Innere Medizin (Heidelberg, Germany)最新文献

Myelofibrosis (MF) is a rare clonal disease of the haematopoietic stem cell characterised by pathological activation of the JAK/STAT signalling pathway. The disease typically manifests clinically as anaemia, splenomegaly and constitutional symptoms. The therapeutic decision between watchful waiting and active treatment is based primarily on the risk profile, symptoms and molecular genetic findings. While low-risk patients without symptoms can be monitored, those at higher risk or with significant symptoms benefit from early treatment, especially with Janus kinase (JAK) inhibitors. Ruxolitinib has been the standard of care since 2012, and newer substances such as momelotinib are expanding the spectrum, especially in anaemic patients. For suitable patients, allogeneic stem cell transplantation remains the only curative option. Future developments are aimed at personalised, disease-modifying therapy that goes beyond mere symptom control.

Background: The incidence and mortality of colorectal cancer in Germany has declined in recent years. Nevertheless, colorectal cancer is still the second most common cancer in women (after breast cancer) and the third most common in men in Germany (after prostate cancer and lung cancer). Screening for colorectal cancer is well-established in many countries. The two most recommended screening strategies are colonoscopy and fecal immunochemical testing (FIT, stool test for occult blood).

Objective: This article explains important conceptual and practical differences between the two strategies offered in Germany and summarizes the latest high-quality evidence for the benefits of the most frequently used screening tests. The aim is to provide physicians with decision aids for patients who show interest in colorectal cancer screening.

Material and methods: Confirmed high-quality evidence from randomized trials on the benefits of screening for colorectal cancer with respect to incidence and mortality.

Results: The lifetime risk to develop colorectal cancer in Germany is 5% for women and 6.5% for men. According to a large randomized trial, a screening colonoscopy reduces the risk of colorectal cancer from 1.2% to 0.8-0.9% after 10 years. New high-quality evidence from a recent Spanish randomized trial also showed that the benefits of FIT screening every other year are comparable to those of 1 colonoscopy over 10 years. The risks of perforation and bleeding during colonoscopy are 0.01% and 0.1%, respectively.

Conclusion: During the medical patient clarification on screening, it is recommended that the abovenamed facts on benefits and risks should be included and explained.

Due to the wide range of interstitial lung diseases (ILD) with varying prognoses, accurate diagnosis and identification of the underlying cause are essential in patients with ILD to enable targeted therapy. In approximately 50% of cases, an underlying cause can be identified [1]. Once the trigger has been successfully determined, avoidance or elimination of the causative agent represents the key therapeutic intervention. If no identifiable or removable cause can be found, or if exposure cessation alone does not lead to recovery, further treatment follows principles similar to those applied in ILDs of unknown etiology. In this context, distinguishing between inflammatory and fibrotic processes is often challenging [2]. Depending on the disease course, anti-inflammatory and/or antifibrotic therapy may be indicated [3].

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by various diseases, with lymphoma being one of the most important triggers. Positron emission tomography/computed tomography (PET/CT) is considered an important tool in establishing the etiology of HLH.

Case descriptions: We present two cases of HLH caused by diffuse large B‑cell lymphoma (DLBCL) in which 18F-fluorodeoxyglucose (18F-FDG) PET/CT showed no abnormal FDG uptake. Case 1: A 72-year-old man presented with intermittent fever and B symptoms. A comprehensive workup, including PET/CT, were inconclusive. HLH was diagnosed with 6 of 8 HLH criteria, a 99% probability in the H‑score, and a positive Optimized HLH Inflammatory (OHI) index. After performing bone marrow aspiration and skin biopsy, HLH-directed therapy with etoposide and dexamethasone was initiated. The patient died unexpectedly. Postmortem histopathologic examination revealed DLBCL in the bone marrow, and additional infiltration of the peripancreatic adipose tissue, and myocardium, and intravascular manifestations in the liver. Case 2: A 58-year-old woman presented with a history of fever and elevated inflammatory markers. Comprehensive diagnostic workup including PET/CT revealed no abnormal findings. The diagnosis of HLH was made (7 of 8 HLH criteria, H‑score > 99%, positive OHI index). Bone marrow and liver aspiration revealed hemophagocytosis without evidence of lymphoma. A biopsy of macroscopically normal skin finally revealed intravascular DLBCL. Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and high-dose methotrexate resulted in complete remission.

Conclusion: HLH is a rare complication of DLBCL. PET/CT may show no evidence of underlying lymphoma. Extensive biopsies, including macroscopically unremarkable structures, may lead to the diagnosis of lymphoma. Persistent fever should be a reason to investigate possible HLH. Once the diagnosis of HLH is established, a rapid work-up with early bone marrow aspiration, skin biopsy and possibly other structures is key for diagnosis.

Numerous new developments in antibacterial substances have been observed in recent years. Most of these are further developments of existing classes, especially beta-lactams, including beta-lactamase inhibitors. These included MRSA-active cephalosporins (ceftaroline and ceftobiprole), new, broadly effective combinations of beta-lactams with beta-lactamase inhibitors, and cefiderocol, a new siderophore cephalosporin that uses the bacteria's own iron uptake systems of gram-negative bacteria to better reach the site of action through the outer membrane.In addition to cefiderocol, the most important active ingredients or fixed combinations already available on the German market include ceftazidime-avibactam, ceftolozane-tazobactam, and aztreonam-avibactam. Imipenem-relebactam and meropenem-vaborbactam are also available; Cefepim-enmetazobactam was recently added. The spectra of these substances are different. Cefiderocol and, in the case of Enterobacterales, Aztreonam-Avibactam are suitable for the treatment of infections caused by Gram-negative bacteria with metallo-beta-lactamases.A further development in the field of betalactamase inhibitors are the boronate-based active ingredients, which can inhibit bacterial ESBL enzymes, carbapenemases of the KPC, OXA-48 and partly OXA-23 type, as well as metallo-beta-lactamases. There are few new or newly initiated developments in the field of oral beta-lactams. However, the oral carbapenems, penems, and trinems could become a kind of milestone in the treatment of mycobacteriosis. On the other hand, fixed combinations of beta-lactams plus beta-lactamase inhibitor for the oral treatment of infections caused by ESBL-positive bacteria, some of which are already available abroad (such as cefpodoxime clavulanic acid), are missing. However, interesting new combinations, such as ceftibutene-avibactam for oral use, are in development. Such combinations could also enable the oral treatment of infections by some carbapenemase producers in the future.

Non-small cell lung cancer (NSCLC) is among the most common and lethal malignancies worldwide, representing a particular oncological challenge due to its frequent diagnosis at an advanced, metastatic stage. Histopathologically, NSCLC is broadly classified into adenocarcinomas and squamous cell carcinomas. This distinction-along with programmed cell death-ligand 1 (PD-L1) expression and molecular pathology-guides therapeutic decision-making. At advanced stages, treatment options include not only traditional platinum-based chemotherapy but also immunotherapy with checkpoint inhibitors. Over the past decade, the rapid identification of actionable driver mutations has firmly established targeted therapies with tyrosine kinase inhibitors as a cornerstone of treatment, significantly improving the historically poor overall survival.