Deutsche medizinische Wochenschrift (1946)最新文献

Almost 60 years after a disastrous clinical vaccine trial in children, which resulted in enhanced disease and even deaths, the world of RSV vaccination is currently undergoing a dramatic positive change and development, closely linked to advances in new vaccine technologies. Three licensed safe and highly efficacious vaccines, Abrysvo, Arexvy and mRESVIA, reduce the incidence of RSV lower respiratory disease by 80% in people older than 60 years of age. Questions regarding long-term protection and effectiveness in specific risk groups with chronic medical conditions remain, and furthermore, innovative and safe concepts to actively vaccinate pregnant women and infants to prevent severe RSV infections - also in these high-risk populations - are eagerly awaited.Passive vaccination with the long-acting monoclonal antibody Nirsevimab for prevention of severe disease in the first RSV season of infants is a major innovation in global health and the importance and benefits of reducing the number of intramuscular injections for high-risk children is immense. In the coming years, results of numerous pediatric candidate RSV vaccine studies are expected, although particular caution seems advisable for historical reasons. In summary, the field of RSV vaccination has been revolutionized in the last 2 years and we will see further significant progress soon.

Menopause is an increasingly discussed topic in recent years. More women are demanding consultancy and help from their doctors via different channels, be it online or in menopause centers.The term genitourinary syndrome of menopause (GSM) comprises vaginal and urological symptoms such as mucosal dryness, itching and burning, dysuria or bleeding and pain during sexual intercourse. GSM can strongly affect quality of life, is common if estrogen deficiency has lasted for 3 months and can be treated locally with very low doses of the weak estrogen estriol."Not feeling like myself anymore" - symptomatic perimenopause may present with sleep disturbances, mastalgia, mood swings, palpitations, panic attacks, but also entail joint pain, vertigo, headache, and brain fog - even years before menopause and in the presence of still adequate estrogen levels. In an online study, 20% of women in the menopausal transition reported symptoms which they could not explain, and which may cause fears of serious illness. This can lead to extensive medical work-ups if the possibility of perimenopause as the cause is disregarded.(Peri-)menopausal complaints last much longer than previously thought: The Study of women's health across the nation (SWAN) reported longer duration of vasomotor symptoms (median: 11,8 years) in women who were already affected in early perimenopause, while those in whom VMS started only after menopause experienced a shorter duration of symptoms (median: 3,4 years).Female hormones protect women from fatty streaks and hypertension, but menopausal hormone therapy (MHT) has positive effects only if started in the first decade after menopause. The interaction with stress, aging and lifestyle factors is complex.For the treatment of VMS, German and international guidelines list both drug and non-drug or non-prescription options, although there is no clear data on their effectiveness.Fezolinetant, a Neurokinin-3 receptor antagonist, is now available in Germany for the treatment of vasomotor symptoms in postmenopausal women with contraindications or aversion against steroid hormones. It modulates the thermoregulation center in the hypothalamus by blocking the KNDy-neurons. Studies on Elinzanetant, another representative of this class of drugs, are still ongoing.

The human brain is a remarkable organ which, in addition to many vital functions, is also extremely adaptable and capable of learning. As a result, the brain is a highly individual organ that is shaped by culture. This complicates the search for a universally valid reason that must be anchored in the brain.

100 years ago Dr. Eli Moschcowitz described the first case of thrombotic thrombocytopenic purpura. For many decades there were no recognized treatment options, and the mortality rate was extremely high. At the beginning of the 1990 s, therapy with steroids and plasma exchange became increasingly popular, although the mortality rate was still over 20 %. It took until the turn of the millennium for the disease mechanisms (ADAMTS13-deficiency) to be decoded in Bern and New York, thus paving the way for new therapy options. It has now become clear that acquired TTP (iTTP) is an autoimmune disease, and the autoantibodies are directed against ADAMTS13, a protease that cleaves large von-Willebrand multimers. This causes a severe ADAMTS13-deficiency. The ultralarge multimers persist and bind platelets, resulting in microvascular thrombosis. This is distinguished from congenital TTP (cTTP), in which severe ADAMTS13-deficiency is caused by mutations in the ADAMTS13-gene (Upshaw-Schulman syndrome). In other forms of thrombotic microangiopathy (TMA, e. g. aHUS), severe ADAMTS13-deficiency does not occur. Two randomized controlled studies demonstrated the benefit of the selective bivalent anti-von-Willebrand factor (vWF) nanobody Caplacizumab, approved in 2019, in the treatment of iTTP. Various publications from national iTTP cohorts improved the data and showed consistent reductions in the time until platelet normalization, a reduction in refractory courses and exacerbations (especially when therapy is controlled according to ADAMTS13-activity) as well as evidence of reduced mortality. Modern therapeutic options include strategies for preemptive therapy for ADAMTS13-relapse as well as plasma exchange-free treatment. The use of recombinant ADAMTS13 may also expand the therapeutic options in iTTP patients in the future.

