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49 p.-9 fig.-1 tab.-1 graph. abst., Background and purpose: The pathogenesis of osteoarthritis (OA) implicates a low-grade inflammation associated to the activation of the innate immune system. Toll like receptor (TLR) stimulation triggers the release of inflammatory mediators, which aggravate OA severity. The aim was to study the preventive effect of 6-shogaol (6S), a potential TLR4 inhibitor, on the treatment of experimental knee OA., Experimental approach: OA was induced in C57BL6 mice by surgical section of the medial meniscotibial ligament, which received 6S for eight weeks. Cartilage damage, inflammatory mediator presence, and disease markers were assessed in the joint tissues by immunohistochemistry. Computational modelling was used to predict binding modes of 6S into the TLR4/MD2 receptor and its permeability across cellular membranes. Employing LPS-stimulated chondrocytes and MAPK assay, we clarified 6S action mechanisms., Key results: 6S treatment was able to prevent articular cartilage lesions, synovitis, and the presence of pro-inflammatory mediators and disease markers in OA animals. Molecular modelling studies predicted 6S interaction with the TLR4/MD-2 heterodimer in an antagonist conformation through its binding into the MD-2 pocket. In cell culture, we confirmed that 6S reduced LPS-induced TLR4 inflammatory signaling pathways. Besides, MAPK assay demonstrated that 6S directly inhibits the ERK1/2 phosphorylation activity., Conclusion and implications: 6S evoked a preventive action on cartilage and synovial inflammation in OA mice. 6S effect may take place not only by hindering the interaction between TLR4 ligands and the TLR4/MD-2 complex in chondrocytes, but also through inhibition of ERK phosphorylation, implying a pleiotropic effect on different mediators activated during OA, which proposes it as an attractive drug for OA treatment., This work was partially supported by grants from the Instituto de Salud Carlos III (PI16/00991,PI18/00261, PI20/00349) and MICINN (CTQ2017-88353-R). AM’s work was funded by the Instituto de Salud Carlos III through the “Miguel Servet” grant program (CP15/00053). PG and AL were founded by Fundación Conchita Rábago, and AM-R was founded by MINECO through the FPI program (PRE2018-086249). This work is co-funded by Fondo Europeo de Desarrollo Regional (FEDER).

Chondrocytes in osteoarthritic (OA) cartilage acquire a hypertrophic-like phenotype, where Hedgehog (Hh) signaling is pivotal. Hh overexpression causes OA-like cartilage lesions, whereas its downregulation prevents articular destruction in mouse models. Mutations in EVC and EVC2 genes disrupt Hh signaling, and are responsible for the Ellis-van Creveld syndrome skeletal dysplasia. Since Ellis-van Creveld syndrome protein (Evc) deletion is expected to hamper Hh target gene expression we hypothesized that it would also prevent OA progression avoiding chondrocyte hypertrophy. Our aim was to study Evc as a new therapeutic target in OA, and whether Evc deletion restrains chondrocyte hypertrophy and prevents joint damage in an Evc tamoxifen induced knockout (EvccKO) model of OA. For this purpose, OA was induced by surgical knee destabilization in wild-type (WT) and EvccKO adult mice, and healthy WT mice were used as controls (n = 10 knees/group). Hypertrophic markers and Hh genes were measured by qRT-PCR, and metalloproteinases (MMP) levels assessed by western blot. Human OA chondrocytes and cartilage samples were obtained from patients undergoing knee joint replacement surgery. Cyclopamine (CPA) was used for Hh pharmacological inhibition and IL-1 beta as an inflammatory insult. Our results showed that tamoxifen induced inactivation of Evc inhibited Hh overexpression and partially prevented chondrocyte hypertrophy during OA, although it did not ameliorate cartilage damage in DMM-EvccKO mice. Hh pathway inhibition did not modify the expression of proinflammatory mediators induced by IL-1 beta in human OA chondrocytes in culture. We found that hypertrophic—IHH—and inflammatory—COX-2—markers co-localized in OA cartilage samples. We concluded that tamoxifen induced inactivation of Evc partially prevented chondrocyte hypertrophy in DMM-EvccKO mice, but it did not ameliorate cartilage damage. Overall, our results suggest that chondrocyte hypertrophy per se is not a pathogenic event in the progression of OA., This work was financially supported by grants from the Instituto de Salud Carlos III [PI20/00349, PI16/00065, PI18/00261] and Fondo Europeo de Desarrollo Regional (FEDER); and by the Spanish Ministry of Science and Innovatin (MICINN) [SAF-2013-43365-R and SAF2016-75434-R] to VLR-P. AL and PG were funded by Fundación Conchita Rábago.

