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Photodynamic therapy (PDT) is an established noninvasive tumor treatment. The hydrophobic natural occurring pigment hypericin shows a lot of attractive properties for the application in PDT. Hence, the administration to biological systems or patients requires the formulation in drug carriers enabling sufficient bioavailability. Therefore, free hypericin was encapsulated by the thin film hydration method or a hypericin-hydroxypropyl-β-cyclodextrin inclusion complex (Hyp-HPβCD) was incorporated by dehydration-rehydration vesicle method in either conventional or ultra-stable tetraether lipid (TEL) liposomes. The hydrodynamic diameter of the prepared nanoformulations ranged between 127 and 212 nm. These results were confirmed by atomic force microscopy. All liposomes showed a good stability under physiological conditions. TEL liposomes which tend to build more rigid bilayers, generate higher encapsulation efficiencies than their conventional counterparts. Furthermore, the suitability for intravenous application was confirmed by hemocompatibility studies resulting in a hemolytic potential less than 20% and a coagulation time less than 50 sec. The uptake of liposomal hypericin into human ovarian carcinoma cells (SK-OV-3) was confirmed using confocal microscopy and further characterized by pathway studies. It was demonstrated that the lipid composition and intraliposomal hypericin localization influenced the anti-vascular effect in the chorioallantoic membrane (CAM). While hypericin TEL liposomes exhibit substantial destruction of the microvasculature drug-in-cyclodextrin TEL liposomes showed no effect. Nevertheless, both formulations yielded severe photocytotoxicity in SK-OV-3 cells in a therapeutic dosage range. Conclusively, hypericin TEL liposomes would be perfectly suited for anti-vascular targeting while Hyp-HPβCD TEL liposomes could deliver the photosensitizer to the tumor site in a more protected manner.

PurposeThe study aims to show how the “Puncture Cube” (PC) (Medical Templates, Egg, Switzerland) compares to the freehand method (FHM) for CT-guided punctures.MethodsThe PC is a patient-mounted disassemblable cube consisting of an upper and lower template with multiple holes each to predefine puncture trajectory. A total of 80 punctures (FHM in-plane, FHM off-plane, PC in-plane, PC off-plane) was performed by 4 radiologists on a target 9.1 cm below surface level of a neoprene covered elliptical cylinder gelatin phantom. The PC was never disassembled. Evaluated parameters were procedure time, number of CT-scans, euclidean distance (ED) and normal distance (ND). Respective parameters of FHM and PC were compared using the Wilcoxon signed-rank test and Levene test with significance levels of 5%.ResultsPC achieved smaller ED and ND values after initial needle insertion without corrections for both in-plane and off-plane punctures (P > 0.05). Variance of initial NDs was off-plane significantly larger for FHM. Final ED after needle path corrections was smaller for FHM both in- and off-plane (P < 0.05). Final off-plane ND was significantly lower for FHM with no significant difference in final in-plane ND. FHM off-plane punctures were significantly faster. There was no significant difference in CT-scans between both methods.ConclusionUtilizing the PC may improve initial needle positioning and safety especially off-plane. However, better final needle positioning after correction with the greater freedom of movement method may suggest need for disassembly of the cube

Purpose Interventional procedures have become a mainstay in the therapy of acute limb ischemia caused by embolism or arterial thrombosis. Treatment options include pharmacological thrombolysis (PT) and mechanical thrombectomy (MT). The aim of this study was to evaluate success and major complication rates of interventional radiological treatments of arterial embolism and thrombosis in Germany in 2021 and to compare their results with accepted international quality standards. Materials and methods Data for PT and MT for 2021 was obtained from the quality management system of the German interventional radiological society (DeGIR). 2431 PT and 1582 MT procedures were documented for 2021, with 459 combinations of PT and MT. Data was analysed for technical and clinical success rates, as well as major complication rates such as intracranial bleeding, major bleeding, distal embolization, aneurysm formation, organ-failure and cardiac-decompensation. Results PT alone had technical and clinical success rate of 90.21% and 81.08%, respectively. MT alone had technical and clinical success rates of 97.41% and 95.39%, respectively. MT&PT had technical and clinical success rates of 91.07% and 84.75%, respectively. Major complications were: distal embolization (PT:2.02%; MT:1.74%; PT&MT:2.61%), major bleeding (PT:0.94%; MT:1.14%; PT&MT:0.87%), aneurysm formation (PT:0.33%;MT: 1.14%;PT&MT: 0%), intracranial bleeding (PT:0.16%;MT:0%;PT&MT:0.22%), cardiac-decompensation (PT:0.21%;MT: 0.06%;PT&MT:0%) and organ-failure (PT:0%;MT:0.06%;PT&MT:0.22%). Technical and clinical success rates were higher, while complication rates were lower than the corresponding threshold recommended by the Society of Interventional Radiology for percutaneous management of acute lower-extremity ischemia. Conclusion Treatment of arterial embolism and thrombosis performed by interventional radiologists in Germany is effective and safe with outcomes exceeding internationally accepted standards.

