HELIOS St. Elisabeth Klinik Oberhausen

PurposeTo assess the association of systemic immune-inflammation biomarkers (SIIBs) and other clinical parameters with objective response rate (ORR), progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS), and immune-related adverse events (irAEs) in patients with advanced cSCC treated with cemiplimab, and to compare baseline SIIBs levels between early-stage and advanced-stage disease.MethodsA retrospective multicenter cohort of 110 immunocompetent advanced cSCC patients treated with cemiplimab was analysed. ORR was assessed using logistic regression; PFS and OS were evaluated using Cox models, and DSS using cause-specific hazards. ROC analyses assessed biomarker discrimination. Baseline SIIBs (LMR, NLR, SIRI) were compared between early-stage (AJCC I/II, non-ICI cohort, n = 59) and advanced-stage disease. Tumor characteristics, body mass index (BMI), and Charlson comorbidity index were evaluated.ResultsAmong 110 patients, 79 (71.8%) achieved an objective response. Baseline LMR showed modest discrimination for ORR (AUC 0.64, 95% CI 0.53–0.75; p = 0.015) but did not retain statistical significance after adjustment for baseline clinical covariates (OR 1.35, 95% CI 0.95–1.91; p = 0.096). Higher BMI was associated with improved PFS (HR 0.94 per kg/m2, 95% CI 0.89–1.00; p = 0.035) and showed a borderline association with OS (HR 0.92 per kg/m2, 95% CI 0.85–1.00; p = 0.051). AJCC stage IV strongly predicted DSS (HR 14.03, 95% CI 1.80–109.67; p = 0.012). Baseline LMR was higher in early-stage than in advanced-stage disease (Hodges-Lehmann difference 0.43; p = 0.011), whereas NLR did not differ significantly between stage groups; SIRI was modestly higher in advanced-stage disease (p = 0.029).ConclusionsIn immunocompetent patients with advanced cSCC receiving PD-1 inhibition, BMI was prognostic for survival and AJCC stage remained the key driver of cSCC-specific mortality. Baseline LMR showed a modest association with response and differed between early- and advanced-stage disease, whereas other SIIBs were not consistently linked to tumor progression. Prospective validation is warranted.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00432-026-06423-x.

