Case–control study assessing the impact of COVID19 in advanced kidney cancer patients treated with antiangiogenics or immunotherapy: the COVID-REN study

Background Cancer is a risk factor for developing severe COVID19. Additionally, SARS-CoV2 has a special tropism for renal cells and complications like thrombosis or cytokine storm could be enhanced by standard treatments in kidney cancer (i.e., antiangiogenics or immunotherapy). Thus, understanding the impact of COVID19 in patients with this tumor is key for their correct management. Methods We designed a retrospective case–control study comparing the outcome of three groups of advanced kidney cancer patients on systemic treatment: cohort A (developed COVID19 while on antiangiogenics), cohort B (developed COVID19 while on immunotherapy) and cohort C (non-infected). Matching factors were age, gender, and treatment. Results 95 patients were recruited in 16 centers in Spain from September 2020 to May 2021. Finally, 85 were deemed as eligible (23 cohort A, 21 cohort B, 41 cohort C). Patients with COVID required more dose interruptions (25 vs. six) and hospitalizations (10 vs. none) than those without COVID (both p = 0.001). No difference between cohorts A and B was observed regarding hospitalization or length of stay. No ICU admission was registered and one patient in cohort B died due to COVID19. Regarding cancer evolution, three patients in cohort A presented progressive disease after COVID19 compared to two in cohort B. One case in cohort B, initially deemed as stable disease, achieved a partial response after COVID19. Conclusions Kidney cancer patients who developed COVID19 while on systemic therapy required more treatment interruptions and hospitalizations than those non-infected. However, no significant impact on cancer outcome was observed. Also, no difference was seen between cases on antiangiogenics or immunotherapy (AU)

Case-control study assessing the impact of COVID19 in advanced kidney cancer patients treated with antiangiogenics or immunotherapy: the COVID-REN study.

BACKGROUND: Cancer is a risk factor for developing severe COVID19. Additionally, SARS-CoV2 has a special tropism for renal cells and complications like thrombosis or cytokine storm could be enhanced by standard treatments in kidney cancer (i.e., antiangiogenics or immunotherapy). Thus, understanding the impact of COVID19 in patients with this tumor is key for their correct management. METHODS: We designed a retrospective case-control study comparing the outcome of three groups of advanced kidney cancer patients on systemic treatment: cohort A (developed COVID19 while on antiangiogenics), cohort B (developed COVID19 while on immunotherapy) and cohort C (non-infected). Matching factors were age, gender, and treatment. RESULTS: 95 patients were recruited in 16 centers in Spain from September 2020 to May 2021. Finally, 85 were deemed as eligible (23 cohort A, 21 cohort B, 41 cohort C). Patients with COVID required more dose interruptions (25 vs. six) and hospitalizations (10 vs. none) than those without COVID (both p = 0.001). No difference between cohorts A and B was observed regarding hospitalization or length of stay. No ICU admission was registered and one patient in cohort B died due to COVID19. Regarding cancer evolution, three patients in cohort A presented progressive disease after COVID19 compared to two in cohort B. One case in cohort B, initially deemed as stable disease, achieved a partial response after COVID19. CONCLUSIONS: Kidney cancer patients who developed COVID19 while on systemic therapy required more treatment interruptions and hospitalizations than those non-infected. However, no significant impact on cancer outcome was observed. Also, no difference was seen between cases on antiangiogenics or immunotherapy.

Relationship between hair cortisol concentrations and cognitive functioning in adolescents with ADHD.

