Caracterización de la introducción y tolerabilidad del tapentadol de liberación prolongada en pacientes con dolor crónico en una unidad del dolor en Portugal: estudio transversal

Introducción. El tapentadol de liberación prolongada (LP) es un analgésico de acción central indicado para el tratamiento del dolor moderado a intenso. El objetivo de este estudio es caracterizar la introducción y la tolerabilidad del tapentadol LP en pacientes seguidos en una unidad de dolor crónico mediante la evaluación de la prevalencia de eventos adversos y las principales razones para la interrupción del tratamiento o la reducción de la dosis. Material y métodos. En este estudio transversal, todos los pacientes seguidos en la unidad de dolor crónico bajo tratamiento con tapentadol LP fueron analizados durante un período de 8 meses. Las características demográficas y clínicas de los pacientes fueron recolectadas retrospectivamente a través de la consulta de los archivos clínicos. Resultados. De los 127 pacientes incluidos en el estudio, 119 (93,7%) reemplazaron analgésicos opioides por tapentadol LP, siendo este el fármaco de primera línea en 8 (6,3%) pacientes. Durante el estudio, 26 (20,5%) pacientes interrumpieron el tratamiento con tapentadol LP y 5 (3,9%) pacientes redujeron su dosis. Las principales razones para la interrupción de tapentadol LP fueron eventos adversos: náuseas o vómitos (32.1%), estreñimiento (19.2%), mareos (19.2%) y ausencia del efecto analgésico deseado. Discusión. La prevalencia de la interrupción del tratamiento con tapentadol LP y los eventos adversos asociados con su uso fue similar a la descrita anteriormente. Se necesitarán más estudios para optimizar el tratamiento de pacientes con dolor crónico tapentadol LP en el contexto de unidades de dolor crónico. Conclusión. En nuestro estudio, los pacientes que suspendieron el tapentadol corresponden a un porcentaje bajo. Encontramos que el motivo más frecuente fueron los efectos adversos gastrointestinales, seguidos por la falta de efecto analgésico y mareos. El tapentadol PR parece ser un fármaco bien tolerado por los pacientes seguidos en la unidad del dolor.Introduction. Tapentadol prolonged-release (PR) is a centrally acting oral analgesic prescribed for the treatment of moderate to severe pain. This study aimed to characterize the introduction and tolerability of tapentadol PR treatment in patients with chronic pain who were attending a hospital-based chronic pain outpatient unit, by assessing the prevalence and main reasons for treatment discontinuation or dose reduction. Material and Methods. In this cross-sectional observational study, all patients visiting an outpatient chronic pain unit who were taking tapentadol PR as their analgesic therapy were included. Demographic and clinical data of patients, and reasons for tapentadol PR treatment discontinuation or reduction during an eight-month period were extracted from the medical records. Results. Of the 127 enrolled patients, 119 (93.7%) were switched from opioids to tapentadol PR and 8 (6.3%) were taking tapentadol PR as their primary medication for the treatment of chronic pain. During the study, 26 (20.5%) patients discontinued tapentadol PR treatment and 5 (3.9%) patients reduced their dose. The most frequently reported reasons for tapendadol PR discontinuation were adverse reactions – nausea or vomiting (32.1%), constipation (19.2%), dizziness (19.2%) – and lack of analgesic effect (30.8%). Discussion. Prevalence of treatment discontinuation and adverse reactions associated with the use of tapentadol PR are similar to the ones previously reported. Further studies are needed to improve the management of chronic pain patients with tapentadol PR in an outpatient setting. Conclusion. Patients with chronic pain in our study discontinued their tapentadol PR treatment at a low percentage. We found that the most frequent reason for discontinuation of tapentadol PR was gastrointestinal disorders, followed by lack of analgesic effect, and dizziness. Tapentadol PR appears to be a well-tolerated for the control of chronic pain in patients attending an outpatient unit

Defining the first bona fide cell model for SMARCA4-deficient, undifferentiated tumor

The World Health Organization’s tumor classification guidelines are frequently updated and renewed as knowledge of cancer biology advances. For instance, in 2021, a novel lung tumor subtype named SMARCA4-deficient, undifferentiated tumor (SMARCA4-dUT, code 8044/3) was included. To date, there is no defined cell model for SMARCA4-dUT that could be used to help thoracic clinicians and researchers in the study of this newly defined tumor type. As this tumor type was recently described, it is feasible that some cell models formerly classified as lung adenocarcinoma (LUAD) could now be better classified as SMARCA4-dUT. Thus, in this work, we aimed to identify a bona fide cell model for the experimental study of SMARCA4-dUT. We compared the differential expression profiles of 36 LUAD-annotated cell lines and 38 cell lines defined as rhabdoid in repositories. These comparative results were integrated with the mutation and expression profiles of the SWI/SNF complex members, and they were surveyed for the presence of the SMARCA4-dUT markers SOX2, SALL4, and CD34, measured by RTqPCR and western blotting. Finally, the cell line with the paradigmatic SMARCA4-dUT markers was engrafted into immunocompromised mice to assess the histological morphology of the formed tumors and compare them with those formed by a bona fide LUAD cancer cell line. NCI-H522, formerly classified as LUAD, displayed expression profiles nearer to rhabdoid tumors than LUAD tumors. Furthermore, NCI-H522 has most of the paradigmatic features of SMARCA4-dUT: hemizygous inactivating mutation of SMARCA4, severe SMARCA2 downregulation, and high-level expression of stem cell markers SOX2 and SALL4. In addition, the engrafted tumors of NCI-H522 did not display a typical differentiated glandular structure as other bona fide LUAD cell lines (A549) do but had rather a largely undifferentiated morphology, characteristic of SMARCA4-dUT. Thus, we propose the NCI-H522 as the first bona fide cell line model of SMARCA4-dUT.Spanish Ministry of Science and Innovation (PID2021-126111OB-I00)Junta de Andalucía (PIGE-0213-2020, PI-0203-2022)University of Granada (B-CTS-480-UGR20)The Fundaci on Científica Asociaci on Española Contra el Cáncer (LAB-AECC-2018)FPU17/01258 fellowshipPrograma Operativo de Empleo Juvenil y de la Iniciativa de Empleo Juvenil (#04/2022-05)Grant from the Scientific Foundation of the Spanish Association Against Cancer in Granada (#PRDGR21428SAN