Women have a higher lifetime risk of venous thromboembolism (VTE) than men. Hormone-associated risk factors such as pregnancy, contraception and hormone replacement therapy contribute significantly to this. Contraception with combined hormonal contraception increases the risk of VTE in young women, with the extent of the increase in risk being determined by the level of the estrogen dose and the progestin component. After hormone associated VTE, temporary anticoagulation is sufficient in many cases, provided there are no additional persistent risk factors. Affected women should be informed that the risk of VTE recurrence is increased in a subsequent pregnancy and usually requires VTE prophylaxis with low molecular weight heparin during pregnancy. If the suspicion of recurrent VTE arises during pregnancy, diagnostics must be carried out promptly so that deep vein thrombosis and/or pulmonary embolism can be reliably confirmed or ruled out.

Lysosomal storage disorders (LSD) are a heterogenous group of inborn errors of metabolism due to lysosomal malfunction. LSDs affect 1 in 5000 live births, albeit every LSD itself has a low incidence. The most common LSDs are Fabry disease and Gaucher disease. The underlying cause mainly is an enzyme deficiency but may also be due to defects in transport or activation proteins, which result in progressive intra- and extra-lysosomal accumulation of undegraded storage material. The lysosomes play a key role in degradation and cellular recycling of macromolecules. Besides disturbance of cellular function, substrate accumulation may result in secondary toxic and/or inflammatory processes. For treatment of Fabry and Gaucher disease, several therapeutic approaches are approved including enzyme replacement therapy, chaperon therapy for Fabry disease and substrate reduction therapy for Gaucher disease.

Despite declining numbers - older people in particular - often die from pulmonary embolism. A rapid assessment of the risk in the event of a suspected embolism, the exclusion of comorbidities and the appropriate therapy are the focus of the current guidelines. Early and subsequent outpatient treatment of a patient with acute PE generally requires 3 criteria: low risk of early complications, the absence of serious comorbidities and the highest possible safety at home and, in the event of a complication, rapid access to acute care in the hospital. For patients with a high risk of VTE recurrence, the long-term dosage of secondary drug prophylaxis is not yet clear - studies are currently underway. In patients at moderate risk of VTE recurrence, low-dose secondary prophylaxis can be used to reduce the risk of bleeding. Outpatient pulmonary embolism follow-up care is becoming increasingly important, because studies have shown several times that serious long-term consequences can occur. In pulmonary embolism patients with persistent dyspnea, reduced performance or risk of CTEPH, an outpatient evaluation of the right ventricle using echocardiography, if necessary, in combination with the determination of natriuretic peptides or spiroergometry, is recommended.

Inadequate treatment of venous thromboembolism can have fatal consequences that are often irreversible. If the indication is given, long-term therapeutic anticoagulation may be necessary to reduce the risk of recurrence for those affected. On the other hand, there is an increased risk of bleeding due to continued anticoagulation, so an individual risk/benefit assessment is necessary. A careful assessment of possible contributing factors is therefore essential. If uncertainty persists, comprehensive environmental diagnostics with regard to thrombophilia or cancer can be helpful.

The post-thrombotic syndrome PTS occurs when a relevant residual thrombus load remains after a deep vein thrombosis and/or the function of the venous valves is disturbed. The knowledge of the different types of PTS generates individualized therapeutic and secondary prophylactic approaches. Immediate compression, movement in compression garments and an effective anticoagulation are crucial for both the prevention and the outcome of post thrombotic syndromes.