Background: Our study aimed to explore whether the hair cortisol concentration (HCC), a measure of long-term cortisol output, is associated with poorer cognitive functioning in adolescents with attention deficit and hyperactivity disorder (ADHD). We further aimed to test the potential moderating effects of sex and childhood maltreatment.Methods: In this cross-sectional study, fifty-three adolescents with ADHD were studied. The ADHD Rating Scale (ADHD-RS) and Childhood Trauma Questionnaire (CTQ) were administered. Seven cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were administered, and two cognitive factors (attention and memory and executive functioning) were identified by confirmatory factor analysis. A 3-cm hair sample from the posterior vertex region of the head was obtained. HCCs were determined by a high-sensitivity enzyme immunoassay kit. Multiple linear regression analyses were used to explore the association between HCCs and either cognitive performance or ADHD severity while adjusting for sex, childhood maltreatment and the ADHD-RS total score.Results: Sex moderated the relationship between HCCs and attention/memory confirmatory factor analysis (CFA) scores, with better performance in boys with higher HCCs. HCCs were not associated with executive functioning or ADHD symptoms. Childhood maltreatment was associated with inattention symptoms in adolescents with ADHD.Conclusions: Our study suggests that HCCs are positively associated with attention and memory performance in adolescents with ADHD, with a moderating effect of sex (the relationship is strongest in boys).

We studied the relationship between cortisol and cognition in adolescents with ADHD.Hair cortisol concentrations (HCCs) were determined.We explored the moderating effects of sex and childhood trauma.Sex moderated the relationship between HCCs and attention and memory.Childhood trauma did not moderate the relationship between HCCs and cognition.

Protocolo de tratamiento con polietilenglicol 3350 con electrolitos para el estreñimiento en el niño crítico / Protocol for treatment of constipation with polyethylene glycol 3350 plus electrolytes in critically ill children

Introducción y objetivos: Ningún estudio ha analizado la efectividad del tratamiento del estreñimiento en niños críticamente enfermos. El objetivo de este estudio fue evaluar la implementación, la eficacia y la seguridad de un protocolo de tratamiento con polietilenglicol 3350 con electrolitos (PEG 3350+E) para el estreñimiento en niños en estado crítico. Métodos: Estudio prospectivo unicéntrico, incluyendo niños que ingresaron en cuidados intensivos pediátricos durante más de 72h y que desarrollaron estreñimiento. Se excluyeron los niños con trastornos o afecciones gastrointestinales previas. Los pacientes fueron tratados con enemas rectales o con PEG 3350+E oral a criterio del médico tratante. Se compararon variables clínicas, demográficas y efectos secundarios (diarrea, distensión abdominal y desequilibrio electrolítico). Resultados: Se estudiaron 56 pacientes de 48,2±11,9 meses de edad, siendo el 55,4% varones. Cuarenta y cuatro pacientes (78,6%) fueron tratados con PEG 3350+E y 12 pacientes (21,4%) con enemas rectales. El porcentaje de efectividad del PEG 3350+E (79,5%) fue mayor que el de los enemas (58,3%), pero la diferencia no fue estadísticamente significativa (p=0,151). No existieron diferencias significativas en ninguno de los efectos secundarios entre los 2 grupos. El PEG 3350+E fue más efectivo en los niños menores de 2 años (100%) que en los mayores de esa edad (65,4%), p<0,01, sin diferencias significativas en la aparición de efectos secundarios. Conclusiones: El tratamiento del estreñimiento en los niños en estado crítico con PEG 3350+E es eficaz y tiene pocos efectos secundarios, incluso en niños menores de 2 años. (AU)

Introduction and objectives: No studies have analysed the effectiveness of treatment for constipation in critically ill children. The aim of this study was to assess the implementation, efficacy and safety of a treatment protocol using polyethylene glycol 3350 with electrolytes (PEG 3350+E) for constipation in critically ill children. Methods: We conducted a single-centre prospective study in children admitted to the paediatric intensive care unit for a minimum of 72h and who developed constipation. Children with previous gastrointestinal disorders or diseases were excluded. The patients were treated with rectal enemas or with the oral PEG 3350+E protocol at the discretion of the treating physician. We compared clinical and demographic variables as well as adverse events (diarrhoea, abdominal distension and electrolyte imbalances). Results: The sample included 56 patients with a mean age of 48.2±11.9 months, of who 55.4% were male. Forty-four patients (78.6%) were treated with PEG 3350+E and 12 (21.4%) with rectal enemas. The proportion of patients who responded well to treatment was greater in the PEG 3350+E group (79.5%) compared to the enema group (58.3%), but the difference was not statistically significant (P=.151). There were no significant differences between the groups in any of the adverse effects. Treatment with PEG 3350+E was more effective in children aged less than 2 years (100%) compared to older children (100% vs. 65.4%; P<.01), with no significant differences in the development of adverse events. Conclusions: The PEG 3350+E treatment protocol for constipation in critically ill children was effective and associated with few adverse events, even in children aged less than 2 years. (AU)

Protocol for treatment of constipation with polyethylene glycol 3350 plus electrolytes in critically ill children.

