Loss or Dilution-A New Diagnostic Method to Assess the Impact of Dilution on Standard Laboratory Parameters.

Intraoperative fluid therapy is regularly used in patients undergoing cardiac surgery procedures with cardiopulmonary bypass (CPB). Although fluid administration has several advantages, it unavoidably leads to hemodilution. The hemodilution may further influence the interpretation of concentration-based laboratory parameters like hemoglobin (Hgb), platelet count (PLT) or prothrombin time (PT). These all parameters are commonly used to guide blood product substitution. To assess the impact of dilution on these values, we performed a prospective observational study in 174 patients undergoing elective cardiac surgery. We calculated the total blood volume according to Nadler's formula, and fluid therapy was correlated with a newly developed dilution coefficient formula at the end of CPB. Intravenously applied fluids were measured from the beginning of the anesthesia (baseline, T0) and 15 min after the end of protamine infusion (end of CPB, T1). The amount of the administered volume (crystalloids or colloids) was calculated according to the percentage of the intravascular fluid effect, and intraoperative diuresis was further subtracted. The median blood volume increased by 148% in all patients at T1 compared to the calculated total blood volume at T0. This led to a dilution-dependent decrease of 38% in all three parameters (Hgb 24%, corrCoeff = 0.53; PLT 41%, corrCoeff = 0.68; PT 44%, corrCoeff = 0.54). The dilution-correlated decrease was significant for all parameters (p < 0.001), and the effect was independent from the duration of CPB. We conclude that the presented calculation-based approach could provide important information regarding actual laboratory parameters and may help in the guidance of the blood product substitution and potential transfusion thresholds. Further research on the impact of dilution and related decision-making for blood product substitution, including its impact on morbidity and mortality, is warranted.

Common variable immunodeficiency with granulomatous-lymphocytic interstitial lung disease treated with monoclonal antibodies against COVID-19: A case report.

Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency. We present a 22-year-old Caucasian woman with CVID and granulomatous lymphocytic interstitial lung disease who contracted COVID-19 and was successfully treated with sotrovimab and molnupiravir. This treatment may have contributed to the relatively mild disease course of COVID-19 in our patient.

Indications for diagnostic use of nuclear medicine in rheumatology: A mini-review.

Nuclear medicine techniques allow important insights not only into oncologic, neurologic, and infectious conditions, but also for the assessment of rheumatic diseases. This review provides a brief, update on the potential role of nuclear imaging in rheumatology, especially on 18F-fluorodeoxyglucose (FDG) positron emission tomography for the diagnosis of giant cell arteritis and other large vessel arteritis according to international recommendations. Besides, the potential role of this and other nuclear imaging techniques for the rheumatologic practice are summarized. With 18F-fluoride as tracer for positron emission tomography, a new option for bone scintigraphy comes up, whereas the use of a semiquantitative sialoscintigraphy is no more supported for classification of Sjögren's syndrome according to current recommendations. Other techniques are used for different organ manifestations in systemic rheumatic diseases like for myocardial infarction and apoplectic insult.

Cardiovascular Risks and Risk Stratification in Inflammatory Joint Diseases: A Cross-Sectional Study.

