DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT

[Esophageal cancer: new developments in prevention and therapy]
Decker A and Quante M
Esophageal carcinomas comprise 2 entities, squamous cell carcinoma and adenocarcinoma, which differ in pathogenesis and treatment. Elimination of inflammatory influences and risk factors, such as obesity and gastroesophageal reflux that contribute to a rising incidence of adenocarcinoma, is crucial for tumor prevention. In Germany, general endoscopic screening for upper GI tumors is not recommended, whereas endoscopic surveillance is applied in the presence of Barrett's metaplasia. In the future, better prediction models will be needed to identify patients at risk who will benefit from endoscopic surveillance. Precancerous lesions and early tumor stages can be removed endoscopically using modern resection methods. In recent years, therapeutic strategies for advanced esophageal tumors have undergone significant changes. In the multimodal treatment of locally advanced stages, radiochemotherapy remains to play a key role for squamous cell carcinoma, whereas new evidence highlights the importance of perioperative chemotherapy for the optimal management of adenocarcinoma. Systemic treatment options for both tumor entities have been significantly expanded due to the successful use of immune checkpoint inhibitors in adjuvant and palliative treatment regimen. Determination of PD-L1 and MSI status has therefore become decisive for the choice of therapy. In metastatic stages of adenocarcinoma, chemotherapy can now be supplemented by multiple antibodies directed against Her2, PD1, or claudin 18.2, and the antibody-drug conjugate trastuzumab deruxtecan has become a Her2-targeted option in second line treatment.
[Vaccination against RSV infections - update and perspective]
Koch T and Kobbe R
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.
[Migration Medicine: infectious and non-infectious diseases]
Distelmaier L, Ehrlich S, Wallrauch C, von Bergwelt-Baildon M and Rothe C
Approximately one third of the German population has a migration background.According to the federal office for migration, in 2022 around 2,7 million people have taken refuge or have immigrated to Germany, causing major challenges for our health system. In this article, important infectious diseases, and non-infectious conditions like hemoglobinopathies are presented. To date, especially the latter are not common in Germany and must therefore move more into focus when taking care of migrants. Furthermore, new treatment options for hemoglobinopathies have been approved in the last couple of years, starting with the introduction of Luspatercept a few years ago for Beta-Thalassemias and in 2023 the introduction of Voxelotor for sickle cell disease. In 2024 the gene therapy with Exagamglogen-Autotemcel using the CRISPR/Cas molecular scissor was authorized as a new promising treatment for both conditions.
[New 2023 ESC Guidelines for the management of endocarditis]
Flachskampf FA
A succinct summary of the 2023 guidelines on the management of infectious endocarditis of the European Society of Cardiology is presented. Main new aspects are (1) the importance of treating endocarditis at a hospital with an endocarditis team and cardiac surgery, (2) a less restrictive recommendation for antibiotic prophylaxis, which now favors an individualized indication in patients with risk, e.g. bicuspid aortic valve and degenerative or rheumatic native valve disease, undergoing orodental interventions, while there is a clear recommendation for prophylaxis in patients (e.g. having prosthetic valves). (3) In patients with left-sided endocarditis caused by streptococci, enterococcus faecalis, staphylococcus aureus, or coagulase-negative staphylococci, who are after at least 10 days of in-hospital intravenous appropriate antibiotic therapy, step-down ambulatory (oral or parenteral) further antibiotic therapy is recommended.
[Handover of intensive care patients]
Banken J, Reifarth E and Braune S
An effective patient handover is a core element of high-quality patient care. Communication during patient handover in the intensive care unit is particularly challenging due to the clinical complexity and rapid changes in patient trajectories, complex interdisciplinary and interprofessional interfaces, linguistic barriers, situational and structural disruptive factors, personnel stress factors as well as the communication and error culture of the teams. In addition to avoiding disruptive factors and creating optimal communication conditions and human resources, the use of standardized and structured handovers with the help of protocols and checklists, as recommended in the literature, plays a decisive role as part of a bundle of measures for effective and safe patient care.
[73-year-old patient with urological emergency]
Thieme F and Meyer HJ
[100 years thrombotic thrombocytopenic purpura (TTP) - lessons learned?]
Wendt R, Völker L, Bommer M, Wolf M, von Auer C, Kühne L, Brinkkötter P, Miesbach W and Knöbl P
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.
[Human versus Artificial Intelligence: who makes the decision?]
