De-imFAR phase II project: a study protocol for a cluster randomised implementation trial to evaluate the effectiveness of de-implementation strategies to reduce low-value statin prescribing in the primary prevention of cardiovascular disease.

INTRODUCTION: This study aims to reduce potentially inappropriate prescribing (PIP) of statins and foster healthy lifestyle promotion in cardiovascular disease (CVD) primary prevention in low-risk patients. To this end, we will compare the effectiveness and feasibility of several de-implementation strategies developed following the structured design process of the Behaviour Change Wheel targeting key determinants of the clinical decision-making process in CVD prevention. METHODS AND ANALYSIS: A cluster randomised implementation trial, with an additional control group, will be launched, involving family physicians (FPs) from 13 Integrated Healthcare Organisations (IHOs) of Osakidetza-Basque Health Service with non-zero incidence rates of PIP of statins in 2021. All FPs will be exposed to a non-reflective decision assistance strategy based on reminders and decision support tools. Additionally, FPs from two of the IHOs will be randomly assigned to one of two increasingly intensive de-implementation strategies: adding a decision information strategy based on knowledge dissemination and a reflective decision structure strategy through audit/feedback. The target population comprises women aged 45-74 years and men aged 40-74 years with moderately elevated cholesterol levels but no diagnosed CVD and low cardiovascular risk (REGICOR<7.5%), who attend at least one appointment with any of the participating FPs (May 2022-May 2023), and will be followed until May 2024. We use the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate outcomes. The main outcome will be the change in the incidence rate of PIP of statins and healthy lifestyle counselling in the study population 12 and 24 months after FPs' exposure to the strategies. Moreover, FPs' perception of their feasibility and acceptability, and patient experience regarding the quality of care received will be evaluated. ETHICS AND DISSEMINATION: The study was approved by the Basque Country Clinical Research Ethics Committee and was registered in ClinicalTrials.gov (NCT04022850). Results will be disseminated in scientific peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04022850.

Position and ranking influence in padel: somatic anxiety and self-confidence increase in competition for left-side and higher-ranked players when compared to pressure training.

This study aimed to analyze the differences in the precompetitive anxiety and self-confidence according to the side of play, the ranking and the match outcome, under different competitive scenarios, in high level men's padel players from Finland who trained under pressure prior to the competition. 10 men's padel players (28.60 (4.17) years old) from the highest category participated in the research. The CSAI-2R (Competitive State Anxiety Inventory-2 Revised) and STAI-S (State-Trait Anxiety Inventory - State) questionnaires were used and descriptive and inferential analyzes were performed, including Mann-Whitney's U tests. The findings illuminate that, across the player spectrum, somatic anxiety and self-confidence levels are higher before competition compared to training matches. This trend holds true for left-side, higher-ranked and match winning players. Even lower-ranked players exhibit heightened self-confidence preceding competitions. These insights offer valuable considerations for players, coaches, and sports psychologists, fostering a deeper understanding of the intricate interplay between pressure training, competition, and the athlete's psychological landscape.

Feasibility of primary aldosteronism diagnosis in initial evaluation without medication withdrawal or confirmatory tests.

PURPOSE: Primary aldosteronism (PA), a frequent cause of hypertension, is highly associated with cardiovascular risk and mortality. PA diagnosis is often difficult due to the need to discontinue antihypertensive medication interfering with the renin-angiotensin-aldosterone system (I-RAAS). Our objective was to ascertain diagnosis of PA through biochemical assessments during screening while maintaining I-RAAS medications. METHODS: Hypertensive patients assessed for PA were involved. Patients were grouped according to the use of I-RAAS drugs during screening and the presence of PA. The diagnostic accuracy of the aldosterone-to-renin ratio (ARR), and other biochemical features were evaluated. RESULTS: 265 patients included, 122/265 with PA, and 192/265 were on I-RAAS therapy. The area under ROC curve (AUROC) of ARR for PA in patients without I-RAAS was 0.769 (95%CI: 0.66-0.877), and was 0.877 (95%CI: 0.828-0.926) in those with I-RAAS drugs. Sensitivity, specificity, positive predictive value, and negative predictive value (PPV) of cut-off of ARR > 50 were: 76%, 81%, 77.5%, and 79.6%. ARR > 50 plus hypokalemia had a PPV of 92.6% for PA. AUROC values of ARR evaluated in each group of antihypertensive drugs were >0.850 in all cases. CONCLUSIONS: ARR during I-RAAS therapy demonstrates reliability and accuracy for PA diagnosis. An ARR > 50 combined with hypokalemia while on I-RAAS medication could be considered indicative of PA diagnosis.

