[Disease-related knowledge acquisition through structured patient information in rheumatoid arthritis (StruPI-RA) : First results of the StruPI-RA study in Germany]. / Krankheitsbezogener Wissenserwerb durch strukturierte Patienteninformation bei Rheumatoider Arthritis (StruPI-RA) : Erste Ergebnisse der StruPI-RA-Studie in Deutschland.

BACKGROUND/OBJECTIVE: The structured patient information for rheumatoid arthritis (StruPi-RA) program was the first standardized outpatient education program in rheumatoid arthritis (RA) in Germany. The main objective of the study was to determine the efficacy of the StruPi-RA program concerning disease-specific knowledge acquisition in patients with early stage RA or after changing the treatment regimen. METHODS: A total of 61 patients were included in a control group design, 32 in the intervention group (IG) and 29 in the control group (CG). Patients of the IG attended 3 modules of 90 min in a structured patient information program (StruPI-RA) including the topics of diagnostics, treatment and living with RA. Patients in the CG only received information material from the German Rheumatism League. The primary target criterion was the disease-related acquisition of knowledge, measured with the patient knowledge questionnaire (PKQ). Data were collected before and after participation in StruPI-RA. RESULTS: The improvement in knowledge in the IG attending the StruPI-RA compared to the CG was significant in time and group comparisons. No influence of disease duration or educational level was observed. The subscale treatment alone showed a significant difference in the group and time comparison. CONCLUSION: Participation in the StruPI-RA program in early RA was associated with a significant increase in disease-specific knowledge compared to the control group of patients. This leads to better decision-making in terms of treatment, a more beneficial doctor-patient communication and better self-management. In the long term an improvement in treatment adherence and quality of life is expected.

COMPARISON OF WEARABLES FOR SELF-MONITORING OF HEART RATE IN CORONARY REHABILITATION PATIENTS.

The leading cause of morbidity and mortality in the world is ischemic heart disease. Physical activity is a major approach in prevention and therapy of cardiac diseases. Self-heart-rate-monitoring in daily life is an important point for health awareness of cardiac patients. Aim of this study was validation of measurement accuracy of seven different devices against ECG-monitoring during cardiac rehabilitation training on a bicycle ergometer. Tested devices were: Garmin Forerunner 35 (Garmin), Mio Fuse (Mio), Fitbit Charge HR (FitbitHR), Fitbit Surge (FitbitS), Withings Pulse™ Ox (Withings), Apple Watch Series 1 (Apple) and Pearl Fitness-Tracker (FBT-50.HR PRO.V4). All devices were tested on 35 participants with six timed measurements during 20 minutes constant load bicycle ergometer workout for each. Simultaneousely, ECG measurements were recorded. Pearson´s correlations were assessed. Apple, Mio, and Garmin showed excellent accuracy with close correlation to ECG for self-monitoring of heart rate (HR) during cycling. FitbitHR, Pearl and FitbitS presented reasonable results. In contrast, Withings showed poor correlation to ECG with significant differences. We found significant differences between the tested devices. Since accuracy is of major importance for cardiac patients, only Apple, Mio and Garmin could be recommended. However, further research within distinct clinical and non-clinical settings is necessary and should take different types of physical activities into account.

[Rehabilitation with the aid of blood flow restriction training]. / Rehabilitation mithilfe des "blood flow restriction training".

BACKGROUND: For various reasons many patient groups are unable to perform high-intensity strength training. OBJECTIVE: Is the application of low-intensity strength training under blood flow restriction (BFR) an alternative to high-intensity training for patients? MATERIAL AND METHODS: Overview and summary of possible applications of BFR training in patients with osteoarthritis of the knee joint, after surgery and in patients with reduced performance. Possible contraindications and application recommendations for clinical practice based on the currently available literature are shown. RESULTS: In patients with arthritic joint complaints, muscular hypertrophy and strength improvement were achieved by low-intensity exercise with the aid of BFR. In the postoperative treatment after knee arthroscopy and anterior cruciate ligament reconstruction, BFR can be used to reduce atrophy. CONCLUSION: The effectiveness of low-intensity BFR training is lower than for classical high-resistance training; however, it may be used as additional training method in rehabilitation programs.