INTRODUCTION AND OBJECTIVES: No studies have analysed the effectiveness of treatment for constipation in critically ill children. The aim of this study was to assess the implementation, efficacy and safety of a treatment protocol using polyethylene glycol 3350 with electrolytes (PEG 3350 + E) for constipation in critically ill children. METHODS: We conducted a single-centre prospective study in children admitted to the paediatric intensive care unit for a minimum of 72 h and who developed constipation. Children with previous gastrointestinal disorders or diseases were excluded. The patients were treated with rectal enemas or with the oral PEG 3350 + E protocol at the discretion of the treating physician. We compared clinical and demographic variables as well as adverse events (diarrhoea, abdominal distension and electrolyte imbalances). RESULTS: The sample included 56 patients with a mean age of 48.2 ±â€¯11.9 months, of who 55.4% were male. Forty-four patients (78.6%) were treated with PEG 3350 + E and 12 (21.4%) with rectal enemas. The proportion of patients that responded well to treatment was greater in the PEG 3350 + E group (79.5%) compared to the enema group (58.3%), but the difference was not statistically significant (P = .151). There were no significant differences between the groups in any of the adverse effects. Treatment with PEG 3350 + E was more effective in children aged less than 2 years (100%) compared to older children (100% vs 65.4%; P < .01), with no significant differences in the development of adverse events. CONCLUSIONS: The PEG 3350 + E treatment protocol for constipation in critically ill children was effective and associated with few adverse events, even in children aged less than 2 years.

Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution.

Background: Managing the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease. Methods: We designed a randomized phase II clinical trial to determine whether the combination of ruxolitinib (5 mg twice a day for 7 days followed by 10 mg BID for 7 days) plus simvastatin (40 mg once a day for 14 days), could reduce the incidence of respiratory insufficiency in COVID-19. 48 cytokines were correlated with clinical outcome. Participants: Patients admitted due to COVID-19 infection with mild disease. Results: Up to 92 were included. Mean age was 64 ± 17, and 28 (30%) were female. 11 (22%) patients in the control arm and 6 (12%) in the experimental arm reached an OSCI grade of 5 or higher (p = 0.29). Unsupervised analysis of cytokines detected two clusters (CL-1 and CL-2). CL-1 presented a higher risk of clinical deterioration vs CL-2 (13 [33%] vs 2 [6%] cases, p = 0.009) and death (5 [11%] vs 0 cases, p = 0.059). Supervised Machine Learning (ML) analysis led to a model that predicted patient deterioration 48h before occurrence with a 85% accuracy. Conclusions: Ruxolitinib plus simvastatin did not impact the outcome of COVID-19. Cytokine profiling identified patients at risk of severe COVID-19 and predicted clinical deterioration. Trial registration: https://clinicaltrials.gov/, identifier NCT04348695.

Biopolymeric Fibrous Aerogels: The Sustainable Alternative for Water Remediation.

The increment in water pollution due to the massive development in the industrial sector is a worldwide concern due to its impact on the environment and human health. Therefore, the development of new and sustainable alternatives for water remediation is needed. In this context, aerogels present high porosity, low density, and a remarkable adsorption capacity, making them candidates for remediation applications demonstrating high efficiency in removing pollutants from the air, soil, and water. Specifically, polymer-based aerogels could be modified in their high surface area to integrate functional groups, decrease their hydrophilicity, or increase their lipophilicity, among other variations, expanding and enhancing their efficiency as adsorbents for the removal of various pollutants in water. The aerogels based on natural polymers such as cellulose, chitosan, or alginate processed by different techniques presented high adsorption capacities, efficacy in oil/water separation and dye removal, and excellent recyclability after several cycles. Although there are different reviews based on aerogels, this work gives an overview of just the natural biopolymers employed to elaborate aerogels as an eco-friendly and renewable alternative. In addition, here we show the synthesis methods and applications in water cleaning from pollutants such as dyes, oil, and pharmaceuticals, providing novel information for the future development of biopolymeric-based aerogel.

