Jutta Gamper

Qualitative α-defensin test (Synovasure) for the diagnosis of periprosthetic infection in revision total joint arthroplasty

Aims The diagnosis of periprosthetic joint infection (PJI) remains demanding due to limitations of all the available diagnostic tests. The synovial fluid marker, &agr;‐defensin, is a promising adjunct for the assessment of potential PJI. The purpose of this study was to investigate the qualitative assessment of &agr;‐defensin, using Synovasure to detect or exclude periprosthetic infection in total joint arthroplasty. Patients and Methods We studied 50 patients (28 women, 22 men, mean age 65 years; 20 to 89) with a clinical indication for revision arthroplasty who met the inclusion criteria of this prospective diagnostic study. The presence of &agr;‐defensin was determined using the qualitative Synovasure test and compared with standard diagnostic methods for PJI. Based on modified Musculoskeletal Infection Society (MSIS) criteria, 13 cases were categorised as septic and 36 as aseptic revisions. One test was inconclusive. Results The Synovasure test achieved a sensitivity of 69% and a specificity of 94%. The positive and negative likelihood ratios were 12.46 and 0.33, respectively. A good diagnostic accuracy for PJI, with an area under the curve of 0.82, was demonstrated. Adjusted p‐values using the method of Hochberg showed that Synovasure is as good at diagnosing PJI as histology (p = 0.0042) and bacteriology with one positive culture (p = 0.0327). Conclusion With its ease of use and rapid results after approximately ten minutes, Synovasure may be a useful adjunct in the diagnosis of PJI.

CD23 surface density on B cells is associated with IgE levels and determines IgE-facilitated allergen uptake, as well as activation of allergen-specific T cells

Background: Increasing evidence suggests that the low‐affinity receptor for IgE, CD23, plays an important role in controlling the activity of allergen‐specific T cells through IgE‐facilitated allergen presentation. Objective: We sought to determine the number of CD23 molecules on immune cells in allergic patients and to investigate whether the number of CD23 molecules on antigen‐presenting cells is associated with IgE levels and influences allergen uptake and allergen‐specific T‐cell activation. Methods: Numbers of CD23 molecules on immune cells of allergic patients were quantified by using flow cytometry with QuantiBRITE beads and compared with total and allergen‐specific IgE levels, as well as with allergen‐induced immediate skin reactivity. Allergen uptake and allergen‐specific T‐cell activation in relation to CD23 surface density were determined by using flow cytometry in combination with confocal microscopy and T cells transfected with the T‐cell receptor specific for the birch pollen allergen Bet v 1, respectively. Defined IgE‐allergen immune complexes were formed with human monoclonal allergen‐specific IgE and Bet v 1. Results: In allergic patients the vast majority of CD23 molecules were expressed on naive IgD+ B cells. The density of CD23 molecules on B cells but not the number of CD23+ cells correlated with total IgE levels (RS = 0.53, P = .03) and allergen‐induced skin reactions (RS = 0.63, P = .008). Uptake of allergen‐IgE complexes into B cells and activation of allergen‐specific T cells depended on IgE binding to CD23 and were associated with CD23 surface density. Addition of monoclonal IgE to cultured PBMCs significantly (P = .04) increased CD23 expression on B cells. Conclusion: CD23 surface density on B cells of allergic patients is correlated with allergen‐specific IgE levels and determines allergen uptake and subsequent activation of T cells.

Relation of Nailfold Capillaries and Autoantibodies to Mortality in Patients With Raynaud Phenomenon.

Background— In incipient Raynaud phenomenon, nailfold capillaroscopy and autoantibody tests are obtained to screen for an emerging connective tissue disease. Whether the presence of abnormal nailfold capillaries and autoantibodies are related to mortality in patients with incipient Raynaud phenomenon is not known. Methods and Results— In 2958 consecutive patients (78% women, median age 45 years) with incipient Raynaud phenomenon without previously known connective tissue disease, nailfold capillaroscopy and laboratory tests for antinuclear antibodies (ANA) and ANA subsets were obtained at initial presentation. During a median follow-up period of 9.3 years, 227 women (9.9% of female patients) and 129 men (20% of male patients) with Raynaud phenomenon died. In comparison with a demographically matched standard population, survival was poorer in patients with Raynaud phenomenon (log-rank test P<0.0001). In patients with Raynaud phenomenon, mortality was higher in men than in women (P<0.0001, Cox proportional hazards model). In women, the presence of abnormal nailfold capillaries, ANA, and anti–Scl-70 antibodies were related to an increase in all-cause mortality. The conjoint presence of abnormal nailfold capillaries and autoantibodies was associated with the highest mortality rates. In men, abnormal nailfold capillaries, and ANA and ANA subsets, as well, were not related to survival. In both sexes, patients’ age and serum creatinine were associated with mortality. Conclusions— In Raynaud phenomenon, male sex, age, and serum creatinine are related to mortality. Abnormal nailfold capillaries and autoantibodies are associated with an increase in all-cause mortality in female patients, but not in male patients with Raynaud phenomenon.