[Trauma-induced coagulopathy]. / Traumainduzierte Koagulopathie.

The main cause of death in the patient group less than 45 years is trauma. Beside severe traumatic brain injury, bleeding remains a leading cause of death in this group. For a causal therapy, it is necessary to understand the pathophysiology of trauma-induced coagulopathy (TIC). Beside the well-known lethal triad of trauma (hypothermia, acidosis, and coagulopathy), dilution and hypoperfusion with activation of the protein C pathway play a crucial role. TIC is a complex independent syndrome which may be present without initial hypercoagulopathy. A rapid and differentiated diagnosis and goal-directed therapy is crucial for causal therapy.

Fast interpretation of thromboelastometry in non-cardiac surgery: reliability in patients with hypo-, normo-, and hypercoagulability.

BACKGROUND: Conventional coagulation test are not useful to guide haemostatic therapy in severe bleeding due to their long turn-around time. In contrast, early variables assessed by point-of-care thromboelastometry (ROTEM(®)) are available within 10-20 min and increasingly used to guide haemostatic therapy in liver transplantation and severe trauma. However, the reliability of early ROTEM(®) variables to predict maximum clot firmness (MCF) in non-cardiac surgery patients with subnormal, normal, and supranormal MCF has not yet been evaluated. METHODS: Retrospective data of 14,162 ROTEM(®) assays (3939 EXTEM(®), 3654 INTEM(®), 3287 FIBTEM(®), and 3282 APTEM(®) assays) of patients undergoing non-cardiac surgery were analysed. ROTEM(®) variables [clotting time (CT), clot formation time (CFT), α-angle, A5, A10, and A15] were related to MCF by linear or non-linear regression, as appropriate. The Bland-Altman analyses to assess the bias between early ROTEM(®) variables and MCF and receiver operating characteristics (ROC) were also performed. RESULTS: Taking the best and worst correlation coefficients for each assay type, CT (r=0.18-0.49) showed the worst correlation to MCF. In contrast, α-angle (r=0.85-0.88) and CFT (r=0.89-0.92) demonstrated good but non-linear correlation with MCF. The best and linear correlations were found for A5 (r=0.93-0.95), A10 (r=0.96), and A15 (r=0.97-0.98). ROC analyses provided excellent area under the curve (AUC) values for A5, A10, and A15 (AUC=0.962-0.985). CONCLUSIONS: Early values of clot firmness allow for fast and reliable prediction of ROTEM(®) MCF in non-cardiac patients with subnormal, normal, and supranormal MCF values and therefore can be used to guide haemostatic therapy in severe bleeding.

Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study.

BACKGROUND: The rapid reversal of the effects of vitamin K antagonists is often required in cases of emergency surgery and life-threatening bleeding, or during bleeding associated with high morbidity and mortality such as intracranial haemorrhage. Increasingly, four-factor prothrombin complex concentrates (PCCs) containing high and well-balanced concentrations of vitamin K-dependent coagulation factors are recommended for emergency oral anticoagulation reversal. Both the safety and efficacy of such products are currently in focus, and their administration is now expanding into the critical care setting for the treatment of life-threatening bleeding and coagulopathy resulting either perioperatively or in cases of acute trauma. METHODS: After 15 yr of clinical use, findings of a pharmacovigilance report (February 1996-March 2012) relating to the four-factor PCC Beriplex P/N (CSL Behring, Marburg, Germany) were analysed and are presented here. Furthermore, a review of the literature with regard to the efficacy and safety of four-factor PCCs was performed. RESULTS: Since receiving marketing authorization (February 21, 1996), ~647 250 standard applications of Beriplex P/N have taken place. During this time, 21 thromboembolic events judged to be possibly related to Beriplex P/N administration have been reported, while no incidences of viral transmission or heparin-induced thrombocytopenia were documented. The low risk of thromboembolic events reported during the observation period (one in ~31 000) is in line with the incidence observed with other four-factor PCCs. CONCLUSIONS: In general, four-factor PCCs have proven to be well tolerated and highly effective in the rapid reversal of vitamin K antagonists.

