State of the art: leadless ventricular pacing : A national expert consensus of the Austrian Society of Cardiology.

BACKGROUND: Cardiac pacing has been shown to improve quality of life and prognosis of patients with bradycardia for almost 60 years. The latest innovation in pacemaker therapy was miniaturization of generators to allow leadless pacing directly in the right ventricle. There is a long history and extensive experience of leadless ventricular pacing in Austria. However, no recommendations of national or international societies for indications and implantation of leadless opposed to transvenous pacing systems have been published so far. RESULTS: A national expert panel of skilled implanters gives an overview on the two utilized leadless cardiac pacing systems and highlights clinical advantages as well as current knowledge of performance and complication rates of leadless pacing. Furthermore, a national consensus for Austria is presented, based on recent studies and current know-how, specifically including indications for leadless pacing, management of infection, suggestions for qualification, and training of the operators and technical standards. CONCLUSIONS: Leadless pacing systems can be implanted successfully with a low complication rate, if suggestions for indications and technical requirements are followed. An overview of the two utilized leadless cardiac pacing systems is given, specifically highlighting clinical advantages as well as current knowledge of performance and complication rates. Furthermore, a national consensus for Austria is presented, specifically including indications for leadless pacing, management of infection, and suggestions for qualification and technical standards.

Real-life clinical use of natalizumab and fingolimod in Austria.

OBJECTIVES: To compare the efficacy of natalizumab or fingolimod in a nationwide observational cohort using prospectively collected data. MATERIALS AND METHODS: We included all patients starting treatment with natalizumab or fingolimod documented in the Austrian MS Treatment Registry (AMSTR) from 2011 and staying on therapy for at least 24 months. We used propensity scores for several matching methods and as a covariate in multivariate models to correct for the bias of this non-randomized registry study. RESULTS: The study cohort includes 588 patients with RRMS. Ten patients did not produce a propensity score in the common support region, thus leaving 578 cases for final analyses, 332 in the fingolimod and 246 in the natalizumab group. Mean annualized relapse rates (ARR) during the 24 months observation period were 0.19 under fingolimod and 0.12 under natalizumab treatment (P = .005). No statistical significant differences were found analysing the log-transformed ARR, probability for experiencing a relapse, EDSS progression and EDSS regression. The hazard ratio for switching treatment from fingolimod comparing with natalizumab was 0.36 (95% CI: 0.247-0.523), P < .001. CONCLUSIONS: The generalized linear model (GLM) for relapse count as Poisson distributed dependent variable and propensity score as covariate showed a statistically significant reduction for the mean relapse count in the natalizumab group compared with fingolimod. This effect was smaller in the analyses of log-transformed ARR with propensity score matching, loosing statistical significance although showing the same direction for the effect. We assume that the GLM was the more sensitive model analysing this question.

Late age onset of amyotrophic lateral sclerosis is often not considered in elderly people.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing an upper and lower motor neuron loss. It is neurology textbook knowledge that the mean age of onset is about 60 years. However, recent investigations show an increasing incidence in older persons. We therefore evaluated whether ALS is potentially not considered in elderly people with ALS symptoms, respectively, not recognized. MATERIALS AND METHODS: We included retrospectively all patients with ALS diagnoses after work-up that were admitted to our neurological and geriatric departments from 2007 to 2010 and collected their clinical data. The diagnosis of ALS was based on the El Escorial criteria. Patients were grouped into three categories according to age (<50, between 50 and 70, >70), and differences in clinical and/ or biographical factors were investigated. RESULTS: We identified 35 patients (18 men and 17 women) with a median age at onset of 71.5 years (range: 36-87 years). When establishing the diagnosis, 51% were older than 70 years, 40% (14/35) between 50 and 70, and only 9% younger than 50. Only in 46 per cent of patients who were sent to our departments with ALS symptoms ALS was considered by the referring physician. CONCLUSION: Late age onset of ALS seems to be more common than formerly assumed and is presumably under-recognized in elderly patients. ALS needs to be considered as a differential diagnosis in older patients. Potential factors accounting for older people being underdiagnosed with ALS relate to frequent presentation with symptoms like dysphagia, frailty or general weakness for other reasons.