Coronectomy of lower third molars in intimate relation to the inferior alveolar nerve: A report of two cases.

Damage to the inferior alveolar nerve (IAN) secondary to the extraction of the lower third molar (LTM) is a relatively frequent complication (0.35-8.40%) that can cause temporary or permanent nerve damage. Coronectomy has been proposed as an alternative, which consists of sectioning the coronary portion of the LTM, and deliberately leaving the radicular portion with the pulp intact. Two clinical cases are presented in this article, in which root migration (0-0.3 mm) and a change of angulation (+2º to +9°) occurred. None of the cases developed complications during the follow-up period (12 months). Therefore, coronectomy is a procedure to be considered in selected cases as an alternative to conventional exodontia of the LTM to avoid possible damage to the IAN. Key words:Case report, third molar, mandibular third molar, coronectomy, mandibular nerve, mandibular nerve injuries, root migration.

In-House 3D Printed Positioning and Cutting Guide System for Mandibular Reconstruction. Protocol and case report.

Maxillofacial surgery planning has been improved by technological advances in 3D printing. The use of customized cutting and positioning guides allows intraoperative reproduction of pre-planned osteotomy cuts, resulting in increased surgical accuracy, reduced surgical time and improved esthetic and functional outcomes. Our paper presents a new method for creating and printing in-house cutting and positioning guides. A computer program (Brainlab iPlan) was used to segment the mandible for three-dimensional planning from imported conventional computed tomography (CT) scans. The virtual model of the mandible was printed on a stereolithography (SLA) 3D printer and a reconstruction plate was adapted to the printed model. The surface of the model and the screw-retained plate was scanned using a structured light surface 3D scanner (Artec Eva). The obtained scan of the jaw and plate in position was processed and transformed into an STL file. Free software (Autodesk Meshmixer) superimposes the initial jaw on the scanned jaw with the plate, designing a customized hybrid cutting guide that allows accurate intraoperative positioning, knowing the exact position of the reconstruction plate screws in the jaw. The total design, fabrication and 3D printing time for the in-house hybrid guide was 595 min. The average total printing cost was EUR 16. We found the technique to be simple and repeatable. We present and describe here a novel and simple technique for in-house 3D printed positioning and cutting guide system which can be applied to overall maxillofacial area. In cases of mandibular reconstruction, this protocol guarantees an adequate esthetic and functional result. Key words:Oral cancer, 3D surgery, CAD/CAM, personalized medicine, surgical guides, in house.

Global epistasis in plasmid-mediated antimicrobial resistance.

Antimicrobial resistance (AMR) in bacteria is a major public health threat and conjugative plasmids play a key role in the dissemination of AMR genes among bacterial pathogens. Interestingly, the association between AMR plasmids and pathogens is not random and certain associations spread successfully at a global scale. The burst of genome sequencing has increased the resolution of epidemiological programs, broadening our understanding of plasmid distribution in bacterial populations. Despite the immense value of these studies, our ability to predict future plasmid-bacteria associations remains limited. Numerous empirical studies have recently reported systematic patterns in genetic interactions that enable predictability, in a phenomenon known as global epistasis. In this perspective, we argue that global epistasis patterns hold the potential to predict interactions between plasmids and bacterial genomes, thereby facilitating the prediction of future successful associations. To assess the validity of this idea, we use previously published data to identify global epistasis patterns in clinically relevant plasmid-bacteria associations. Furthermore, using simple mechanistic models of antibiotic resistance, we illustrate how global epistasis patterns may allow us to generate new hypotheses on the mechanisms associated with successful plasmid-bacteria associations. Collectively, we aim at illustrating the relevance of exploring global epistasis in the context of plasmid biology.