Background: It is well established that patients with inflammatory joint diseases (IJD) have an increased cardiovascular (CV) mortality and morbidity. According to the 2016 EULAR recommendations on CV risk management, rheumatologists should ensure appropriate management of CV risk in rheumatoid arthritis (RA) and other IJDs. The aim was to assess the CV risk and CV disease in Middle-European patients with IJD. Methods: A retrospective chart review was performed for CV risk factors and CV disease in outpatients of a rheumatology outpatient clinic. CV risk was assessed according to the 2016 European Guidelines on CV disease prevention and also using 2 other approaches to compare the results with data from Norwegian and Spanish cohorts. Results: Out of 432 patients, the prevalence of CV disease reached from 8.7% in spondyloarthritis (SpA) and 12.8% in psoriatic arthritis (PsA) to 18.7% in patients with RA. The number of CV risk factors did not differ between patients with RA, SpA, PsA, and non-inflammatory rheumatic disease (NIRD) (with 1.68 ± 0.13, 1.70 ± 0.13, 2.04 ± 0.16, and 1.78 ± 0.34, respectively). CV risk assessment could be performed in 82 patients after exclusion because of missing data and age. Stratification according to ESC guidelines showed low in 50%, moderate in 12.2%, high in 20.7%, and very high CV risk in 17.1% of patients aged between 40 and 65 years. CV risk in the Middle-European patients with IJD was higher than in the German general population (p = 0.004), and similar to the Norwegian patients with IJD, although patients with Middle-European PsA were at higher risk than the Norwegian patients (p = 0.045). Compared to the Spanish patients, Middle-European patients with IJD were more likely assigned to the high- to a very high-risk group (34.2 vs. 16.2%, p < 0.001), especially in RA disease (49.1 vs. 21%, respectively, p < 0.001). Discussion: High prevalence of established CV disease together with high CV risk in patients with IJD urges for increased vigilance for CV risk factors followed by appropriate interaction by the treating physicians. The prospective use of an international CV risk assessment tool will allow not only estimation of the individual CV risk but also provide data for direct comparisons with the general population and other international cohorts.

Identification of Five Quality Needs for Rheumatology (Text Analysis and Literature Review).

Background: While the use of the term "quality" in industry relates to the basic idea of making processes measurable and standardizing processes, medicine focuses on achieving health goals that go far beyond the mere implementation of diagnostic and therapeutic processes. However, the quality management systems used are often simple, self-created concepts that concentrate on administrative processes without considering the quality of the results, which is essential for the patient. For several rheumatic diseases, both outcome and treatment goals have been defined. This work summarizes current mainstreams of strategies with published quality efforts in rheumatology. Methods: PubMed, Cochrane Library, and Web of Science were used to search for studies, and additional manual searches were carried out. Screening and content evaluation were carried out using the PRISMA-P 2015 checklist. After duplicate search in the Endnote reference management software (version X9.1), the software Rayyan QCRI (https://rayyan.qcri.org) was applied to check for pre-defined inclusion and exclusion criteria. Abstracts and full texts were screened and rated using Voyant Tools (https://voyant-tools.org/). Key issues were identified using the collocate analysis. Results: The number of selected publications was small but specific (14 relevant correlations with coefficients >0.8). Using trend analysis, 15 publications with relative frequency of keywords >0.0125 were used for content analysis, revealing 5 quality needs. The treat to target (T2T) initiative was identified as fundamental paradigm. Outcome parameters required for T2T also allow quality assessments in routine clinical work. Quality care by multidisciplinary teams also focusing on polypharmacy and other quality aspects become essential, A global software platform to assess quality aspects is missing. Such an approach requires reporting of multiple outcome parameters according to evidence-based clinical guidelines and recommendations for the different rheumatic diseases. All health aspects defined by the WHO (physical, mental, and social health) have to be integrated into the management of rheumatic patients. Conclusion: For the future, quality projects need goals defined by T2T based initiatives in routine clinical work, secondary quality goals include multidisciplinary cooperation and reduction of polypharmacy. Quality indicators and standards in different health systems will provide new information to optimize patients' care in different health systems.

Hyperspectral imaging as a diagnostic tool to differentiate between amalgam tattoos and other dark pigmented intraoral lesions.

The goal of this project is to identify any in-depth benefits and drawbacks in the diagnosis of amalgam tattoos and other pigmented intraoral lesions using hyperspectral imagery collected from amalgam tattoos, benign, and malignant melanocytic neoplasms. Software solutions capable of classifying pigmented lesions of the skin already exist, but conventional red, green and blue images may be reaching an upper limit in their performance. Emerging technologies, such as hyperspectral imaging (HSI) utilize more than a hundred, continuous data channels, while also collecting data in the infrared. A total of 18 paraffin-embedded human tissue specimens of dark pigmented intraoral lesions (including the lip) were analyzed using visible and near-infrared (VIS-NIR) hyperspectral imagery obtained from HE-stained histopathological slides. Transmittance data were collected between 450 and 900 nm using a snapshot camera mounted to a microscope with a halogen light source. VIS-NIR spectra collected from different specimens, such as melanocytic cells and other tissues (eg, epithelium), produced distinct and diagnostic spectra that were used to identify these materials in several regions of interest, making it possible to distinguish between intraoral amalgam tattoos (intramucosal metallic foreign bodies) and melanocytic lesions of the intraoral mucosa and the lip (each with P < .01 using the independent t test). HSI is presented as a diagnostic tool for the rapidly growing field of digital pathology. In this preliminary study, amalgam tattoos were reliably differentiated from melanocytic lesions of the oral cavity and the lip.

