Increased Serum Levels of soluble ST2 as a Predictor of Disease Progression in Systemic Sclerosis.

OBJECTIVE: Interleukin-33 (IL-33) has been investigated as a mediator in the pathogenesis of fibrosis in lung, liver, and heart. There is accumulating evidence for the involvement of the IL-33/IL-33 receptor ST2L signalling pathway in systemic sclerosis (SSc). Little is known about the role of serum sST2 in SSc, which is the subject of the present investigation. METHOD: Serum levels of sST2 were measured in 49 patients with SSc, recruited prospectively between November 2017 and March 2019. Patients were divided into those with progressive and those with stable disease. Receiver operating characteristics (ROC) curve analysis was applied to study sST2 as a marker for identifying patients with progressive disease. We used multivariate logistic regression analysis to evaluate the predictive value of sST2 for progressive disease after adjustment for potential confounding factors. RESULTS: Serum sST2 levels in patients with progressive disease were significantly elevated compared with patients with stable disease (mean ± sem: 50.4 ± 4.7 ng/mL vs 29.2 ± 2.97 ng/mL, p < 0.001). ROC curve analysis identified an sST2 cut-off value of 37.8 ng/mL as optimal for discriminating patients with progressive disease from those with stable disease (sensitivity 80.0%, specificity 79.3%, area under the curve 0.80). After controlling for potential confounding factors (age, gender, C-reactive protein, pro-brain natriuretic peptide, and sum of internal medicine comorbidities), sST2 remained predictive of progressive disease (odds ratio 1.070, 95% confidence interval 1.017-1.126, p < 0.009). CONCLUSION: In the present study, sST2 serum levels were predictive of disease progression in patients with SSc.

Increased extracellular water measured by bioimpedance analysis and increased serum levels of atrial natriuretic peptide in polymyalgia rheumatica patients : Signs of volume overload.

BACKGROUND: Water retention is a typical feature of acute inflammatory episodes, chiefly implemented by the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This is an important compensatory mechanism counteracting expected water loss, e.g., due to sweating. Both the SNS and HPA axis are activated in polymyalgia rheumatica (PMR). As retention mechanisms may similarly apply in this disease, we hypothesized increased water retention in PMR. METHODS: Using bioimpedance analysis body composition was investigated in 64 healthy controls and 32 treatment-naive PMR patients. All PMR patients satisfied the 2012 EULAR/ACR classification criteria for PMR. 32 PMR patients were tested before and after 7 days of glucocorticoid-based therapy. Serum levels of pro-atrial natriuretic peptide (proANP) were investigated in all PMR patients and 15 healthy controls. RESULTS: Extracellular water (ECW) was markedly higher in PMR patients than in controls (mean ± SD: 49.1 ± 6.0% versus 36.3 ± 2.5% of total body water, p < 0.001). Patients with PMR demonstrated significantly higher serum levels of proANP compared to controls. Even before glucocorticoid treatment was initiated, systolic and diastolic blood pressure were higher in PMR patients compared to controls. Extracellular water levels did not change in PMR patients upon 7 days of intensified treatment. CONCLUSION: This study demonstrated increased extracellular water and elevated serum levels of proANP as signs of fluid overload in patients with PMR. Volume changes are imprinted as long-lasting mechanisms as water distribution is not affected by short-term anti-inflammatory therapy.

[Imaging diagnostics in large vessel vasculitis]. / Bildgebende Diagnostik bei Großgefäßvaskulitiden.

Imaging procedures have become an important diagnostic tool in vasculitis. In large vessel vasculitides, such as giant-cell arteritis (GCA) and Takayasu arteritis, ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) can depict specific abnormalities of the arterial wall. A clinically suspected diagnosis can be confirmed by imaging if performed by a trained specialist using appropriate equipment, without histological investigations. Ultrasound, MRI and CT show a homogeneous, concentric thickening of the arterial wall and PET can detect increased glucose metabolism of the arterial wall. Ultrasound is the method of choice, especially in predominantly cranial GCA. Imaging should be performed before or within the first few days of glucocorticoid treatment as the PET findings of all arteries as well as ultrasound and MRI findings in temporal arteries normalize quickly with treatment. A planned imaging examination must not delay initiation of glucocorticoid treatment.