Lipoparticles are the core-shell type lipid-polymer hybrid systems comprising polymeric nanoparticle core enveloped by single or multiple pegylated lipid layers (shell), thereby melding the biomimetic properties of long-circulating vesicles as well as the mechanical advantages of the nanoparticles. The present study was aimed at the development of such an integrated system, combining the photodynamic and chemotherapeutic approaches for the treatment of multidrug-resistant cancers. For this rationale, two different sized Pirarubicin (THP) loaded poly lactic-co-glycolic acid (PLGA) nanoparticles were prepared by emulsion solvent evaporation technique, whereas liposomes containing Temoporfin (mTHPC) were prepared by lipid film hydration method. Physicochemical and morphological characterizations were done using dynamic light scattering, laser doppler anemometry, atomic force microscopy, and transmission electron microscopy. The quantitative assessment of cell damage was determined using MTT and reactive oxygen species (ROS) assay. The biocompatibility of the nanoformulations was evaluated with serum stability testing, haemocompatibility as well as acute in vivo toxicity using female albino (BALB/c) mice. The mean hydrodynamic diameter of the formulations was found between 108.80 ± 2.10 to 405.70 ± 10.00 nm with the zeta (ζ) potential ranging from -12.70 ± 1.20 to 5.90 ± 1.10 mV. Based on the physicochemical evaluations, the selected THP nanoparticles were coated with mTHPC liposomes to produce lipid-coated nanoparticles (LCNPs). A significant (p< 0.001) cytotoxicity synergism was evident in LCNPs when irradiated at 652 nm, using an LED device. No incidence of genotoxicity was observed as seen with the comet assay. The LCNPs decreased the generalized in vivo toxicity as compared to the free drugs and was evident from the serum biochemical profile, visceral body index, liver function tests as well as renal function tests. The histopathological examinations of the vital organs revealed no significant evidence of toxicity suggesting the safety and efficacy of our lipid-polymer hybrid system.

Photodynamic therapy (PDT) that involves ergonomically delivered light in the presence of archetypical photosensitizer such as Protoporphyrin IX (PpIX) is a time-honored missile strategy in cancer therapeutics. Yet, the premature release of PpIX is one of the most abundant dilemma encounters the therapeutic outcomes of PDT due to associated toxicity and redistribution to serum proteins. In this study, ultrastable tetraether lipids (TELs) based liposomes were developed. PpIX molecules were identified to reside physically in the monolayer; thereby the inherent π-π stacking that leads to aggregation of PpIX in aqueous milieu was dramatically improved. TEL 29.9 mol% and TEL 62mol% based liposomes revealed PpIX sustained release diffusion pattern from spherical particles as confirmed by converged fitting to Baker & Lonsdale model. Stability in presence of human serum albumins, a key element for PDT accomplishment was emphasized. The epitome candidates were selected for vascular photodynamic (vPDT) in in-Ovo chick chorioallantoic membrane. Profoundly, TEL 62mol% based liposomes proved to be the most effective liposomes that demonstrated localized effect within the irradiated area without eliciting quiescent vasculatures damages. Cellular photodynamic therapy (cPDT) revealed that various radiant exposure doses of 134, 202, 403 or 672 mJ.cm −2 could deliberately modulate the photo-responses of PpIX in TEL-liposomes.