Polypharmacy in Middle-European Rheumatoid Arthritis-Patients: A Retrospective Longitudinal Cohort Analysis With Systematic Literature Review.

Objective: To assess polypharmacy and related medication aspects in Middle-European rheumatoid arthritis (RA) patients, and to discuss the results in view of a systematic literature review. Methods: In this retrospective cohort study, charts were reviewed from RA-patients consecutively recruited between September 27, 2017 and April 29, 2019. Drugs were assigned to the Anatomical Therapeutic Chemical (ATC) groups as proposed by the World Health Organization (WHO). Results were compared to those of a systematic literature review. Results: One hundred seventy-five consecutive RA-patients were included. The mean number of drugs was 6.6 ± 3.5, with 2.4 ± 1.2 drugs taken specifically for RA-compared to 2.6 in the literature. 33.7% of patients experienced polypharmacy defined by ≥5 drugs, compared to 61.6% in the literature-with women affected more frequently than men. After 7 years of follow-up, the number of drugs increased in all ATC-groups by an average of 12.7 %, correlating with age (Corrcoeff = 0.46) and comorbidities (Corrcoeff = 0.599). In the literature, polypharmacy is not always defined precisely, and has not been considered in management guidelines so far. Conclusion: Polypharmacy is a frequent issue in RA-management. With an increasing number of comorbidities during the course of the disease, polypharmacy becomes even more relevant.

Measurement properties of the ASAS Health Index: results of a global study in patients with axial and peripheral spondyloarthritis.

OBJECTIVES: To evaluate construct validity, interpretability, reliability and responsiveness as well as determination of cut-off points for good and poor health within the original English version and the 18 translations of the disease-specific Assessment of Spondyloarthritis international Society Health Index (ASAS HI) in 23 countries worldwide in patients with spondyloarthritis (SpA). METHODS: A representative sample of patients with SpA fulfilling the ASAS classification criteria for axial (axSpA) or peripheral SpA was used. The construct validity of the ASAS HI was tested using Spearman correlation with several standard health outcomes for axSpA. Test-retest reliability was assessed by intraclass correlation coefficients (ICCs) in patients with stable disease (interval 4-7 days). In patients who required an escalation of therapy because of high disease activity, responsiveness was tested after 2-24weeks using standardised response mean (SRM). RESULTS: Among the 1548 patients, 64.9% were men, with a mean (SD) age 42.0 (13.4) years. Construct validity ranged from low (age: 0.10) to high (Bath AnkylosingSpondylitisFunctioning Index: 0.71). Internal consistency was high (Cronbach's α of 0.93). The reliability among 578 patients was good (ICC=0.87 (95% CI 0.84 to 0.89)). Responsiveness among 246 patients was moderate-large (SRM=-0.44 for non-steroidal anti-inflammatory drugs, -0.69 for conventional synthetic disease-modifying antirheumatic drug and -0.85 for tumour necrosis factor inhibitor). The smallest detectable change was 3.0. Values ≤5.0 have balanced specificity to distinguish good health as opposed to moderate health, and values ≥12.0 are specific to represent poor health as opposed to moderate health. CONCLUSIONS: The ASAS HI proved to be valid, reliable and responsive. It can be used to evaluate the impact of SpA and its treatment on functioning and health. Furthermore, comparison of disease impact between populations is possible.

Tocilizumab for the treatment of giant cell arteritis.