PCR analysis is superior to histology for diagnosis of Whipple's disease mimicking seronegative rheumatic diseases.

OBJECTIVES: The diagnosis of Whipple's disease (WD) is commonly confirmed by histology demonstrating Periodic Acid Schiff (PAS)-positive macrophages in the duodenal mucosa. Analysis of intestinal tissue or other specimens using polymerase chain reaction (PCR) is a more sensitive method. However, the relevance of positive PCR findings is still controversial. Therefore, we evaluated the relevance of histology and PCR findings to establishing the diagnosis of WD in a series of WD patients initially presenting with suspected rheumatic diseases. METHOD: Between 2006 and 2014, 20 patients with seronegative rheumatic diseases tested positive for Tropheryma whipplei (Tw) by PCR and/or histology and were enrolled in a retrospective analysis of the diagnostic value of both procedures. RESULTS: Seven of the 20 cases (35%) were diagnosed with 'classic' WD as indicated by PAS-positive macrophages. In the remaining 13 patients, the presence of Tw was detected by intestinal (n = 10) or synovial PCR analysis (n = 3). Two of the 20 patients (10%) with evidence of Tw did not respond to antibiotic therapy. They were not considered to suffer from WD. Therefore, relying only on histological findings of intestinal biopsies would have missed 11 (61%) of the 18 patients with WD in our cohort. In comparison, PCR of intestinal biopsies detected Tw-DNA in 14 (93%) of the 15 WD patients evaluated. Patients with a positive histology did not differ from PCR-positive patients with regard to sex, age, or duration of disease, but more often presented with gastrointestinal symptoms. CONCLUSIONS: A substantial number of WD patients present without typical intestinal histology findings. Additional PCR analysis of intestinal tissue or synovial fluid increased the sensitivity of the diagnostic evaluation and should be considered particularly in patients presenting with atypical seronegative rheumatic diseases and a high-risk profile for WD.

[Rhabdomyolysis and creatine kinase elevation]. / Rhabdomyolyse und Erhöhung der Kreatinkinase.

Creatine kinase (CK) plays an important role in cellular energy metabolism in various tissues and skeletal muscle is recognized as being the largest reservoir of this enzyme. Elevated CK levels can be induced by various harmless or severe conditions implying multiple differential diagnoses for the physician. Trauma, inflammation, drug-induced toxicity, genetic disorders as well as metabolic, endocrine or rheumatic diseases might lead to cell degeneration and leakage of CK and other cellular components. Massive destruction of muscular tissue leads to rhabdomyolysis, defined as CK elevation combined with organ damage, which requires immediate diagnostic and therapeutic intervention.

[Ultrasound in rheumatology. What's new?]. / Sonographie in der Rheumatologie. Was gibt es Neues?

Ultrasound has become an established imaging modality in rheumatology and is now indispensible in the clinical routine. In the last few years the technology has remarkably improved and new areas of application have been introduced. This review provides an overview of the innovations that are relevant in rheumatologic practice.

[Joint sonography in rheumatology]. / Gelenksonographie in der Rheumatologie.

Sonographic examination of joints has become a decisive component in rheumatological diagnostics and is now indispensible in the clinical routine. The exceptional representation of acute inflammatory soft tissue processes, very early recognition of bony destruction and the ubiquitous availability of the method have been major contributors to this success. In recent years there have been new developments in technology and in examination methods. The substantial importance of sonography for early detection of arthritis, differential diagnostics, therapy monitoring and estimation of prognosis is underlined by the continuously increasing number of international publications. Several scoring systems have been developed for small and large joints and have been proven not only under study conditions but also in practice. Subclinical inflammatory processes which are held responsible for the so-called silent progression can be detected using sonography.

