Julian Steininger

Early detection of active melanoma metastasis is crucial. Serum metabolomics may offer non-invasive biomarkers, but real-world applicability needs validation. This study aimed to identify ¹H-NMR-based serum metabolic signatures for active metastasis in a large clinical cohort. Serum from 963 melanoma patients (1698 samples) underwent ¹H-NMR spectroscopy. Patients were classified by active metastasis status. OPLS-DA and RFE followed by logistic regression models were developed on a patient-level training/test split. Subgroup analyses assessed signatures related to Immune Checkpoint Inhibitor (ICI) therapy, brain metastases, and BRAF status. Models for active metastasis showed moderate test set discrimination (Area Under the Curve [AUCs]: OPLS-DA 0.609, RFE 0.630). The RFE-model highlighted seven significant metabolites: increased pyruvate, phenylalanine, acetoacetate, glutamate, glucose, and decreased histidine and citrate were associated with active metastasis. OPLS-DA yielded concordant metabolites. Subgroup analyses revealed distinct metabolic associations, e.g., for ICI therapy (citrate, RFE AUC 0.721) and BRAF status (acetate, RFE AUC 0.655), but limited performance for brain metastases (RFE AUC 0.553). ¹H-NMR serum metabolomics detects systemic metabolic alterations of active melanoma metastasis with moderate accuracy in a real-world setting. Identified disruptions in energy and amino acid metabolism offer pathobiological insights and warrant investigation for multimodal biomarker panels.

Food allergies are a significant health concern worldwide, with anaphylaxis being one of the most severe manifestations. This report describes a case of a 65‐year‐old male patient with recurrent grade III anaphylaxis of unknown origin. Through detailed diagnostic testing, a prick‐to‐prick test revealed an allergy to honey, identifying it as the trigger for his severe allergic reactions. Honey allergies are rare but often associated with sensitization to pollen from the Compositae family, to which our patient was also sensitized. Based on these findings, the patient was advised to strictly avoid honey and was provided with an emergency kit. To date, the patient experienced no further anaphylactic episodes.

Background/Objectives: To ensure that non-melanoma skin cancer (NMSC) is completely removed in healthy tissue, micrographically controlled surgery (3D histology) is often performed, which can prolong the inpatient stay. This study examined ex vivo reflectance confocal microscopy (evRCM) for perioperative assessment of surgical margins, specifically in cases where re-excision was necessary due to incomplete removal of cutaneous tumor tissue. Methods: NMSC re-excisions were evaluated using evRCM by a cutaneous surgeon, with retrospective review by an independent pathologist when results differed from histology. Results: evRCM demonstrated high specificity (0.96; 95% CI, 0.90–0.99) but low sensitivity (0.20; 95% CI, 0.06–0.51). Unlike pathology, which discards outer surgical margins, evRCM examined the true surgical margins. Retrospective pathology analysis of the misdiagnosed cases confirmed that 25% (n = 2/8) were false negative and 75% (n = 6/8) were potentially false positive, resulting in a sensitivity of 0.2–0.8. Notably, evRCM led to a 113-day reduction in in-hospital stays, probably resulting in increased patient satisfaction and cost-effectiveness. Conclusions: evRCM was valuable for speeding up the assessment of surgical margins in patients with re-excised NMSC. Proper tissue preparation and assessment require interdisciplinary collaboration between cutaneous surgeons, pathologists, and physician assistants, emphasizing the need for standardized operating procedures.

Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799_1810delinsATG, p.(V600_W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography–tandem mass spectrometry analysis confirmed the drugs’ presence in the patient’s cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies.

Modern diagnostic procedures, such as three-dimensional total body photography (3D-TBP), digital dermoscopy (DD), and reflectance confocal microscopy (RCM), can improve melanoma diagnosis, particularly in high-risk patients. This study assessed the benefits of combining these advanced imaging techniques in a three-step programme in managing high-risk patients. This study included 410 high-risk melanoma patients who underwent a specialised imaging consultation in addition to their regular skin examinations in outpatient care. At each visit, the patients underwent a 3D-TBP, a DD for suspicious findings, and an RCM for unclear DD findings. The histological findings of excisions initiated based on imaging consultation and outpatient care were compared. Imaging consultation detected sixteen confirmed melanomas (eight invasive and eight in situ) in 39 excised pigmented lesions. Outpatient care examination detected seven confirmed melanomas (one invasive and six in situ) in 163 excised melanocytic lesions. The number needed to excise (NNE) in the imaging consultation was significantly lower than that in the outpatient care (2.4 vs. 23.3). The NNE was 2.6 for DD and 2.3 for RCM. DD, 3D-TBP, or RCM detected melanomas that were not detected by the other imaging methods. The three-step imaging programme improves melanoma detection and reduces the number of unnecessary excisions in high-risk patients.