INTRODUCTION: Giant cell arteritis (GCA) is the most frequent type of vasculitis, occurring in people older than 50 years. So far, treatment has been limited to corticosteroids and methotrexate only. Areas covered: Interleukin-6 (IL-6) plays a role in the pathophysiology of GCA. This review covers recent advances in the treatment of GCA with tocilizumab (TCZ), which specifically binds to both soluble and membrane-bound IL-6R and inhibits IL-6R-mediated signaling. Expert commentary: Two randomized controlled trials recently showed the efficacy of the IL-6 receptors inhibitor monoclonal antibody TCZ for the induction and maintenance of remission in patients with new-onset and relapsing GCA. Furthermore, addition of TCZ to prednisone led to a reduction in the cumulative prednisone doses required to control GCA. The profile of adverse events was balanced across treatment groups and no safety concerns were raised during the trial.

Differential clinical presentation of Adamantiades-Behçet's disease in non-endemic and endemic areas: retrospective data from a Middle-European cohort study.

OBJECTIVES: To assess demographical and clinical data in a Middle-European cohort of patients with Adamantiades-Behçet's disease (ABD), together with the use of medication in adherence to international guidelines. METHODS: In a retrospective cohort study, in- and outpatients of an Austrian secondary and tertiary university hospital center were analyzed independent from the medical discipline involved. After ethics approval, screening for ABD-patients in the clinical information system resulted in 1821 documents from 1997 to 2016. Patients fulfilling the International Criteria for Behçet's Disease were included, and ABD symptoms and signs together with medical interventions for immunosuppression, anticoagulation and pain management were identified by individual chart reviews and evaluated for conformity with international recommendations. RESULTS: A total of 76 ABD patients were identified with 39.1% Austrian and 37.0% Turkish origin. Genital aphthae and skin manifestations were more frequent, neurological, gastrointestinal and vascular manifestations less frequent in ABD patients of Turkish origin living in Austria compared to those living in Turkey (each P < 0.05). The male-to-female ratio averaged 0.86 (0.39 in patients with Austrian and 1.43 with Turkish backgrounds), and was 3.3 in patients with venous manifestations. Out of 174 medical interventions, 55.2% fully matched the European League Against Rheumatism recommendations of 2008, and 93.7% were considered at least as equal to the recommendations. Indications for tumor necrosis factor inhibition were in line with the 2007 Sfikakis recommendations. CONCLUSIONS: In this Middle-European ABD cohort clinical presentations between patients of Austrian and Turkish origin do not strongly vary, whereas Turkish patients from the non-endemic Innsbruck cohort present differently compared to patients living in Turkey. The role of such cohort analyses will increase, from the epidemiological as well as the management perspective.

Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography.

Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (re)modeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (re)modeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region.

[Immune system and rheumatic diseases in the elderly]. / Immunsystem und rheumatische Erkrankungen im Alter.

Impairments of the immune system play an important role in all immun-mediated rheumatic diseases. Recently, the following news were reported: · Early aging of the immune system with thymus insufficiency has now been reported for both patients with rheumatoid arthritis and axial spondyloarthritis, without prethymic lack of progenitors at least in rheumatoid arthritis.. · For giant cell arteritis, the most frequent vasculitis in the elderly, an increased expression of IL-17A in temporal artery biopsies coincides with good prognosis and reponse to glucocorticoids.. · Concerning immunosenescence in systemic lupus erythematosus, BAFF appears to have an important role for relapses after B-cell depletion.. For the future it can be anticipated that the use of unified classification criteria for rheumatic diseases (as with the new 2012 EULAR / ACR classification criteria for polymyalgia rheumatica) will ensure better comparability of immunological studies also in the elderly.

The story of CD4+ CD28- T cells revisited: solved or still ongoing?

CD4(+)CD28(-) T cells are a unique type of proinflammatory T cells characterised by blockade of costimulatory CD28 receptor expression at the transcriptional level, which is still reversible by IL-12. In healthy individuals older than 65 years, these cells may accumulate to up to 50% of total CD4(+) T lymphocytes as in many immune-mediated diseases, immunodeficiency, and specific infectious diseases. Here we focus on CD4(+)CD28(-) T cells in chronic immune-mediated diseases, summarizing various phenotypic and functional characteristics, which vary depending on the underlying disease, disease activity, and concurrent treatment. CD4(+)CD28(-) T cells present as effector/memory cells with increased replicative history and oligoclonality but reduced apoptosis. As an alternative costimulatory signal instead of CD28, not only natural killer cell receptors and Toll-like receptors, but also CD47, CTLA-4, OX40, and 4-1BB have to be considered. The proinflammatory and cytotoxic capacities of these cells indicate an involvement in progression and maintenance of chronic immune-mediated disease. So far it has been shown that treatment with TNF-α blockers, abatacept, statins, and polyclonal antilymphocyte globulins (ATG) mediates reduction of the CD4(+)CD28(-) T cell level. The clinical relevance of targeting CD4(+)CD28(-) T cells as a therapeutic option has not been examined so far.