Complete and robust magnetic field confinement by superconductors in fusion magnets.

The fusion created by magnetically confined plasma is a promising clean and essentially unlimited future energy source. However, there are important problems hindering controlled fusion like the imperfect magnetic confinement and the associated plasma instabilities. We theoretically demonstrate how to create a fully confined magnetic field with the precise three-dimensional shape required by fusion theory, using a bulk superconducting toroid with a toroidal cavity. The vacuum field in the cavity consists of nested flux surfaces. The coils creating the field, embedded in the superconducting bulk, can be chosen with very simple shapes, in contrast with the cumbersome arrangements in current experiments, and can be spared from large magnetic forces between them. Because of the superconductor properties, the system will tend to maintain the optimum field distribution in response to instabilities in the plasma. We numerically demonstrate how a fully-confined magnetic field with the three-dimensional spatial distribution required in two of the most advanced stellarators, Large Helical Device and Wendelstein 7-X, can be exactly generated, using simple round coils as magnetic sources. Current high-temperature superconductors can be employed to construct the bulk superconducting toroid. This can lead to optimized robust magnetic confinement and largely simplified configurations in future fusion experiments.

The optimization of microbial functions through rational environmental manipulations.

Microorganisms play a central role in biotechnology and it is key that we develop strategies to engineer and optimize their functionality. To this end, most efforts have focused on introducing genetic manipulations in microorganisms which are then grown either in monoculture or in mixed-species consortia. An alternative strategy to optimize microbial processes is to rationally engineer the environment in which microbes grow. The microbial environment is multidimensional, including factors such as temperature, pH, salinity, nutrient composition, etc. These environmental factors all influence the growth and phenotypes of microorganisms and they generally "interact" with one another, combining their effects in complex, non-additive ways. In this piece, we overview the origins and consequences of these "interactions" between environmental factors and discuss how they have been built into statistical, bottom-up predictive models of microbial function to identify optimal environmental conditions for monocultures and microbial consortia. We also overview alternative "top-down" approaches, such as genetic algorithms, to finding optimal combinations of environmental factors. By providing a brief summary of the state of this field, we hope to stimulate further work on the rational manipulation and optimization of the microbial environment.

Altered CELF4 splicing factor enhances pancreatic neuroendocrine tumors aggressiveness influencing mTOR and everolimus response.

Pancreatic neuroendocrine tumors (PanNETs) comprise a heterogeneous group of tumors with growing incidence. Recent molecular analyses provided a precise picture of their genomic and epigenomic landscape. Splicing dysregulation is increasingly regarded as a novel cancer hallmark influencing key tumor features. We have previously demonstrated that splicing machinery is markedly dysregulated in PanNETs. Here, we aimed to elucidate the molecular and functional implications of CUGBP ELAV-like family member 4 (CELF4), one of the most altered splicing factors in PanNETs. CELF4 expression was determined in 20 PanNETs, comparing tumor and non-tumoral adjacent tissue. An RNA sequencing (RNA-seq) dataset was analyzed to explore CELF4-linked interrelations among clinical features, gene expression, and splicing events. Two PanNET cell lines were employed to assess CELF4 function in vitro and in vivo. PanNETs display markedly upregulated CELF4 expression, which is closely associated with malignancy features, altered expression of key tumor players, and distinct splicing event profiles. Modulation of CELF4 influenced proliferation in vitro and reduced in vivo xenograft tumor growth. Interestingly, functional assays and RNA-seq analysis revealed that CELF4 silencing altered mTOR signaling pathway, enhancing the effect of everolimus. We demonstrate that CELF4 is dysregulated in PanNETs, where it influences tumor development and aggressiveness, likely by modulating the mTOR pathway, suggesting its potential as therapeutic target.

