Meniscus-shaped cell-free polyglycolic acid scaffold for meniscal repair in a sheep model.

Since loss of meniscus is correlated with an increasing risk for osteoarthritis, meniscal scaffolds are proposed as new strategies. Development of a suitable scaffold has to take into account differing meniscus thickness, exposure to compressive and tensile forces combined with high porosity and biocompatibility of the material. After physical testing of three flat scaffolds composed of different modified polyglycolic acid (PGA) fibers, a three-dimensional meniscus-shaped PGA-hyaluronan implant was generated. Micro-computed tomography showed 90% porosity in the outer area with 50% in the inner area of the implant. Biocompatibility and expression of meniscus typical cartilaginous genes were shown for human meniscus cells cultivated in the implant with 10% human serum or 5% platelet-rich plasma for 14 days in vitro. The proof-of-concept study in sheep demonstrated proteoglycan- and collagen type I-rich repair tissue formation in partial meniscectomy combined with a meniscus-shaped PGA-hyaluronan implant after 6 months. In contrast, the control showed nearly no repair tissue formation. Thus, meniscus-shaped PGA-hyaluronan implants might be a suitable therapeutic approach to support repair tissue formation in partial meniscectomy.

[Pharmacological therapy of heart failure with reduced ejection fraction]. / Medikamentöse Therapie der Herzinsuffizienz mit verminderter Auswurffraktion.

Pharmacological therapy of heart failure with reduced ejection fraction Abstract. Pharmacological therapy for heart failure has made great progress over the last three decades and evidence-based therapies have significantly improved survival and quality of life. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers are the cornerstone of the heart failure therapy; indicated in virtually every patient with heart failure and reduced ejection fraction. As soon as the left ventricular ejection fraction decreases below 35 % and / or symptoms are still present (NYHA II-IV), a mineralocorticoid receptor antagonist should be added. A rather recent addition to current heart failure therapy with convincing data is the substance combination sacubitril / valsartan. It is indicated for patients with persistent symptomatic heart failure despite optimal medical therapy with ACE inhibitors or ARBs, beta-blockers, and MRAs. Crucial for all mentioned substances is to aim for the maximal tolerated dose. Various additional therapies have no proven survival benefit but are important for symptom control in everyday life. Above all the diuretics, where loop diuretics show a better effect profile compared to thiazide diuretics. Furthermore, achieving an optimal iron status (the limit to start a substitution is significantly higher than in patients without heart failure), decreasing the heart frequency with Ivabradine (if heart rate persists above 70 / min despite fully dosed betablocker) and «lifestyle changes¼ can add to the success of the medical treatment. The importance of digoxin has been steadily decreasing. The previously advocated therapeutic anticoagulation in patients with severely reduced LVEF is not propagated anymore. Significant arrhythmias (especially atrial fibrillation and ventricular arrhythmias) are common in advanced diseases. In addition to beta-blockers, amiodarone is clearly the antiarrhythmic drug of choice. According to latest data, an early interventional treatment of atrial fibrillation by pulmonary vein ablation may be beneficial and has the potential to reduce mortality in special subgroups of patients. New developments in the field of antidiabetic drugs seem to be promising for reduction of mortality and hospitalization in patients with heart failure.

[Advanced heart failure - treatment options beyond medical management]. / Chronische Herzinsuffizienz im fortgeschrittenen Stadium - konservativ medikamentöse Therapie, Kunstherz- oder Herztransplantation?

Improvement of heart failure therapy has led to a far better survival and quality of life of patients. Treatment of the underlying disease, patient education and improvement of compliance and consequent upgrading of medical heart failure therapy often delays further progression to an advanced stage of heart failure. Nevertheless heart failure remains a chronic progressive disease and it is up to the treating clinician to identify the signs of advanced heart failure in a timely manner in order to evaluate patients for further treatment strategies such as heart transplantation. This article should help define advanced heart failure and illustrate how patients are evaluated for further therapy. Outcome of heart transplantation or mechanically assisted circulatory support is strongly associated to proper patient selection and timing.