Deutsche medizinische Wochenschrift (1946)最新文献

Novel developments in the diagnosis and treatment of endometrial cancer will likely improve the prognosis of early, advanced and recurrent tumors. Molecular pathology currently classifies endometrial carcinoma into 4 molecular subtypes with prognostic significance. POLE mutated tumors, amounting to about 7% of all endometrial cancer cases, dubbed "ultra-mutated", have an excellent prognosis in early stages - even without adjuvant therapy. Mismatch repair deficient (MMRd) tumors are called "hypermutated" and have an intermediate prognosis in early stages. In advanced stages, they are highly sensitive to immune checkpoint inhibitors which are an integral part of their treatment. The tumors with "no specific molecular profile" have a prognosis that is similar to MMRd endometrial cancers. Finally, TP53 mutated cancers have a dismal prognosis, and aggressive adjuvant therapy is indicated. The 2023 FIGO classification recognizes for the first time the prognostically favorable synchronous endometrial and ovarian carcinomas, the importance of lymph node metastases depending on size and pattern, and the relevance of peritoneal involvement inside versus outside the pelvis. In metastatic disease, in mismatch repair proficient cases, the combination of carboplatin and paclitaxel chemotherapy with durvalumab has been recently approved as first line therapy in the European Union, followed by maintenance therapy with the PARP inhibitor olaparib, in combination with durvalumab. For MMRd tumors, several immune checkpoint inhibitors in combination with chemotherapy or as monotherapy have been approved in recent years. Tumors that are overexpressing Her2/neu have an additional treatment option with trastuzumab.

The 2023 ESC Cardiomyopathy Guidelines offer a comprehensive framework for diagnosing and managing cardiomyopathies. Building on a nuanced classification system, the guidelines introduce phenotypic descriptions that integrate genetic and non-genetic etiologies. Notably, the guidelines redefine cardiomyopathies, such as non-dilated left ventricular cardiomyopathy, emphasizing detailed myocardial tissue characterization and advanced imaging techniques like cardiac magnetic resonance to enhance diagnosis and treatment. Additionally, the role of genetic testing is highlighted, including family screening and personalized risk stratification for sudden cardiac death prevention. The guidelines stress a patient-centered, multidisciplinary approach, ensuring individualized care across all life stages, from pediatric to adult care. Key updates include new therapeutic options, such as myosin inhibitors for hypertrophic cardiomyopathy. The guidelines also underscore the importance of distinguishing transient syndromes, such as Takotsubo syndrome, from chronic cardiomyopathies, recommending careful assessment of arrhythmias and phenotypic traits to avoid misclassification. This refined approach aims to optimize clinical outcomes through accurate diagnosis, genetic evaluation, and a focus on lifelong management.

Coeliac disease is the most common chronic inflammatory disease of the small intestine, with a prevalence of around 1% almost worldwide. It is caused by the consumption of cereals containing gluten (wheat, spelt, rye, barley). The initial diagnosis is made in equal proportions in children and adults. Classic symptoms are abdominal pain, diarrhea, malabsorption with anemia or osteoporosis, weight loss, and in children failure to thrive. Non-specific symptoms such as poor performance, headaches and joint pain are also common. Often undetected and untreated, coeliac disease can lead to serious complications, and up to 30% of adult coeliac patients suffer from associated autoimmune diseases, including thyroid and rheumatoid diseases or type 1 diabetes. The pathogenesis of coeliac disease is well studied. Incompletely digested gluten peptides reach the immune system of the intestinal mucosa and activate glute-reactive T cells, which lead to inflammation and atrophy of the absorptive villi. The prerequisite for the development of coeliac disease is the carrier status for HLA-DQ2 or DQ8, as well as the enzyme and coeliac disease autoantigen transglutaminase-2 expressed in the intestine, which modifies the gluten peptides by deamidation and thus increases their binding to HLA-DQ2/DQ8 and subsequent T-cell activation. Despite the gluten-free diet, 30-50% of diagnosed patients continue to suffer from symptoms with signs of inflammation, partly due to unavoidable minimal gluten contamination in everyday life. Supportive pharmacological therapy is therefore urgently needed. Promising therapeutic approaches are currently in clinical phase 2 development, including an inhibitor of intestinal TG2, blocking antibodies against interleukin-15 or Ox40 ligand, the improvement of the intestinal barrier using a sirtuin-6 agonist, as well as nanoparticular therapies that can induce tolerance to gluten by addressing the spleen or liver.

