Apolipoprotein E controls Dectin-1-dependent development of monocyte-derived alveolar macrophages upon pulmonary ß-glucan-induced inflammatory adaptation.

The lung is constantly exposed to the outside world and optimal adaptation of immune responses is crucial for efficient pathogen clearance. However, mechanisms that lead to lung-associated macrophages' functional and developmental adaptation remain elusive. To reveal such mechanisms, we developed a reductionist model of environmental intranasal ß-glucan exposure, allowing for the detailed interrogation of molecular mechanisms of pulmonary macrophage adaptation. Employing single-cell transcriptomics, high-dimensional imaging and flow cytometric characterization paired with in vivo and ex vivo challenge models, we reveal that pulmonary low-grade inflammation results in the development of apolipoprotein E (ApoE)-dependent monocyte-derived alveolar macrophages (ApoE+CD11b+ AMs). ApoE+CD11b+ AMs expressed high levels of CD11b, ApoE, Gpnmb and Ccl6, were glycolytic, highly phagocytic and produced large amounts of interleukin-6 upon restimulation. Functional differences were cell intrinsic, and myeloid cell-specific ApoE ablation inhibited Ly6c+ monocyte to ApoE+CD11b+ AM differentiation dependent on macrophage colony-stimulating factor secretion, promoting ApoE+CD11b+ AM cell death and thus impeding ApoE+CD11b+ AM maintenance. In vivo, ß-glucan-elicited ApoE+CD11b+ AMs limited the bacterial burden of Legionella pneumophilia after infection and improved the disease outcome in vivo and ex vivo in a murine lung fibrosis model. Collectively these data identify ApoE+CD11b+ AMs generated upon environmental cues, under the control of ApoE signaling, as an essential determinant for lung adaptation enhancing tissue resilience.

Zero-Quantum-Defect Method and the Fundamental Vibrational Interval of H_{2}

The fundamental vibrational interval of H_{2}^{+} has been determined to be ΔG_{1/2}=2191.126 614(17) cm^{-1} by continuous-wave laser spectroscopy of Stark manifolds of Rydberg states of H_{2} with the H_{2}^{+} ion core in the ground and first vibrationally excited states. Extrapolation of the Stark shifts to zero field yields the zero-quantum-defect positions -R_{H_{2}}/n^{2}, from which ionization energies can be determined. Our new result represents a 4-order-of-magnitude improvement compared to earlier measurements. It agrees, within the experimental uncertainty, with the value of 2191.126 626 344(17)(100) cm^{-1} determined in nonrelativistic quantum electrodynamic calculations [V. Korobov, L. Hilico and J.-Ph. Karr, Phys. Rev. Lett. 118, 233001 (2017)PRLTAO0031-900710.1103/PhysRevLett.118.233001].

Vascular risk factor control and adherence to secondary preventive medication after ischaemic stroke.

BACKGROUND: Studies regarding adequacy of secondary stroke prevention are limited. We report medication adherence, risk factor control and factors influencing vascular risk profile following ischaemic stroke. METHODS: A total of 664 home-dwelling participants in the Norwegian Cognitive Impairment After Stroke study, a multicenter observational study, were evaluated 3 and 18 months poststroke. We assessed medication adherence by self-reporting (4-item Morisky Medication Adherence Scale) and medication persistence (defined as continuation of medication(s) prescribed at discharge), achievement of guideline-defined targets of blood pressure (BP) (<140/90 mmHg), low-density lipoprotein cholesterol (LDL-C) (<2.0 mmol L-1 ) and haemoglobin A1c (HbA1c) (≤53 mmol mol-1 ) and determinants of risk factor control. RESULTS: At discharge, 97% were prescribed antithrombotics, 88% lipid-lowering drugs, 68% antihypertensives and 12% antidiabetic drugs. Persistence of users declined to 99%, 88%, 93% and 95%, respectively, at 18 months. After 3 and 18 months, 80% and 73% reported high adherence. After 3 and 18 months, 40.7% and 47.0% gained BP control, 48.4% and 44.6% achieved LDL-C control, and 69.2% and 69.5% of diabetic patients achieved HbA1c control. Advanced age was associated with increased LDL-C control (OR 1.03, 95% CI 1.01 to 1.06) and reduced BP control (OR 0.98, 0.96 to 0.99). Women had poorer LDL-C control (OR 0.60, 0.37 to 0.98). Polypharmacy was associated with increased LDL-C control (OR 1.29, 1.18 to 1.41) and reduced HbA1c control (OR 0.76, 0.60 to 0.98). CONCLUSION: Risk factor control is suboptimal despite high medication persistence and adherence. Improved understanding of this complex clinical setting is needed for optimization of secondary preventive strategies.

