There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Prospective Cohort Study

ALAT
: alanine aminotransferase
ASAT
: aspartate aminotransferase
APAH
: associated pulmonary arterial hypertension
BAS
: balloon atrial septostomy
BMPR2
: bone morphogenetic protein receptor 2
BNP
: brain natriuretic peptide
BPA
: balloon pulmonary angioplasty
BREATHE
: Bosentan

/pdf/2015-esc-ers-guidelines-for-the-diagnosis-and-treatment-of-y26yabnnom.pdf

2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).

In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at

/pdf/eular-recommendations-for-the-management-of-rheumatoid-4fujp4paik.pdf

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Updated clinical classification of pulmonary hypertension.

Among the various organ manifestations, scleroderma renal crisis (SRC) is the acutest and most life-threatening manifestation of systemic sclerosis (SSc), which occurs predominantly in patients having diffuse cutaneous involvement (dSSc). Until the availability of angiotensin converting enzyme (ACE) inhibitors in 1979, scleroderma renal crisis usually presented as malignant hypertension with rapidly progressive renal failure and a high risk for mortality. Among the initiating causes, antecedent use of high-dose corticosteroids appears to be the most important. All patients with SSc who have new-onset hypertension, with or without evidence of renal involvement, should therefore be treated and maintained on a maximum tolerable dose of an ACE inhibitor (ACE-I), even if renal failure develops. Patients with scleroderma renal crisis treated with ACE-I have a substantially improved 1-year survival of 76% and a 5-year survival of 65% compared to 1-year and 5-year survival rates of 15% and 10%, respectively, of patients not receiving ACE-I despite the use of aggressive other antihypertensive treatment. In a small group of patients with “normotensive” scleroderma renal crisis, ACE-I therapy has also shown to improve survival.

A Patient with Diffuse Systemic Sclerosis with Hypertension and Acute Renal Failure

Reply to: Moyamoya disease and systemic sclerosis (MoSys syndrome): a combination of two rare entities: comment to the authors.

In rheumatoid arthritis (RA), osteoclasts are one of the most important mediators of bone erosion. In addition, RA synovial fibroblasts (RASF) have a major influence on joint erosion in RA. They affect osteoclast differentiation e.g. by increased RANKL production or secretion of other pro-osteoclastogenic factors such as IL-6. In addition to the pro-osteoclastogenic effect of soluble factors such as RANKL and IL-1, visfatin inhibits osteoclast differentiation. Furthermore, visfatin increases the secretion of pro-inflammatory factors by RASF, such as IL-6 or matrix degrading enzymes.In this study, the effect of RASF with/without activation by visfatin and IL-1 on osteoclastogenesis was evaluated.Blood from healthy donors and RA patients was used for PBMC isolation. RANKL, TGF-β and hM-CSF were added to induce osteoclast differentiation. RASF-conditioned media (CM) were prepared from confluent RASF cultured for 48h. Differentiating PBMCs in monoculture were compared to PBMC cultured with CM from RASF (CM: 10%, 20%, 30%) as well as in direct co-culture with RASF with/without stimulation with IL-1 (0.05ng/ml), visfatin (25ng/ml). After two weeks in culture, cells were stained using TRAP staining. 3-5 images per well were used for quantification dependent on the variability of the wells. IL-6 was measured by ELISA in supernatants collected at day 14.IL-6 production increased by IL-1 (e.g. co-culture: 2,8-fold) and visfatin (CM-visfatin: 10%=4,3-fold, 20%=5,4-fold, 30%=4,2-fold; co-culture: 9,5-fold) compared to unstimulated control in all settings. In addition, IL-6 was increased with the addition of CM compared to unstimulated controls (healthy donors CM 30%: unstimulated p=0.0342, IL-1 p=0.0133, visfatin p=0,0133; RA: unstimulated p=0.0133, IL-1 p=0.0342, visfatin p=0.0133, n=3 each). Of note, baseline IL-6 concentrations were higher in PBMC from RA patients compared to healthy donors. Co-culture showed an additional increase in IL-6 levels in all settings (e.g. monoculture: IL-1 4.71±5.75pg/ml, visfatin 141.09±182.79pg/ml; co-culture: IL-1 7241±10398pg/ml, visfatin 24535±16994pg/ml;). During osteoclast differentiation, addition of CM showed similar osteoclastogenesis with similar proportion of osteoclasts with 2 and 3-5 vs. higher numbers of nuclei per cell compared to control. In coculture with RASF osteoclasts showed a stronger TRAP signal compared to monoculture especially for unstimulated and IL-1 stimulated co-cultures.Both, in monoculture with CM and in coculture, IL-6 levels were increased compared to control, whereas in RA patients the IL-6 levels were higher compared to healthy donors. The CM containing secreted factors of RASF did not have a prominent influence on osteoclastogenesis. However, the presence of RASF increased the TRAP signal showing an increased activity of differentiated osteoclasts especially in unstimulated and IL-1 stimulated co-cultures but not with addition of visfatin.None.None declared.

/pdf/pos0429-activated-rheumatoid-arthritis-synovial-fibroblasts-1pkf3yan.pdf

Pos0429 activated rheumatoid arthritis synovial fibroblasts alter osteoclast differentiation and activity

The immune system is a human defense system that can be adapted to external conditions and is present ubiquitously throughout the organism. Its main purpose is to prevent damage caused by pathogens or toxins. In addition, it is capable of recognizing and destroying defective or degenerated endogenous cells. The immunological network in the body consists of various organs and organ systems, different immunoactive cell types as well as extra- and intracellular signaling molecules and signal complexes. The immune system is divided into the innate immune system and the acquired immune system. Pathological conditions, which may be short- or long-lasting, range from the congenital disorders of autoinflammation to the numerous autoimmune diseases, triggered by various stimuli. From a treatment perspective, nonspecific immunosuppressants or direct immune cell inhibitors or antibodies can be used for excessive reactions.Das Immunsystem ist ein den äußeren Gegebenheiten anpassbares und nahezu ubiquitär vorhandenes Abwehrsystem höherer Organismen, das vor allem Schädigungen durch Krankheitserreger oder Toxine verhindern soll. Zudem kann es fehlerhafte oder entartete körpereigene Zellen erkennen und zerstören. Das immunologische Netzwerk des Menschen besteht aus verschiedenen Organen und Organsystemen, verschiedenen immunaktiven Zelltypen sowie extra- und intrazellulären Signalmolekülen und Signalkomplexen. Unterteilt wird das Immunsystem in das angeborene und erworbene Immunsystem. Pathologische Zustände, die kurz oder länger andauern können, reichen von den angeborenen Störungen der Autoinflammationserkrankungen bis hin zu den zahlreichen Autoimmunerkrankungen. Diese überschießenden Immunreaktionen werden durch verschiedenste Stimuli getriggert. Therapeutisch können bei überschießenden Reaktionen unspezifische Immunsuppressiva oder direkte Immunzellhemmer bzw. Antikörper eingesetzt werden. 

/pdf/immunologisches-basiswissen-fur-die-praxis-3ip0tbv4.pdf

Ulf Müller-Ladner

Papers

A Patient with Diffuse Systemic Sclerosis with Hypertension and Acute Renal Failure

Reply to: Moyamoya disease and systemic sclerosis (MoSys syndrome): a combination of two rare entities: comment to the authors.

Pos0429 activated rheumatoid arthritis synovial fibroblasts alter osteoclast differentiation and activity

Immunologisches Basiswissen für die Praxis

Regulation of Synovial Adipocytokines—Reply