Sophie Frantal

Prospective analysis of factors related to migraine aura--the PAMINA study.

Objectives.— The aim of this study was to examine factors increasing and decreasing the risk of occurrence of migraine aura and of headache and migraine not associated with aura (HoA, MoA) prospectively by means of a daily diary.

Impact of dental implant length on early failure rates: a meta-analysis of observational studies

AIM To test the null hypothesis of no difference in failure rates of short (minimum length: 7 mm) and longer dental implants (≥ 10 mm), a meta-analysis was performed on prospective observational trials. MATERIALS AND METHODS A systematic electronic and hand search was performed to identify eligible studies. Having additional data supplied by the authors, 54 publications were included (19,083 implants). RESULTS In case of mandibular implants, the null hypothesis of no impact of reduced implant length on failure within the first year of prosthetic loading could not be rejected. A significant impact of implant length could be substantiated for short machined implants in the anterior [odds ratio (OR) 5.4] and posterior maxilla (OR 3.4), while short rough-surfaced implants demonstrated increased failure rates in the anterior maxillary sites. No influence of implant diameter and denture type on the failure rate of short implants could be revealed. CONCLUSION In areas of reduced alveolar bone height the use of short dental implants may reduce the need for invasive bone augmentation procedures.

Significant differences in B-cell subpopulations characterize patients with chronic graft-versus-host disease-associated dysgammaglobulinemia

Manifestations of chronic graft-versus-host disease (cGVHD) can resemble those seen in immunodeficiency states and autoimmune disorders. Reports by us and others suggest an involvement of B cells in the pathogenesis of cGVHD. We investigated B-lymphocyte subpopulations in cGVHD cohorts defined by serum immunoglobulin G (IgG) levels to characterize novel biomarkers for impairment of humoral immunity after allogeneic hematopoietic stem cell transplantation. Seventy-six patients were enrolled a median of 46 months after hematopoietic stem cell transplantation. The hypogammaglobulinemia group had significantly diminished CD19(+) B cells (165 vs 454 vs 417 × 10⁶L) with elevated CD19(+)CD21(low) immature (16.5%, 7.7%, and 9.1%) and CD19(+)CD21(int-high)CD38(high)IgM(high) transitional (10.5% vs 4.2% vs 6.3%) B-cell proportions compared with the normogammaglobulinemia and hypergammaglobulinemia groups. CD19(+)CD10(-)CD27(-)CD21(high) naive B cells were highly elevated in all patients with cGVHD. CD19(+)CD27(+)IgD(+) non-class-switched (4 vs 12 vs 11 × 10⁶/L) and class-switched (7 vs 35 vs 42 × 10⁶/L) memory B cells were significantly lower in the hypogammaglobulinemia group compared with the others. Besides significantly higher B-cell activation factor/B-cell ratios, significantly more cGVHD patients with hypergammaglobulinemia had autoantibodies compared with the hypogammaglobulinemia subgroup (68% vs 24%, P = .024). In conclusion, B-cell subpopulations can serve as novel cellular biomarkers for immunodeficiency and autoimmunity indicating different pathogenetic mechanisms of cGVHD and encouraging future prospective longitudinal studies.

Choroidal blood flow and progression of age-related macular degeneration in the fellow eye in patients with unilateral choroidal neovascularization.

PURPOSE Cardiovascular risk factors such as smoking, hypertension, and atherosclerosis seem to play an important role in the development of choroidal neovascularization (CNV). Recent studies have also provided evidence suggesting that choroidal and retinal blood flow is decreased in patients with AMD. On the basis of these results, the hypothesis for this study was that lower choroidal blood flow is associated with an increased risk of CNV in patients with AMD. METHODS Forty-one patients with unilateral choroidal neovascular AMD were included in this observational longitudinal study. The fellow eyes of the patients served as study eyes. Subfoveal choroidal blood flow (FLOW) and fundus pulsation amplitude (FPA) were assessed with laser Doppler flowmetry and laser interferometry, respectively. A multivariate COX-regression model was used to test the hypothesis that low choroidal perfusion parameters are associated with the development of CNV. RESULTS Of the 37 patients that were followed up until the end of the study, 17 developed CNV and 20 did not. The univariate COX-regression analysis shows that lower FLOW, systolic blood pressure, intraocular pressure, and FPA are risk factors for development of CNV. Moreover, the more advanced the AMD in the study eye, the higher the risk for CNV to develop in the fellow eye. Multivariate COX regression analysis indicated that only FLOW (P = 0.0071), FPA (P = 0.0068), and staging (P = 0.031) had statistically significant influences on the progression to CNV. CONCLUSIONS The present study indicates that lower choroidal perfusion is a risk factor for the development of CNV in the fellow eye of patients with unilateral CNV.