[Role of thrombelastometry for the monitoring of factor XIII. A prospective observational study in neurosurgical patients]. / Stellenwert der Thrombelastometrie für das Monitoring von Faktor XIII. Prospektive Observationsstudie bei neurochirurgischen Patienten.

UNLABELLED: Recently published studies give evidence, that an increased maximum lysis in the APTEM® - test (ML60 > 12%) of the ROTEM® (Tem International GmbH, Munich, Germany) might indicate a factor XIII deficiency (FXIII < 70%). It was the aim of this study to investigate the feasibility of thrombelastometric measurements with the ROTEM device to reflect the isolated influence of FXIII on clot stability and therefore to indicate potential factor XIII deficiencies. PATIENTS, METHOD: After approval by the local Scientific and Ethic Review Board, 26 consecutive patients, scheduled for elective craniotomy for tumour resection, were prospectively enrolled into this study. Blood samples were taken for conventional laboratory coagulation analyses, FXIII analyses and thrombelastometric measurements (EXTEM, FIBTEM and APTEM tests) after induction of general anaesthesia (T1), before skin incision (T2) as well as at (T3) and 24 hours after (T4) postoperative admission to ICU, respectively. Statistical analyses included Spearman rank order correlations and multiple linear regressions. RESULTS: FXIII concentrations did not correlate with the ML60 in the APTEM test at any measuring point. Neither platelet count nor fibrinogen nor FXIII concentrations were of predictive value for ML60 of the APTEM test. CONCLUSION: The results lead to the assumption that thrombelastometric measurements may not be appropriate for the perioperative monitoring of FXIII concentration.

Spinal anaesthesia and caesarean section in a patient with hypofibrinogenaemia and factor XIII deficiency.

We report the peri-operative management of a 32-year-old patient suffering from symptomatic hypofibrinogenaemia and factor XIII deficiency scheduled for caesarean section. Starting with an impaired fibrinogen (1.04 g x l(-1)) and factor XIII level (48%), fibrinogen and factor XIII administration was guided by point-of-care rotational thrombelastometry (ROTEM) to achieve normal whole blood coagulation, which allowed uncomplicated spinal anaesthesia and an uneventful surgical procedure. We conclude that rotational thrombelastometry may be suitable to guide administration of coagulation factors in patients with hereditary bleeding disorders and allow otherwise contraindicated neuraxial anaesthesia and surgery to proceed without increased risk of blood loss.

Effects of desmopressin on platelet function under conditions of hypothermia and acidosis: an in vitro study using multiple electrode aggregometry*.

SUMMARY: Hypothermia and acidosis lead to an impairment of coagulation. It has been demonstrated that desmopressin improves platelet function under hypothermia. We tested platelet function ex vivo during hypothermia and acidosis. Blood samples were taken from 12 healthy subjects and assigned as follows: normal pH, pH 7.2, and pH 7.0, each with and without incubation with desmopressin. Platelet aggregation was assessed by multiple electrode aggregometry. Baseline was normal pH and 36 degrees C. The other samples were incubated for 30 min and measured at 32 degrees C. Acidosis significantly impaired aggregation. Desmopressin significantly increased aggregability during hypothermia and acidosis regardless of pH, but did not return it to normal values at low pH. During acidosis and hypothermia, acidosis should be corrected first; desmopressin can then be administered to improve platelet function as a bridge until normothermia can be achieved.

Impact of platelet count on results obtained from multiple electrode platelet aggregometry (Multiplate).

