Johannes Woltsche

In an international registry analysis of 201 patients with SM-AHN, KIT D816V-selective TKI exposure was associated with longer overall survival (37.9 vs 17.8 months; P <.001) and lower 36-month incidence of acute myeloid leukemia transformation (5.9% vs 27.1%; P <.001).

Cutaneous T-cell lymphomas (CTCL), including mycosis fungoides (MF) and Sézary syndrome (SS), are histopathologically characterized by a prominent inflammatory infiltrate, accompanying the malignant cells in the skin. This infiltrate contributes to diagnostic uncertainty and appears to support the persistence of malignant T cells. Growing evidence supports an inflammation-driven disease model, in which cytokine networks, microbial triggers, and direct cellular interactions shape a tumor-permissive microenvironment. In this perspective, we discuss how established skin-directed therapies achieve clinical benefits not only by directly affecting malignant cells, but also by remodeling the lesional immune milieu and reducing supportive inflammatory infiltrates. We also highlight the importance of targeting microenvironmental signaling pathways, focusing on the OX40/OX40L costimulatory axis and JAK/STAT pathway dysregulation as therapeutic targets. Overall, we propose that integrating tumor-directed therapy with approaches that modify the inflammatory niche may offer a rational strategy to improve long-term disease control in MF/SS.

Background Microplastics (MPs) have been found in human tissues, indicating widespread exposure, but little is known about their excretion and influencing factors. We investigated MP-like particles in human urine and potential differences related to menstrual cycle status in women. Methods Urine samples from 30 healthy adults (15 women, 15 men) were collected twice, with female samples timed for menstruation and non-menstruation, and male samples at random. Samples were purified (hydrogen peroxide), stained (Nile-Red), filtered (3 mm gold coated membrane), scanned (FITC fluorescence) and examined for MP-like particles (manual counted and categorised). Participants completed a questionnaire, statistical analyses explored links between exposure factors and particle counts. Results 30 volunteers provided 2 urine samples; 59 samples could be collected, of which 53 were evaluable. MP-like particles were detected in 48 samples, counts varied across individuals and timepoints (up to 15 particles/mL). No significant difference was observed between sexes, though a trend toward lower counts during menstruation was noted (p = 0.076). In explanatory modelling, self-reported period pad use, composite-packaged drink consumption, coffee preparation method, intimate shaving habits, and sea-salt intake emerged as potential explanatory factors for particle concentrations. Conclusion MP-like particles were detectable in the majority of urine samples analysed using a Nile Red/DAPI fluorescence microscopy workflow. Considerable variability in particle concentrations was observed between individuals and across sampling timepoints. Several questionnaire-derived variables emerged in exploratory analyses; however, given the limited sample size, and the absence of polymer-specific particle identification, these findings should be viewed as exploratory signals needing further confirmation.

Background: In patients with liver cirrhosis, intestinal permeability and the composition of the gut microbiome are altered. Thus, the microbiome might be a therapeutic target for the treatment of both liver diseases and intestinal permeability. We aimed to investigate the relationship between the intestinal barrier and microbiome composition in cirrhosis and elucidate potential mechanisms for how bacteria influence permeability. Methods: We analyzed the fecal permeability biomarker zonulin by ELISA and microbiome composition by 16s rDNA sequencing in a discovery ( n = 78) and a validation cohort ( n = 90) of patients with liver cirrhosis. In the validation cohort, we analyzed the composition of the fecal metabolome by NMR spectroscopy. For mechanistic exploration, an intestinal barrier cell culture model using T84 cells was used. Results: In the discovery cohort ( n = 78, 77% Child‐Pugh Grade A, 21% Child‐Pugh Grade B, 3% Child‐Pugh Grade C), decreasing zonulin levels in stool over 6 months were associated with higher Phascolarctobacterium abundance in the microbiome. Phascolarctobacterium was associated with better liver function (lower bilirubin, p = 0.04, INR p = 0.04, MELD Score, p = 0.02). Lower Phascolarctobacterium levels were observed in decompensated cirrhosis and were associated with 36‐month mortality in two cohorts. Metabolomics analysis showed an association between Phascolarctobacterium and lower succinate levels. Succinate increased gut permeability in vitro, and Phascolarctobacterium succinatutens strains improved the intestinal permeability, potentially by alleviating the effect of succinate. Conclusion: Phascolarctobacterium may represent a candidate biomarker of adverse outcomes in cirrhosis and a promising target for further investigation as a next‐generation probiotic involved in gut barrier function and succinate homeostasis. Trial Registration: NCT01607528, NCT03080129

Immune checkpoint inhibitors (ICIs) have improved survival in advanced melanoma; however, a considerable number of patients does not respond, and side effects are common. Studies suggest that the gut microbiome may influence ICI outcomes, with certain bacteria and microbial functions being linked to a positive response in some patient groups. However, findings are inconsistent across studies, and no universal microbial biomarkers have been identified. Longitudinal and multi-omic analyses indicate that microbial dynamics may matter, and that other body sites, such as the skin and the intratumoral environment, could also be relevant. More systematic research and testing of multiple hypotheses is needed before microbiome-based strategies may be reliably applied in clinical practice. Here, we summarize evidence connecting the human microbiome to ICI response in melanoma.

INTRODUCTION: Cirrhosis is associated with microbiome alterations beyond the gut, including skin, saliva, and serum. This study investigated the urinary microbiome in patients with cirrhosis, who have an increased risk of urinary tract infections. METHODS: Midstream urine from 137 patients was analyzed by 16S rRNA sequencing; 68 patients with cirrhosis and 32 noncirrhotic controls met inclusion criteria. RESULTS: Patients with cirrhosis showed significantly reduced alpha-diversity. The urinary microbiome of controls was enriched in Streptococcus species. DISCUSSION: Reduced microbial diversity and lower Streptococcus abundance in patients with cirrhosis might help to explain their heightened susceptibility to urinary tract infections.

This report illustrates the case of a female patient suffering from severe ocular discomfort, tinnitus and ageusia, 7 months after a SARS-CoV-2 infection. The medical history implicated a diagnosis of LONG-COVID with ocular pain as the most debilitating symptom. In-vivo confocal microscopy revealed corneal microneuromas with hyperreflectivity and irregular enlargement of nerve endings in both eyes, which led to the diagnosis of neuropathic corneal pain. The aim of this report is to increase awareness that COVID-19 induced neuropathic pain can also occur in the cornea representing the human body’s most richly innervated tissue.