Migraine and weather: A prospective diary-based analysis

Aims: Weather is mentioned as a trigger factor by migraine patients most frequently. We examined the impact of meteorological factors and the impact of their day-to-day change on the risk of occurrence and persistence of headache and migraine and the correlation of subjective weather perception with objective weather data. Methods: We performed a prospective, diary-based cohort study in 238 patients suffering from migraine with or without aura. Patients had to live within 25 km of the Vienna meteorological station and were required to keep a diary for 90 days. We analysed 11 meteorological parameters and 17 synoptic weather situations. For evaluating the hazard of occurrence and persistence of migraine and headache, we performed a univariate and a stepwise multivariate Cox regression analysis. We calculated correlations between subjective weather perception and meteorological data. Results: In the uni- and multivariate analysis, a ridge of high pressure increased the risk of headache occurrence, lower mean daily wind speed increased the risk of migraine occurrence and a day-to-day change of daily sunshine duration increased the risk of migraine occurrence. A day-to-day change of the daily minimum temperature decreased the risk of migraine persistence. After correction for multiple testing, none of these findings remained statistically significant. Subjective weather perceptions did not correlate with the occurrence or persistence of migraine or headache. Subjective perception of cold and too-cold weather and of too-warm weather correlated with daily minimum, mean and maximum temperature. Conclusion: The influence of weather factors on migraine and headache is small and questionable.

Leukocytosis as an important risk factor for arterial thrombosis in WHO‐defined early/prefibrotic myelofibrosis: An international study of 264 patients

We aimed to determine risk factors for thrombotic events in early/prefibrotic myelofibrosis diagnosed according to the World Health Organization criteria. Multivariate Cox regression analysis was calculated on a total number of 264 patients derived from an international database. After a median follow‐up of 6.28 years, 42 (15.9%) patients experienced arterial (n = 31) or venous thrombosis (n = 11). A higher leukocyte count correlated with an increased risk for total thrombosis and in particular, with an increased risk for arterial thrombosis (P = 0.005, HR 1.15 and P = 0.047, HR 1.12, respectively). A platelet count above 870 × 109/L was associated with a lower risk for total thrombosis and also for venous thrombosis (P = 0.022, HR 0.44 and P = 0.027, HR 0.19). Moreover, a lower hemoglobin level was associated with an increased risk for venous thrombosis (P = 0.007, HR 0.59). Our data indicate that leukocytosis is a prominent risk factor for thrombosis in early/prefibrotic MF. Am. J. Hematol. 87:669–672, 2012.

A critical cross-validation of high throughput structural binding prediction methods for pMHC

T-cells recognize antigens via their T-cell receptors. The major histocompatibility complex (MHC) binds antigens in a specific way, transports them to the surface and presents the peptides to the TCR. Many in silico approaches have been developed to predict the binding characteristics of potential T-cell epitopes (peptides), with most of them being based solely on the amino acid sequence. We present a structural approach which provides insights into the spatial binding geometry. We combine different tools for side chain substitution (threading), energy minimization, as well as scoring methods for protein/peptide interfaces. The focus of this study is on high data throughput in combination with accurate results. These methods are not meant to predict the accurate binding free energy but to give a certain direction for the classification of peptides into peptides that are potential binders and peptides that definitely do not bind to a given MHC structure. In total we performed approximately 83,000 binding affinity prediction runs to evaluate interactions between peptides and MHCs, using different combinations of tools. Depending on the tools used, the prediction quality ranged from almost random to around 75% of accuracy for correctly predicting a peptide to be either a binder or a non-binder. The prediction quality strongly depends on all three evaluation steps, namely, the threading of the peptide, energy minimization and scoring.

Total hip arthroplasty using imageless computer-assisted hip navigation: a prospective randomized study.