Battegay E
[Vaccinations in pulmonary diseases - part 2: herpes zoste, RSV, pneumococcal infection and pertussis]
Kodde C and Sander LE
RSV is a common cause of respiratory tract infections, posing a risk of severe disease, particularly for newborns and infants, as well as in older individuals with pre-existing conditions. Two safe and effective RSV vaccines were approved in 2023. These vaccines elicit protective antibodies and offer robust protection with no additional benefit from annual boosters. Both vaccines have been approved for individuals aged 60 years and older, while one of the vaccines has also been approved in pregnant women to elicit maternal immunity for passive protection of the unborn child. In Germany, RSV vaccination is currently recommended for all individuals aged 75 years and older, as well as people aged 60-74 years of age with severe underlying conditions. PNEUMOCOCCAL INFECTION: is a primary cause of community-acquired pneumonia (CAP). Since early 2022, a 20-valent conjugate vaccine (PCV20) is approved and recommended for people over 60 years of age and individuals over 18 years of age with risk factors. PCV20 replaces the 23-valent polysaccharide vaccine (PPV23) previously recommended for those over 60 years of age.
[Human intelligence: is the human brain reasonable?]
Jäncke L
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.
[50-year-old female patient with unilateral breast eczema]
Stratmann AEP, Wehry UP and Kreuter A
[Clinical reasoning, the art of medicine and artificial intelligence]
Bassetti S, Hirsch MC and Battegay E
"Clinical reasoning" refers to all the thought processes that physicians use to make a diagnosis and determine a treatment and care plan. Artificial intelligence (AI) will enhance, improve, and accelerate human clinical diagnostic thinking, but it is unlikely to replace it. Its application in medicine has the potential to drastically reduce medical diagnostic errors and give doctors more time to care for their patients. Here, we provide an overview of some of the key elements of clinical diagnostic reasoning and the potential impacts of AI on clinical reasoning.
[Differential diagnosis of dizziness: what's the contribution of Artificial Intelligence?]
Zwergal A, Wuehr M and Filippopulos F
Dizziness is one of the most common reasons for medical consultations. The interdisciplinary range of differential diagnoses often leads to difficulties in proper classification. Artificial Intelligence and machine learning can assist through data-driven algorithms and facilitate the collection of important clinical signs as digital biomarkers. The article will present and critically discuss the current evidence on the topic.
[Renal infarction by cannabis consumption]
Kolks O, Stahlhoff S and Lichtenberg M
 Renal infarction is a rare cause for an acute renal failure. At the time being, there is no sufficient correlation to the consumption of cannabis described.
[Chronic constipation]
Andresen V and Layer P
Chronic constipation is one of the most common health disorders in all of medicine. Its extent ranges from mild discomfort, which is usually easy to improve, to severe functional limitations that may significantly reduce quality of life and may be refractory to various treatment approaches. Our understanding of the pathomechanism has grown considerably in recent years and has also led to important new therapeutic developments. The resulting treatment options and recommendations are presented in the current update of the S2k constipation guideline in an evidence-based and practical manner. The respective significance of traditional and recent drug developments is classified and categorized in modern "step-up" treatment strategies. In particular, numerous important aspects of everyday practice are addressed, such as questions on long-term treatment and therapeutic options in specific constellations (adequate treatment of constipation in older people, constipation during pregnancy, and drug-induced [especially opioid-induced]constipation).The most important new developments (i.e. new therapeutic approaches, but also re-evaluations of "traditional" laxatives and the importance of careful diagnostics in therapy-refractory patients) are summarized in this article.
[Outpatient exercise training for chronic lung disease - for whom, how and why?]
Gloeckl R, Jarosch I and Koczulla AR
There is a legal entitlement to participate in outpatient exercise groups in accordance with the German Social Code (Book IX) which regulates and facilitates prescriptions for patients with chronic respiratory diseases. A medical examination with specific inclusion and exclusion criteria prior to admission to an exercise group ensures safe participation.Traditional outpatient exercise groups are conducted in face-to-face groups for 60 to 90 minutes, once a week, with structured warm-up, main and cool-down phases. In addition, since the coronavirus pandemic, the introduction of online exercise groups via videoconferencing has enabled flexible participation (even without a prescription). To date, more than 11,000 German patients have participated in online exercise groups since 2021.Scientific evidence confirms the significant benefits of regular exercise, such as improved physical performance and reduced breathlessness. The psychosocial benefits and the promotion of self-efficacy are additionally supported by the supervision of a specialized trainer. Regular exercise (e.g. in outpatient exercise groups) is an inexpensive and very effective form of therapy to improve the quality of life of people with chronic respiratory diseases.