How people affected by Chagas disease have struggled with their negligence: history, associative movement and World Chagas Disease Day.

It is well documented that Chagas disease (CD) can pose a public health problem to countries. As one of the World Health Organization Neglected Tropical Diseases undoubtedly calls for comprehensive healthcare, transcending a restricted biomedical approach. After more than a century since their discovery, in 1909, people affected by CD are still frequently marginalised and/or neglected. The aim of this article is to tell the story of their activism, highlighting key historical experiences and successful initiatives, from 1909 to 2019. The first association was created in 1987, in the city of Recife, Brazil. So far, thirty associations have been reported on five continents. They were created as independent non-profit civil society organisations and run democratically by affected people. Among the common associations' objectives, we notably find: increase the visibility of the affected; make their voice heard; build bridges between patients, health system professionals, public health officials, policy makers and the academic and scientific communities. The International Federation of Associations of People Affected by CD - FINDECHAGAS, created in 2010 with the input of the Americas, Europe and the Western Pacific, counts as one of the main responses to the globalisation of CD. Despite all the obstacles and difficulties encountered, the Federation has thrived, grown, and matured. As a result of this mobilisation along with the support of many national and international partners, in May 2019 the 72nd World Health Assembly decided to establish World Chagas Disease Day, on 14 April. The associative movement has increased the understanding of the challenges related to the disease and breaks the silence around Chagas disease, improving surveillance, and sustaining engagement towards the United Nations 2030 agenda.

Stress-related biomarkers and cognitive functioning in adolescents with ADHD: Effect of childhood maltreatment.

Our study aimed to explore whether stress-related hormones (hypothalamic-pituitary-adrenal [HPA] axis hormones and prolactin) are associated with poorer cognitive functioning in adolescents with attention deficit and hyperactivity disorder (ADHD) and to test the potential moderating effect of childhood maltreatment. Seventy-six adolescents with ADHD were studied. The ADHD rating scale (ADHD-RS) and Childhood Trauma Questionnaire (CTQ) were administered. Seven cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were administered, and two cognitive factors (attention and memory as well as executive functioning) were identified by confirmatory factor analysis. Stress-related hormone levels were assessed at the clinic (plasma prolactin and cortisol levels and salivary cortisol levels) before cognitive testing and at home for two consecutive days (cortisol awakening response [CAR] and diurnal cortisol slope). Multiple linear regression analyses were used to explore the association between hormone levels and ADHD severity or cognitive functioning while adjusting for sex and childhood maltreatment. Regarding hormonal measurements obtained at the clinic, female sex moderated the relationship between salivary cortisol levels and executive functioning, whereas childhood maltreatment moderated the relationship between salivary cortisol levels and inattention symptoms of patients with ADHD. Prolactin levels were not associated with cognitive functioning or the severity of ADHD. Regarding HPA axis measurements performed at home, lower cortisol levels at awakening were associated with poorer executive functioning. Neither CAR nor the cortisol diurnal slope were associated with cognitive functioning or ADHD severity. Our study suggests that HPA axis hormone levels are associated with the severity of cognitive and inattention symptoms of patients with ADHD and that childhood maltreatment and sex exert distinct moderating effects depending on the symptom type.