OBJECTIVES: Use of potent antiplatelet drugs requires evaluation of platelet function. While platelet function in elective cases is usually assessed in a central laboratory environment, there is also an urgent need for rapid perioperative point-of-care assessment. Recently, multiple electrode platelet aggregometry has been developed and assumed to measure platelet function independent from platelet count. We tested the hypothesis that results of multiple electrode platelet aggregometry are affected by platelet count, in particular if platelet count is below normal range. METHODS: Whole blood samples from 20 healthy volunteers were prepared containing platelet concentrations of 50,000, 100,000, 150,000, 200,000, and 250,000 microl(-1) while maintaining hematocrit. Platelet aggregation was induced by collagen, thrombin receptor activating peptide 6 (TRAP-6), adenosine-diphoshate (ADP), and arachidonic acid, respectively, and aggregation was measured by multiple electrode platelet aggregometry (Multiplate). RESULTS: Results of multiple electrode platelet aggregometry significantly decreased in blood samples with platelet count below normal range. Compared to results measured in blood samples with platelet count within normal range, aggregometry results decreased by 18.4 % (p<0.001) and 37.2 % (p<0.001) in blood samples with a platelet count of 100.000 and 50.000 microl(-1), respectively. On the other hand, large interindividual variation has been observed and some blood samples showed normal results even with platelet counts of 50.000 microl(-1). CONCLUSION: The results obtained with Multiplate. Analyzer are influenced by platelet function as well as platelet count thus displaying the overall platelet aggregability within the blood sample rather than platelet function alone.

Substitution of cyclophosphamide and busulfan by fludarabine, treosulfan and melphalan in a preparative regimen for children and adolescents with Shwachman-Diamond syndrome.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only definitive treatment for severe bone marrow dysfunction and clonal disorders in patients diagnosed with Shwachman-Diamond syndrome (SDS). In an attempt to minimize regimen-related toxicity (RRT), we have initiated a fludarabine/treosulfan/melphalan-based pilot protocol avoiding the combination of busulfan and cyclophosphamide. Median age at transplantation was 9.6 years (range 1.5-17 years). All three patients received conditioning with fludarabine (30 mg/m2/day x 6), treosulfan (12 g/m2/day x 3) and melphalan (140 mg/m2/day x 1). CAMPATH-1H (0.1 mg/kg x 2) was added in two cases, while rabbit ATG (Genzyme; 3 x 2.5 mg/kg) was given to the cord blood recipient. One patient was transplanted with a non-manipulated marrow graft from an HLA-identical sibling, one with a marrow graft from a 10/10 matched unrelated donor, and one with a 9/10 matched unrelated umbilical cord blood (UCB) unit. Mean cell doses given were 3.6 x 10(8) nucleated cells/kg BW for the bone marrow recipients and 4.2 x 10(7) nucleated cells/kg BW for UCB recipient. Overall, two of three patients are alive and display 100% donor chimerism. Acute graft-versus-host disease grade II was seen in one patient, while no GVHD exceeding grade I occurred in the remaining two.

Exercise increases serum brain-derived neurotrophic factor in patients with major depressive disorder.

BACKGROUND: Brain derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of major depressive disorder (MDD). Existing data on exercise treatment in people with MDD are inconsistent concerning the effect of exercise on BDNF pointing either to increased or unaltered BDNF concentrations. However, studies in non-depressed persons demonstrated a significant effect on resting peripheral BDNF concentrations in aerobic training interventions. Given the lack of clarity mentioned above, the current study aimed at examining the effect of adjunctive exercise on serum BDNF levels in guideline based treated patients with MDD. METHODS: 42 depressed inpatients were included, and randomized either to a 6 week structured and supervised exercise intervention plus treatment as usual (EXERCISE, n=22), or to treatment as usual (TAU, n=20). BDNF serum concentrations were assessed before and after the intervention in both study groups with established immunoassays. RESULTS: Serum BDNF slightly decreased in the TAU group, whilst there was an increase in BDNF levels in the exercise group. There was a significant time x group effect concerning sBDNF (p=0.030) with repeated ANOVA measures with age and BMI as covariates, suggesting an increase in BDNF concentrations in the EXERCISE group compared to TAU. LIMITATIONS: Though there was no statistic difference in the antidepressant medication between EXERCISE and TAU potential interactions between exercise and medication on the effects of exercise in BDNF cannot be excluded. Gender was not considered as a covariate in ANOVA due to the small number of objects. CONCLUSIONS: Exercise training given as adjunct to standard guideline based treatment appears to have additional effects on BDNF serum concentrations in people with MDD. Our results add further evidence to the beneficial effects of exercise in the treatment of MDD.