Background The chick chorioallantoic membrane (CAM) model has been utilized for radiofrequency ablation and electroporation, but not yet for cryoablation. This study aims to evaluate the feasibility of the CAM model for preclinical cryoablation research. Methods Two cryoablation protocols were established for the study: 120 s-freeze-120 s-thaw-120 s freeze (120 s protocol) and 180 s-freeze-120 s-thaw-180 s freeze (180 s protocol). The study was divided into two parts. First, to evaluate embryo survival, fertilized chicken eggs were incubated. On embryonic day (ED) 12, cryoablation on CAM was performed according to the two protocols. During cryoablation, the temperature of the CAM was recorded using a thermal camera. Embryo survival was monitored until ED 14. Second, to evaluate tumor cryoablation, human neuroendocrine tumor cells (BON-1) were xenografted onto the CAM of fertilized chicken eggs at ED 8. Cryoablation of the xenografted tumors was then performed on ED 12 according to the two protocols. Ablation outcomes were evaluated by stereomicroscopic and histological assessments after harvesting on ED 14. Results Embryo survival rates were 8/9 in both protocols. A decrease in the peripheral temperature of 4.5 (± 0.9) °C and 6.7 (± 1.0) °C was observed in the 120 s and 180 s protocols, respectively. Complete ablation of CAM-grown tumors was observed in 2/6 (120 s protocol) and 2/5 (180 s protocol) cases, few scattered tumor cells remaining in 2/6 (120 s protocol) and 2/5 (180 s protocol) cases. Residual interconnected tumor cells were visible in 2/6 (120 s protocol) and 1/5 (180 s protocol) cases. Conclusion The CAM model is a feasible platform for preclinical cryoablation studies. Relevance statement Chorioallantoic membrane model is a suitable platform for preclinical cryoablation research. Key Points Chick embryos tolerate the temperature drop during cryoablation well with high survival. Effectiveness of cryoablation on xenografted tumors can be histologically evaluated. Cryoablation protocols for xenografted tumors can be further optimized. Graphical Abstract

The alarming growth of multi-drug resistant bacteria has led to a quest for alternative antibacterial therapeutics. One strategy to circumvent the already existing resistance is the use of photodynamic therapy. Antimicrobial photodynamic therapy (aPDT) involves the use of non-toxic photosensitizers in combination with light and in situ oxygen to generate toxic radical species within the microbial environment which circumvents the resistance building mechanism of the bacteria. Hydrogels are used ubiquitously in the biological and pharmaceutical fields, e.g., for wound dressing material or as drug delivery systems. Hydrogels formed by water-insoluble low-molecular weight gelators may potentially provide the much-needed benefits for these applications. Bolalipids are a superior example of such gelators. In the present work, two artificial bolalipids were used, namely PC-C32-PC and Me2PE-C32-Me2PE, which self-assemble in water into long and flexible nanofibers leading to a gelation of the surrounding solvent. The aim of the study was to create stable hydrogel formulations of both bolalipids and to investigate their applicability as a novel material for drug delivery systems. Furthermore, methylene blue—a well-known photosensitizer—was incorporated into the hydrogels in order to investigate the aPDT for the treatment of skin and mucosal infections using a custom designed LED device.

Background: Hypoxic-ischemic brain injury (HIBI) is a feared complication post-cardiac arrest (CA). The timing of brain imaging remains a topic of ongoing debate. Early computed tomography (CT) scans can reveal acute intracranial pathologies but may have limited predictive value due to delayed manifestation of HIBI-related changes. Radiomics analyses present a promising approach to identifying subtle imaging markers, potentially aiding early HIBI detection. Methods: This study retrospectively assessed post-CA patients between 2016 and 2023 who received immediate brain CTs. Patients without acute intracranial pathology on initial scans and who underwent follow-up brain CTs within 14 days post-return of spontaneous circulation (ROSC) were included. Image segmentation involved manual basalganglia segmentation and automated whole-brain segmentation. Radiomics features were calculated using Pyradiomics (v3.0.1) in 3DSlicer (v5.2.2). Feature selection involved reproducibility analysis via ICC and LASSO regression, retaining five features per segmentation method. A logistic regression model for each segmentation method underwent 5-fold cross-validation. Results were summarized with ROC analyses and average sensitivity and specificity. Results: A total of 83 patients (average age: 65 ± 13.3 years, 19 women) with CA and ROSC were included. Follow-up CT scans after 5.2 ± 2.9 days revealed brain edema in 47 patients. The model using manual segmentation achieved an average AUC of 0.76, sensitivity of 0.59, and specificity of 0.78. The automated segmentation model showed an average AUC of 0.66, sensitivity of 0.49, and specificity of 0.68. Conclusions: Radiomics, particularly focused on the basalganglia area in normal-appearing brain CTs after CA and ROSC, may enhance predictive insights for HIBI and the development of brain edema.