[Surgical Treatment of Calcaneus Fractures with C-Nail]. / Operacní lécení zlomeniny patní kosti pomocí C-hrebu.

PURPOSE OF THE STUDY The calcaneus bone is the largest tarsal bone of a complex shape, the restoration of which after fracturing, often caused by a high-energy injury, is critical. The top priority in treating these fractures is to correctly asses the condition of the surrounding soft tissues that may be further excessively traumatized by inappropriate timing, surgical approach or technique. Even when adhering to all the rules and guidelines, complications in surgical wound healing have been described in up to 16-33% cases when the extended lateral approach was used. Therefore, the development of minimally invasive techniques, approaches and implants are a promise for improvement. One of them is the C-Nail developed by Medin. MATERIAL AND METHODS In the period from 1 January 2014 to 30 March 2017, a total of 25 patients with calcaneus bone fracture treated with C-Nail using the sinus tarsi approach were followed up at our department. Radiological assessment was made in the patients, the fractures were classified by Sanders and Essex-Lopresti classification systems, the Böhler and Gissane angles before and after reduction were measured. The occurrence of postoperative complications in soft tissue healing and complications caused by the C-Nail and the functional outcome according to the Ankle-Hindfoot Score (AOFAS) were tracked. RESULTS Only one complication in wound healing, namely in case of sinus tarsi approach, was reported in this group of patients. In 9 patients, prominence of osteosynthesis material was observed. Of whom in 4 patients a clinically significant prominence into posterior talocalcaneal articulation was present. Severely limited subtalar range of motion was seen in 5 patients, in other three patients ankylosis was observed, or arthrodesis performed. 8 patients experienced mild reduction of subtalar joint range of motion. 6 patients suffered from mild reduction of range of motion in talocrural joint. The functional outcome according to the Ankle-Hindfoot Score (AOFAS) was 89.4 on average. CONCLUSIONS Our so far limited experience with the osteosynthesis of calcaneal fractures using the C-Nail entitles us to claim that this type of osteosynthesis material allows for adequate stability and subsequent healing of a correctly reduced calcaneal fracture. It is an implant inserted by a minimally invasive surgery and the fracture reduction, when mastering the learning curve, can be efficiently performed from sinus tarsi approach. In our group of patients, the number of complications in soft tissue healing was low, which is why we believe that this type of osteosynthesis is another suitable option to treat the comminuted calcaneal fractures. The handling of the implant as such and other osteosynthesis material is safe provided all the rules covered in detail in the discussion are observed. Key words: calcaneal fracture, C-Nail, sinus tarsi approach.

[Influence of the Weather on the Incidence of Fractures in the Elderly]. / Vliv pocasí na výskyt zlomenin ve stárí.

PURPOSE OF THE STUDY The incidence of geriatric fractures (proximal femur, distal radius, proximal humerus and thoracolumbar spine injuries) in the population increases with ageing. However, the role of weather conditions, such as icy and slippery winter, should not be overlooked. A deeper insight into this relationship may bring about a better understanding of the fracture aetiology and thus allow for improvement in the prevention of fractures in elderly people. MATERIAL AND METHODS This prospective study included 676 patients (469 women and 207 men) aged 65 and over. Relationships between the incidence of geriatric fractures in these patients and the season, weather phenomena (i.e., air temperature, atmospheric pressure, air humidity, wind speed, visibility, rain, snow, mist and storm) and global biometeorological data in the period from 1 January 2012 to 31 December 2013 were investigated. Patients with high velocity trauma or those with pathological fractures were excluded. Time (day/night), the place of injury (outdoor/indoor/home environment), comorbidities and chronicuse medication were also recorded. Weather forecast records with weather health loads (biotropic indices) were obtained from the commercial service Weather Underground and the Czech Hydrometeoro-logical Institute. The results were statistically analysed using the Statistika 12 programme. RESULTS The incidence of fractures was higher in winter months but there was no statistically significant correlation between the number of fractures and various weather characteristics (temperature, atmospheric pressure, air humidity, wind speed, visibility, rainfall, snow, mist or storm). On the other hand, a relationship between the incidence of geriatric fractures and the biometeorological data (biotropic index) for that day was significant (r = 0.65, p= 0.0401). The majority of fractures occurred during the daytime (83.7%) and in the indoor environment (83.1%); of the latter fractures, 85.2% were home injuries. The most frequent comorbidities included cardiovascular disease (36.2%), obesity (31.1%) and diabetes mellitus (25.4%). DISCUSSION Studies investigating seasonal patterns in relation to the incidence of geriatric fractures are contradictory. Sixteen previous studies have examined seasonal variations and the incidence of some types of geriatric fractures in different parts of the world. The majority of them have dealt with hip fractures, three with forearm injuries and one compared the incidence of hip, distal forearm, proximal humerus and ankle fractures in the four seasons of the year. Of 13 studies in geographic areas located north of 40°latitude, eight showed no seasonal variation in the incidence of fractures, four recorded an increase in the number of fractures in winter and two showed an increased number of fractures in summer. Three of them also studied the effect of daily temperature. Only one study paid attention to biometeorological data and related the biotropic index to the number of injuries treated at the emergency department. Three studies showed that fractures occurred most frequently in the home environment and during the daytime. CONCLUSIONS This study did not prove any statistically significant relationship between the incidence of geriatric fractures and different weather phenomena. Nevertheless, it showed a higher incidence of fractures in winter, from December to February. Most fractures occurred in indoor environments and during the day. A high value of the biotropic index was significantly related to the incidence of geriatric fractures. The most frequent comorbidities included cardiovascular disease, obesity and diabetes mellitus. Key words: geriatric fracture, season, weather, biometeorological forecast.

RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features.

We evaluated the frequency, genetic architecture, clinico-pathologic features and prognostic impact of RUNX1 mutations in 2439 adult patients with newly-diagnosed acute myeloid leukemia (AML). RUNX1 mutations were found in 245 of 2439 (10%) patients; were almost mutually exclusive of AML with recurrent genetic abnormalities; and they co-occurred with a complex pattern of gene mutations, frequently involving mutations in epigenetic modifiers (ASXL1, IDH2, KMT2A, EZH2), components of the spliceosome complex (SRSF2, SF3B1) and STAG2, PHF6, BCOR. RUNX1 mutations were associated with older age (16-59 years: 8.5%; ⩾60 years: 15.1%), male gender, more immature morphology and secondary AML evolving from myelodysplastic syndrome. In univariable analyses, RUNX1 mutations were associated with inferior event-free (EFS, P<0.0001), relapse-free (RFS, P=0.0007) and overall survival (OS, P<0.0001) in all patients, remaining significant when age was considered. In multivariable analysis, RUNX1 mutations predicted for inferior EFS (P=0.01). The effect of co-mutation varied by partner gene, where patients with the secondary genotypes RUNX1mut/ASXL1mut (OS, P=0.004), RUNX1mut/SRSF2mut (OS, P=0.007) and RUNX1mut/PHF6mut (OS, P=0.03) did significantly worse, whereas patients with the genotype RUNX1mut/IDH2mut (OS, P=0.04) had a better outcome. In conclusion, RUNX1-mutated AML is associated with a complex mutation cluster and is correlated with distinct clinico-pathologic features and inferior prognosis.

[Soft tissue plastic surgery for complications in the skull region]. / Weichteilplastische Maßnahmen bei Komplikationen im Schädelbereich.

Tumor resection and trauma may leave devastating defects in the head and neck area complicating and preventing patient rehabilitation; therefore, plastic surgery methods are required which are able to prevent further complications and provide efficient functional and aesthetic reconstruction. In this review article typical cases and the interdisciplinary management of plastic surgery are presented.

High interindividual variability in the CD4/CD8 T cell ratio and natalizumab concentration levels in the cerebrospinal fluid of patients with multiple sclerosis.