Extracorporeal cardiopulmonary resuscitation (ECPR) is an invasive medical intervention using mechanical circulatory support for treating cardiac arrest beyond the limits of conventional cardiopulmonary resuscitation (CCPR). ECPR uses veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to maintain organ perfusion while treating reversible causes of cardiac arrest. Commonly applied criteria to select suitable patients include witnessed cardiac arrest, early bystander CPR, and a time frame of less than 60 minutes from collapse to ECPR initiation.A meta-analysis by Low et al. (2023), which included 11 studies with 4,595 ECPR and 4,597 CCPR patients, demonstrated that ECPR was not only associated with higher survival rates, but also better long-term neurological outcomes. Additionally, a higher number of ECPR procedures per center was linked to reduced mortality rates. A 2024 updated meta-analysis confirmed these findings and demonstrated further that ECPR significantly reduced in-hospital mortality in patients with out-of-hospital cardiac arrest (OHCA).Further insights on this topic can be gained from the individual studies on ECPR for treatment of OHCA: In general, there are several different modalities of how ECPR can be deployed, ranging from implantation at the site of the index event vs. implantation in the hospital, and even the place of implantation in the hospital varies. However, it seems that the actual pathway of how the VA-ECMO is implanted is of lower importance, and highly depends on the local infrastructure of a given hospital (rural area vs. municipal area), while achieving the lowest possible low-flow time should be the primary goal.The available data also shows that, despite all the advances, ECPR is still a high-risk intervention which is very demanding on the personnel and requires an abundance of resources.Overall, ECPR is a promising therapy for patients with OHCA to improve survival with good neurological outcome, but only if applied in a highly structured and standardized way, and in carefully selected patients.

Anaphylactic shock is a severe, potentially life-threatening systemic allergic reaction. It can involve multiple organ systems and is triggered by medication, food, or insect stings. Epidemiological data vary due to differing definitions, but studies estimate that 0,26% of hospital admissions are due to anaphylaxis, with 1-3 deaths per million annually. The incidence of allergic reactions has increased, though anaphylaxis-related mortality remains stable. Triggers vary by age, with food allergies being common in children, and insect stings and medication predominant in adults.An initial allergen exposure sensitizes the immune system, resulting in IgE production and binding to mast cells and basophils. Upon re-exposure, allergen-IgE binding triggers the release of mediators like histamine, prostaglandins, and cytokines, causing vasodilation, bronchospasm, and capillary leakage. Risk factors include asthma, cardiac or thyroid conditions, and elevated IgE levels. Symptoms usually affect 4 organ systems: skin, gastrointestinal tract, respiratory tract, and cardiovascular system. Grading is based on the severeness of symptoms, ranging from mild skin reactions (grade 1) to respiratory or circulatory arrest (grade 4). A reliable diagnostic marker is elevated serum tryptase.The cornerstone of treatment is adrenaline, administered intramuscularly for rapid action. Fluid resuscitation with balanced electrolyte solutions and high-flow oxygen are also fundamental. Antihistamines and corticosteroids are used a bit later to prevent recurrence but have delayed onset. Adrenaline can also be nebulized or given intravenously in severe cases.Post-crisis management includes patient education, allergy identification, and an emergency kit with an adrenaline auto-injector.