How people affected by Chagas disease have struggled with their negligence: history, associative movement and World Chagas Disease Day

It is well documented that Chagas disease (CD) can pose a public health problem to countries. As one of the World Health Organization Neglected Tropical Diseases undoubtedly calls for comprehensive healthcare, transcending a restricted biomedical approach. After more than a century since their discovery, in 1909, people affected by CD are still frequently marginalised and/or neglected. The aim of this article is to tell the story of their activism, highlighting key historical experiences and successful initiatives, from 1909 to 2019. The first association was created in 1987, in the city of Recife, Brazil. So far, thirty associations have been reported on five continents. They were created as independent non-profit civil society organisations and run democratically by affected people. Among the common associations' objectives, we notably find: increase the visibility of the affected; make their voice heard; build bridges between patients, health system professionals, public health officials, policy makers and the academic and scientific communities. The International Federation of Associations of People Affected by CD - FINDECHAGAS, created in 2010 with the input of the Americas, Europe and the Western Pacific, counts as one of the main responses to the globalisation of CD. Despite all the obstacles and difficulties encountered, the Federation has thrived, grown, and matured. As a result of this mobilisation along with the support of many national and international partners, in May 2019 the 72nd World Health Assembly decided to establish World Chagas Disease Day, on 14 April. The associative movement has increased the understanding of the challenges related to the disease and breaks the silence around Chagas disease, improving surveillance, and sustaining engagement towards the United Nations 2030 agenda.

In vivo performance of decellularized tracheal grafts in the reconstruction of long length tracheal defects: Experimental study.

BACKGROUND: The repair of long-segment tracheal lesions remains an important challenge. Nowdays no predictable and dependable substitute has been found. Decellularized tracheal scaffolds have shown to be a promising graft for tracheal transplantation, since it is non-immunogenic. OBJECTIVE: Evaluate in vivo decellularized tracheal allografts performance to replace long tracheal segment. METHODS: Forty-five swines underwent surgery as follows: Fifteen trachea donors and 30 receptors of decellularized trachea allografts. The receptors were randomly divided in five groups (n = 6). In groups I and II, donor trachea segment was decellularized by 15 cycles with sodium deoxycholate and deoxyribonuclease, in group II, the allograft was reinforced with external surgical steel wire. Groups, III, IV, and V decellularization was reduced to seven cycles, supplemented with cryopreservation in group IV and with glutaraldehyde in group V. A 10 rings segment was excised from the receptor swine and the decellularized trachea graft was implanted to re-establish trachea continuity. RESULTS: Both decellularization cycles caused decreased stiffness. All trachea receptors underwent euthanasia before the third post-implant week due to severe dyspnea and trachea graft stenosis, necrosis, edema, inflammation, hemorrhage, and granulation tissue formation in anastomotic sites. Histologically all showed total loss of epithelium, separation of collagen fibers, and alterations in staining. CONCLUSIONS: Both decellularization techniques severely damaged the structure of the trachea and the extracellular matrix of the cartilage, resulting in a no functional graft, in spite of the use of surgical wire, cryopreservation or glutaraldehyde treatment. An important drawback was the formation of fibrotic stenosis in both anastomosis.

Training in healthcare during and after COVID-19: proposal for simulation training.

INTRODUCTION: The challenge of facing COVID-19 falls under all health care structures, and without specific training to health care professionals they are probably the professionals with the highest level of exposure. Regardless of the level of health care, the training of professionals aims to optimize resources and attend patients while assuring quality and security. POINT OF VIEW: This report proposes simulation training for health care professionals to update professionals for attending patients during the pandemic. This training was built with five simulated stations, considering different stages of a patient with COVID-19. This report takes advantage of different simulation techniques, such as skills training, standardized patient, medium- and high-fidelity simulator, rapid cycle of deliberate practice, and in situ simulation. DISCUSSION: Medical procedures for COVID-19 patients offer additional risk for health care professionals, especially considering exposure to procedures that generate aerosols, such as compression, mask ventilation, and orotracheal intubation. Thus, finding educational strategies that allow training is essential to simulate the evolution of COVID-19 patients in a safe manner. CONCLUSION: Simulation has proven to be a useful and effective form of training around the world for training health teams on the front lines for patient care in COVID-19.

Cytokines secretion from human mesenchymal stem cells induced by bovine bone matrix.

