[Relevant aspects of the ESC guidelines for the management of cardiovascular diseases during pregnancy for obstetric anaesthesia (update 2018)]. / Anästhesiologisch relevante Aspekte der ESC-Leitlinien für das Management von kardiovaskulären Erkrankungen während der Schwangerschaft (Update 2018).

The current update of the ESC (European Society of Cardiology) guidelines on managing cardiovascular diseases during pregnancy provides instructions for doctors in daily practice. Heart diseases are the most common reason for maternal death during pregnancy in western countries. Among other things, the following topics are dealt with: congenital heart disease, pulmonary hypertension, aortic and valvular diseases as well as arrhythmias and hypertensive disorders. Compared to the guidelines from 2011 some changes have been made regarding the recommendations to classify maternal risk according to the modified World Health Organization (mWHO) classification or in recommendations on anticoagulation for low-dose and high-dose requirements of vitamin K antagonists. The main focus of this summary of recent recommendations is the impact on the anesthesia management in order to provide responsible anesthesiologists with relevant background knowledge.

[Update of the ESC guidelines 2018 on cardiovascular diseases during pregnancy : Most important facts]. / Update 2018 der ESC-Leitlinie zu kardiovaskulären Erkrankungen in der Schwangerschaft : Die wichtigsten Fakten.

Heart diseases are the most common cause of maternal death during pregnancy in Western countries. The current ESC guidelines 2018 for the management of cardiovascular diseases during pregnancy is a guide for any physician facing the challenge of caring for pregnant women with cardiovascular diseases. Among the new concepts compared to 2011, are recommendations to classify maternal risk due to the modified World Health Organization (mWHO) classification, introduction of the pregnancy heart team, guidance on assisted reproductive therapy, specific recommendations on anticoagulation for low-dose and high-dose requirements of vitamin K antagonists and the potential use of bromocriptine in peripartum cardiomyopathy. The Food and Drug Administration (FDA) categories A-D and X should no longer be used. Therefore, the table of drugs was completed with detailed information from animal and human studies on maternal and fetal risks. The new findings on specific heart diseases are presented in detail in the respective chapters.

[Gender Aspects in Gastrointestinal Tumours and Their Prognosis in Regard to Multimodal Treatment Concepts]. / Genderaspekte bei Tumoren des Gastrointestinaltrakts und ihre Prognose, insbesondere im Rahmen multimodaler Therapiekonzepte.

Systematic analyses of gender effects in gastrointestinal malignancies are currently lacking, partly because sex and gender have not been used as stratification criteria in major studies on the topic. It is, however, indisputable that gastrointestinal tumours differ in risk factors, incidence and prognosis between the genders. This review summarises the most important findings on differences related to biological sex and sociocultural gender and discusses anatomic specifics with immediate significance for surgical interventions. Epidemiological differences in upper gastrointestinal malignancies are most prominent in regard to histological subtypes, directly affecting diagnostics, therapy, and prognosis. Women have a better prognosis in many of these tumour subtypes. For colorectal carcinoma, sex hormones, specifically oestrogens, appear to play a distinct role in tumourigenesis. Histopathological analysis of the expression of oestrogen receptor beta (ERß) in the tumour tissue has attracted interest since it was shown that women with low ERß expression have a better prognosis than men with comparable ERß status. Data on the higher incidence of right-sided colon carcinoma and non-polypoid neoplasms in women could lead to improved screening programmes. Men and women cite differing reasons for avoidance of screening colonoscopies, thus gender specific approaches could improve colon cancer prevention programmes. Data on differing bioavailability of 5-fluorouracil between the genders are useful to minimise adverse effects of chemotherapy and should be accounted for in dosage. Further systematic analysis of gender effects on gastrointestinal tumours is warranted and would be a substantial step towards personalised oncological surgery.

Effects of AT1- and beta-adrenergic receptor antagonists on TGF-beta1-induced fibrosis in transgenic mice.

BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) is involved in interstitial remodelling promoting collagen synthesis and suppressing collagen degradation by inhibition of collagenases. TGF-beta1 mediates angiotensin II-dependent effects and modulates beta1-adrenergic signalling. To study the effect of neuroendocrine antagonism on TGF-beta-induced hypertrophic and fibrotic phenotype, we treated TGF-beta1 (Cys223,225Ser) transgenic mice (TGF-beta1-TG) with either the beta1-receptor blocker metoprolol (MET), the angiotensin II type I (AT1)-receptor antagonist telmisartan (TEL) or an antibody blocking TGF-beta1 signalling (TGFbeta1-sR-Ab). MATERIAL AND METHODS: Transforming growth factor-beta1-TG mice (8 weeks) overexpressing TGF-beta1 were treated with either TEL (10 mg kg(-1)), MET (350 mg kg(-1)) or a soluble TGF-beta1 receptor antibody (1 mg kg(-1)) for 6 weeks. Morphological analyses of interstitium and cardiomyocytes were related to expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) by immunoblotting and zymography. RESULTS: In TGF-beta1-TG mice, myocardial interstitial total collagen content was fourfold elevated compared to that of controls (P < 0.05) and was lowered under the treatment with TEL (P < 0.05). Protein expression of TIMP-1 and -4 was increased in TGF-beta1-TG but inhibited by TEL (TIMP-1 and TIMP-4) and MET (TIMP-1), while collagenase activity was decreased in TGF-beta1-TG and normalized by treatment with TEL (MMP-1 and MMP-13) and MET (MMP-1) (P < 0.05). Morphometric measurements of cardiomyocyte diameter and area demonstrated similar antihypertrophic effects for all treatment groups. CONCLUSION: The AT1-antagonist TEL reduced myocardial hypertrophy and interstitial fibrosis in TGF-beta1-TG mice by normalizing MMP/TIMP ratio. beta1-Adrenergic inhibition by MET as well as TGF-beta1 antagonism induced antihypertrophic rather than antifibrotic effects. Inhibition of both renin-angiotensin system and beta1-adrenergic system may exert different but synergistic effects to reduce myocardial remodelling.

Myocardial fibrosis in transforming growth factor-beta(1) (TGF-beta(1)) transgenic mice is associated with inhibition of interstitial collagenase.

BACKGROUND: TGF-beta(1) mediates effects on fibroblast proliferation and collagen synthesis in the myocardium. The extracellular matrix remodeling depends on the fibrillar collagen degrading matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). The in vivo effects of TGF-beta(1) on the MMP/TIMP system in TGF-beta(1) overexpressing transgenic mice were studied. METHODS: Male Alb/TGF-beta(1)(cys(223,225)ser) transgenic mice (TG) and nontransgenic controls (C; 8 weeks) were examined. Protein expression of collagen type I, -III, interstitial collagenase (Int Coll), MMP-2, -9, TIMP-1, -2, -4 and TGF-beta(1) as well as enzyme activity (MMP-2, -9) were measured (Western blots, zymographic assays). mRNA expression of the interstitial collagenase and MMP-9 was studied with the Light-Cycler based real-time PCR. RESULTS: Overexpression of TGF-beta(1) resulted in a 10-fold increase in plasma and a seven-fold increase in myocardial TGF-beta(1) concentrations. Relative heart weights increased (mg g(-1): 7.8 +/- 0.4 vs. 4.8 +/- 0.6, n = 6; P < 0.01) in TG compared to C. Collagen type I and III increased in TG (1.9-fold and 1.7-fold) compared to controls. Interstitial collagenase protein activity (- 91%) and mRNA expression (-75%) in TG were reduced (P < 0.05-P < 0.001). Gelatinase (MMP-2, MMP-9) expression and activity were not significantly alterated. MMP-inhibitors were increased 2.5-fold (TIMP-1, -4) and 6-fold (TIMP-2) in TG. CONCLUSIONS: TGF-beta(1) produces myocardial fibrosis in vivo. This effect is not only produced by a stimulation of matrix protein formation: a complex regulation of MMP and TIMP interaction, namely decrease of expression and activity of interstitial collagenase and an enhanced inhibition by increased levels of TIMPs, are involved. These mechanisms are optional targets for therapeutic interventions in myocardial diseases.