Intranasal administration of allergen increases specific IgE whereas intranasal Omalizumab does not increase serum IgE levels – a pilot study

Administration of the therapeutic anti‐IgE antibody omalizumab to patients induces strong increases in IgE antibody levels.

The Distribution of Leakage on Fluorescein Angiography in Diabetic Macular Edema: A New Approach to Its Etiology

Purpose To determine the distribution of leakage on fluorescein angiography (FA) and explore the clinically protective role of astrocytes against damage to the inner blood retinal barrier (iBRB) in diabetic macular edema (DME). Methods A consecutive case series of 87 eyes of 87 patients with DME was included. We measured the leakage area in each field of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid on late-phase FA images. The normative thickness of the nerve fiber layer (NFL), in which the astrocytes are confined, was derived from a previous work using spectral-domain optical coherence tomography. We explored the difference in leakage areas in every two fields. Moreover, we investigated the correlation between the mean of the leakage area and the mean of thickness of the NFL in each ETDRS field. Results The leakage areas in the nasal, inferior, superior, and temporal fields were 2.34 mm2, 2.84 mm2, 3.03 mm2, and 3.96 mm2. The difference in leakage area between each two fields was significant in all cases (P < 0.05) except between the inferior and superior fields (P = 0.65). The temporal field was the only field that showed leakage in all 87 cases. The correlation between the leakage area and the thickness of the NFL in the ETDRS fields was negative and highly significant: r = -0.96 (95% confidence interval -0.99 to -0.02). Conclusion The distribution of leakage correlates inversely and statistically significantly with the thickness of the NFL, suggesting astrocytes in the NFL play a pivotal role in preventing damage to the iBRB and subsequent evolution of microaneurysms in DME. Moreover, fluid extravasation due to damage to the iBRB is expressed earlier in the temporal than in the other three fields.

Microvascular function in women with former gestational diabetes: A cohort study

Objective: In the long term, diabetes mellitus is potentially associated with the occurrence of microvascular damage. This study sought to assess whether a history of prior gestational diabetes mellitus is associated with long-term effects on the women’s microcirculation. Methods: Within the scope of a long-term follow-up of the ‘Viennese Post-Gestational Diabetes Project’, women with prior gestational diabetes mellitus as well as women with previous pregnancy but with no history of gestational diabetes mellitus (controls) were enrolled in this cross-sectional study. Microvascular function was assessed by post-occlusive reactive hyperaemia using laser Doppler fluxmetry. Baseline perfusion, biological zero, peak perfusion, time to peak and recovery time were recorded and compared between both groups. Results: Microvascular function was assessed in 55 women with prior gestational diabetes mellitus (46.1 ± 4.6 years) and 32 women with previous pregnancy but without prior gestational diabetes mellitus (42.9 ± 5.3 years). The mean period of time between delivery and the assessment of microvascular function was 16.2 ± 5.2 years in women with prior gestational diabetes mellitus group and 14.2 ± 4.8 years in controls. Regarding microvascular function, baseline perfusion, biological zero, peak perfusion, time to peak and recovery time did not differ between women with prior gestational diabetes mellitus and controls (all p > 0.05). Conclusion: In the long term, microvascular function appears not to be impaired in women with prior gestational diabetes mellitus.

Efficacy of different revision procedures for infected megaprostheses in musculoskeletal tumour surgery of the lower limb

Purpose The incidence of recurrent infections in patients following one or two stage revision for infected megaprostheses after resection of bone tumours was investigated. The difference between retaining at least one well fixed stem and a complete removal of the megaprosthesis during a two stage revision was also analysed. Methods 627 patients who experienced a replacement of a musculoskeletal tumour by megaprostheses were recorded. An infection occurred in 83 of 621 patients available for follow-up. 61 patients underwent one stage revision, and 16 patients two stage revision for the first revision surgery. In the entire study period, two stage revision was performed 32 times (first, second, and third revision). Results The cumulative incidence analysis showed a reinfection probability after one stage revision of 18% at one year, 30% at two years, 39% at five years, 46% at ten years, and 56% at 15 years. After two stage revision, a reinfection probability of 28% at two years, and 48% at five years was calculated. Cumulative incidence curves did not differ significantly (Gray’s test; p = 0.51) between one and two stage revision (with and without complete removal of the stems). In two stage revision (n = 32), a statistically significant difference in infection rates between patients treated with complete removal of the megaprosthesis (n = 18) including anchorage stems and patients with at least one retained stem (n = 14) was shown (Fisher’s exact test, p = 0.029). Conclusion Two stage revisions with complete removal of the megaprosthesis showed the best results among limb salvage procedures for the treatment of infected megaprosthesis.