BACKGROUND: Bovine bone matrix is a natural material that has been used in the treatment of bone lesions. In this study, bovine bone matrix Nukbone® (NKB) was investigated due its osteoconductive and osteoinductive properties. This biomaterial induces CBFA-1 activation and osteogenic differentiation, although the cytokines involved in these processes is still unknown. OBJECTIVE: The aim of this work was to determine the influence of NKB on the pro-osteoblastic and anti-osteoblastic cytokines secretion from human mesenchymal stem cells (hMSCs). METHODS: The hMSCs were cultured onto NKB and cytokines IL-2, IL-4, IL-6, IL-10, IL-12, IFN-γ and TNF-α were analized at 0-14 days by immunoassay. In addition, hemocompatibility of NKB and characterization of hMSCs were evaluated. RESULTS: NKB induces an increase on pro-osteoblastic cytokine secretion IL-4 and a decrease on anti-osteoblastic cytokine IL-6 secretion, at days 7 and 14 of cell culture. Interestingly, there was no statistical difference between secretion profiles of others cytokines analized. CONCLUSIONS: The up-regulation of IL-4 and down-regulation of IL-6, and the secretion profiles of other cytokines examined in this work, are findings that will contribute to the understanding of the role of NKB, and similar biomaterials, in bone homeostasis and in the osteoblastic differentiation of hMSCs.

Comparing the first and second waves of COVID-19 in a tertiary university hospital in Barcelona.

BACKGROUND: Hospitals have constituted the limiting resource of the healthcare systems for the management of the COVID-19 pandemic. As the pandemic progressed, knowledge of the disease improved, and healthcare systems were expected to be more adapted to provide a more efficient response. The objective of this research was to compare the flow of COVID-19 patients in emergency rooms and hospital wards, between the pandemic's first and second waves at the University Hospital of Vall d'Hebron (Barcelona, Spain), and to compare the profiles, severity and mortality of COVID-19 patients between the two waves. METHODS: A retrospective observational analysis of COVID-19 patients attending the hospital from February 24 to April 26, 2020 (first wave) and from July 24, 2020, to May 18, 2021 (second wave) was carried out. We analysed the data of the electronic medical records on patient demographics, comorbidity, severity, and mortality. RESULTS: The daily number of COVID-19 patients entering the emergency rooms (ER) dropped by 65% during the second wave compared to the first wave. During the second wave, patients entering the ER were significantly younger (61 against 63 years old p<0.001) and less severely affected (39% against 48% with a triage level of resuscitation or emergency; p<0.001). ER mortality declined during the second wave (1% against 2%; p<0.000). The daily number of hospitalised COVID-19 patients dropped by 75% during the second wave. Those hospitalised during the second wave were more severely affected (20% against 10%; p<0.001) and were referred to the intensive care unit (ICU) more frequently (21% against 15%; p<0.001). Inpatient mortality showed no significant difference between the two waves. CONCLUSIONS: Changes in the flow, severity and mortality of COVID-19 patients entering this tertiary hospital during the two waves may reflect a better adaptation of the health care system and the improvement of knowledge on the disease.

Training in healthcare during and after COVID-19: proposal for simulation training

SUMMARY INTRODUCTION: The challenge of facing COVID-19 falls under all health care structures, and without specific training to health care professionals they are probably the professionals with the highest level of exposure. Regardless of the level of health care, the training of professionals aims to optimize resources and attend patients while assuring quality and security. POINT OF VIEW: This report proposes simulation training for health care professionals to update professionals for attending patients during the pandemic. This training was built with five simulated stations, considering different stages of a patient with COVID-19. This report takes advantage of different simulation techniques, such as skills training, standardized patient, medium- and high-fidelity simulator, rapid cycle of deliberate practice, and in situ simulation. DISCUSSION: Medical procedures for COVID-19 patients offer additional risk for health care professionals, especially considering exposure to procedures that generate aerosols, such as compression, mask ventilation, and orotracheal intubation. Thus, finding educational strategies that allow training is essential to simulate the evolution of COVID-19 patients in a safe manner. CONCLUSION: Simulation has proven to be a useful and effective form of training around the world for training health teams on the front lines for patient care in COVID-19.