Shape Resonances in H_{2} as Photolysis Reaction Intermediates.

Shape resonances in H_{2}, produced as reaction intermediates in the photolysis of H_{2}S precursor molecules, are measured in a half-collision approach. Before disintegrating into two ground state H atoms, the reaction is quenched by two-photon Doppler-free excitation to the F electronically excited state of H_{2}. For J=13, 15, 17, 19, and 21, resonances with lifetimes in the range of nano- to milliseconds were observed with an accuracy of 30 MHz (1.4 mK). The experimental resonance positions are found to be in excellent agreement with theoretical predictions when nonadiabatic and quantum electrodynamical corrections are included. This is the first time such effects are observed in collisions between neutral atoms. From the potential energy curve of the H_{2} molecule, now tested at high accuracy over a wide range of internuclear separations, the s-wave scattering length for singlet H(1s)+H(1s) scattering is determined at a=0.2735_{31}^{39} a_{0}.

Photolysis Production and Spectroscopic Investigation of the Highest Vibrational States in H2 (X1Σg+ v = 13, 14).

Rovibrational quantum states in the X1Σg+ electronic ground state of H2 are prepared in the v = 13 vibrational level up to its highest bound rotational level J = 7, and in the highest bound vibrational level v = 14 (for J = 1) by two-photon photolysis of H2S. These states are laser-excited in a subsequent two-photon scheme into F1Σg+ outer well states, where the assignment of the highest (v,J) states is derived from a comparison of experimentally known levels in F1Σg+, combined with ab initio calculations of X1Σg+ levels. The assignments are further verified by excitation of F1Σg+ population into autoionizing continuum resonances, which are compared with multichannel quantum defect calculations. Precision spectroscopic measurements of the F-X intervals form a test for the ab initio calculations of ground state levels at high vibrational quantum numbers and large internuclear separations, for which agreement is found.

Determination of the Interval between the Ground States of Para- and Ortho-H_{2}.

Nuclear-spin-symmetry conservation makes the observation of transitions between quantum states of ortho- and para-H_{2} extremely challenging. Consequently, the energy-level structure of H_{2} derived from experiment consists of two disjoint sets of level energies, one for para-H_{2} and the other for ortho-H_{2}. We use a new measurement of the ionization energy of para-H_{2} [E_{I}(H_{2})/(hc)=124 417.491 098(31) cm^{-1}] to determine the energy separation [118.486 770(50) cm^{-1}] between the ground states of para- and ortho-H_{2} and thus link the energy-level structure of the two nuclear-spin isomers of this fundamental molecule. Comparison with recent theoretical results [M. Puchalski et al., Phys. Rev. Lett. 122, 103003 (2019)PRLTAO0031-900710.1103/PhysRevLett.122.103003] enables the derivation of an upper bound of 1.5 MHz for a hypothetical global shift of the energy-level structure of ortho-H_{2} with respect to that of para-H_{2}.

Dissociation Energy of the Hydrogen Molecule at 10

The ionization energy of ortho-H_{2} has been determined to be E_{I}^{o}(H_{2})/(hc)=124 357.238 062(25) cm^{-1} from measurements of the GK(1,1)-X(0,1) interval by Doppler-free, two-photon spectroscopy using a narrow band 179-nm laser source and the ionization energy of the GK(1,1) state by continuous-wave, near-infrared laser spectroscopy. E_{I}^{o}(H_{2}) was used to derive the dissociation energy of H_{2}, D_{0}^{N=1}(H_{2}), at 35 999.582 894(25) cm^{-1} with a precision that is more than one order of magnitude better than all previous results. The new result challenges calculations of this quantity and represents a benchmark value for future relativistic and QED calculations of molecular energies.

[How Patients View and Accept Health Care Services Provided by Health Care Assistants in the General Practice: Survey of Participants of the GP-centered Health Care Program in Baden-Wuerttemberg]. / Wie bewerten und akzeptieren Patienten die Betreuung durch Medizinische Fachangestellte in der Hausarztpraxis? Ergebnisse einer Patienten-Befragung in der HzV in Baden-Württemberg.