[Ultrasound-guided puncture : an inexpensive and effective learning model]. / Ultraschallgesteuerte Punktion : Ein kostengünstiges und effektives Lernmodell.

Ultrasound is present in almost any practice and hospital clinic today. In clinical practice, puncture of structures, injections of local anesthetics or glucocorticoids are frequently performed. However, unguided puncture into tissue may have deleterious side-effects if the target is not reached or the drug is not injected properly, such as bleeding, traumatization of delicate structures, glucocorticoid-induced tendon rupture and skin necrosis. Coordination of eye, probe and the manipulation hand needs practice before being used on patients.Therefore, we developed an inexpensive, easy to make and effective learning model for ultrasound-guided puncture and injections. We describe how the model is made and how it can be used to efficiently enhance learning success. It was found that a person unskilled in ultrasonography needs about 40-60 coached punctures in order to confidently hit the target.This model has already been used in our medical education program for rheumatologists, internists, surgeons, orthopedic specialists, anesthetists and general practitioners with great success.

[Ultrasound-guided joint injections in patients with rheumatic diseases]. / Sonographisch geführte Gelenkpunktionen in der Rheumatologie.

Joint and soft tissue injections are routinely performed in daily rheumatology practice to establish the diagnosis or as part of the treatment in patients suffering from rheumatic diseases. Consequently, joint injections have been included in the rheumatology further training curriculum. Despite numerous studies demonstrating a poor accuracy and outcome of joint injections guided only by clinical examination, most of the injection procedures are still performed in a "blind" fashion based on clinical judgment. Ultrasound has evolved as an established imaging method in rheumatology within the past decade and is considered the preferred imaging modality for joint interventions due to its availability and lack of radiation exposure. In this article the indications and important aspects of the practical management of ultrasound-guided injections performed in daily rheumatology practice are summarized.

[Examination of the painful wrist]. / Diagnostik des schmerzhaften Handgelenks.

The anatomy of the wrist is complex. Mechanical, neurological or systemic causes are responsible for a painful wrist. In many cases a specific diagnosis can already be made by taking a precise medical history. Physical examination includes inspection, palpation of landmarks and a dynamic examination in regard to joint regions. Plane X-Ray examinations are the basic tools in diagnostic imaging. Additional radiographic adjustments, ultrasound-, MRI- and CT-examinations may lead to more detailed information in special cases. A diagnostic arthroscopy is accomplished, if a pathological cause for wrist-pain with non-invasive methods cannot be found.

[Rheumatoid arthritis and autoimmune hemolysis: B-cell depletion for remission induction in a patient with rheumatoid arthritis and cold agglutinin disease]. / Rheumatoide Arthritis und Autoimmunhämolyse: Remissionsinduktion durch B-Zell-Depletion bei einer Patientin mit rheumatoider Arthritis und Autoimmunhämolyse durch Kälteagglutinine.

Autoimmune hemolysis is a rare complication of systemic rheumatic diseases. We report on a 68-year-old female patient with established, long-standing rheumatoid arthritis, who complained of progressive weakness and worsening of her arthralgia under therapy with leflunomide. Physical and laboratory examination revealed autoimmune hemolysis due to cold agglutinin disease. As hemolysis and arthritis were refractory to steroid treatment, B-cell depletion with rituximab was performed leading to a marked reduction of hemolytic parameters as well as remission of her rheumatoid arthritis.

[Detection of psoriasis arthritis with the GEPARD patient questionnaire in a dermatologic outpatient setting]. / GEPARD-Patientenfragebogen: Erfassung von Patienten mit Psoriasisarthritis aus einem ambulanten dermatologischen Patientenpool.