Laparoscopic versus open approach for interval cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced epithelial ovarian cancer: a matched comparative study.

BACKGROUND: The use of the laparoscopic approach for the treatment of carcinomatosis from epithelial ovarian cancer (EOC) is controversial. The aim of this study was to compare the short-term outcomes of both laparoscopic and open approach for interval CRS+HIPEC in a matched cohort of patients with advanced EOC. METHODS: A retrospective analysis of a prospectively maintained database including 254 patients treated with interval CRS-HIPEC between January 2016 and December 2021 was performed. Patients with primary disease and limited carcinomatosis (PCI ≤ 10) were selected. A comparative analysis of patients treated by either open (O-CRS-HIPEC) or the laparoscopic (L-CRS-HIPEC) approach was conducted. Overall survival (OS), disease-free survival (DFS), and perioperative outcomes were analysed. RESULTS: Fifty-three patients were finally selected and enrolled into two comparable groups in this study. Of these, 14 patients were treated by interval L-CRS-HIPEC and 39 by interval O-CRS-HIPEC. The L-CRS-HIPEC group had a shorter hospital stay (5.6 ± 1.9 vs. 9.7 ± 9.8 days; p < 0.001) and a shorter time to return to systemic chemotherapy (4.3 ± 1.9 vs. 10.3 ± 16.8 weeks; p = 0.003). There were no significant differences in postoperative complications between both groups. The 2-year OS and DFS was 100% and 62% in the L-CRS-HIPEC group versus 92% and 60% in the O-CRS-HIPEC group, respectively (p = 0.96; p = 0.786). CONCLUSION: This study suggests that the use of interval L-CRS-HIPEC for primary advanced EOC is associated with shorter hospital stay and return to systemic treatment while obtaining similar oncological results compared to the open approach. Further prospective research is needed to recommend this new approach for these strictly selected patients.

Environmental modulation of global epistasis in a drug resistance fitness landscape.

Interactions between mutations (epistasis) can add substantial complexity to genotype-phenotype maps, hampering our ability to predict evolution. Yet, recent studies have shown that the fitness effect of a mutation can often be predicted from the fitness of its genetic background using simple, linear relationships. This phenomenon, termed global epistasis, has been leveraged to reconstruct fitness landscapes and infer adaptive trajectories in a wide variety of contexts. However, little attention has been paid to how patterns of global epistasis may be affected by environmental variation, despite this variation frequently being a major driver of evolution. This is particularly relevant for the evolution of drug resistance, where antimicrobial drugs may change the environment faced by pathogens and shape their adaptive trajectories in ways that can be difficult to predict. By analyzing a fitness landscape of four mutations in a gene encoding an essential enzyme of P. falciparum (a parasite cause of malaria), here we show that patterns of global epistasis can be strongly modulated by the concentration of a drug in the environment. Expanding on previous theoretical results, we demonstrate that this modulation can be quantitatively explained by how specific gene-by-gene interactions are modified by drug dose. Importantly, our results highlight the need to incorporate potential environmental variation into the global epistasis framework in order to predict adaptation in dynamic environments.

Antitumor effect of a small-molecule inhibitor of KRASG12D in xenograft models of mucinous appendicular neoplasms.

Pseudomyxoma peritonei (PMP) is a rare disease characterized by a massive accumulation of mucus in the peritoneal cavity. The only effective treatment is aggressive surgery, aimed at removing all visible tumors. However, a high percentage of patients relapse, with subsequent progression and death. Recently, there has been an increase in therapies that target mutated oncogenic proteins. In this sense, KRAS has been reported to be highly mutated in PMP, with KRASG12D being the most common subtype. Here, we tested the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in a high-grade PMP xenograft mouse model carrying a KRASG12D mutation. The results obtained in this work showed a profound inhibition of tumor growth, which was associated with a reduction in cell proliferation, an increase in apoptosis, and a reduction in the MAPK and PI3K/AKT/mTOR signaling pathways. In conclusion, these results demonstrate the high potency and efficacy of MRTX1133 in KRASG12D-PMP tumors and provide a rationale for clinical trials.