[What is new on peri- and postmenopause?]
Tropschuh K and Seifert-Klauss V
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.
[Genetics in nephrology - any news?]
Bartram MP, Beck BB and Müller RU
While genetic kidney diseases were long regarded as a rare cause of kidney failure, it has been shown in recent years that they account for a relevant proportion of cases. In cohorts of kidney transplant recipients, a monogenic cause is found in up to 30% of cases. Identifying the genetic cause of kidney disease has become much easier thanks to technological advances in DNA sequencing. The focus has now shifted to understanding the significance of the findings and identifying diagnostic gaps. It is still not possible to clarify all CKD cases of unclear aetiology. Besides very effective generic treatments for monogenic kidney disease (e.g., ACE-inhibitor use in Alport Syndrome), increasing knowledge of the pathophysiology of genetic kidney diseases has led to a growing number of targeted therapies. These include the treatment of ADPKD with Tolvaptan, which has now been in use for 10 years. Recently, exciting, and completely new approaches have been added, such as the first siRNA therapies in nephrology for primary hyperoxaluria type 1, the targeted treatment of hyperphagia in Bardet-Biedl syndrome, the therapy of APOL1-associated kidney disease or the use of the HIF-2 antagonist Belzutifan for renal cell carcinoma associated with Von-Hippel-Lindau syndrome. The new possibilities in the treatment of patients with genetic kidney diseases have also clearly revealed deficits in current patient care. Centers of excellence with extensive experience in this area therefore play an important role in improving care. This also applies to the further training of colleagues in the field. In Germany, the National Action Alliance for People with Rare Diseases (NAMSE) and the nationwide establishment of - to date - 36 centers for rare diseases play an important role in this regard.
[Nutrition for patients on dialysis]
Kuhlmann MK and Fleig S
Dietary recommendations for patients on dialysis are changing as our understanding of enteral microbiotal metabolism and bioavailability of nutrients from food improves.A diet low in phosphate and potassium is recommended for patients on hemodialysis. However, the absolute content does not reflect bioavailability: How much phosphate or potassium is taken up depends on food source (plant vs. animal) and to which grade it is processed. While both are nearly 100% bioavailable from industrially processed foods (additives such as dipotassium-phosphate and other salts), a much lower proportion is taken up from unprocessed plant foods high in fibre (ca. 20-40%). The DIET-HD study showed no significant association between dietary potassium and serum potassium in > 8 000 dialysis patients; and those with the highest low-processed, fresh plant-food consumption have the best survival. Dietary fibre improves colon transit time and thereby lessens symptoms of constipation. A diet low in sodium improves blood pressure and volume management in dialysis patients. The energy and protein requirements on dialysis are high: 25-35 kcal and 1-1,2 g protein per kg body weight per day (in relation to "ideal" body weight, if patient is overweight). Protein energy wasting is associated with higher stages of kidney disease, and malnutrition is associated with worse survival on dialysis. Nutritional status should be assessed on a regular basis using validated scores, and malnutrition should be addressed and treated.
[Hemochromatosis - too much iron]
Pammer LM and Schäfer B
Hemochromatosis is a disorder of genetic origin which affects iron hemostasis, resulting in an increased transferrin saturation, hyperferritinemia and parenchymal iron overload.Recently, a new system for the classification of hemochromatosis has been proposed, wherein patients are separated into 4 groups, based on the disease affected iron regulatory genes. Excess iron and increased transferrin saturation results in the formation of non-transferrin bound iron which leads to tissue damage. Hemochromatosis is a common genetic disease, but screening of the general population is not routinely recommended. In order to provide ideal care for hemochromatosis patients, it is crucial to delineate hemochromatosis from other causes of hyperferritinemia, which is a common finding in patients with metabolic disorders. This article summarizes the diagnostic algorithm for hemochromatosis. Furthermore, recommendations for optimal care - including targets for phlebotomy - are discussed.
[Laboratory diagnostics of autoimmune liver diseases in primary care settings - short review]
Moßhammer D and Reichert MC
 Elevated liver enzymes (ELE) are common in Germany. Primary care physicians are paramount in the early detection of liver diseases. The aim of this article is to provide an overview of autoimmune liver disease for primary care physicians (PCP) with a focus on laboratory diagnostics.