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Distinct Epitopes Are Associated With Clinical Phenotypes in Autoimmune Nodopathies With Anti-Contactin1 Autoantibodies
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Advancing liquid biopsy: whispering gallery mode laser detection of the HER2 cancer biomarker on extracellular vesicles
No full textDevelopment of mechanically tough, sustainable, and naturally sourced, material for circular economy
No full textThe thesis explores the development of a water-based system derived from sustainable resources with the aim of replicating the properties of traditional petroleum-based materials and expanding the application scope of natural materials.It begins with an overview of the linear and circular economy concepts, comparing their approaches and discussing the challenges and business models associated with implementing a circular economy. The thesis then dives into two classes of macromolecules: synthetic materials and biopolymers, particularly marine-based macromolecules, examining their properties and applications.The concept of Interpenetrating Networks (IPNs) and strategies for enhancing mechanical properties in polymers and metals are discussed, followed by predominant chemical techniques for polysaccharide functionalization and their applications in various fields.A system engineered to produce tough marine-based materials using double IPNs is presented, utilizing physically crosslinked carboxylated agarose (CA) and ionically crosslinked alginate (Alg). This system demonstrates the capability to yield films surpassing the mechanical properties of PLA and HDPE, with a focus on the structure-property-functional relationship.Finally, a process involving the modification of CA backbone with amine groups is outlined, enabling the blending of amine-functionalized CA with inert materials agarose. This opens up possibilities for utilizing these materials in biofunctionalized bioinks for cell printing applications
Neutralizing the odds: biomechanical protection by adiposity offsets physiological burden to explain the trauma ’obesity-paradox’
No full textBackgroundThe global rise in obesity presents a complex challenge in trauma care, characterized by the "Obesity Paradox." This study aimed to evaluate the biomechanical protection hypothesis and its influence on initial injury severity and clinical outcome in severely injured patients.MethodsThis retrospective study analyzed 1549 adult trauma patients (ISS≥9) divided into Non-Obese (NO, BMIResultsThe OB cohort was significantly older and presented higher pre-existing comorbidity. Supporting the cushioning effect, OB patients exhibited a significantly lower overall ISS (p=0.035) and lower regional AIS scores for the Head/Neck (p=0.008) and Abdomen/Pelvis (p=0.036). OB patients suffered greater morbidity however, with higher SAPS II scores (p1.08, pConclusionsOur findings strongly suggest that the "Obesity Paradox" in major trauma is not a mere statistical anomaly, but a reproducible phenomenon with a distinct mechanistic explanation: Biomechanical protection which results in a lower ISS, neutralizes the increased physiological and comorbidity burden of the obese state
Iterative hepatic and pulmonary metastasectomy in stage IV colorectal cancer: impact on survival and surgical outcomes
No full textBackgroundColorectal cancer frequently metastasizes to the liver and lungs. Despite curative-intent resections, recurrence rates are high. While initial hepatic and pulmonary metastasectomies have been well-studied, data are limited on outcomes following iterative resections for recurrent metastases in both locations.MethodsWe retrospectively assessed the long-term outcome (> 10 years) of 97 patients who underwent iterative hepatic and pulmonary resections for recurrent colorectal cancer metastases.ResultsPost initial hepatic metastasectomy survival rates showed no difference for synchronous and metachronous colorectal liver metastases. Multiple hepatic as well as pulmonary metastasectomies did ameliorate patient survival compared to single resections. Postoperative complications ≥ Clavien Dindo grade II after a second hepatic metastasectomy were associated with reduced overall survival, while complication profiles did not alter survival rates after pulmonal metastasectomies. Importantly, iterative liver and lung surgery did not increase subsequent postoperative complications, with median complication severity remaining at Clavien Dindo grade II-IIIa across successive resections.ConclusionsOur data suggest comparable benefits from hepatic metastasectomy regardless of metastatic sequence. Our findings demonstrate the safety and potential survival benefits of iterative hepatic and pulmonary resections for recurrent colorectal cancer metastases. These data support an aggressive surgical approach in selected patients with recurrent colorectal metastases
ESMO-ESTRO consensus statements on the safety of combining radiotherapy with immune checkpoint inhibitors, VEGF(R) inhibitors, or multitargeted tyrosine kinase inhibitors
No full textBackgroundThe combination of radiotherapy (RT) with targeted agents or immunotherapy may result in improved outcomes, but it can also increase toxicity. However, there is a paucity of high-quality toxicity data, leading to an absence of evidence-based guidelines.DesignTo address this, European Society for Medical Oncology (ESMO) and European SocieTy for Radiotherapy and Oncology (ESTRO) initiated a series of systematic reviews followed by a Delphi consensus process to develop multidisciplinary, evidence-based consensus statements regarding the safety of combining RT with such agents. The current publication describes the combination of RT with immune checkpoint inhibitors (ICIs), vascular endothelial growth factor (receptor) [VEGF(R)] inhibitors, or multitargeted tyrosine kinase inhibitors (TKIs). By systematically covering different drug classes and irradiated areas, 76 clinical scenarios were evaluated during two Delphi rounds with 20 international experts. Safety statements were developed for each scenario, based on the systematic literature reviews.ResultsA total of 5921 records were screened during the systematic literature review process for ICIs, VEGF(R) inhibitors, and multitargeted TKIs, and 159 reports were selected for inclusion in the final literature reviews and the database. During the two Delphi rounds, agreement was reached regarding the safety statements for 74 clinical scenarios.ConclusionsGenerally, the expected toxicity of combining RT with ICIs is low, particularly for programmed death(-ligand) 1 inhibitors. For most combinations with VEGF(R) inhibitors and multitargeted TKIs, exercising caution is recommended. The evidence-based safety statements developed during this comprehensive project provide practical guidance on combining RT with targeted cancer therapies and immunotherapy