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Background: Photodynamic therapy (PDT) is an excellent treatment option for actinic keratosis. However the side effects lead to an impairment of the patients' quality of life. Objectives: To evaluate the impact of PDT on patients' quality of life and to determine the frequency and intensity of side effects over the course of 4 weeks post PDT. Patients and Methods: 22 patients with actinic keratosis in the face were included into this prospective study. Pain was measured using a visual analog scale immediately and 8 h after PDT. The Dermatology Life Quality Index (DLQI) was assessed at screening, after treatment as well as 2 and 4 weeks after PDT. The physician and patient evaluated the intensity of side effects during the treatment, 2 and 4 weeks post PDT. Additionally, the patient documented side effects daily from the 1st to the 14th day after PDT and on day 28 post PDT, using a diary. Results: We observed a significant (p < 0.001) increase in the DLQI from 1.6 ± 1.7 prior to PDT to 7.3 ± 4.9 post PDT. The DLQI normalized in the following 4 weeks. Immediately and 8 h after PDT mean pain was 4.3 ± 2.5 and 2.3 ± 2.1. Side effects documented by the patients were erythema (100%), pain, burning, edema (90.9%), itching (86.4%), scaling (81.8%) and pustules (59.1%). No scar formation, hyper-/hypopigmentation or infections were observed. Conclusion: PDT has a significant temporary impact on patients' DLQI. Transitory side effects are common and show typical kinetics.

Background: Extended skin malignancies of the head and neck region are among the most common cancer types and are associated with numerous diagnostic and therapeutical problems. The radical resection of skin cancer in the facial area often leads to severe functional and aesthetic impairment, and precise margin assessments can avoid the extensive safety margins. On the other hand, the complete removal of the cancer is essential to minimize the risk of recurrence. Reliable intraoperative assessments of the wound margins could overcome this discrepancy between minimal invasiveness and safety distance in the head and neck region. With the help of reflectance confocal laser microscopy (RCM), cells can be visualized in high resolution intraoperatively. The combination with deep learning and automated algorithms allows an investigator independent and objective interpretation of specific confocal imaging data. Therefore, we aimed to apply a deep learning algorithm to detect malignant areas in images obtained via in vivo confocal microscopy. We investigated basal cell carcinoma (BCC), as one of the most common entities with well-described in vivo RCM diagnostic criteria, within a preliminary feasibility study. Patients and Methods: We included 62 patients with histologically confirmed BCC in the head and neck region. All patients underwent in vivo confocal laser microscope scanning. Approximately 382 images with BCC structures could be obtained, annotated, and proceeded for further deep learning model training. Results: A sensitivity of 46% and a specificity of 85% in detecting BCC regions could be achieved using a convolutional neural network model (“MobileNet”). Conclusion: The preliminary results reveal the potential and limitations of the automated detection of BCC with in vivo RCM. Further studies with a larger number of cases are required to obtain better predictability.

Background: Topical photodynamic therapy (PDT) is an excellent treatment option for actinic keratosis (AK). Pain is one of the major adverse effects. Objective: To compare the pain intensity during the extensive treatment of cosmetic units using 5-aminolaevulinic acid methylester (MAL) or 5-aminolaevulinic acid nanoemulsion (BF-200-ALA). Methods: 173 patients with 965 treated areas were enrolled in this retrospective monocentric study. All patients had multiple AKs and received an extensive treatment of the photodamaged area. 424 areas were treated with MAL and 541 with BF-200-ALA. Pain was rated using a standardized visual analogue scale (VAS). The number of PDT treatment interruptions was documented. Results: PDT with MAL led to a lower mean VAS score (5.0 vs. 5.8), a lower number of treatment interruptions (13.2 vs. 19.9%) and a lower amount of patients experiencing severe pain (25.0 vs. 36.0%) compared to PDT with BF-200-ALA. Conclusion: Our data shows that PDT using MAL is less painful than PDT using BF-200-ALA resulting in a significantly lower mean VAS score (p < 0.001), significantly fewer patients experiencing severe pain (p < 0.001) and a significantly (p < 0.05) lower number of treatment interruptions. Differences in selectivity for tumour cells and transport of ALA in peripheral neurons may play a role.