Measuring the angular dependent energy distribution of backscattered electrons at variable geometry.

An aluminium semisphere system with 120 points of entry and eight detection areas, assembled on a meridian covering 0.0026 steradian each, was put over a solid bulk sample (e.g., aluminium), which was mounted in the eucentric point so that the incident electron beam could be varied by a polar rotation of the sphere in steps of 11.25 degrees. The complete angular distribution of the backscattered electrons became available by a rotation in steps of 11.25 degrees azimuthally. For this particular setup, the signals from the detection areas as well as the signal from the rest of the semisphere were amplified by operational amplifiers (Burr-Brown OPA128LM). However the signal of the semisphere was not available at that time. Specimen current measurements made the total amount of electrons accessible, providing a possibility for normalization of the results and comparison with total backscattering coefficients. By use of counter voltage variable up to 10 kV inside the detection assembly, it was possible to measure an energy resolution of the backscattered electrons for each detection area at the same time. Details of the construction and calibration procedures, possible errors, and sources of systematic deviations as well as first test results are discussed.

Critical adsorption on defects in ising magnets and binary alloys

Long-range correlations in a magnet close to its critical point or in a binary alloy close to a continuous order-disorder transition can substantially enhance the effect of local perturbations. It is demonstrated using a position-space renormalization procedure that quasi-one-dimensional defects which break the symmetry of the order parameter have pronounced effects: They cause long-range critical adsorption profiles and give rise to new universal critical exponents, which are identified and calculated using field-theoretical methods.

The cytomorphological spectrum of mantle cell lymphoma is reflected by distinct biological features.

Mantle cell (centrocytic) non-Hodgkin's lymphoma (MCL) is a malignant tumour with unique biological features. The pathogenesis of MCL seems to be strongly associated with aberrant function of the cell cycle. 110 cases of MCL have been analysed for their cytomorphological features, mitotic and proliferation indices, bcl-1 rearrangements, p53 expression patterns and DNA content by both interphase cytogenetic as well as DNA flow cytometric analyses. According to cytomorphology, three subtypes were recognized: a common, a lymphoblastoid and a pleomorphic variant of MCL. Blastic MCL subtypes were characterized by distinctly elevated mitotic and proliferation indices, frequent bcl-1 rearrangements at the MTC locus, and overexpression of p53. The most interesting finding, however, was a striking tendency of blastoid MCL subtypes to harbour chromosome numbers in the tetraploid range, a feature clearly separating these neoplasms from other types of B-cell NHL and possibly being related to its unphysiological expression of cyclin D1. Although characterised by a uniform immunophenotype and common biological background, MCL shows a broad spectrum of morphological features ranging from small cell to blastic types, and this spectrum is mirrored by distinct biological features.

Polymer depletion interaction between two parallel repulsive walls.

The depletion interaction between two parallel repulsive walls confining a dilute solution of long and flexible polymer chains is studied by field-theoretic methods. Special attention is paid to self-avoidance between chain monomers relevant for polymers in a good solvent. Our direct approach avoids the mapping of the actual polymer chains on effective hard or soft spheres. We compare our results with recent Monte Carlo simulations [A. Milchev and K. Binder, Eur. Phys. J. B 3, 477 (1998)] and with experimental results for the depletion interaction between a spherical colloidal particle and a planar wall in a dilute solution of nonionic polymers [D. Rudhardt, C. Bechinger, and P. Leiderer, Phys. Rev. Lett. 81, 1330 (1998)].

[Dynamic imaging of the nasal cavity and the paranasal sinuses with polarized 3helium MRI]. / Dynamische Bildgebung der Nasenhaupthöhle und der Nasennebenhöhlen im MR mittels polarisiertem 3Helium.