Ein 64-jähriger Patient wurde mit seit circa 30 Jahren bestehenden, rezidivierenden, an wechselnden Körperregionen auftretenden Hautveränderungen in unserer Ambulanz vorstellig. Mehrere in den vergangenen Jahren entnommene Probebiopsien erbrachten den histopathologischen Nachweis eines Ekzems. Unter Applikation diverser kortikosteroidhaltiger Salben zeigte sich der Hautbefund nur kurzfristig gebessert. Bei Vorstellung imponierten an beiden oberen Extremitäten, am Rücken, intertriginös sowie abdominell mittig über die Hüften bis zu beiden Oberschenkeln ziehend disseminierte, großflächig konfluierende, retikulär anmutende, indurierte, erythematöse Plaques (Abbildung 1a, b). Es bestanden weder Pruritus noch Schmerzen. Der Lymphknotenstatus sowie die orientierende körperliche Untersuchung verblieben ohne pathologischen Befund. B-Symptomatik und Allergien wurden verneint. Nebenbefundlich waren eine Hypothyreose, Hypercholesterinämie sowie arterielle Hypertonie vorhanden. Die Borrelien- sowie Syphilis-Serologie fiel, ebenso wie das Routinelabor und die Lymphozyten-Subpopulationsanalyse, unauffällig aus. Der CD4/CD8-Quotient lag im Referenzbereich. Die im Rahmen der Erstvorstellung durchgeführten Rebiopsien zeigten eine regelrecht geschichtete Epidermis mit abgeflachten Reteleisten sowie mildem Epidermotropismus. Abschnittsweise zeigte sich eine aufgelockerte Basalzellschicht mit Keratinozyten-Apoptosen und subepithelial gelegenen Melanophagen (Abbildung 2). In der Dermis fanden sich interstitielle und perivaskuläre Infiltrate mit junktionaler Aufreihung von T-Lymphozyten, welche immunhistochemisch einen CD3+CD4+CD30− Phänotyp aufwiesen. Vereinzelt fanden sich CD8+ T-Lymphozyten. Interstitiell fanden sich zudem zahlreiche CD68+ Makrophagen (Abbildung 3a–d). Auf molekularpathologischer Ebene erfolgte der Nachweis einer T-Zell-Klonalität. Ihre Diagnose? … Diagnose: Interstitielle Mycosis fungoides Mittels Computertomografie konnte eine extrakutane Beteiligung ausgeschlossen werden. Therapeutisch initiierten wir, nach bis dato frustraner Anwendung topischer Glukokortikosteroide und Bade-PUVA-Therapie, eine Behandlung mit Chlormethin-Gel im Bereich der betroffenen Hautareale. Aufgrund starker lokaler Entzündungsreaktionen unter Chlormethin-Gel erfolgte seitens des Patienten ein vorzeitiger Therapieabbruch, sodass wir uns für die Einleitung einer extrakorporalen Photopherese (ECP) im vierwöchigen Rhythmus entschieden. Bisher erfolgten vier Zyklen einer ECP-Monotherapie. Hierunter zeigte sich klinisch eine deutliche Befundverbesserung. Ergänzend verwendet der Patient aktuell pflegende Externa. Die interstitielle Mycosis fungoides (IMF), erstmalig 1994 von Shapiro und Pinto erwähnt, ist eine seltene Variante der Mycosis fungoides (MF),1, 2 die in der WHO-Klassifikation bisher keinen Eingang als Subentität gefunden hat.3 Bisher sind in der internationalen Literatur weniger als 100 Fälle der IMF veröffentlicht worden.1, 4 Die von Chung et al. publizierte, bisher größte retrospektive Studie zur IMF mit insgesamt 31 Patienten dokumentiert ein überwiegend männliches Patientenkollektiv (61 % der Fälle männlich; mittleres Alter bei Erstdiagnose: 43 Jahre), bei denen die Hautveränderungen im Durchschnitt bereits 7 Jahre vor Diagnosestellung bestanden.4 Klinisch manifestiert sich die IMF zumeist unter dem Bild der „klassischen“ MF mit Patches und Plaques an unterschiedlichen Körperregionen, die sich insbesondere intertriginös zeigen und die teilweise mit einer Alopezie einhergehen.4, 5 Häufig wird die IMF klinisch als Morphea, interstitielle granulomatöse Dermatitis, Granuloma anulare oder auch extragenitaler Lichen sclerosus fehlinterpretiert.6, 7 Differenzialdiagnostisch abzugrenzen sind ebenso die follikulotrope MF und das granulomatous slack skin syndrome.4, 8 Histopathologisch zeigt sich ein interstitielles lymphozytäres Infiltrat, welches zumeist, so auch in unserem Fall, einen CD3+CD4+-Phänotyp und einen fehlenden bis milden Epidermotropismus aufweist.4 Sowohl Therapie als auch Prognose der IMF entsprechen der „klassischen“ MF.5 Laut der zuletzt im Jahr 2021 aktualisierten S2k-Leitlinie der AWMF zu kutanen Lymphomen wird der therapeutische Einsatz der ECP erst ab Stadium III empfohlen. In unserem Patientenfall kam die ECP bereits in Stadium IB zum Einsatz und führte zu einem deutlichen klinischen Therapieansprechen. Weitere Untersuchungen sind unserer Meinung nach erforderlich, um zu überprüfen, inwieweit sich die ECP auch als Therapieoption in früheren Stadien der IMF eignet.10 Keiner.

ObjectiveThe common gain-of-function variant rs35705950, located in the promoter of MUC5B gene, has been strongly associated with interstitial lung diseases (ILDs) of different aetiology, such as idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated ILD (RA-ILD). In this study, we aimed to investigate the association of this variant and its nearby single nucleotide polymorphisms (SNPs) in the largest cohort of systemic sclerosis-associated ILD (SSc-ILD) to date.MethodsSamples were collected from blood/saliva, followed by DNA extraction and genotyping using SNP arrays. Data for rs35705950 and additional 903 variants within 100 Kb were obtained using genomic imputation. Subsequently, we tested their association in a meta-analysis to increase the consistency of the results, including 10 European ancestry cohorts comprising 2363 patients with SSc-ILD, 3526 SSc patients without ILD and 15 076 controls.ResultsMeta-analysis showed no significant association between rs35705950 and SSc-ILD, either comparing patients with SSc with and without ILD (p value: 0.588, OR: 1.05, 95% CI: 0.87 to 1.27) nor patients with SSc-ILD with controls (p value: 0.061, OR: 1.16, 95% CI: 0.99 to 1.36). Moreover, none of the additional 903 variants tested in the genomic region reached statistical significance.ConclusionDespite analysing the largest and most statistically powered SSc-ILD cohort to date, we found no evidence of association between the MUC5B promoter variant rs35705950 and its surrounding SNPs with SSc-ILD. These results suggest that the pathogenic mechanisms underlying SSc-ILD may only partially overlap with those of other similar ILDs, such as IPF or RA-ILD. This highlights the need for further studies regarding their genetic architecture.