Strongly decreased leucocyte counts and a reduced CD4/CD8 T cell ratio in the cerebrospinal fluid (CSF) of natalizumab (NZB)-treated multiple sclerosis (MS) patients may have implications on central nervous (CNS) immune surveillance. With regard to NZB-associated progressive multi-focal leucoencephalopathy, we aimed at delineating a relationship between free NZB, cell-bound NZB, adhesion molecule (AM) expression and the treatment-associated shift in the CSF T cell ratio. Peripheral blood (PB) and CSF T cells from 15 NZB-treated MS patients, and CSF T cells from 10 patients with non-inflammatory neurological diseases and five newly diagnosed MS patients were studied. Intercellular adhesion molecule-1 (ICAM-1), leucocyte function antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), NZB saturation levels, and T cell ratios were analysed by flow cytometry. NZB concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Lower NZB saturation levels (P<0.02) and a higher surface expression of ICAM-1 and LFA-1 (P<0.001) were observed on CSF CD8 T cells. CSF T cell ratios (0.3-2.1) and NZB concentrations (0.01-0.42 µg/ml) showed a pronounced interindividual variance. A correlation between free NZB, cell-bound NZB or AM expression levels and the CSF T cell ratio was not found. Extremely low NZB concentrations and a normalized CSF T cell ratio were observed in one case. The differential NZB saturation and AM expression of CSF CD8 T cells may contribute to their relative enrichment in the CSF. The reduced CSF T cell ratio appeared sensitive to steady-state NZB levels, as normalization occurred quickly. The latter may be important concerning a fast reconstitution of CNS immune surveillance.

Metamorphosis enhances the effects of metal exposure on the mayfly, Centroptilum triangulifer.

The response of larval aquatic insects to stressors such as metals is used to assess the ecological condition of streams worldwide. However, nearly all larval insects metamorphose from aquatic larvae to winged adults, and recent surveys indicate that adults may be a more sensitive indicator of stream metal toxicity than larvae. One hypothesis to explain this pattern is that insects exposed to elevated metal in their larval stages have a reduced ability to successfully complete metamorphosis. To test this hypothesis we exposed late-instar larvae of the mayfly, Centroptilum triangulifer, to an aqueous Zn gradient (32-476 µg/L) in the laboratory. After 6 days of exposure, when metamorphosis began, larval survival was unaffected by zinc. However, Zn reduced wingpad development at concentrations above 139 µg/L. In contrast, emergence of subimagos and imagos tended to decline with any increase in Zn. At Zn concentrations below 105 µg/L (hardness-adjusted aquatic life criterion), survival between the wingpad and subimago stages declined 5-fold across the Zn gradient. These results support the hypothesis that metamorphosis may be a survival bottleneck, particularly in contaminated streams. Thus, death during metamorphosis may be a key mechanism explaining how stream metal contamination can impact terrestrial communities by reducing aquatic insect emergence.

JLK1486, a N,N-[(8-hydroxyquinoline)methyl]-substituted benzylamine analogue, inhibits melanoma proliferation and induces autophagy.

OBJECTIVES: To investigate anti-proliferatory activity of a selected N,N-[(8-hydroxyquinoline)methyl]-substituted benzylamine (JLK1486) on melanoma cells and to characterize its mechanism of cell population growth inhibition. MATERIALS AND METHODS: In vitro cultures of B16F10 (mouse melanoma) cells were used as a model to characterize anti-proliferatory activity of JLK1486 using MTT growth assay, trypan blue viability assessment, cell cycle analysis, melanin production, ß-galactosidase and acridine orange staining. RESULTS: Proliferating B16F10 and also MeWo (human melanoma) cells were strongly growth inhibited by JLK1486, displaying IC50 values of 196 nm and 110 nm respectively. Anti-proliferatory effects were independent of cell death and were characterized by a distinct accumulation of cells in G0 /G1 phase. Tyrosinase activity and relative melanin content remained unchanged indicating that the anti-proliferatory activity was not due to phenotype differentiation. Although treated B16F10 cells stained strongly positive for senescence marker ß-galactosidase, cells regained near normal proliferatory activity after removal of JLK1486. Increased acridine orange staining and presence of perinuclear vacuoles suggested induction of autophagy in B16F10 cells. Furthermore, JLK1486 pre-treatment completely abolished melphalan and antimycin A-induced apoptosis. CONCLUSION: JLK1486 provides a promising chemical scaffold to develop new anti-melanoma drugs or combination therapies, due to its potent inhibition of cell proliferation and induction of autophagy, at pharmacologically relevant concentrations.

Pilot study: Association between Helicobacter pylori in adenoid hyperplasia and reflux episodes detected by multiple intraluminal impedance in children.