Challenges in the diagnosis of chronic immune-mediated rheumatic diseases.

Diagnosing patients with immune-mediated rheumatic diseases has many facets to be considered, but early and rapid diagnosis is an important prerequisite for correct and straight-forward future management of the patients. For optimal results physicians should not miss any diagnosis (assuring high sensitivity of the diagnostic process), and high specificity is needed in view of future therapeutic interventions. This review focuses on select principal aspects of diagnosis in clinical practice: Challenges of diagnostic approaches in immune-mediated rheumatic diseases include the frequent lack of diagnostic criteria (with subsequent misuse of classification criteria), the urgent need for diagnostic values of history and further examinations to support diagnosis-finding strategies, and differential diagnoses to be excluded (e.g., infections during early disease and follow-up). First, pure application of classification criteria without expert's experience as diagnostic criteria may lead to inappropriate diagnoses in 4-32% of all patients with immune-mediated rheumatic diseases. Second, sensitivity and specificity data for history and clinical examination are necessary not only for routine clinical work, but also for purposes of teaching students and learning physicians. Third, conditions to be excluded before classification of a certain disease are not necessarily excluding a certain diagnosis. Specific interest is given to differentiate infections from early onset or relapse of immune-mediated rheumatic diseases.

NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica.

OBJECTIVE: To investigate functional expression of NKG2D on CD4 and CD8 T-cells in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: Peripheral blood was drawn from patients with GCA (n=16), PMR (n=78) and healthy controls (HC, n=64). Tissue samples were obtained from GCA patients and controls. Proliferation and cytokine production assays were performed using CFSE and intracellular IFN-γ or TNF-α staining, respectively, and flow cytometry analysis. Immunofluorescence and immunohistology were applied to analyse the presence of NKG2D-expressing T-cells and NKG2D-ligands in temporal arteries, respectively. mRNA levels of NKG2D-ligands were determined by RT-PCR. RESULTS: In both GCA and PMR patients, NKG2D was preferentially expressed on senescent CD4CD28(-) and CD8CD28(-), as well as on CD8CD28 T-cells. Frequencies of senescent T-cells were increased in GCA and PMR patients compared to HC. In GCA tissue samples, infiltrating T-cells were predominately CD28(-). NKG2D expressing T-cells concentrated around the vasa vasorum of the adventitia. Antigenic stimulation induced rapid up-regulation of NKG2D on CD4CD28(-) and CD4CD28 T-cells, whereas TNF-α and interleukin-15 enhanced NKG2D expression on senescent CD4 and CD8 T-cells only. NKG2D cross-linkage augmented anti-CD3 triggered proliferation, IFN-γ and TNF-α production of CD8 T-cells. In CD4CD28(-) T-cells, NKG2D ligation resulted in increased IFN-γ production only. NKG2D ligands were expressed in temporal arteries from GCA patients, particularly in the adventitial and medial layers of affected vessels. CONCLUSIONS: NKG2D is functionally expressed on CD4CD28(-) and CD8 T-cells in GCA and PMR. NKG2D-ligands are present in temporal arteries and may co-stimulate NKG2D expressing T-cells.

Treatment of refractory giant cell arteritis with cyclophosphamide:a retrospective analysis of 35 patients from three centres.