BACKGROUND: In recent years, models for the delegation of GP tasks to non-physician medical staff have been tested, implemented in a general practice setting and, to some extent, funded by health insurance companies. AIM: How were changes in the spectrum of tasks performed by non-physician staff viewed and accepted by patients? METHODS: Between October 2014 and January 2015, a written survey was conducted among chronically ill patients (≥ 65 years of age) receiving health care from health care assistants (HCA) with or without the additional "health care assistant in the family practice", or VERAH qualification. Using a self-developed survey, based on a previous collection of data, patients were asked about various aspects of health care provided by HCAs. RESULTS: 77 practices participated and a total of 1 266 patients were surveyed. The patients said the HCAs had a role to play in many aspects of their health care. More than half the patients said HCAs could take responsibility for some of the home visits and contacts in the practice. Almost without exception, patients regarded the organisational, healthcare and other supporting services performed by the HCAs as very good. The results were more heterogeneous for specific consulting services. While consultations on vaccinations, preventive services, medical examinations and medication adherence were well accepted, this was much less often the case with advice on lifestyle. Many patients see HCAs as additional and competent persons they can trust, and could well imagine HCAs taking on responsibility for further delegable services. CONCLUSION: At least among GP-centered health care programme participants, many healthcare services delegated to HCAs were appreciated and accepted by patients. Home visits and case management, in the sense of structured individual health care for patients with special needs, are further services that may be well suited for delegation. This should be investigated in further studies (including qualitative studies).

Mineral mediated isotope fractionation of soil water.

RATIONALE: The ability to recover the isotopic signature of water added to soil samples that have previously been oven-dried decreases with the increasing presence of silt and clay. The effects on the isotopic signature of water associated with physicochemical soil properties are not yet fully understood, for either hydration or dehydration of soil samples. METHODS: The soil sample chemistry and the crystallinity of minerals were measured by X-ray fluorescence and X-ray diffraction. The organic carbon and the cation-exchange capacity were also determined. Water of known isotopic signature was used to spike an oven-dried substrate and subsequently extracted by cryogenic vacuum extraction at a temperature of 105°C. In addition, the soils were oven-dried at 205°C and water extractions were also performed at 205°C. The isotopic signatures of the water samples were determined by cavity-ring-down spectrometry. RESULTS: The isotope effects caused by the cryogenic vacuum extraction method applied to soils with elevated clay content were reduced. First, by increasing the extraction temperature to 205°C, we improved the precision of the cryogenic vacuum extraction method and the recovery of the known isotopic signature of the spike water. Secondly, the post-correction of data based on the physicochemical soil properties and a common extraction temperature of 105°C improved the measurement trueness. CONCLUSIONS: The isotopic signature of soil water is influenced by mineral-water interaction. During the hydration of clay, different minerals deplete free water in heavy isotopes. The extracted soil water (dehydration water) gathered from clay-rich soils is generally more depleted in the heavy isotopes than the spike water, making results obtained for different soil types difficult to compare. Isotope effects observed at the mineral-water interface highlight potential explanations for eco-hydrological separation of water pools. Copyright © 2016 John Wiley & Sons, Ltd.

Migraine in patients with systemic lupus erythematosus is associated with reduced cerebral grey matter volume but not with measures of glial activation or anti-NR2 or anti-P antibodies.

BACKGROUND AND PURPOSE: Migraine is frequent in patients with systemic lupus erythematosus (SLE), but the pathogenesis and pathophysiology are poorly understood. Migraine is assumed to be a consequence of abnormal neuronal excitability. Based on the hypothesis that the threshold for migraine is lower in SLE patients due to cerebral disturbances, whether structural abnormalities of the brain or relevant biomarkers are associated with headaches in SLE was investigated. METHODS: Sixty-seven SLE patients and age- and gender-matched healthy subjects participated. Volumes of grey matter (GM) and white matter (WM) were estimated from cerebral magnetic resonance images with SPM8 software. Anti-NR2 and anti-P antibodies and protein S100B were measured in cerebrospinal fluid. RESULTS: In regression analyses, larger GM volumes in SLE patients reduced the odds for headache in general [odds ratio (OR) 0.98, P = 0.048] and for migraine in particular (OR 0.95, P = 0.004). No localized loss of GM was observed. Larger WM volumes in patients increased the odds for migraine (OR 1.04, P = 0.007). These findings could not be confirmed in healthy subjects. Neither anti-NR2 and anti-P antibodies nor S100B were associated with headaches in SLE patients. CONCLUSIONS: Systemic lupus erythematosus patients with migraine have a diffuse reduction in GM compared to patients without migraine. This finding was not observed in healthy subjects with migraine, and selected biomarkers did not indicate specific pathophysiological processes in the brain. These findings indicate that unknown pathogenic processes are responsible for the increased frequency of migraine in SLE patients.