Cuestionario de autoevaluación CAMBRA como método de cribado poblacional del riesgo de caries sin métodos exploratorios: un estudio piloto observacional transversal / Modified CAMBRA questionnaire as a method for population-based caries risk screening without exploratory methods: a cross-sectional observational pilot study

Fundamentos: Caries Management by Risk Assessment (CAMBRA) es un cuestionario de diagnóstico del riesgo global de caries dental. Este estudio tuvo como objetivo presentar un cuestionario de autoevaluación basado en CAMBRA que, a diferencia del original, es cumplimentado por padres/madres/cuidadores, sin necesidad de una exploración odontológica, permitiendo establecer un diagnóstico de presunción en menores de siete años excluidos del programa de salud oral del Sistema Nacional de Salud, con el fin de instaurar recomendaciones individualizadas al riesgo de caries y su inclusión precoz en programas preventivos del Servicio Madrileño de Salud (Madrid, España). Métodos: Se llevó a cabo un estudio observacional transversal basado en las recomendaciones STROBE, empleando por primera vez un cuestionario de autoevaluación basado en CAMBRA en niños/as de tres a seis años de una escuela infantil de Madrid (España). Los resultados se analizaron mediante una estadística descriptiva y para el estudio de la relación entre variables cualitativas se utilizó el estadístico exacto de Fisher. Resultados: El cuestionario fue respondido por padres de 120 niños, de los cuales, el 40,8% presentó, a priori, un riesgo de caries bajo, el 42,5% un riesgo moderado y el 16,7% un riesgo alto de caries. Conclusiones: El presente estudio permite la identificación de pacientes en riesgo de presentar y/o desarrollar caries. No obstante, futuros estudios han de evaluar su sensibilidad y especificidad mediante su comparativa frente a un diagnóstico de confirmación tras una exploración odontológica. Pese a ello, el cuestionarioCAMBRA modificado podría ser una herramienta útil para el cribado poblacional, facilitandoel acceso de la población en riesgo de caries y en riesgo de exclusión a planes preventivos y comunitarios.(AU)

Background:Caries Management by Risk Assessment (CAMBRA) is a questionnaire used to diagnose the patient’s overall caries risk. This study aimed to present a self-assessment questionnaire based on CAMBRA which, unlike the original, is completed by parents/caregivers, without the need for a dental examination, allowing a presumptive diagnosis to be established in children under seven years of age excluded from the oral health programme of the National Health System to establish individualised recommendations for caries risk and their early inclusion in preventive programmes of the Madrid Health Service (Madrid, Spain). Methods: A cross-sectional observational study was carried out following STROBE guidelines using for the first time a self-assessment questionnaire based on CAMBRA in a population of children aged from three to six years from a nursery school in Madrid (Spain). The results were analysed using descriptive statistics and Fisher’s exact statistic was used to study the relationship between qualitative variables. Results: The questionnaire was answered by the parents of 120 children (response rate=53.1%), of whom 40.8% presented a low a priori caries risk, 42.5% a moderate risk and 16.7% a high caries risk. Conclusion: The present study allow the identification of patients at risk of presenting and/or developing caries. However, future studies should evaluate its sensitivity and specificity by comparing it with a confirmatory diagnosis after a dental examination. Nevertheless, the modified CAMBRA questionnaire could be a useful tool for population screening, facilitating the access of the population at risk of caries and risk of exclusion to preventive and community plans.(AU)

Recommendations for the optimal management of peritoneal metastases in patients with colorectal cancer: a TTD and GECOP-SEOQ expert consensus statement