PURPOSE: Reduced or blocked ventilation of the paranasal sinuses is probably the most important factor in the development of sinusitis. Recently, the use of optically polarized noble gas isotopes has attracted increasing interest for use in a variety of promising MR applications. The aim of this study was to test the feasibility of imaging and visualization ventilation of the nasal cavity and paranasal sinus in MR by inhalation of hyperpolarized (3)helium. The goal was to evaluate ventilation defects of the paranasal sinuses. VOLUNTEERS AND METHODS: Three volunteers were enrolled in the study. (3)Helium was polarized to 40 - 50 % by direct optical pumping. 300 ml of 100 % (3)helium were administered in the left nasal vestibule through a glass tube. With a closed contralateral nasal vestibule, the Valsalva maneuver was performed twice. Using a dedicated application unit, which is also used in MR imaging of the lung, an exact amount of (3)helium gas was administered at the beginning of inspiration. Measurements were carried out on a clinical 1.5 T scanner. Coronal images of the nasal cavity and paranasal sinuses were acquired using ultrafast gradient-echo pulse sequence (TR = 2 ms, TE = 0.7 ms, FA < 2 degrees, 75 x 128, FOV = 500) with an image aquisition time of 130 ms. RESULTS: The oral cavity and nasal cavities display a very high signal intensity after inhalation of polarized (3)helium gas. The signal intensity in the left maxillary sinus was higher compared to the right one. The mean signal intensity on the left side was 526 +/- 86 and on the right side 336 +/- 102. The left and right frontal sinus and ethmoid sinus only show signal of hyperpolarized (3)helium after two Valsalva maneuvers. Because of the low signal intensity of the frontal and ethmoid cells their visualization was incomplete. The signal to noise ratio was 14.1 for the left maxillary sinus, 8.9 for the right side, 6.3 for the left ethmoid sinus, 5.8 for the right side and 6.6 for the left frontal sinus and 7.8 for the right side. CONCLUSION: (3)Helium MR allows imaging of the nasal cavity and the paranasal sinuses. Perhaps this method could be a new tool to visualize the ventilation of the maxillary sinus without ionizing radiation. Interpretations about the ventilation of the frontal and ethmoid cells remain speculative.

Thromboelastometry guided therapy of severe bleeding. Essener Runde algorithm.

Both, severe haemorrhage and blood transfusion are associated with increased morbidity and mortality. Therefore, it is of particular importance to stop perioperative bleeding as fast and as possible to avoid unnecessary transfusion. Viscoelastic test (ROTEM® or TEG®) allow for early prediction of massive transfusion and goal-directed therapy with specific haemostatic drugs, coagulation factor concentrates, and blood products. Growing consensus points out, that plasma-based coagulation screening tests like aPTT and PT are inappropriate for monitoring coagulopathy or guide transfusion therapy. Increasing evidence of more than 5000 surgical or trauma patients points towards the beneficial effects of a thrombelastography or -metry based approach in diagnosis and goal-directed therapy of perioperative massive haemorrhage. The Essener Runde task force is a group of clinicians of various specialties (anaesthesiology, intensive care, haemostaseology, haematology, internal medicine, transfusion medicine, surgery) interested in perioperative coagulation management. The ROTEM diagnostic algorithm of the Essener Runde task force was created to standardise and simplify the interpretation of ROTEM® results in perioperative settings and to present their possible implications for therapeutic interventions in severe bleeding. To exemplify, this text mainly focuses on coagulation management in trauma.

Perioperative use of modified thrombelastography in factor XI deficiency: a helpful method to assess drug effects.

Factor XI deficiency is a rare, hereditary bleeding disorder associated with a trauma-related bleeding tendency, caused by insufficient generation of the thrombin activatable fibrinolysis inhibitor (TAFI) evoking increased fibrinolysis. We present the case of a five year old girl with homozygote, severe factor XI deficiency presenting for surgery on two occasions. Modified thrombelastography (ROTEM) was used to assess effects of factor XI deficiency on coagulation, endogenous fibrinolysis, and potential effects of tranexamic acid, aprotinin and recombinant, activated Factor VII in an in vitro model of hyperfibrinolysis. According to our data and in consideration of the mechanisms of factor XI deficiency we decided on prophylactic use of tranexamic acid.