Objectives In the presence of escalating global concerns regarding physician burnout, this study aims to analyze the prevalence and associated factors of burnout among radiologists in Germany. Methods A comprehensive online survey, inclusive of 73 targeted questions including a German-modified version of the Maslach Burnout Inventory, was distributed among all members of the German Radiological Society and the German Interventional Radiological Society between May and August 2023. The survey encompassed aspects of employment, workload, well-being, and coping mechanisms. Data from 172 completed surveys were analyzed, with correlations explored via crosstabs and the Pearson-chi-square test. Results In total, 76.7% of participating radiologists were identified to be burnt out. The prevalence was significantly associated with increased workload, reduced sleep quality, suboptimal working conditions, reduced job satisfaction, and the negative interplay between work, family life, and health. Median work satisfaction was described as “satisfied” while median workload was assessed as “frequently overwhelming of work.” A total of 41.9% of respondents noted facing daily time pressure. Radiologists’ concerns about work interfering with private family life were voiced by approximately 70%, and 73.3% highlighted the perceived negative effects on their health. Conclusion The pronounced prevalence of burnout among German radiologists demonstrates an urgent, unmet need for comprehensive interventions and systemic changes. Our findings act as a catalyst for initiating targeted, multifaceted strategies and dialogs, essential for fostering a resilient and effective healthcare ecosystem. Further large-scale systematic studies should follow to analyze the findings in broad. Clinical relevance statement Consistent with other countries, there is a high prevalence of burnout among radiologists in Germany. A call for further investigation is recommended to help mitigate adverse outcomes associated with physician burnout. Key Points • The prevalence of burnout has yet not been evaluated for German radiologists. • German radiologists have a high prevalence of burnout. • Steps must be implemented to engage this problem to prevent worsening. Graphical abstract

Background We evaluated the feasibility of a chick chorioallantoic membrane (CAM) tumor model for preclinical research on tumor radiofrequency ablation (RFA). Methods Fertilized chicken eggs were incubated and divided into five cohorts: RFA for 30 s ( n  = 5), RFA for 60 s ( n  = 5), RFA for 120 s ( n  = 4), sham ( n  = 8), and controls ( n  = 6). Xenografting using pancreatic neuroendocrine tumor cells of the BON-1 cell line was performed on embryonic day (ED) 8. The RFA was performed on ED 12. Survival, stereomicroscopic observations, and histological observations using hematoxylin–eosin (H&E) and Ki67 staining were evaluated. Results The survival rates in the 30-s, 60-s, and 120-s, sham and control cohort were 60%, 60%, 0%, 100%, and 50%, respectively. Signs of bleeding and heat damage were common findings in the evaluation of stereomicroscopic observations. Histological examination could be performed in all but one embryo. Heat damage, bleeding, thrombosis, and leukocyte infiltration and hyperemia were regular findings in H&E-stained cuts. A complete absence of Ki67 staining was recorded in 33.3% and 50% of embryos in the 30-s and 60-s cohorts that survived until ED 14, respectively. Conclusions The CAM model is a feasible and suiting research model for tumor RFA with many advantages over other animal models. It offers the opportunity to conduct in vivo research under standardized conditions. Further studies are needed to optimize this model for tumor ablations in order to explore promising but unrefined strategies like the combination of RFA and immunotherapy. Relevance statement The chick chorioallantoic membrane model allows in vivo research on tumor radiofrequency ablation under standardized conditions that may enable enhanced understanding on combined therapies while ensuring animal welfare in concordance with the “Three Rs.” Key points • The chorioallantoic membrane model is feasible and suiting for tumor radiofrequency ablation. • Radiofrequency ablation regularly achieved reduction but not eradication of Ki67 staining. • Histological evaluation showed findings comparable to changes in humans after RFA. • The chorioallantoic membrane model can enable studies on combined therapies after optimization. Graphical Abstract