of the patients from Survey 1 vs 17% from Survey 2, vomiting by 25 vs 11% and fatigue by 76% in Survey 1 vs 30% in Survey 2 (P<0.0001). Life quality and patients' satisfaction improved in Survey 2 vs Survey 1 (P<0.001). CONCLUSIONS: The implementation of QMS allowed the reduction in POP intensity with a simultaneous decrease in analgesia-related side-effects. This has led to an increased quality of life and patient satisfaction.

Effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on rat vascular smooth muscle in vitro--the role of the endothelium.

Hypotension is a frequent side effect of the antidepressant treatment. It is controversial whether this effect is attributable to interactions within the central nervous or the cardiovascular system. We examined often used antidepressants for their vasoactive properties in vitro in rat aortal rings with and without endothelium. The influence of pre-incubation with the antidepressants (0.5 µM) on adrenergic elicited smooth muscle contraction and the effects of cumulative concentrations (0.05 µM-500 µM) of the antidepressants on isometric tension were measured. In addition, conceivable modulation of the NO-cGMP, adrenergic and potassium channel pathways were examined. Amitriptyline and fluoxetine inhibited, whereas tranylcypromine enhanced adrenergic elicited responses of smooth muscle contraction. The antidepressants amitriptyline, fluoxetine and tranylcypromine showed, to a different extent, vasorelaxing properties in the preparations pre-contracted with phenylephrine 0.1 µM; the pEC50, (means and S.E.M.) in descending order of potency: amitriptyline 6.98 (0.13), fluoxetine 6.11 (0.05), tranylcypromine 5.33 (0.05) (n=8 each, preparations with endothelium); or after pre-contraction with KCl 20 mM: fluoxetine 6.00 (0.06), tranylcypromine 4.99 (0.30), amitriptyline, 4.89 (0.11), (n=7 each, preparations with endothelium). Venlafaxine did not relax the aortal rings and even lead to further contraction of the endothelium intact preparations. The observed effects were partially endothelium dependent via activation of the NO-cGMP pathway and some probably mediated through K+ channel activation. Amitriptyline, fluoxetine and tranylcypromine relax rat aorta in vitro. They partially delay vascular smooth muscle reactions to adrenergic agonists and can lead to sustained hypotension episodes despite administration of sympathomimetic drugs.

Rituximab in relapsing or refractory ANCA-associated vasculitis: a case series of 16 patients.

OBJECTIVES: Cyclophosphamide (CYC) and corticosteroids are generally considered standard induction therapy for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, a subset of patients are refractory or intolerant to this treatment. Rituximab, a chimeric anti-CD20 antibody, has emerged as a second-line therapy, although controlled studies are scarce in patients with relapsing or refractory disease. METHODS: We report 16 patients with AAV who received rituximab for refractory or relapsing vasculitis having previously received CYC. The treatment protocols were 375 mg/m(2) × IV in five patients, 1000 mg × II in six patients, and 500 mg × II in five patients, all in combination with corticosteroids. A majority of patients used other concurrent immunosuppression, most commonly mycophenolate mofetil. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS 2003) at baseline and during follow-up together with C-reactive protein (CRP) and ANCA. Complete remission was defined as a BVAS score of 0 and partial remission as a reduction in BVAS of at least 50%. RESULTS: Twelve patients achieved complete remission, three patients partial remission, and one patient died during follow-up (median of 20 months, range 3-48 months). Six patients relapsed and received rituximab again. Four of these were positive for capture proteinase 3 (PR-3) ANCA but negative with conventional PR-3 ANCA upon retreatment. Seven patients had an adverse event, including two hepatitis B reactivations and one fatal sepsis. CONCLUSION: Treatment with rituximab in AAV was associated with prolonged remission in a subset of patients otherwise difficult to manage.