Introduction Photodynamic therapy (PDT) is an effective treatment option for extensively photodamaged skin with multiple actinic kerastosis. However, the main drawback of PDT is the intensive pain experienced during its application, which makes it frequently necessary to interrupt or even terminate the process resulting in incomplete treatment. Several strategies for controlling pain during PDT have been studied but few effective methods are currently available. Alternative options are urgently needed. Livopan, a nitrous oxide/oxygen mixture, is indicated for the treatment of short-term pain conditions when rapid analgesic onset and offset effects are wanted. But so far, there are no studies evaluating the effect of Livopan on pain intensity during PDT. Therefore, it remains unclear whether patients benefit from this inhalation analgesia. Within the Livopan study, this issue will be evaluated for the first time. Methods and analysis The Livopan study is a prospective, single-centre, explorative, controlled, observational study to investigate the pain reduction in patients after applying a nitrous oxide/oxygen mixture (Livopan) during PDT according to the visual analogue scale in 60 patients. Ethics and dissemination Ethics approval was provided by the ethics committee of the medical faculty of the University of Heidelberg. Ethics approval number S-169/2014. Trial registration number German Clinical Trial Register (DRKS): DRKS00006054.

Outcome assessment of a novel optical fiber probe for the 1470 nm diode laser under real-world conditions. Prospective clinical pilot study in 10 patients undergoing endovenous laser ablation with a follow-up period of 1 year. Primary endpoints were efficacy and safety. Secondary endpoints include, inter alia, quality of life and patient satisfaction. After a follow-up period of 1 year all treated vein segments were still occluded. Only mild and short-term side effects (hematoma, ecchymosis and hyperpigmentation) were observed. No intake of pain medication was needed and a quick return to normal activity was documented (0.9 days). Clinical hallmarks of the venous disease (VCSS) improved significantly (p= .003). All patients were very satisfied with the treatment and quality of life (AVVQ) was significantly improved after the procedure (p=.008). The study demonstrates that the endoluminal treatment with the novel fiber probe is highly effective and safe.

Study Design: Expert opinion. Objectives: Osteoporotic vertebral fractures are of increasing medical importance. For an adequate treatment strategy, an easy and reliable classification is needed. Methods: The working group “Osteoporotic Fractures” of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU) has developed a classification system (OF classification) for osteoporotic thoracolumbar fractures. The consensus decision followed an established pathway including review of the current literature. Results: The OF classification consists of 5 groups: OF 1, no vertebral deformation (vertebral edema); OF 2, deformation with no or minor (<1/5) involvement of the posterior wall; OF 3, deformation with distinct involvement (>1/5) of the posterior wall; OF 4, loss of integrity of the vertebral frame or vertebral body collapse or pincer-type fracture; OF 5, injuries with distraction or rotation. The interobserver reliability was substantial (κ = .63). Conclusions: The proposed OF classification is easy to use and provides superior clinical differentiation of the typical osteoporotic fracture morphologies.

Angiosarcoma is an aggressive malignancy of endothelial differentiation. Potential roles of the endothelial angiopoietin-tunica interna endothelial cell kinase (ANGPT-TIE) system in angiosarcoma diagnosis, pathogenesis, prognosis and treatment are undefined. To examine the expression and prognostic significance of angiopoietin-1, angiopoietin-2, TIE1 and TEK (TIE2) proteins in angiosarcoma, we immunohistochemically evaluated clinically annotated human angiosarcoma samples. Correlations of protein expression with overall survival and pathological features were explored. The cohort included 51 patients diagnosed with angiosarcoma at the age of 30–86 years (median 67). The 5-year overall survival was 45% with a median of 26 months. Moderate to strong expression of angiopoietin-1, TIE1 and TEK (TIE2) was identified in the majority of angiosarcomas and moderate to strong expression of angiopoietin-2 was observed in 42% of angiosarcomas. Increased angiopoietin-1 expression correlated with improved survival. Non-significant trends toward longer survival were also observed with increased TIE1 and TEK (TIE2) expression. Increased expression of angiopoietin-2, TIE1 and TEK (TIE2) was associated with vasoformative architecture. No differences in expression of these proteins were observed when patients were segregated by age, gender, presence or absence of metastases at diagnosis, primary tumor location, radiation association or the presence of necrosis. We conclude that components of the ANGPT-TIE system are commonly expressed in angiosarcomas. Reduced expression of these proteins is associated with non-vasoformative and clinically more aggressive lesions.