BACKGROUND: Diagnosis of psoriasis arthritis (PsA) is often delayed in an outpatient dermatological setting. Therefore, we compiled a patient questionnaire (GEPARD, GErman Psoriasis ARthritis Diagnostic questionnaire) to detect PsA in psoriasis outpatients. PATIENTS AND METHODS: Initially, between 2005 and 2007, we evaluated GEPARD in the outpatient setting of our Department of Dermatology with the Vasey and Espinoza criteria. In May 2008, the questionnaire was distributed to practices in the Regensburg area, Germany. Patients who filled out the GEPARD questionnaire were invited for a rheumatological work-up and, where indicated, arthrosonography, conventional X-ray, MRI, and scintigraphy examinations were performed. PsA was classified on the basis of the CASPAR criteria. RESULTS: We calculated a sum cut-off score of >or= 4 positive answers in the first cohort. Of all 54 patients examined 63% could be diagnosed with PsA according to the CASPAR criteria. After a complete work-up with all diagnostic means 79.6% (43 patients) could be detected with inflammatory joint manifestations. CONCLUSION: It is possible to detect PsA patients in a dermatologic outpatient setting with the GEPARD questionnaire.

[Examination of the painful wrist]. / Diagnostik des schmerzhaften Handgelenks.

The anatomy of the wrist is complex. Mechanical, neurological or systemic causes are responsible for a painful wrist. In many cases a specific diagnosis can already be made by taking a precise medical history. Physical examination includes inspection, palpation of landmarks and a dynamic examination in regard to joint regions. Plane X-Ray examinations are the basic tools in diagnostic imaging. Additional radiographic adjustments, ultrasound-, MRI- and CT-examinations may lead to more detailed information in special cases. A diagnostic arthroscopy is accomplished, if a pathological cause for wrist-pain with non-invasive methods cannot be found.

Arthritis of the Knee Joint in Rheumatoid Arthritis - Evaluation of Treatment Response by Ultrasound in Daily Clinical Practice.

BACKGROUND: Rheumatoid arthritis (RA) commonly involves the knee joint in up to 30% of patients. Musculoskeletal ultrasound enables the skilled clinician to easily assess disease activity. OBJECTIVE: To evaluate the sensitivity to change of the sonography score of large joints in Rheumatology (SOLAR) for different treatments of knee arthritis in RA. METHOD: Joints were assessed by ultrasound at 4 visits. Laboratory, immunological and clinical parameters were recorded. RESULTS: 225 RA patients were analyzed. The DAS 28 in the subgroup receiving systemic steroids was significantly higher (p < 0.001) than in patients treated with intraarticular glucocorticosteroids (GCs) at T0, comparing the values from T0 to T3 the same appeared (p=0.003). Concerning the acute GC treatment regimens, the gray scale ultrasound (GSUS) sum score was found to be significantly higher in patients receiving intraarticular GCs versus no GCs (p=0,035), as well as in patients receiving systemic versus intraarticular GCs (p=0.001). Regarding the differences from T0 and T3, similar to the baseline analysis, a high GSUS sum score was significantly associated with intraarticular GCs, a low to no GC administration (p=0.035), while a high GSUS sum score was significantly linked to intraarticular GCs, rather than systemic GCs (p=0.008). CONCLUSION: SOLAR score is sensitive to change in knee arthritis. Intraarticular GC administration is performed in patients with high GSUS scores. Systemic administration of GC is linked to high disease activity (DAS28) rather than GSUS or power Doppler ultrasound (PDUS) results.

Abscisic acid-lipid interactions: a phospholipid monolayer study.

