Innere Medizin (Heidelberg, Germany)最新文献

Diffuse large B‑cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, with a median age at diagnosis of 71 years, predominantly affecting older adults. Risk factors include immunodeficiency, autoimmune disorders, viral infections, and certain environmental exposures, although most cases lack a clear predisposition. Diagnosis is based on lymph node excision, histopathological and molecular analysis, and positron emission tomography-computed tomography (PET-CT) staging. First-line standard therapy is R‑CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), de-escalated to four cycles for young, low-risk patients (FLYER trial). For patients with International Prognostic Index (IPI) ≥ 2, the POLARIX trial showed superior progression-free survival with polatuzumab vedotin-R-CHP (rituximab, cyclophosphamide, doxorubicin, prednisone) over R‑CHOP. Older patients are generally treated with dose-reduced R‑mini-CHOP or alternatives. In relapsed/refractory disease, chimeric antigen receptor (CAR) T‑cell therapy with axicabtagene ciloleucel or lisocabtagene maraleucel has replaced high-dose chemotherapy with autologous stem cell transplantation for refractory or early relapses, including transplant-ineligible patients. Additional antibody-based therapies-such as polatuzumab-bendamustine-rituximab, tafasitamab-lenalidomide, loncastuximab, and bispecific antibodies (glofitamab, epcoritamab, odronextamab)-expand treatment options, some achieving durable remissions. Glofitamab plus gemcitabine-oxaliplatin is a new standard for first relapse when CAR T‑cell therapy is not feasible or as bridging before CAR T. Future directions include earlier integration of immunotherapies, personalized strategies guided by genetic subgroups, and broader use of liquid biopsy for subtyping, minimal residual disease detection, and treatment guidance.

Cotrimoxazole is a combination antibiotic composed of the two active substances trimethoprim and sulfamethoxazole (TMP-SMX). TMP-SMX is known to affect renal function parameters. It can cause true acute kidney injury but may also mimic acute kidney injury by inhibiting the renal secretion of creatinine. The present case demonstrates a significant increase in creatinine and urea levels, along with a reduced glomerular filtration rate, while cystatin C levels remained unchanged, representing an extent of alteration not previously reported in this form.

The treatment of heart failure varies depending on left ventricular ejection fraction (LVEF) and poses a significant clinical challenge in patients with reduced (HFrEF), mildly reduced (HFmrEF), or preserved ejection fraction (HFpEF). In HFrEF/HFmrEF, the diagnosis is based on clinical symptoms such as dyspnea or peripheral edema, as well as an LVEF < 50%. Treatment primarily relies on renin-angiotensin system (RAS) inhibitors (preferably angiotensin receptor-neprilysin-inhibitors, ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose co-transporter 2 inhibitors (SGLT2i). These agents have a class I recommendation and significantly reduce both mortality and hospitalization rates. Rapid and comprehensive implementation of this therapeutic strategy substantially improves prognosis. Additional agents such as ivabradine or vericiguat can be considered. With the recent publication of the DIGIT-HF study, evidence now also supports the use of digitoxin in advanced HFrEF to further reduce mortality and hospitalizations. Iron deficiency is common in HFrEF and is associated with worse outcomes. Intravenous iron supplementation improves exercise capacity and reduces the risk of hospitalization especially after a decompensation. In patients with HFpEF, treatment focuses on symptomatic relief and rigorous management of comorbidities. Diuretics for volume overload have a class I recommendation, as they effectively alleviate symptoms. SGLT2i also play a key role in HFpEF and are recommended with class I evidence in current guidelines. FINEARTS-HF recently showed promising results for the non-steroidal MRA finerenone, which reduces cardiovascular death/hospitalizations. Furthermore, metabolically targeted therapies such as GLP‑1 receptor agonists are gaining importance in obese HFpEF patients, as they have been shown to improve quality of life and reduce heart failure-related events.

Resistant hypertension is defined as blood pressure remaining above the target level despite treatment with three different antihypertensive agents, including a diuretic, prescribed at maximum or maximally tolerated doses. Prior to any escalation of therapy, the existing standard treatment should be optimized and simplified. In addition to the use of a potent diuretic, reducing potential barriers to adherence is particularly important due to the high prevalence of non-adherence. The simpler the medication regimen is structured, the more likely patient adherence can be positively influenced. National and international guidelines recommend spironolactone as the fourth-line antihypertensive agent. In cases of intolerance or contraindications, alternative pharmacological options with a lower level of evidence are available. For selected patient groups, interventional procedures may also be considered. Decisions regarding such interventions should be made within the framework of comprehensive patient counseling and shared decision-making in specialized centers.

A 48-year-old female patient with known autoimmune hemolytic anemia (AIHA) presented with severe anemia and pancytopenia. Despite typical hemolysis parameters and a positive direct antiglobulin test confirming the presence of warm autoantibodies, erythropoiesis was found to be hyporegenerative. This constellation suggested a combined mechanism of increased erythrocyte destruction and impaired hematopoietic capacity. Further diagnostic workup revealed active parvovirus B19 infection. This case highlights that the coincidence of AIHA and parvovirus B19 infection can lead to an atypical hematologic presentation and significantly complicate the diagnostic process.