358 Background: Currently, no specific measures are used in Spain to evaluate quality of care in head and neck cancer, and programs such as the Quality Oncology Practice Initiative developed by the American Society of Clinical Oncology does not include head-and-neck-specific measures. Methods: A systematic literature review was carried out to identify measures useful for evaluating quality of care in head and neck cancer. A scientific committee, comprising 9 medical oncologists specialized in head and neck cancer, reviewed the literature findings and developed measures to be evaluated in a 2-step Delphi method. Experts in head and neck cancer practicing in Spain—specialized in medical oncology, radiotherapy oncology, maxillofacial surgery, pathology or otorhinolaryngology—participated in the Delphi, scoring the appropriateness of the measures using a 9-point Likert scale (1, extremely inappropriate; 9, extremely appropriate). Consensus was defined as at least two-thirds of Delphi respondents selecting a score sub-category (1–3, 4–6, or 7–9) that encompassed the median score of the group. Results: Out of the 833 documents found with the literature review, 20 were selected from to identify measures of interest. Fifty measures, covering diagnosis (13), treatment (28), follow-up (5), and outcome (4), were evaluated with the Delphi method. The 52 Delphi participants reached consensus on the appropriateness of using all 50 measures to evaluate the quality of care in head and neck cancer. Measures with lowest scores concerned re-hospitalization shortly after surgery and long hospitalization after surgery. Measures with highest scores regarded the use of imaging for follow-up, a histology study prior to treatment, and complete resection of the tumor. The scientific committee then selected 29 measures based on their applicability and cost-effectiveness and developed index cards with definitions, formulas, acceptable level of attainment, and rationale for their use in clinical practice. Conclusions: The goal of this study was to develop measures to evaluate and improve the quality of care in head and neck cancer. These results show unanimous consensus from a group of experts on the proposed measures for diagnosis, treatment, follow-up, and outcome. The index cards developed with measures are easy to follow and their use could improve quality of care.

305 Background: Measuring and tracking quality of care is highly relevant in today’s healthcare. The Quality Oncology Practice Initiative (QOPI) program is a referral for evaluating oncology practices worldwide. The ECO Foundation (Excellence and Quality in Oncology), a collaboration of oncology experts from the major Spanish hospitals involved in cancer treatment, reached an agreement with ASCO (American Society of Clinical Oncology) to include Spanish hospitals in its QOPI program. Methods: We analyzed the scores of the QOPI rounds from 14 Spanish hospitals, which submitted their charts from 2016 to 2021, and the measures obtained from 2018 to 2021, regarding the core/symptom, breast, colorectal (CRC) and NSCLC modules, in comparison with the QOPI aggregate measures. Results: Since 2016, 14 Spanish hospitals have participated in the QOPI program, achieving the certification 12 of them, and 3 are in process. Along the years, they have obtained a score over 85%, being 87,41% the worse in 2021, and 92,80% the best in 2020. We also analyzed the outstanding measures from 2018 onwards. The highest scores in Spanish hospitals were for information of infertility risks and chemotherapy intent prior to prescription, and documented plan for oral chemotherapy. However, measures regarding pain addressed, appropriate antiemetic therapy for high- and moderate-emetic-risk antineoplastic agents and action taken to address problems with emotional well-being by the second office visit, were among the lowest scored measures. When we focused in breast and NSCLC modules, Spanish hospitals didn´t show negative values, highlighting in the administration of Tamoxifen or AI within 1 year of diagnosis by patients with AJCC Stage IA (T1c) and IB - III ER or PR positive and in the status documentation for patients with initial AJCC Stage IV or distant metastatic NSCLC. In CRC module, Spanish hospitals showed lower scores in colonoscopy before or within 6 months of curative colorectal resection or completion of primary adjuvant chemotherapy. Conclusions: This study evaluates QOPI scores in Spain, showing that repeated participation enhances quality of care, although there is room for improvement. ECO Foundation will continue supporting Spanish practices to increase their participation aiming of improve oncology care in Spain.

Background Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, although both subchondral bone deterioration and synovial inflammation are also hallmarks of the disease. Chiropractic manipulation (CM) is a therapeutic approach focused on the diagnosis, treatment and prevention of musculoskeletal disorders. It is essentially manual, allowing the chiropractor to restore the normal range of motion and function of the joints, muscles, and ligaments. Clinical evidences suggest that CM might exert positive effects in OA patients. Objectives The aim of this study was to evaluate the effects of CM on cartilage, subchondral bone and synovitis state in an OA rabbit model. Methods Ten (4 months old) male New Zealand rabbits underwent knee surgery to induce OA by transection of anterior cruciate ligament. One week after the surgery, CM was performed using the chiropractic adjusting instrument ActivatorV as follows: Force 2 setting was applied onto the tibial tubercle of the right hind limb (true manipulation, TM-OA group), at an angle of approximately 90°, from medial to lateral, whereas the corresponding left hind limb received a false manipulation (FM-OA group) consisting of ActivatorV firing in the air and slightly touching the tibial tubercle. These procedures were repeated 3 times a week for 8 weeks. Three healthy animals were used as control. Following sacrifice, μCT and histological damage evaluation (Mankin score) were done in femur and tibiae. RANKL/OPG protein expressions were studied by immunohistochemistry in tibia samples. Sinovitis was assessed by Krenn score and immunohistochemistry for macrophages (RAM11) and angiogenesis (CD31) were done. Protein expression of VEGF, COX2, TNFa, IL-1b and MMP3 were determinated by Western Blot. Results In the OA rabbits, subchondral BMD decreased in relation to control, been partially reversed in the tibiae of TM-OA group. When subchondral trabecular bone structural parameters were analyzed by microCT, a significant decrease of bone volume/trabecular volume (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th) was observed in the OA rabbits, while trabecular separation (Tb.S) increased compared to control animals. TM-OA group showed a significant improvement of these parameters compare to FM-OA group. FM-OA joints had higher Mankin score (cartilage damage) than control joints, and TM decreased Mankin score compare to FM-OA (p Conclusion These results suggest that mechanical stimulus induced by CM may retard the pathologic progression of OA. The beneficial effects of CM might be associated with an improvement in bone and cartilage damage and also inflammatory state. Disclosure of Interests None declared