OBJECTIVES: The aim of this pilot study was to investigate an association between laryngopharyngeal reflux detected by combined multiple intraluminal impedance and pH monitoring and Helicobacter pylori in adenoid hyperplasia detected with real time polymerase chain reaction (PCR). METHODS: The study group consisted of 30 children (median age 5.34 years) with extraesophageal symptoms of gastroesophageal reflux disease with adenoid hyperplasia. All children underwent adenoidectomy with subsequent PCR detection of H. pylori DNA in the tissue and multiple intraluminal impedance and pH monitoring. The most proximal impedance sensor was located 1cm caudal to the entrance of the oesophagus. RESULTS: We found significant differences in the number of reflux episodes among patients with PCR positivity (median 35) and negativity (median 0) of H. pylori (p-value of Mann-Whitney U-test 0.0056). Patients with PCR positivity of H. pylori had significantly more reflux episodes reaching the upper oesophageal sphincter (p-value of Mann-Whitney U-test 0.023). The absence of reflux episode was the only independent factor for PCR negativity of H. pylori in the multiple logistic regression model. CONCLUSIONS: These results support the hypothesis that reflux episodes reaching the upper oesophageal sphincter may play an important role in the transmission of H. pylori into lymphoid tissue of the nasopharynx and thus may contribute to adenoid hyperplasia in children.

What to expect after natalizumab cessation in a real-life setting.

BACKGROUND: To minimize the risk of progressive multifocal leucoencephalopathy (PML), treatment with natalizumab is often stopped after 2 years, but evidence upon rebound of disease activity is limited and controversial. OBJECTIVE: To evaluate effects of natalizumab discontinuation on clinical disease activity within twelve months after cessation. METHODS: We retrospectively analyzed data of 201 patients with MS who discontinued natalizumab between 2007 and 2012. Mean change scores of annualized relapse rate (ARR) and expanded disability status scale (EDSS) were calculated for detection of rebound disease activity after twelve months. RESULTS: Natalizumab exposure did not exceed 2 years in 50.2% of patients, and the most common reasons for discontinuation were a long treatment period and concern of PML (56%). A total of 11.9% experienced a rebound phenomenon within twelve months. Mean ARR prenatalizumab was lower (P = 0.001, 95% CI -1.0-0.000) and treatment response to natalizumab poorer (P < 0.001, 95% CI 0.4-1.3) in patients with rebound compared to those without, but rebound was not associated with brief exposure to natalizumab (P = 0.159, 95% CI -9.3-1.5). 86.1% of patients switched to another therapy. Patients without rebound were found more often in the group starting an alternative treatment early (P = 0.013). CONCLUSION: Our data suggest that rebound of MS disease activity affects a subgroup of patients (11.9%), especially those with low disease activity before natalizumab therapy and a longer treatment gap after its withdrawal.

Natalizumab saturation: biomarker for individual treatment holiday after natalizumab withdrawal?

BACKGROUND: More and more patients with multiple sclerosis (MS) switch from natalizumab to fingolimod because of the risk of progressive multifocal leukoencephalopathy. The duration of the treatment holiday is still under debate referring to a possible recurrence of disease activity. AIM OF THE STUDY: The aim of this study was to evaluate the prognostic value of natalizumab saturation on T cells for the recurrence of clinical and radiological disease activity. METHODS: Cell surface-bound natalizumab saturation (in%) of CD8+ and CD4+ T cells from five patients with MS was determined before initiation of fingolimod by flow cytometry and related to clinical and MRI outcome during a 6-month follow-up. RESULTS: In two patients with either clinical or radiological disease activity, the natalizumab saturation on CD8+ and CD4+ T cells was <30%. In contrast, the remaining three patients with absence of disease activity had a median natalizumab saturation of 70% (range 59-79%) on CD4+ and 66% (range 52-68%) on CD8+ T cells. CONCLUSIONS: The data of this pilot study indicate that clinical and radiological disease activity is closely linked to natalizumab saturation at the time point of switch. The determination of natalizumab saturation may be an essential tool to monitor cessation of natalizumab treatment.

High-dose intravenous interferon-beta in multiple sclerosis patients with high-titer neutralizing antibodies (HINABS II) - A pilot study.