[Delegation of GP Work to Qualified Medical Staff in Germany - An Overview]. / Delegation hausärztlicher Tätigkeiten an qualifiziertes medizinisches Fachpersonal in Deutschland - eine Übersicht.

AIM: To assure nationwide provision of family medical care, a greater involvement of non-physician healthcare professionals has been discussed in Germany for some time. Currently, there are various delegation models. The aim of this study is to provide an overview of existing delegation models in a German family practice setting and to investigate to what extent they are implemented in practice. METHOD: Internet search was made for delegation models for non-physician healthcare staff, and various experts were contacted in April 2014. Models that explicitly addressed family practice, involved continuing education of more than 80 h, and for which health insurance funds bore the costs, were taken into consideration. The models were judged in accordance with the PDCA implementation cycle (Plan-Do-Check-Act). RESULTS: 6 delegation models used in family practice were identified for which only 4 qualifications were still available in 2014. The duration, content and aims of the training courses differed markedly. Since 2015, training to become a NäPA non-physician practice assistant (or a VERAH healthcare assistant in the family practice if the necessary supplementary qualification is achieved) is the basic qualification for which costs are reimbursed. However, one important quality criterion for its broad implementation, namely evaluation, is missing in NäPA training. Only the VERAH qualification fulfills all quality criteria. CONCLUSIONS: In order to fully implement the delegation models and to strengthen and promote the healthcare assistant profession, the delegation models for which training costs are generally reimbursable should satisfy all quality criteria and also be subject to continual evaluation.

Sentinel lymph node biopsy and risk factors for predicting metastasis in cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a common cancer capable of metastasis. Sentinel lymph node biopsy (SLNB) may be a valuable adjunct for patients with cSCC at high risk for metastasis. However, data on risk factors for metastasis and results of SLNB from patients with cSCC are limited. OBJECTIVES: To evaluate risk factors for metastasis in patients with cSCC in a large cohort study with long-term follow-up and to determine the value of SLNB. METHODS: We retrospectively analysed all records of patients who underwent excision of cSCC between January 2005 and August 2009 at a tertiary referral centre. In total, 143 patients were included in the cohort, including 17 patients with SLNB and a follow-up time of ≥ 24 months. RESULTS: Tumour thickness > 4 mm and recurrent cSCC were strongly associated with metastatic disease. All metastases in this cohort occurred within 24 months of follow-up. SLNB showed a low sensitivity with regard to the development of metastasis. Six of 17 patients developed metastatic disease despite a negative SLNB. CONCLUSIONS: Patients with risk factors (cSCC with a tumour thickness > 4 mm or recurrent disease) may develop metastases within the first 2 years despite a negative SLNB. Therefore these patients should be closely monitored during the follow-up. Based on our data SLNB does not provide diagnostic value for patients with cSCC.

[Rationale and dissemination of "GP centered health care" ("HzV") in Germany]. / Rationale und Stand der hausarztzentrierten Versorgung in Deutschland.

BACKGROUND: In the face of demographic changes, the aging of the population, and the increase in chronic morbidity and complexity, efficient primary care is needed to ensure comprehensive and high-quality health care. The general practitioner (GP) can only cope with this task, if certain preconditions are met. OBJECTIVES: To strengthen primary health care, the German legislator added § 73b, "GP-centered health care" ("Hausarztzentrierte Versorgung", HzV) to the Social Code Book V. This article seeks to illustrate the rationale and general set-up of the HzV and to report on its dissemination. We discuss whether or not the HzV can promote the preconditions required. MATERIALS AND METHODS: Literature search, querying participants. RESULTS: Several elements of the HzV, such as lump-sum reimbursement, obligatory participation in structured quality circles, continuing education, and the qualification of non-medical health care assistants help to promote an environment that enables GPs to fulfill their new role. Considering all assured people and the Federal Republic as a whole, the distribution of the HzV is poor. However, a growing number of contracts (currently: 79) and participants (currently > 3.6 million) is expected. CONCLUSIONS: The establishment of efficient primary care is heavily promoted by the HzV. In future, ways must be found to overcome the inflexible borders between sectors and to integrate community-based health care, which truly focuses on the patients needs. The HzV can be seen as a starting point.