Acute liver failure (ALF) is a severe, potentially reversible form of liver insufficiency, which is defined by the occurrence of hepatic coagulopathy and hepatic encephalopathy in patients with no previous hepatic disease. Acute liver failure is preceded by severe acute liver injury (ALI) with an increase in transaminases, jaundice, and deterioration in general condition over a period of hours to weeks. Every year 200-500 people develop ALF in Germany, most frequently on the background of toxic liver injury (e.g. drug induced liver injury). Other potential causes include viral infections (e.g. hepatitis A and B), autoimmune hepatitis, Budd-Chiari Syndrome or Wilson's disease. Patients usually present at the stage of acute liver damage. Initial diagnostics should include a detailed medical history, clinical examination, laboratory diagnostics and abdominal sonography. The course of acute liver failure is very difficult to predict, so all patients with severe acute liver damage should be evaluated for transfer to a center. At the latest when hepatic encephalopathy occurs and thus when all the definition criteria of acute liver failure are met, the patient should be transferred to a liver transplant center immediately. While specific medical therapies may be available in the early stages of the disease, depending on the etiology, the focus in advanced stages is on preventing complications and treating associated organ dysfunctions. In progressive cases, liver transplantation is often the only life-saving measure. Overall, the mortality rate in Germany is 47%, and approximately 8% of annual liver transplants in the European Union are performed due to ALF.

In spite of available vaccines the frequency of sepsis caused by Streptococcus pneumoniae still remains rather high.In the years 2015-2022 Streptococcus pneumoniae could be isolated from 925 blood cultures in our laboratory. Serotyping was performed from 754 strains. In addition, their in vitro susceptibility to some antibiotics was assessed.In this period 925 blood cultures were positive, predominantly from aged patients (older than 60 years) and more frequently from men than from women. In the years 2020 and 2021 less positive blood cultures were found, which could be interpreted as a result from non-pharmaceutical interventions preventing aerogenically transmitted diseases such as coronavirus infections during the epidemic. Children were also relatively susceptible in their first year of life. 653 strains were serotyped, with serotypes 3 and 8 predominating. 67% of the serotypes found were covered by the 20-valent conjugate vaccine whereas the polysaccharide vaccine (PPV23) included 75%. The vast majority of isolates was susceptible to penicillin, erythromycin as well as to doxycycline. Multi-drug resistant strains were not detected.A large part of the infections might have been prevented by vaccination assuming a high vaccine effectiveness. However, 27% of S. pneumoniae serotypes detected were not covered by any of the vaccines currently available.

Heart failure is the leading cause of hospital admissions in Germany. The prevention of hospitalizations due to heart failure has recently improved, encompassing guideline-based basic therapy, targeted medication escalation options, and structured outpatient care incorporating telemedicine. An early identification of parameters that precede or indicate acute heart failure is crucial. The term "worsening heart failure" is broader than the term "acute heart failure". Worsening heart failure includes patients identified through clinical examination, biochemical methods (especially natriuretic peptides), and imaging (echocardiography, chest X-ray, lung ultrasound, computed tomography, magnetic resonance imaging), and innovative cardiac telemonitoring. Early detection of worsening heart failure is only beneficial if followed by appropriate management that stabilizes heart failure, reduces mortality, and decreases hospital admissions and emergency contacts. Dedicated guidelines for the treatment of worsening heart failure are not yet available. It is recommended to start or up-titrate guideline-recommended medical therapy and additionally initiate treatment with the soluble guanylate cyclase stimulator Vericiguat in patients with heart failure with a reduced ejection fraction. Initiation and up-titration should begin during hospitalization and should be completed during careful follow-up within the first 6 weeks after discharge. This guide provides recommendations for the comprehensive and coordinated treatment of worsening heart failure, considering all these aspects which are crucial for improving patient outcomes.

An 83-year-old female patient presented with angina pectoris, hemoglobinuria and jaundice. Laboratory diagnostics proved difficult due to hemolysis in all blood tubes, following re-evaluation after warming the blood sample.With low haptoglobin, elevated lactate dehydrogenase and elevated indirect bilirubin, we made a suspected diagnosis of autoimmune hemolytic anemia with cold antibodies, which was confirmed through a positive Coombs test and detection of C3d-loaded erythrocytes. Complications included NSTEMI type 2 in the context of hemolysis and acute kidney damage. A Proteus mirabilis bacteremia was diagnosed as the cause of the AIHA.After treatment of the underlying infection and high-dose prednisolone therapy, the hemolysis parameters regressed and the patient could be discharged to outpatient hematologic follow-up.Interdisciplinary and multi-professional collaboration with laboratory staff and transfusion medicine is crucial for both rapid diagnosis and further treatment. Blood transfusions in AIHA should only be carried out according to strict indications.