Accurate and efficient modeling of atmospheric composition, including aerosols and trace gases and their interactions with radiation, clouds, and dynamics is essential for improving predictions and understanding of air quality, weather, climate, and related health impacts. The Aerosols and Reactive Trace gases (ART) component extends the ICOsahedral Nonhydrostatic (ICON) modeling framework by enabling online, fully coupled simulations of atmospheric composition processes across scales. ICON-ART includes modules for emissions, transport, gas-phase chemistry, and aerosol microphysics in both the troposphere and stratosphere, allowing for the investigation of feedbacks between atmospheric composition and physical processes from the large-eddy to global scale. This paper presents an updated overview of the ICON-ART framework as implemented in version 2025.10, highlighting recent developments in emission parameterizations, chemical mechanisms, aerosol processes, and coupling to the physical core of ICON via aerosol–radiation and aerosol–cloud interactions. We summarize the structure of the code infrastructure and demonstrate the model’s flexibility and scalability across a wide range of applications. ICON-ART provides a unified and modular platform for research and operational use in atmospheric composition, bridging the gap between regional air quality modeling and global Earth system simulations.

The microbiome is a complex host factor and key determinant of the outcome of antibody-based and cellular immunotherapy. Its postbiotics are a blend of soluble commensal byproducts that are released into the host environment and have been associated with the regulation of immune homeostasis, particularly through impacts on epigenetics and cell signaling. In this study, we show that the postbiotic pentanoate is metabolized to citrate within the TCA cycle via both the acetyl- and succinyl-CoA entry points, a feature uniquely enabled by the chemical structure of the C5 aliphatic chain. We identified ATP-citrate lyase as the crucial factor that redirects pentanoate-derived citrate from the succinyl-CoA route to the nucleus, thereby linking metabolic output and histone acetylation. This epigenetic-metabolic crosstalk mitigated T cell exhaustion and promoted naive-like differentiation in pentanoate-programmed chimeric antigen receptor (CAR) T cells. The predictive and therapeutic potential of pentanoate was corroborated in two independent patient cohorts and three syngeneic models of CAR T adoptive therapy. Our data demonstrate that postbiotics are integrated into mitochondrial metabolism and subsequently incorporated as epigenetic imprints. This bridge between microbial and mammalian interspecies communication can ultimately impact T cell differentiation and efficacy.

Emerging data have highlighted a correlation between microbiome composition and cancer immunotherapy outcome. While commensal bacteria and their metabolites are known to modulate the host environment, contradictory effects and a lack of mechanistic understanding impede the translation of microbiome-based therapies into the clinic. In this study, we demonstrate that abundance of the commensal metabolite pentanoate is predictive for survival of chimeric antigen receptor (CAR) T cell patients in two independent cohorts. Its implementation in the CAR T cell manufacturing workflow overcomes solid tumor microenvironments in immunocompetent cancer models by hijacking the epigenetic-metabolic crosstalk, reducing exhaustion and promoting naive-like differentiation. While synergy of clinically relevant drugs mimicked the phenotype of pentanoate-engineered CAR T cells in vitro, in vivo challenge showed inferior tumor control. Metabolic tracing of 13C-pentanoate revealed citrate generation in the TCA cycle via the acetyl- and succinyl-CoA entry points as a unique feature of the C5 aliphatic chain. Inhibition of the ATP-citrate lyase, which links metabolic output and histone acetylation, led to accumulation of pentanoate-derived citrate from the succinyl-CoA route and decreased functionality of SCFA-engineered CAR T cells. Our data demonstrate that microbial metabolites are incorporated as epigenetic imprints and implementation into CAR T cell production might serve as embodiment of the microbiome-host axis benefits for clinical applications.