[GP-centered health care in Baden-Württemberg, Germany: Results of a quantitative and qualitative evaluation]. / Hausarztzentrierte Versorgung in Baden-Württemberg : Ergebnisse einer qualitativen und querschnittlich quantitativen Evaluation.

BACKGROUND: GP-centered health care ("Hausarztzentrierte Versorgung", HzV)-the terms of which are described in § 73b of the Social Code Book V-came into effect in Baden-Württemberg, Germany, on 1 July 2008. The HzV is aimed at enhancing health care for patients with chronic diseases and complex health care needs (e.g., those requiring long-term care). OBJECTIVES: On the basis of four working packages (WP I-WP IV), the present paper examines the impact that GP-centered health care has had on patients insured by the "AOK" regional sickness fund and their GPs. WP I addresses the association between HzV participation and the corresponding health care utilization of patients on the basis of claims data. WP II looks at any changes that GPs and patients noticed were potentially attributable to HzV participation. WP III focuses on health care assistants in primary care ("Versorgungsassistenten in der Hausarztpraxis", VERAH). These assistants play a special role within the framework of the HzV. WP IV analyzes the quality of health care for patients aged 65 years and over, also on the basis of claims data. MATERIALS AND METHODS: A mixed methods design was used for this evaluation, and quantitative and qualitative approaches taken. This design enabled insights into the implementation of the HzV in regular health care to be obtained from different perspectives. RESULTS: Numerous positive associations between HzV participation and the variables of interest were observed for all WPs. These are presented in detail in the paper. CONCLUSION: The results obtained so far clearly support the continuation of HzV and associated evaluations.

Loss of cerebral white matter in primary Sjögren's syndrome: a controlled volumetric magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Although brain involvement is common in primary Sjögren's syndrome (pSS), results from cerebral imaging studies are inconsistent. This study aimed to perform both voxel-wise and global brain volume analyses in a nearly population-based pSS cohort to explore whether the patients displayed any focal or diffuse volume differences compared with healthy subjects. METHODS: Global grey matter (GM) and white matter (WM) volumes were measured and compared in 60 patients with pSS and 60 age- and gender-matched healthy subjects. Regression models were constructed with potential explanatory variables for GM and WM volumes. In the same groups, voxel-wise morphometric analyses were performed. RESULTS: In analyses of global GM and WM, the patients had lower WM volumes than healthy subjects (540 ± 63 cm(3) vs. 564 ± 56 cm(3), P = 0.02), but no differences in GM. Voxel-wise analyses displayed no localized areas of GM or WM volume differences between pSS patients and healthy subjects. CONCLUSION: Individuals with pSS have a diffuse reduction of cerebral WM but no localized loss of WM or GM. This indicates a general deleterious effect on WM due to pSS itself.

[Cutaneous Rosai-Dorfman syndrome. Successful therapy with intrralesional corticosteroids]. / Kutanes Rosai-Dorfman-Syndrom. Erfolgreiche Therapie mit intraläsional applizierten Steroiden.

BACKGROUND: Cutaneous Rosai-Dorfman disease is a rare disorder belonging to the spectrum of non-Langerhans cell histiocytoses. It is characterized by dermal and subcutaneous infiltrates of histiocytes as well as accompanying lymphocytes, plasma cells and granulocytes. Because it is so rare, standard therapies have not been established. CASE REPORT: A 27-year-old man showed an excellent response to intralesional corticosteroids after unsuccessful prior treatment with methotrexate, systemic steroids and surgery as well as laser therapy.

Ultrafast transient generation of spin-density-wave order in the normal state of BaFe2As2 driven by coherent lattice vibrations.

The interplay among charge, spin and lattice degrees of freedom in solids gives rise to intriguing macroscopic quantum phenomena such as colossal magnetoresistance, multiferroicity and high-temperature superconductivity. Strong coupling or competition between various orders in these systems presents the key to manipulate their functional properties by means of external perturbations such as electric and magnetic fields or pressure. Ultrashort and intense optical pulses have emerged as an interesting tool to investigate elementary dynamics and control material properties by melting an existing order. Here, we employ few-cycle multi-terahertz pulses to resonantly probe the evolution of the spin-density-wave (SDW) gap of the pnictide compound BaFe(2)As(2) following excitation with a femtosecond optical pulse. When starting in the low-temperature ground state, optical excitation results in a melting of the SDW order, followed by ultrafast recovery. In contrast, the SDW gap is induced when we excite the normal state above the transition temperature. Very surprisingly, the transient ordering quasi-adiabatically follows a coherent lattice oscillation at a frequency as high as 5.5 THz. Our results attest to a pronounced spin-phonon coupling in pnictides that supports rapid development of a macroscopic order on small vibrational displacement even without breaking the symmetry of the crystal.