Automated tube voltage selection in pediatric non-contrast chest CT

Background Modern CT scanners provide automatic dose adjustment systems, which are promising options for reducing radiation dose in pediatric CT scans. Their impact on patient dose, however, has not been investigated sufficiently thus far. Objective To evaluate automated tube voltage selection (ATVS) in combination with automated tube current modulation (ATCM) in non-contrast pediatric chest CT, with regard to the diagnostic image quality. Materials and methods There were 160 non-contrast pediatric chest CT scans (8.7±5.4 years) analyzed retrospectively without and with ATVS. Correlations of volume CT Dose Index (CTDIvol) and effective diameter, with and without ATVS, were compared using Fisher’s z-transformation. Image quality was assessed by mean signal-difference-to-noise ratios (SDNR) in the aorta and in the left main bronchus using the independent samples t-test. Two pediatric radiologists and a general radiologist rated overall subjective Image quality. Readers’ agreement was assessed using weighted kappa coefficients. A p value <0.05 was considered significant. Results CTDIvol correlation with the effective diameter was r = 0.62 without and r = 0.80 with ATVS (CI: -0.04 to -0.60; p = 0.025). Mean SDNR was 10.88 without and 10.03 with ATVS (p = 0.0089). Readers’ agreement improved with ATVS (weighted kappa between pediatric radiologists from 0.1 (0.03–0.16) to 0.27 (0.09–0.45) with ATVS; between general and each pediatric radiologist from 0.1 (0.06–0.14) to 0.12 (0.05–0.20), and from 0.22 (0.11–0.34) to 0.36 (0.24–0.49)). Conclusion ATVS, combined with ATCM, results in a radiation dose reduction for pediatric non-contrast chest CT without a loss of diagnostic image quality and prevents errors in manual tube voltage setting, and thus protecting larger children against an unnecessarily high radiation exposure.

Concordance of three alternative gestational age assessments for pregnant women from four African countries: A secondary analysis of the MIPPAD trial

Background At times, ultrasound is not readily available in low resource countries in Africa for accurate determination of gestational age, so using alternative methods is pivotal during pregnancy. These assessments are used to aid the risk analysis for an infant and management strategies for premature delivery, if necessary. Currently, date of last menstrual period, fundal height measurements, and the New Ballard Score are commonly used in resource-limited settings. However, concordance of these measures is unknown for sub-Saharan Africa. We obtained data from an open-label randomized controlled trial, to assess the concordance of these alternative assessment methods. The purpose of our study was to determine the agreement between these alternative methods when used in sub-Saharan African populations. Methods A total of 4,390 pregnant women from Benin, Gabon, Mozambique and Tanzania were included in our analysis. The assessment methods compared were: 1) reported last menstrual period, 2) symphysis-fundal height measurement, and 3) the New Ballard Score. The Bland-Altman method and intraclass correlation coefficient (ICC) were used to test the degree of agreement. Survival range gestational age, used as an inclusion criterion for further analysis, was from 22 to 44 weeks. Findings Plots showed a lack of agreement between methods and the 95% limits of agreement too wide to be clinically useful. ICC = 0.25 indicated poor agreement. A post-hoc analysis, restricted from 32 to 42 weeks, was done to check for better agreement in this near-term population. The plots and ICC = 0.16 still confirmed poor agreement. Conclusion The alternative assessments do not result in comparable outcomes and discrepancies are far beyond the clinically acceptable range. Last menstrual period should not be used as the only estimator of gestational age. In the absence of reliable early ultrasound, symphysis-fundal height measurements may be most useful during pregnancy for fetal risk assessment and the New Ballard Score after delivery as a confirmation of these estimations and for further neonatal management. However, promotion of portable ultrasound devices is required for accurate assessment of gestational age in sub-Sahara Africa.

Chronic inflammation predicts long-term mortality in patients with Raynaud′s phenomenon

Subclinical chronic inflammation could be the driving force behind the recently revealed association between abnormal nailfold capillaries as well as autoantibodies and long‐term mortality in patients with incipient Raynauds phenomenon. Whether laboratory markers that reflect a chronic inflammatory process are directly related to mortality in Raynauds phenomenon is not known.