Tissue gene expression profiles and communication networks inform candidate blood biomarker identification in psoriasis and atopic dermatitis.

Overlapping clinical and pathomechanistic features can complicate the diagnosis and treatment of inflammatory skin diseases, including psoriasis and atopic dermatitis (AD). Spatial transcriptomics allows the identification of disease- and cell-specific molecular signatures that may advance biomarker development and future treatments. This study identified transcriptional signatures in keratinocytes and sub-basal CD4+ and CD8+ T lymphocytes from patients with psoriasis and AD. In silico prediction of ligand:receptor interactions delivered key signalling pathways (interferon, effector T cells, stroma cell and matrix biology, neuronal development, etc.). Targeted validation of selected transcripts, including CCL22, RELB, and JUND, in peripheral blood T cells suggests the chosen approach as a promising tool also in other inflammatory diseases. Psoriasis and AD are characterized by transcriptional dysregulation in T cells and keratinocytes that may be targeted therapeutically. Spatial transcriptomics is a valuable tool in the search for molecular signatures that can be used as biomarkers and/or therapeutic targets.

[Preoperative diagnostics and typing of abdominal soft tissue sarcomas]. / Präoperative Diagnostik und Typisierung abdomineller Weichteilsarkome.

BACKGROUND: Abdominal sarcomas are a heterogeneous group of rare soft tissue tumors and can be localized intraperitoneally or retroperitoneally. A pretherapeutic differentiated subtyping is essential for planning an individual, multimodal treatment concept in an interdisciplinary team of experts. OBJECTIVE: The central aspects of histology acquisition, imaging diagnostics and (molecular) pathological subtyping of abdominal soft tissue sarcomas are described in detail. MATERIAL AND METHODS: Imaging and pathological diagnostics are depicted based on the German S3 guidelines on adult soft tissue sarcomas, a current literature search and personal experiences at the Sarcoma Center at the National Center for Tumor Diseases in Dresden (NCT/UCC). RESULTS: Preoperative imaging and (molecular) pathological subtyping of abdominal soft tissue sarcomas place high demands on surgeons, radiologists and pathologists. Genome analyses of sarcomas have the potential to identify points of attack for individualized treatment options. The limitations of resectability can only be assessed by experienced sarcoma surgeons at specialized centers. CONCLUSION: The treatment of abdominal soft tissue sarcomas at an experienced center is associated with a better prognosis. Even at the first suspicion of an abdominal sarcoma, a referral to an experienced center should be made in order to guarantee optimal expertise in diagnostics and treatment.

CD14+ monocytes contribute to inflammation in chronic nonbacterial osteomyelitis (CNO) through increased NLRP3 inflammasome expression.

The pathophysiology of chronic nonbacterial osteomyelitis (CNO) remains incompletely understood. Increased NLRP3 inflammasome activation and IL-1ß release in monocytes from CNO patients was suggested to contribute to bone inflammation. Here, we dissect immune cell infiltrates and demonstrate the involvement of monocytes across disease stages. Differences in cell density and immune cell composition may help to discriminate between BOM and CNO. However, differences are subtle and infiltrates vary in CNO. In contrast to other cells involved, monocytes are a stable element during all stages of CNO, which makes them a promising candidate in the search for "drivers" of inflammation. Furthermore, we link increased expression of inflammasome components NLRP3 and ASC in monocytes with site-specific DNA hypomethylation around the corresponding genes NLRP3 and PYCARD. Our observations deliver further evidence for the involvement of pro-inflammatory monocytes in the pathophysiology of CNO. Cellular and molecular alterations may serve as disease biomarkers and/or therapeutic targets.

[Therapy-resistant swelling of the upper eyelid in childhood]. / Therapieresistente Oberlidschwellung im Kindesalter.

HISTORY: Swelling of the upper eyelid in childhood is caused by a variety of diseases and is very often generated by inflammation but orbital tumors should always be considered in the differential diagnostics. METHODS: We report about a 4-year-old girl with a drug-resistant swelling of the upper eyelid and ptosis of the right eye. This case report demonstrates the route from initial clinical examination to diagnosis and additionally reviews the current status of therapeutic options. RESULTS: After magnetic resonance imaging (MRI) and diagnostic excision, Langerhans cell histiocytosis (LCH) could be histologically proven. Visual acuity and levator muscle function improved from 0.5 to 1.25 and from 2 mm to 12 mm, respectively, by amblyopic prophylaxis and immunosuppressive therapy. CONCLUSIONS: Persistent and drug-resistant swelling of the upper eyelid in childhood is also strongly suspicious for tumors. The suspicion of rare orbital tumors in children can be frequently substantiated by MRI. Biopsy and histological diagnosis are essential to plan adequate treatment and to estimate the prognosis. Particularly in Langerhans cell histiocytosis the methods of choice for over 10 years are specific immunochemical procedures (detection of protein s100 and CD1a).