Doctora, ¿estas manchas me deberían haber salido? / Doctor, should these spots have appeared

La púrpura pigmentosa de Schamberg (púrpura pigmentaria progresiva) es una dermatosis purpúrica pigmentaria. Suele localizarse en las extremidades inferiores bilateralmente. Es asintomática, aunque en ocasiones presentan prurito leve. El curso de la condición es típicamente crónico, con numerosas exacerbaciones y remisiones. También puede ocurrir una resolución espontánea. La biopsia es la prueba fundamental para su diagnóstico, mostrando capilaritis linfocítica

Schamberg's purpura pigmentosa (progressive pigmentary purpura) is a pigmentary purpuric dermatosis. It usually occurs bilaterally on lower limbs. It is asymptomatic, though it occasionally presents slight itching. The course of the disease is typically chronic, with numerous exacerbations and remissions. Spontaneous resolution may also occur. Biopsy is the crucial test for diagnosis, which shows lymphocytic capillaritis

Fast cyclical-decellularized trachea as a natural 3D scaffold for organ engineering.

Commonly reported decellularization protocols for trachea may take up from several weeks to months in order to remove the cellular materials. Two years ago, we significantly reduced the time of decellularization trachea process using trypsin. Despite the positive outcome, the protocol was useful to produce 5 cm graft length, an unsuitable length graft for most patients with tracheal disorders. In this work we improved the decellularization procedure for longer sections up to 10 cm without considerable extension in the necessary time process (2 weeks). Herein, for the first time, we completely describe and characterize the process for pig tracheal bioactive scaffolds. Histological and molecular biology analysis demonstrated effective removal of cellular components and nuclear material, which was also confirmed by the Immunohistochemical (IHC) analysis of the major histocompatibility complexes (MHCs) and DNA stain by 4'-6-diamidino-2-phenylindole (DAPI). The images and data obtained from scanning electron microscopy (SEM) and thermal analysis showed conservation of the hierarchical structures of the tracheal extracellular matrix (ECM), the biomechanical tests showed that decellularization approach did not lead to a significant alteration on the mechanical properties. In this paper, we demonstrate that the proposed cyclical-decellularization protocol allowed us to obtain a non-immunological 10 cm natural tracheal scaffold according to the in vivo immunological assessment. Furthermore, the recellularization of the matrix was successfully achieved by demonstrating first-stage cellular differentiation from stem cells to chondrocytes expressed by the SOX9 transcription factor; this organ-engineered tracheal matrix has the potential to act as a suitable template for organ regeneration.

The INTERACT Trial: Long-term results of a randomised trial on preoperative capecitabine-based radiochemotherapy intensified by concomitant boost or oxaliplatin, for cT2 (distal)-cT3 rectal cancer.

BACKGROUND AND PURPOSE: Capecitabine-based radiochemotherapy (cbRCT) is standard for preoperative long-course radiochemotherapy of locally advanced rectal cancer. This prospective, parallel-group, randomised controlled trial investigated two intensification regimens. cT4 lesions were excluded. PRIMARY OBJECTIVE: pathological outcome (TRG 1-2) among arms. MATERIALS AND METHODS: Low-located cT2N0-2M0, cT3N0-2M0 (up to 12 cm from anal verge) presentations were treated with cbRCT randomly intensified by either radiotherapy boost (Xelac arm) or multidrug concomitant chemotherapy (Xelox arm). Xelac: concomitant boost to bulky site (45 Gy/1.8 Gy/die, 5 sessions/week to the pelvis, +10 Gy at 1 Gy twice/week to the bulky) plus concurrent capecitabine (1650 mg/mq/die). Xelox: 45 Gy to the pelvis + 5.4 Gy/1.8 Gy/die, 5 sessions/week to the bulky site + concurrent capecitabine (1300 mg/mq/die) and oxaliplatin (130 mg/mq on days 1,19,38). Surgery was planned 7-9 weeks after radiochemotherapy. RESULTS: From June 2005 to September 2013, 534 patients were analysed: 280 in Xelac, 254 in Xelox arm. Xelox arm presented higher G ≥ 3 haematologic (p = 0.01) and neurologic toxicity (p < 0.001). Overall, 98.5% patients received curative surgery. The tumour regression grade distribution did not differ between arms (p = 0.102). TRG 1+2 rate significantly differed: Xelac arm 61.7% vs. Xelox 52.3% (p = 0.039). Pathological complete response (ypT0N0) rates were 24.4 and 23.8%, respectively (p non-significant). Median follow-up:5.62 years. Five-year disease-free survival rate were 74.7% (Xelac) and 73.8% (Xelox), respectively (p = 0.444). Five-year overall survival rate were 80.4% (Xelac) and 85.5% (Xelox), respectively (p = 0.155). CONCLUSION: Xelac arm significantly obtained higher TRG1-2 rates. No differences were found about clinical outcome. Because of efficacy on TRG, inferior toxicity and good compliance, Xelac schedules or similar radiotherapy dose intensification schemes could be considered as reference treatments for cT3 lesions.