Lipid monolayer studies were performed on a Langmuir trough in the absence and in the presence of the plant hormone abscisic acid (ABA). The ABA-induced effects on the lipid monolayers can be summarized as follows: (i) ABA as the free acid (pH below 5.3) increased the molecular area and slightly decreased the surface pressure in the collapse points of monolayers made of saturated, unsaturated and of mixed lipids; ABA as the anion showed only minor effects. (ii) The ABA-induced area increase of the lipid monolayers decreased when the surface pressure increased, but some ABA remained in the monolayers made of unsaturated phospholipids even at collapse pressure. (iii) The incorporation of ABA into the monolayers could be inhibited by adding the plant sterol beta-sitosterol to the monolayer forming phospholipids. (iv) There was no substantial difference of ABA action on plant phospholipids as compared with other phospholipids. (v) ABA had a much stronger influence on unsaturated phospholipids than on saturated ones. (vi) ABA decreased the phase-transition temperature of saturated phospholipids. These results, which agree with those obtained from phospholipid vesicle studies, indicate that the physical state of the lipid is important for the ability of ABA penetrating into the lipid monolayer. Finally, a possible relevance of these results is discussed in terms of the action of ABA on guard cell membranes of plants.

Magnetic resonance imaging of the sacroiliac joints in patients with suspected spondyloarthritis - comparison of turbo spin-echo and gradient-echo sequences for the detection of structural alterations.

PURPOSE: Magnetic resonance imaging (MRI) is the method of choice for the evaluation of spondyloarthritis (SpA). According to the guidelines of the Assessment of Spondyloarthritis International Society (ASAS) and Outcome Measures in Rheumatology (OMERACT), MRI findings in SpA of the spine and the sacroiliac joints (SIJ) are classified as inflammatory and structural alterations. Modern gradient-echo sequences (GRE) are recommended for optimized detection of structural alterations of the SIJ. We assess the benefit of GRE in the detection of structural alterations of the SIJ in comparison to conventional turbo spin-echo sequences (TSE). MATERIAL AND METHODS: Retrospective study of 114 patients who received MRI of the SIJ for the evaluation of SpA. Structural alterations of the SIJ were assessed by two blinded readers separately for T1 TSE and T2* GRE. The findings were classified according to a previously published chronicity score separately for both sides and sequences. Interobserver reliability was calculated with Cohen's Kappa, and the significance of findings was assessed with the Wilcoxon test. P-values < 0.05 were required for statistical significance. RESULTS: 68 of 114 (60 %) patients showed SpA-typical findings of the SIJ. The average chronicity score for GRE (score 3.3) was significantly higher than for TSE (score 2.6), p = 0.001. The Kappa-values for the interobserver reliability were 0.86 - 0.90 without any statistically significant differences between both sides and sequences. CONCLUSION: Both T1 TSE and T2* GRE showed a high interobserver reliability in the detection of structural alterations in patients with SpA. However, T2* GRE detected significantly more structural alterations than T1 TSE and should be an integral part of a modern MRI protocol for the diagnostic workup of patients with suspected SpA.

Magnetic resonance imaging of the sacroiliac joints in patients with suspected spondyloarthritis--comparison of turbo spin-echo and gradient-echo sequences for the detection of structural alterations.

PURPOSE: Magnetic resonance imaging (MRI) is the method of choice for the evaluation of spondyloarthritis (SpA). According to the guidelines of the Assessment of Spondyloarthritis International Society (ASAS) and Outcome Measures in Rheumatology (OMERACT), MRI findings in SpA of the spine and the sacroiliac joints (SIJ) are classified as inflammatory and structural alterations. Modern gradient-echo sequences (GRE) are recommended for optimized detection of structural alterations of the SIJ. We assess the benefit of GRE in the detection of structural alterations of the SIJ in comparison to conventional turbo spin-echo sequences (TSE). MATERIAL AND METHODS: Retrospective study of 114 patients who received MRI of the SIJ for the evaluation of SpA. Structural alterations of the SIJ were assessed by two blinded readers separately for T1 TSE and T2* GRE. The findings were classified according to a previously published chronicity score separately for both sides and sequences. Interobserver reliability was calculated with Cohen's Kappa, and the significance of findings was assessed with the Wilcoxon test. P-values <0.05 were required for statistical significance. RESULTS: 68 of 114 (60%) patients showed SpA-typical findings of the SIJ. The average chronicity score for GRE (score 3.3) was significantly higher than for TSE (score 2.6), p=0.001. The Kappa-values for the interobserver reliability were 0.86-0.90 without any statistically significant differences between both sides and sequences. CONCLUSION: Both T1 TSE and T2* GRE showed a high interobserver reliability in the detection of structural alterations in patients with SpA. However, T2* GRE detected significantly more structural alterations than T1 TSE and should be an integral part of a modern MRI protocol for the diagnostic workup of patients with suspected SpA. KEY POINTS: T2* gradient-echo sequences are superior to T1 turbo spin-echo sequences in the detection of structural SI-joint alterations.