UNLABELLED: Patients with giant cell arteritis (GCA) refractory to standard immunosuppressive therapy may constitute a significant clinical problem with a high risk of glucocorticoid-related adverse effects. OBJECTIVES: To evaluate efficacy and safety of cyclophosphamide for remission induction in GCA patients with persistent disease activity despite standard immunosuppressive treatment. METHODS: Thirty-five individuals from 3 tertiary rheumatological centres treated for persistently active GCA unresponsive to treatment with glucocorticoids plus at least either methotrexate or azathioprine for a minimum of 3 months and unable to reduce daily glucocorticoid dose to <10 mg prednisolone equivalent. We recorded signs of disease activity (clinical, laboratory, imaging); course of glucocorticoid doses during cyclophosphamide treatment and follow-up; relapse rate; treatment-related adverse events; and survival. Since all patients had been refractory to standard therapy, a matched control group could not be defined. RESULTS: Data from 31 patients completing cyclophosphamide treatment were available for analysis. Twenty-eight patients (90.3%) responded with improved disease activity and sustained reduction of daily prednisolone intake to <10 mg (mean reduction -13.1 mg or -51.6%, p<0.001). Twelve months later, doses <7.5 or <5 mg were achieved in 89.3% and 67.7% of these patients on maintenance immunosuppressive treatment, respectively. Relapses occurred in 12 patients after a median of 20.5 months. Survival over 5 years was similar to expected rates of the general population. Adverse events comprised transient leucopenia, infections and 1 case of haemorrhagic cystitis. CONCLUSIONS: Cyclophosphamide can be considered a therapeutic option with an acceptable safety profile for remission induction in GCA refractory to standard immunosuppressive treatment.

Apoptotic effects of antilymphocyte globulins on human pro-inflammatory CD4+CD28- T-cells.

BACKGROUND: Pro-inflammatory, cytotoxic CD4(+)CD28(-) T-cells with known defects in apoptosis have been investigated as markers of premature immuno-senescence in various immune-mediated diseases. In this study we evaluated the influence of polyclonal antilymphocyte globulins (ATG-Fresenius, ATG-F) on CD4(+)CD28(-) T-cells in vivo and in vitro. PRINCIPAL FINDINGS: Surface and intracellular three colour fluorescence activated cell sorting analyses of peripheral blood mononuclear cells from 16 consecutive transplant recipients and short-term cell lines were performed. In vivo, peripheral levels of CD3(+)CD4(+)CD28(-) T-cells decreased from 3.7 ± 7.1% before to 0 ± 0% six hours after ATG-F application (P = 0.043) in 5 ATG-F treated but not in 11 control patients (2.9 ± 2.9% vs. 3.9 ± 3.0%). In vitro, ATG-F induced apoptosis even in CD4(+)CD28(-) T-cells, which was 4.3-times higher than in CD4(+)CD28(+) T-cells. ATG-F evoked apoptosis was partially reversed by the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) and prednisolon-21-hydrogensuccinate. ATG-F triggered CD25 expression and production of pro-inflammatory cytokines, and induced down-regulation of the type 1 chemokine receptors CXCR-3, CCR-5, CX3CR-1 and the central memory adhesion molecule CD62L predominately in CD4(+)CD28(-) T-cells. CONCLUSION: In summary, in vivo depletion of peripheral CD3(+)CD4(+)CD28(-) T-cells by ATG-F in transplant recipients was paralleled in vitro by ATG-F induced apoptosis. CD25 expression and chemokine receptor down-regulation in CD4(+)CD28(-) T-cells only partly explain the underlying mechanism.

Generation of clean iron nanocrystals on an ultra-thin SiO(x) film on Si(001).

Upon exposure to Fe(CO)(5), the formation of pure cubic Fe nanocrystals with dimensions up to ~75 nm is reported on ultra-thin SiO(x) films (thickness ≈ 0.5 nm) on Si(001), which have been prepared in situ under UHV conditions. The active centers for initial decomposition of Fe(CO)(5) resulting in the growth of the Fe clusters are proposed to be SiO sites. After nucleation at these sites, further crystal growth is observed due to autocatalytic dissociation of Fe(CO)(5) at room temperature. The density of the Fe clusters can be increased by irradiating the surface with a focused electron beam (15 keV) prior to gas exposure. The formation of the active SiO sites upon electron irradiation is attributed to oxygen desorption via the Knotek-Feibelman mechanism.