SARS-CoV-2 associated Guillain-Barré syndrome.

Presented herein is a severe case of SARS-CoV-2 associated Guillain-Barré syndrome (GBS), showing only slight improvement despite adequate therapy. To date, only few cases of GBS associated with this infection have been described. This case report summarizes the insights gain so far to GBS with this antecedent trigger. So far, attention has mostly focused on complications of the CNS involvement. Taking into account that GBS can cause a considerable impairment of the respiratory system, clinicians dealing with SARS-CoV-2 positive-tested patients should pay attention to symptoms of the peripheral nervous system. As far as we know from this reported case and the review of the current literature, there seems to be no association with antiganglioside antibodies or a positive SARS-CoV-2 RT-PCR in CSF. An obvious frequent occurrence of a bilateral facial weakness or bilateral peripheral facial diplegia should be emphasized.

Comparison of the ecarin chromogenic assay and different aPTT assays for the measurement of argatroban concentrations in plasma from healthy individuals and from coagulation factor deficient patients.

INTRODUCTION: The aim of this study was to assess the usefulness of different aPTT assays and the ecarin chromogenic assay reaction time (ECA) for measurement of argatroban concentration in plasma from healthy persons as well as in different patient subgroups. METHODS: We spiked plasma samples from healthy individuals, patients under oral anticoagulation (OAT) or with liver dysfunction (LD) with increasing argatroban concentrations (0-2000 ng/ml) and performed 4 different aPTTs assays and the ECA. RESULTS: Depending on argatroban concentrations aPTTs increased in a curvilinear fashion; in plasma from healthy individuals means of calculated argatroban concentration at 2-fold aPTT differed extensively depending on the aPTT reagent used (725 ng/ml to 1136 ng/ml) and were even more pronounced in plasma from coagulation factor deficient patients (460 ng/ml in patients with LD vs. 1172 ng/ml in patients with OAT), whereas ECA showed linear argatroban influence and reliable results in all subgroups. CONCLUSIONS: Because of wide differences in aPTT measurements depending on the aPTT reagent used, interindividual variations and different clinical conditions the aPTT is not the method of choice for monitoring argatroban and the ECA should be preferred.

Influence of direct thrombin inhibitor argatroban on coagulation assays in healthy individuals, patients under oral anticoagulation therapy and patients with liver dysfunction.

We assumed that argatroban, a direct thrombin inhibitor, has a strong influence on different coagulation tests which is even more pronounced in patients with an established reduced factor activity like those under oral anticoagulation therapy or with liver dysfunction. To validate this influence we spiked plasma samples from healthy individuals, patients under oral anticoagulation therapy or with liver dysfunction with increasing argatroban concentrations (0-2000 ng/ml) and performed routine laboratory coagulation tests. Consequently, prothrombin time, activated partial thromboplastin time, thrombin time, batroxobin time, coagulation factor activity (FII-FXIII), protein S (activity), protein C (chromogen) and fibrinogen (derived and Clauss fibrinogen method) were measured. Furthermore, the influence of argatroban on the induced platelet aggregation was evaluated. Argatroban interference on standard coagulation assays differed markedly depending on the different subgroups of patients investigated. Prolongation of prothrombin time by argatroban (at 2000 ng/ml 2.7-fold in healthy persons) was significantly higher in oral anticoagulation therapy (3.9-fold) and even more pronounced in liver dysfunction (6.0-fold). The fibrinogen concentration was determined falsely even at low-argatroban concentrations using functional methods in healthy persons and all patient subgroups. The influence of argatroban on standard laboratory coagulation tests is significantly increased by a preexisting factor deficiency. Functional fibrinogen measurement may be helpful to assess in-vivo fibrinogen function but should be avoided to evaluate fibrinogen concentration in argatroban treated patients. Argatroban had no influence on chromogenic protein C measurement, batroxobin time and induced platelet aggregation. Knowledge of argatroban interference is a prerequisite for the reliable interpretation of coagulation assays.

Test-retest reliability of the physical performance test for persons with Parkinson disease.

BACKGROUND AND PURPOSE: Reliable measures are needed to document functional status and disease progression for people with Parkinson disease (PD). We, therefore, evaluated the reliability of the Physical Performance Test (PPT) for people with PD. METHODS: Fourteen community-dwelling subjects with PD participated: 8 males, 6 females; modified Hoehn and Yahr Stages 2 and 2.5; mean age 62.4 years (+6.3). The test was administered twice, 1 week apart. The 7-item and 9-item summary scores of the PPT were each compared between sessions using repeated measures analysis of variance (ANOVA). The intraclass correlation coefficient (ICC) and method error (ME) were calculated to further assess reliability. RESULTS: Between sessions, 7- and 9-item summed scores were not statistically different. The range of summed scores fell in the midst of the available score range for both the 7- and 9-item tests suggesting resistance to floor and ceiling effects. The ICCs showed good agreement (7-item = 0.818; 9-item = 0.895) indicating test reliability for this population. Based on the ME, an examiner can expect a 6% variation for the 7-item summary score and a 4% variation for the 9-item score summary between testing sessions. CONCLUSIONS: The 7- and 9-item PPTs were demonstrated to be reliable objective measures in individuals with PD. Simple props and brief administration time (10-15 minutes) make the test practical to use.