Blisters - an unusual effect during radiotherapy.

The skin reaction to radiation is regularly monitored in order to detect enhanced radiosensitivity of the patient, unexpected interactions (e.g. with drugs) or any inadvertent overdosage. It is important to distinguish secondary disease from radiation reaction to provide adequate treatment and to avoid unnecessary discontinuation of radiotherapy. A case of bullous eruption or blisters during radiotherapy of the breast is presented. Differential diagnoses bullous pemphigoid, pemphigus vulgaris, and bullous impetigo are discussed and treatment described.

Long-term outcome of intravenous therapy with rituximab in patients with primary cutaneous B-cell lymphomas.

BACKGROUND: The monoclonal antibody rituximab directed against the B-cell antigen CD20 was approved for the treatment of B-cell lymphomas and maintenance therapy in follicular lymphomas more than a decade ago. However, median follow-up in case series of intravenous rituximab therapy in primary cutaneous B-cell lymphomas (CBCL) lasts only up to 3 years. We retrospectively analysed a cohort of CBCL patients treated with rituximab to gain more long term information. PATIENTS AND METHODS: Eighteen patients, treated intravenously with rituximab for a primary cutaneous B-cell lymphoma [follicle centre lymphoma (PCFCL), n = 11; diffuse large B-cell lymphoma, leg type (PCLBCL, leg type), n = 5; marginal zone B-cell lymphoma (PCMZL), n = 2] were included. The response rate (RR), time to relapse (TTR), and course of the disease after treatment were analysed. RESULTS: The overall RR was 89% (16 of 18 patients). Within the median follow-up time of 52 months, 81% (13 of 16) of patients experienced a relapse; the median TTR was 25 months. The duration of remission was significantly shorter in patients presenting with generalized skin lesions at start of therapy. Both nonresponding patients suffered from PCLBCL, leg type, with extracutaneous manifestations. In responders severe adverse events, the occurrence of extracutaneous dissemination or nodal lymphomas were not observed during follow-up. CONCLUSIONS: Therapy with rituximab is effective and safe for the treatment of PCFCL, but relapses, in particular in patients with generalized skin involvement, are commonly observed. However, all patients with relapses responded well to treatment and therefore maintenance therapy does not seem to be indicated. Patients with PCLBCL, leg type, should receive chemotherapy in addition to rituximab.

Survivin in adrenocortical tumors - pathophysiological implications and therapeutic potential.

Treatment options for adrenocortical carcinoma (ACC) are very limited. In other solid tumors, small vaccination trials targeting the anti-apoptotic molecule survivin suggested immunological and clinical benefit in selected patients. Therefore, we investigated whether survivin might be a suitable target for immunotherapy in ACC. Survivin mRNA and protein expression was assessed in adrenal tissue specimens [by real-time-PCR in 29 ACC, 24 adrenocortical adenomas (ACA) and 12 normal adrenal glands; by immunohistochemistry in 167 ACCs, 15 ACA, and 5 normal adrenal glands]. Expression was correlated with clinical outcome using Kaplan-Meier and Cox regression analyses. The anti-apoptotic role of survivin was investigated in the SW13 ACC cell line using survivin siRNA. The presence of spontaneous survivin specific T-cells in peripheral blood was assessed by FACS dextramere staining in 29 ACC patients in comparison to healthy controls. Survivin mRNA in ACC was significantly overexpressed when compared with ACA or normal adrenal glands. Immunohistochemistry confirmed survivin protein expression in 97% of the ACCs. In 83% of samples, staining was moderate or high and clinical outcome in this subgroup showed a trend towards poorer prognosis [hazard ratio for death 2.28 (95% CI 0.99-5.28); p=0.053]. Survivin knockdown in SW-13 cell significantly increased the rate of apoptosis. Finally, spontaneous survivin-reactive T cells were detectable in 3 of 29 ACC patients. In conclusion, our data suggest that survivin could play an important role in the anti-apoptotic mechanisms in ACC and provide first hints that targeting survivin might be an interesting new therapeutic approach in this rare disease.