Effect of Ions Released and pH of Two Glass Ionomer Cements in Human Gingival Fibroblasts / Efecto de la liberación de iones y pH de dos cementos de ionómero de vidrio en fibroblastos gingivales humanos

Abstract 20. Conventional glass ionomer cements are used as dental provisional restorative materials, which present several advantages such as adhesion to the tooth mineral phase among others. On the other hand, the knowledge about biological property of glass ionomers shows various approaches and results. In this work, it was studied the in vitro biological response of human gingival fibroblasts in contact with commercial cements of glass ionomer: Mirafil® and Ionglass® and with their extracts, according to ISO 10993. The extracts of the cements, in which the cells were cultured, were adjusted at different concentrations ranging 0.1% to 100%. The cellular metabolic activity of gingival fibroblasts was measured using the Alamar Blue® reagent. The results showed a significant effect on the cellular metabolic activity correlated with the concentration of liberated ions (Al³+ and Ca²+) for both ionomers, as well as the pH variations of the culture media. This could mean that the cellular metabolic activity is substantially influenced by ions and pH of the cell culture.

Resumen 24. Los cementos de ionómero de vidrio convencionales se utilizan como materiales de restauración provisional para uso dental, los cuales presentan varias ventajas como la adhesión a la fase mineral de los dientes. Por otro lado, las propiedades biológicas de los ionómeros de vidrio muestran diversos enfoques y resultados. En éste trabajo se estudió la respuesta biológica in vitro de fibroblastos gingivales humanos en contacto con cementos comerciales de ionómero de vidrio: Mirafil® e Ionglass® y con sus respectivos extractos según la norma ISO 10993. Los extractos de los cementos en los que se cultivaron las células estaban en diferentes concentraciones: de 0.1% a 100%. La actividad metabólica celular se midió usando el reactivo Alamar Blue®. Los resultados mostraron un efecto significativo sobre la actividad metabólica celular correlacionada con la concentración de iones liberados (Al³+ y Ca²+) para ambos ionómeros, así como las variaciones de pH de los medios de cultivo. Ello podria explicar la influencia por los iones y el pH del cultivo celular en la actividad metabólica celular.

Effect of blueberry extract, carriers, and combinations on the growth rate of probiotic and pathogenic bacteria.

The blueberry is recognised as a source of phenolic compounds that have beneficial effects on human health; however, they possess low bioavailability and can be degraded by gastrointestinal conditions. Encapsulation has been widely used to mitigate these disadvantages; Gum Arabic (GA) and Corn Syrup Solids (CSS) are common carriers used in this technique. The aim of this study was to evaluate the effect of Blueberry Extract (BE), carriers and their mixtures on the kinetic growth and maximal growth rate of probiotics and pathogenic bacteria. Kinetics were performed in MRS medium with and without a carbon source through Optical Density (OD) measurements and fitting these to the logistic model to compare the maximal growth rates (µmax) of the microorganisms. Each food component and its mixtures exert a different influence on the µmax of the bacteria studied (p < 0.05). This knowledge is important to improve the design of additives and functional foods.