Peritoneal metastases (PM) occur when cancer cells spread inside the abdominal cavity and entail an advanced stage of colorectal cancer (CRC). Prognosis, which is poor, correlates highly with tumour burden, as measured by the peritoneal cancer index (PCI). Cytoreductive surgery (CRS) in specialized centres should be offered especially to patients with a low to moderate PCI when complete resection is expected. The presence of resectable metastatic disease in other organs is not a contraindication in well-selected patients. Although several retrospective and small prospective studies have suggested a survival benefit of adding hyperthermic intraperitoneal chemotherapy (HIPEC) to CRS, the recently published phase III studies PRODIGE-7 in CRC patients with PM, and COLOPEC and PROPHYLOCHIP in resected CRC with high-risk of PM, failed to show any survival advantage of this strategy using oxaliplatin in a 30-min perfusion. Final results from ongoing randomized phase III trials testing CRS plus HIPEC based on mitomycin C (MMC) are awaited with interest. In this article, a group of experts selected by the Spanish Group for the Treatment of Digestive Tumours (TTD) and the Spanish Group of Peritoneal Oncologic Surgery (GECOP), which is part of the Spanish Society of Surgical Oncology (SEOQ), reviewed the role of HIPEC plus CRS in CRC patients with PM. As a result, a series of recommendations to optimize the management of these patients is proposed (AU)

[Modified CAMBRA questionnaire as a method for population-based caries risk screening without exploratory methods: a cross-sectional observational pilot study]. / Cuestionario de autoevaluación CAMBRA como método de cribado poblacional del riesgo de caries sin métodos exploratorios: un estudio piloto observacional transversal.

OBJECTIVE: Caries Management by Risk Assessment (CAMBRA) is a questionnaire used to diagnose the patient's overall caries risk. This study aimed to present a self-assessment questionnaire based on CAMBRA which, unlike the original, is completed by parents/caregivers, without the need for a dental examination, allowing a presumptive diagnosis to be established in children under seven years of age excluded from the oral health programme of the National Health System to establish individualised recommendations for caries risk and their early inclusion in preventive programmes of the Madrid Health Service (Madrid, Spain). METHODS: A cross-sectional observational study was carried out following STROBE guidelines using for the first time a self-assessment questionnaire based on CAMBRA in a population of children aged from three to six years from a nursery school in Madrid (Spain). The results were analysed using descriptive statistics and Fisher's exact statistic was used to study the relationship between qualitative variables. RESULTS: The questionnaire was answered by the parents of 120 children (response rate=53.1%), of whom 40.8% presented a low a priori caries risk, 42.5% a moderate risk and 16.7% a high caries risk. CONCLUSIONS: The present study allow the identification of patients at risk of presenting and/or developing caries. However, future studies should evaluate its sensitivity and specificity by comparing it with a confirmatory diagnosis after a dental examination. Nevertheless, the modified CAMBRA questionnaire could be a useful tool for population screening, facilitating the access of the population at risk of caries and risk of exclusion to preventive and community plans.

OBJETIVO: Caries Management by Risk Assessment (CAMBRA) es un cuestionario de diagnóstico del riesgo global de caries dental. Este estudio tuvo como objetivo presentar un cuestionario de autoevaluación basado en CAMBRA que, a diferencia del original, es cumplimentado por padres/madres/cuidadores, sin necesidad de una exploración odontológica, permitiendo establecer un diagnóstico de presunción en menores de siete años excluidos del programa de salud oral del Sistema Nacional de Salud, con el fin de instaurar recomendaciones individualizadas al riesgo de caries y su inclusión precoz en programas preventivos del Servicio Madrileño de Salud (Madrid, España). METODOS: Se llevó a cabo un estudio observacional transversal basado en las recomendaciones STROBE, empleando por primera vez un cuestionario de autoevaluación basado en CAMBRA en niños/as de tres a seis años de una escuela infantil de Madrid (España). Los resultados se analizaron mediante una estadística descriptiva y para el estudio de la relación entre variables cualitativas se utilizó el estadístico exacto de Fisher. RESULTADOS: El cuestionario fue respondido por padres de 120 niños, de los cuales, el 40,8% presentó, a priori, un riesgo de caries bajo, el 42,5% un riesgo moderado y el 16,7% un riesgo alto de caries. CONCLUSIONES: El presente estudio permite la identificación de pacientes en riesgo de presentar y/o desarrollar caries. No obstante, futuros estudios han de evaluar su sensibilidad y especificidad mediante su comparativa frente a un diagnóstico de confirmación tras una exploración odontológica. Pese a ello, el cuestionario CAMBRA modificado podría ser una herramienta útil para el cribado poblacional, facilitando el acceso de la población en riesgo de caries y en riesgo de exclusión a planes preventivos y comunitarios.