SummaryPeople with HIV are up to 100 times more likely to develop anal carcinoma compared to the general population. Diagnosing and treating precursor lesions, specifically high‐grade anal dysplasia, can significantly reduce the risk of developing anal carcinoma. This S2k‐guideline outlines the factors that increase the likelihood of developing anal carcinoma and its precursors, including advancing age, a low CD4+ T‐lymphocyte nadir, active cigarette smoking, receptive anal intercourse, or persistent infection with high‐risk (HR) types of human papillomavirus (HPV). Screening is primarily recommended for all men who have sex with men (MSM) and transgender women with HIV starting at age 35, and all people with HIV starting at age 45.After inspection and digital anorectal examination, anal cytology is collected. An HR‐HPV test may be performed. If clinical abnormalities are present or if cytology shows “ASC‐US or worse”, a referral for high‐resolution anoscopy (HRA) is indicated. If lesions are found during HRA, a biopsy should be obtained. Anal intraepithelial neoplasia (AIN) grade‐III or AIN‐II p16‐positive correspond to high‐grade dysplasia and require treatment. The most strongly recommended therapeutic options are electrocautery, 85% trichloroacetic acid, and surgical excision.Finally, the guideline discusses how these screening recommendations can be applied to individuals without HIV.

BackgroundLeishmania infantum is the only prevalent Leishmania species in Europe and manifesting predominantly as cutaneous or visceral leishmaniasis, whereas new world species like Leishmania (L.) braziliensis are well known pathogens in mucocutaneous leishmaniasis. Mucosal leishmaniasis caused by L. infantum is a rare clinical condition with only few cases described in literature. In contrast to our case, mostly immunocompromised patients with no history of leishmaniasis are affected.Case presentationWe describe the case of a 77-year-old German male who developed an ulcerous lesion of the tongue. As oral cancer was suspected, the patient underwent surgery. After suspected diagnosis of Leishmania spp. in histopathology, the patient was referred to our department for further diagnostics and treatment. Relapse from a cutaneous leishmaniasis acquired in Spain is likely, as L. infantum could be identified as the causative agent. The patient recovered after treatment.ConclusionsMucosal leishmaniasis caused by L. infantum is rare and usually mistaken for malignancy. As demonstrated, it can be preceded by cutaneous leishmaniasis of the immunocompetent. Due to possible dissemination systemic treatment should be applied.

Bariatric surgery is an effective long-term treatment for severe obesity, but relapse rates remain high. Digital interventions can enhance patient care, yet research on the intention to use digital discharge management interventions is lacking. This study aims to assess the behavioral intention to use digital discharge management interventions after bariatric surgery and to identify differences in sociodemographic and medical characteristics, as well as potential key drivers and barriers. A cross-sectional study with N = 514 patients was conducted using the Unified Theory of Acceptance and Use of Technology (UTAUT). Mean scores for behavioral intention and predictors were calculated. Group differences were analyzed with independent t-tests and analyses of variance with post hoc tests. Drivers and barriers were assessed through multiple hierarchical regression analysis. The behavioral intention to use digital discharge management interventions was high. Significant predictors included age (β = −0.17, p < 0.001), eHealth literacy (β = 0.10, p = 0.037), internet anxiety (β = −0.15, p = 0.003), and time since bariatric operation (β = −0.13, p = 0.005). The predictors performance expectancy (β = 0.23, p < 0.001), effort expectancy (β = 0.36, p < 0.001), and social influence (β = 0.26, p < 0.001) were significantly positive key factors. These results confirm the need for implementing digital discharge interventions after bariatric surgery, with various drivers and barriers identified for application usage.