In a prospective randomized study of two groups of 65 patients each, we compared the acetabular component position when using the imageless navigation system compared to the freehand conventional technique for cementless total hip arthroplasty. The position of the component was determined postoperatively on computed tomographic scans of the pelvis. There was no significant difference for postoperative mean inclination (P = 0.29), but a significant difference for mean postoperative acetabular component anteversion (P = 0.007), for mean deviation of the postoperative anteversion from the target position of 15° (P = 0.02) and for the outliers regarding inclination (P = 0.02) and anteversion (P < 0.05) between the computer-assisted and the freehand-placement group. Our results demonstrate the importance of imageless navigation for the accurate positioning of the acetabular component.

Role of vascular endothelial growth factor polymorphisms in the treatment success in patients with wet age-related macular degeneration.

PURPOSE Along with environmental risk factors such as smoking, hypertension, and atherosclerosis, genetic susceptibility is a primary contributor to the development and progression of exudative age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a central angiogenic regulator and there has been general agreement now that it is an important trigger for the progression of exudative AMD. In the present study, we tested the hypothesis that VEGF gene polymorphisms play a role in the treatment success with VEGF inhibitors in patients with exudative AMD. DESIGN Prospective cohort study. PARTICIPANTS We included 185 eyes of 141 patients with exudative AMD who were scheduled for their first treatment with intravitreally administered bevacizumab in this trial. METHODS All patients were aged >50 years and had angiographically verified exudative AMD. Blood from the finger pad was collected on blood cards for genotyping for the VEGF polymorphisms rs1413711, rs3025039, rs2010963, rs833061, rs699947, rs3024997, and rs1005230. At each follow-up visit, visual acuity was reassessed and an ophthalmic examination was carried out. Visual acuity outcome, number of retreatments, and overall time of treatment were analyzed in dependence of the VEGF polymorphisms. MAIN OUTCOME MEASURES Mean change in visual acuity at the end of the treatment period. RESULTS The included patients were reinjected with bevacizumab 1 to 15 times, resulting in a total treatment period of 42 to 1182 days. In univariate analysis only the G/G genotypes of rs3024997 and rs2010963 compared with all other 5 single nucleotide polymorphisms (SNPs) showed a significantly lower visual acuity at the end of treatment. In multivariate analysis including parameters such as time, baseline visual acuity, and number of reinjections, none of the SNPs showed a significant correlation. CONCLUSIONS The current study indicates that VEGF polymorphisms are not major predictors of anti-VEGF treatment success in patients with exudative AMD.

Measuring the activity of apixaban and rivaroxaban with rotational thrombelastometry.

BACKGROUND Routine drug monitoring is not required for the two novel direct factor Xa inhibitors apixaban and rivaroxaban. Rapidly available test results might be beneficial in case of bleeding or prior to urgent surgery. OBJECTIVES The aim of this study was to evaluate the applicability of the two rotational thrombelastometry (ROTEM®) -modifications Low-tissue factor activated ROTEM® (LowTF-ROTEM®) and Prothrombinase induced clotting time - activated ROTEM® (PiCT®-ROTEM®) for determination of apixaban and rivaroxaban in vitro and ex vivo. METHODS Blood samples from 20 volunteers were spiked with apixaban / rivaroxaban to yield samples with ascending drug concentrations ranging from 50 - 400ng/mL. LowTF - and PiCT® modified ROTEM® tests and determination of the corresponding antifactor Xa activity were performed in duplicate in 280 samples. LowTF-ROTEM® tests were performed in samples from 20 patients on apixaban or rivaroxaban therapy and 20 controls. RESULTS There was a strong correlation between apixaban / rivaroxaban plasma concentrations and the LowTF-ROTEM® parameters Clotting time (CT; spearman correlation coefficient (SCC) 0.81 and 0.81, respectively) and Time to maximum velocity (t,MaxVel; SCC: 0.81 and 0.80, resp.) and a low to moderate correlation for the PiCT®-ROTEM® parameters CT (SCC: 0.38 and 0.59, resp.) and t,MaxVel. (0.51 and 0.69, resp.) in the in vitro experiments. LowTF-ROTEM CT was significantly prolonged in patients on apxiaban or rivaroxaban therapy compared to controls. CONCLUSIONS LowTF-ROTEM® could be a valuable diagnostic tool for rapid determination of the effect of apixaban and rivaroxaban at the point of care.