In vitro comparison of human plasma-based and self-assembled tissue-engineered skin substitutes: two different manufacturing processes for the treatment of deep and difficult to heal injuries.

Background: The aim of this in vitro study was to compare side-by-side two models of human bilayered tissue-engineered skin substitutes (hbTESSs) designed for the treatment of severely burned patients. These are the scaffold-free self-assembled skin substitute (SASS) and the human plasma-based skin substitute (HPSS). Methods: Fibroblasts and keratinocytes from three humans were extracted from skin biopsies (N = 3) and cells from the same donor were used to produce both hbTESS models. For SASS manufacture, keratinocytes were seeded over three self-assembled dermal sheets comprising fibroblasts and the extracellular matrix they produced (n = 12), while for HPSS production, keratinocytes were cultured over hydrogels composed of fibroblasts embedded in either plasma as unique biomaterial (Fibrin), plasma combined with hyaluronic acid (Fibrin-HA) or plasma combined with collagen (Fibrin-Col) (n/biomaterial = 9). The production time was 46-55 days for SASSs and 32-39 days for HPSSs. Substitutes were characterized by histology, mechanical testing, PrestoBlue™-assay, immunofluorescence (Ki67, Keratin (K) 10, K15, K19, Loricrin, type IV collagen) and Western blot (type I and IV collagens). Results: The SASSs were more resistant to tensile forces (p-value < 0.01) but less elastic (p-value < 0.001) compared to HPSSs. A higher number of proliferative Ki67+ cells were found in SASSs although their metabolic activity was lower. After epidermal differentiation, no significant difference was observed in the expression of K10, K15, K19 and Loricrin. Overall, the production of type I and type IV collagens and the adhesive strength of the dermal-epidermal junction was higher in SASSs. Conclusions: This study demonstrates, for the first time, that both hbTESS models present similar in vitro biological characteristics. However, mechanical properties differ and future in vivo experiments will aim to compare their wound healing potential.

Normothermic Regional Perfusion in Controlled Donation After Circulatory Determination of Death Simultaneous Pancreas - Kidney Transplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation is the optimal treatment for patients with type 1 diabetes and renal failure. The use of pancreas grafts from donation after circulatory death (DCD), using normothermic regional perfusion (NRP), is still marginal worldwide, mainly due to possible additional risks of graft dysfunction and complications compared with grafts from donors after brain death. METHODS: Case series of patients who underwent simultaneous pancreas-kidney transplantation after DCD-NRP between January 2018 and September 2022. This study evaluated early postoperative grafts and survival outcomes. RESULTS: Four patients were included. One patient lost the pancreatic graft due to arterial thrombosis requiring transplantectomy. Another patient required a laparotomy due to hemoperitoneum. Overall, 1-year pancreas and kidney graft survival was 75% and 100%, respectively. One patient developed a lymphoma during the follow-up. CONCLUSION: The use of pancreas grafts from DCD after NRP preservation is safe and feasible. Comparative studies with donors after brain death grafts and larger series are required to confirm the feasibility of DCD-NRP pancreas transplantation.