Regulation of the ABA-sensitive Arabidopsis potassium channel gene GORK in response to water stress.

The phytohormone abscisic acid (ABA) regulates many stress-related processes in plants. In this context ABA mediates the responsiveness of plants to environmental stresses such as drought, cold or salt. In response to water stress, ABA induces stomatal closure by activating Ca2+, K+ and anion channels in guard cells. To understand the signalling pathways that regulate these turgor control elements, we studied the transcriptional control of the K+ release channel gene GORK that is expressed in guard cells, roots and vascular tissue. GORK transcription was up-regulated upon onset of drought, salt stress and cold. The wilting hormone ABA that integrates responses to these stimuli induced GORK expression in seedlings in a time- and concentration-dependent manner and this induction was dependent on extracellular Ca2+. ABA-responsive expression of GORK was impaired in the ABA-insensitive mutants abi1-1 and abi2-1, indicating that these protein phosphatases are regulators of GORK expression. Application of ABA to suspension-cultured cells for 2 min followed by a 4 h chase was sufficient to manifest transcriptional activation of the K+ channel gene. As predicted for a process involved in drought adaptation, only 12-24 h after the release of the stress hormone, GORK mRNA slowly decreased. In contrast to other tissues, GORK expression as well as K+(out) channel activity in guard cells is ABA insensitive, allowing the plant to adjust stomatal movement and water status control separately.

Clinical relevance of stored electrograms for implantable cardioverter-defibrillator (ICD) troubleshooting and understanding of mechanisms for ventricular tachyarrhythmias.

A major problem in patients with cardioverter-defibrillators is to determine reliably the mechanism for spontaneous implantable cardioverter-defibrillator (ICD) discharges. Electrogram storage in ICD devices is comparable to that in permanent Holter monitors. Stored bipolar electrograms obtained from the sensing or shocking lead system contain a wide variety of different information. Intracardiac electrograms (EGMs) recorded from pace/sense electrodes (or "near-field" EGMs) show bipolar signals that have a distinct absence of any atrial activity during ventricular tachycardia or sinus rhythm. In contrast, the EGMs recording from the shocking electrodes, integrating a much larger area of myocardium, provide a more global visualization of electrical activity, which includes both atrial and ventricular deflections. Improved diagnostic capabilities available in the new generation ICD devices, in particular the stored intracardiac EGMs, facilitate sensing error diagnosis, permit a better evaluation of device function and ICD detection algorithms, and are helpful for reprogramming in order to overcome or prevent errors. In addition, EGMs give us a unique opportunity to gather information about the arrhythmic mechanism of the sudden cardiac death syndrome. Information such as the day and time of the episode, the preceding heart rate, the influence of the coupling interval of preceding premature beats, and their morphology can be gained from the analysis of stored EGM recordings. Although the availability of stored intracardiac EGMs are of enormous value in troubleshooting of ICD problems, they are occasionally not conclusive and must be complemented by additional techniques in order to complete the diagnosis. The information obtained by the analysis of stored intracardiac EGMs together with a database of EGMs can be of great importance for further improvements in future devices and may provide insights as to which patients are likely to benefit most from ICD therapy.