Evaluation of two different albumin depletion strategies for improved analysis of human CSF by SELDI-TOF-MS.

OBJECTIVES: Two different depletion strategies for removing albumin from human cerebrospinal fluid (CSF), Microcon Centrifugal Filter vs. Montage Albumin Deplete kit, were evaluated for improving protein profiling pattern and reproducibility in SELDI analysis. DESIGN AND METHODS: Pooled CSF was divided into 20 aliquots and these aliquots were subjected to SELDI analysis either after albumin depletion or without preprocessing. Protein profiles were obtained by using CM10, Q10 and IMAC chips. RESULTS: Both strategies resulted in reliable albumin depletion (<6.2 mg/L, filter; 8.1 mg/L, depletion kit). Investigated methods of albumin depletion showed no significant differences in coefficients of variation (CVs) of peak intensities compared to unprocessed CSF on almost all chip types. Peak intensities were significantly higher after albumin depletion compared to CSF without preprocessing on Q10 and on CM10 chips. Nevertheless, the two strategies of albumin depletion led to a decrease in the number of detected peaks on all chip types compared to unprocessed CSF, but several additional peaks, not detected in unprocessed CSF, occurred. CONCLUSIONS: This study demonstrates that reduction of sample complexity by albumin depletion of CSF can be performed without CV impairment. However, the significance of this strategy needs to be evaluated separately for each individual biomarker discovery study.

Comparison of six D-dimer assays for the detection of clinically suspected deep venous thrombosis of the lower extremities.

Deep venous thrombosis is a common disease that may lead to life-threatening embolism of the lung as a common complication. Therefore, early diagnosis followed by sufficient treatment is necessary to decrease mortality of this disease. D-dimer testing is established as a standard to rule out deep venous thrombosis in selected patient groups. However, there is no standardization among D-dimer assays, and a periodical comparison of assay performance in a select patient group is indispensable. We evaluated six commonly used D-dimer assays for their assay performance in an outpatient cohort with clinically suspected deep venous thrombosis. Although area under the curve for these assays did not differ significantly (0.83-0.88), differences in sensitivity (90-100%) and specificity (10-40%) of the assays were detected. Alternative cut-offs were established, and these cut-offs could enhance assay performance in some cases. This points to the fact that the manufacturers should more regularly review studies on the performance of their respective assays to widen the data basis for their recommended cut-offs and increase assay performance.

Correction of ventricular cerebrospinal fluid (CSF) samples for blood content does not increase sensitivity and specificity for the detection of CSF infection.

BACKGROUND: Blood contamination is commonly observed in ventricular cerebrospinal fluid (CSF) samples from patients with extraventricular drainage systems. Because the introduction of blood may interfere with the white blood cell count as a useful marker for the diagnosis of an infection, correction for blood content would be desirable. METHODS: In a retrospective study, we analysed the use of correction formulas in 724 blood-contaminated ventricular CSF samples. RESULTS: Using a standard correction method the white blood cell count was not normalised in most CSF samples, with pleocytosis indicating an inflammatory stimulus set by the blood itself or by the foreign body. When correcting white blood cell counts in the CSF of culture-positive patients, some samples were normalised or overcorrected. In addition, correction of the CSF white blood cell count did not increase sensitivity and specificity for the detection of culture-positive CSF samples. CONCLUSIONS: Correction is not necessary when using the white blood cell count as a parameter to predict CSF infection in ventricular CSF samples.

Use of SELDI-TOF mass spectrometry for identification of new biomarkers: potential and limitations.

Surface-enhanced laser desorption time of flight mass spectrometry (SELDI-TOF-MS) is an important proteomic technology that is immediately available for the high throughput analysis of complex protein samples. Over the last few years, several studies have demonstrated that comparative protein profiling using SELDI-TOF-MS breaks new ground in diagnostic protein analysis particularly with regard to the identification of novel biomarkers. Importantly, researchers have acquired a better understanding also of the limitations of this technology and various pitfalls in biomarker discovery. Bearing these in mind, great emphasis must be placed on the development of rigorous standards and quality control procedures for the pre-analytical as well as the analytical phase and subsequent bioinformatics applied to analysis of the data. To avoid the risk of false-significant results studies must be designed carefully and control groups accurately selected. In addition, appropriate tools, already established for analysis of highly complex microarray data, need to be applied to protein profiling data. To validate the significance of any candidate biomarker derived from pilot studies in appropriately designed prospective multi-center studies is mandatory; reproducibility of the clinical results must be shown over time and in different diagnostic settings. SELDI-TOF-MS-based studies that are in compliance with these requirements are now required; only a few have been published so far. In the meantime, further evaluation and optimization of both technique and marker validation strategies are called for before MS-based proteomic algorithms can be translated into routine laboratory testing.