Background: Systemic amyloidoses are a heterogeneous group of rare diseases characterized by deposition of misfolded proteins. Amyloid A (AA) amyloidosis results from chronic inflammatory processes, with autoinflammatory diseases-particularly familial Mediterranean fever (FMF)-representing one of the most common causes. Genetic autoinflammatory diseases should be considered in the differential diagnosis, especially in patients from high-prevalence regions with unexplained renal insufficiency.

Case report: The case of a 50-year-old female patient of Armenian origin who underwent kidney transplantation in 2022 for end-stage renal failure of unknown etiology is reported. Despite adequate immunosuppression, she developed progressive graft dysfunction with increasing proteinuria. In addition, persistently elevated serological inflammatory markers were observed, but without accompanying clinical symptoms. Repeat transplant biopsy ultimately revealed glomerular amyloid deposits on Congo red staining, and immunohistochemistry confirmed AA amyloidosis. Genetic analysis demonstrated compound heterozygosity in the Met694Val/Val726Ala (MEFV) gene. A diagnosis of familial Mediterranean fever type II with systemic amyloidosis was established, and anti-inflammatory therapy with colchicine was initiated. Type II FMF typically follows a primarily subclinical course and first manifests through the development of systemic, most commonly renal, AA amyloidosis.

Conclusion: This case highlights the need for a thorough differential diagnostic work-up in progressive renal failure of unknown etiology combined with persistent serological inflammation. In end-stage renal failure of unknown cause and systemic inflammatory signs, rare conditions such as AA amyloidosis should also be considered. Genetic testing for FMF may be useful, particularly in the presence of familial or ethnic predisposition.

Despite the development of numerous drugs for the treatment of high blood pressure, there are still many difficulties in achieving successful treatment of patients with high blood pressure in routine clinical practice. The renin-angiotensin-aldosterone system plays a central role in blood pressure regulation and drugs such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers and mineralocorticoid receptor antagonists are used in routine treatment. For decades it was not possible to specifically inhibit the formation of aldosterone, a key hormone in blood pressure regulation but in recent years this has been very successfully achieved pharmacologically. Several so-called aldosterone synthase inhibitors are currently being tested in clinical trials, primarily in patients with uncontrolled or treatment-resistant hypertension. Of the active ingredients two (baxdrostat and lorundrostat) have already been shown to be very successful in phase 3 trials, demonstrating that the use of both drugs can further reduce systolic blood pressure by approximately 10 mm Hg in complicated blood pressure situations. The safety profile of the drugs has been unremarkable so far. As expected, blocking the formation of aldosterone increases potassium levels but this has not caused any clinically unmanageable problems. This is a promising group of drugs for the treatment of complicated blood pressure but also perhaps for early treatment.

Helicobacter pylori was first characterized as an obligate bacterial pathogen in 1983. Since then, substantial advances have been made in understanding the pathophysiology of H. pylori infection, optimizing diagnostic and therapeutic strategies, and expanding testing and treatment-including in the prevention of gastric malignancies. The recognition of H. pylori-associated gastritis as an infectious disease led to the recommendation to initiate eradication therapy after any confirmed detection of the pathogen. The marked increase in resistance to commonly used antibiotics has prompted revisions in both national and international clinical guidelines. These include changes to empirical first-line therapy and have fueled ongoing debate regarding the pros and cons of routine pre-treatment antimicrobial susceptibility testing. This CME article provides an overview of the clinical relevance of the topic and also explains indications and methods for guideline-based diagnostics and therapy.

A 19-year-old female patient presented to our clinic with abdominal pain, psychomotor agitation and disorientation. The laboratory analysis revealed severe hyponatremia. Cerebral magnetic resonance imaging (MRI) showed characteristic neuroradiological features of a posterior reversible encephalopathy syndrome (PRES). The detection of a significant increase in the serum concentration of porphyrins confirmed the clinical suspicion of acute intermittent porphyria (AIP). The likely trigger for the sudden AIP exacerbation was the use of levonorgestrel for postcoital contraception. Under treatment with high-dose glucose solution and haem arginate, the abdominal symptoms regressed rapidly. In contrast, neuropsychiatric symptoms improved only gradually, making neurological rehabilitation necessary.

Antibodies against platelet-derived factor 4 (anti-PF4) lead to severe acute or chronic thrombosis. Anti-PF4-associated immune thromboses include heparin-induced thrombocytopenia (HIT) and HIT-related diseases, vaccine- or virus-induced immune thrombocytopenia and thrombosis (VITT), and chronic monoclonal gammopathy of thrombotic significance (MGTS). The etiology of anti-PF4-associated diseases varies, but all share the positive detection of platelet-activating antibodies against PF4. Clinically, arterial and venous thrombosis develops, usually accompanied by moderate thrombocytopenia. In acute forms, these symptoms typically occur within a time window of 4-12 days (HIT) or 4-30 days (VITT) after a trigger, e.g., heparin therapy or a viral infection. Laboratory diagnosis is based on the detection of anti-PF4 antibodies and functional evidence of platelet activation in the presence of heparin (HIT) or PF4 (VITT). Acute treatment is based on alternative anticoagulation at therapeutic doses and high-dose intravenous immunoglobulins (IVIG). In chronic immune thrombosis, an underlying monoclonal gammopathy must be treated. Bruton's tyrosine kinase inhibitors (e.g., ibrutinib) can reduce platelet activation and thus control the clinical picture. This review article summarizes the classification, diagnosis, and treatment of anti-PF4-associated diseases.