BACKGROUND: Neutralizing antibodies (NAb) against interferon-beta (IFNß) affect its treatment efficacy. So far, there are no anti-NAb strategies available. OBJECTIVES: To investigate if the repeated administration of high-dose IFNß-1b intravenous in NAb positive multiple sclerosis (MS) patients induces tolerance and establishes IFNß bioavailability as measured by the induction of myxovirus protein A (MxA). METHODS: Nine MS patients with NAb titers >500 10-fold reduction units (TRU) received 1500µg IFNß-1b intravenously once weekly over three months. Blood samples were collected at screening, monthly during the treatment period (before and four hours after IFNß administration), and at follow-up after 6 months for determination of NAbs and MxA expression. RESULTS: Median NAb titer at baseline was 1429TRU. NAb titers determined before each infusion did not significantly change over the treatment period and were not different at follow-up compared to baseline. However, NAb titers were significantly decreased four hours after IFNß infusions (by roughly 50%) and MxA mRNA levels were significantly elevated reaching a median value of 206. CONCLUSIONS: Weekly intravenous administration of IFNß in patients with high NAb titers established its bioavailability, but failed to induce tolerance towards IFNß.

Glatiramer acetate attenuates the pro-migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis.

An altered expression pattern of adhesion molecules (AM) on the surface of immune cells is a premise for their extravasation into the central nervous system (CNS) and the formation of acute brain lesions in multiple sclerosis (MS). We evaluated the impact of glatiramer acetate (GA) on cell-bound and soluble AM in the peripheral blood of patients with relapsing-remitting MS (RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule (ICAM)-1, ICAM-3, lymphocyte function-associated antigen (LFA)-1 and very late activation antigen (VLA)-4 were assessed in T cells (CD3(+) CD8(+) , CD3(+) CD4(+) ), B cells, natural killer (NK) cells, natural killer T cells (NK T) and monocytes by five-colour flow cytometry. Soluble E-selectin, ICAM-1, ICAM-3, platelet endothelial cell adhesion molecule (PECAM)-1, P-selectin and vascular cell adhesion molecule (VCAM)-1 were determined with a fluorescent bead-based immunoassay. The pro-migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up-regulation of LFA-1 (CD3(+) CD4(+) T cells, B cells), VLA-4 (CD3(+) CD8(+) T cells, NK cells), ICAM-1 (B cells) and ICAM-3 (NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA-1 (CD3(+) CD4(+) ) and VLA-4 (CD3(+) CD4(+) , CD3(+) CD8(+) , NK, NK T, monocytes). Further effects included lowering of ICAM-1 and ICAM-3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro-migratory expression profile of cell-bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects.

Circadian rhythmicity of inflammatory serum parameters: a neglected issue in the search of biomarkers in multiple sclerosis.

Inflammatory serum parameters are intensely investigated in the search of biomarkers for disease activity and treatment response in multiple sclerosis (MS). A reason for contradictory results might be the timing of blood collection for analyzing serum concentrations of inflammatory parameters which are subject to diurnal changes. We included 34 untreated patients with relapsing-remitting MS and 34 age- and sex-matched healthy controls. 12 MS patients showed acute disease activity in corresponding MRI scans. Blood samples were obtained at 7.00, 11.00 am, 2.30, 6.00 and 9.30 pm within 1 day. We determined serum levels of cortisol and inflammatory markers including soluble tumor necrosis factor-beta (sTNF-ß), soluble TNF-Receptor-1 (sTNF-R1) and -2 (sTNF-2), soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) by ELISA. We observed significantly higher serum levels of sTNF-R1 (p < 0.001) and sTNF-R2 (p < 0.001) in the morning and a significant decline of sICAM-1 (p < 0.005) and sVCAM-1 (p < 0.001) in the afternoon in both, MS patients and healthy controls. Comparison of diurnal serum levels between MS patients with active versus with non-active disease revealed significantly higher serum levels of sVCAM-1 (p < 0.05) around noon and in the early afternoon in MS patients with active disease. A significant decline of sICAM-1 (p < 0.05) in the afternoon was seen in MS patients with active and non-active disease. Our data indicate that increased awareness of potential diurnal serum concentration changes of biomarkers can eliminate one major cause of biased data as they occur in most of the investigated immunological parameters.