Changes in foot posture during pregnancy and their relation with musculoskeletal pain: A longitudinal cohort study

Aim: To examine foot posture changes during the three trimesters of pregnancy and to determine whether there is a relationship between these changes and the pain experienced in this period. Methods: The study sample consisted of 62 pregnant women who attended the Gynaecology Service at Hospital Santa María del Puerto (Cádiz, Spain), between January 2013 and May 2014. In their first visit, the following sociodemographic and anthropometric data were recorded: age, weight, height and foot size. In addition, information was obtained regarding pain in the lower back, knees, ankles and feet. In this first visit, too, the Foot Posture Index (FPI) was assessed, and three subsequent controls were performed during the first, second and third months of pregnancy (termed Stages 1, 2 and 3, respectively). Results: In Stage 1, the average foot size (i.e., shoe size) was 38.3 (SD 1.5). This size did not change between Stages 1, 2 and 3. However, body weight and BMI did present statistically significant changes during this period (p < 0.0001). The FPI varied during pregnancy but no relation was observed between these changes and the onset of pain. Conclusions: During pregnancy, pronation increases but this does not appear to influence the onset of pain in the lower limb

Current Advanced Therapies Based on Human Mesenchymal Stem Cells for Skin Diseases

Skin disease may be related with immunological disorders, external aggressions, or genetic conditions. Injuries or cutaneous diseases such as wounds, burns, psoriasis, and scleroderma among others are common pathologies in dermatology, and in some cases, conventional treatments are ineffective. In recent years, advanced therapies using human mesenchymal stem cells (hMSCs) from different sources has emerged as a promising strategy for the treatment of many pathologies. Due to their properties; regenerative, immunomodulatory and differentiation capacities, they could be applied for the treatment of cutaneous diseases. In this review, a total of thirteen types of hMSCs used as advanced therapy have been analyzed, considering the last 5 years (2015–2020). The most investigated types were those isolated from umbilical cord blood (hUCB-MSCs), adipose tissue (hAT-MSCs) and bone marrow (hBM-MSCs). The most studied diseases were wounds and ulcers, burns and psoriasis. At preclinical level, in vivo studies with mice and rats were the main animal models used, and a wide range of types of hMSCs were used. Clinical studies analyzed revealed that cell therapy by intravenous administration was the advanced therapy preferred except in the case of wounds and burns where tissue engineering was also reported. Although in most of the clinical trials reviewed results have not been posted yet, safety was high and only local slight adverse events (mild nausea or abdominal pain) were reported. In terms of effectiveness, it was difficult to compare the results due to the different doses administered and variables measured, but in general, percentage of wound’s size reduction was higher than 80% in wounds, Psoriasis Area and Severity Index and Severity Scoring for Atopic Dermatitis were significantly reduced, for scleroderma, parameters such as Modified Rodnan skin score (MRSC) or European Scleroderma Study Group activity index reported an improvement of the disease and for hypertrophic scars, Vancouver Scar Scale (VSS) score was decreased after applying these therapies. On balance, hMSCs used for the treatment of cutaneous diseases is a promising strategy, however, the different experimental designs and endpoints stablished in each study, makes necessary more research to find the best way to treat each patient and disease.Instituto de Salud Carlos III (European Regional Development Fund "A way to make Europe") PI13/02576 PI17/02083Andalusian Regional Government SAS PI-0458-2016 PIGE-0242-2019Instituto de Salud Carlos III (European Social Fund "Investing in your future") FI18/0026

Evaluation of patient satisfaction with anaesthesia. Cross-sectional study

Objetivos: La satisfacción de los pacientes es un concepto subjetivo y complejo, ya que depende de varios factores. Unos dependen del propio paciente, como la edad, el sexo o nivel cultural, y otros de los cuidados prestados. Este estudio tiene como objetivos evaluar el grado de satisfacción de los pacientes sometidos a procedimientos quirúrgicos con necesidad de anestesia general y determinar los factores que puedan tener una relación directa con esa satisfacción. Métodos: Se realizaron cuestionarios a pacientes sometidos a anestesia general para cirugía general electiva, durante tres meses consecutivos. Tras la obtención del consentimiento informado, las preguntas y respuestas fueron registradas por un elemento externo al equipo que prestó cuidados anestésicos al paciente, entre 12 a 36 horas tras el acto anestésico. El cuestionario está constituido por 16 preguntas relacionadas con el periodo pre-operatorio, intra-operatorio y pos-operatorio. Resultados: La mayoría de los pacientes encuestados (68,1%) se encontraban muy satisfechos con su anestesia. En cuanto al dolor pos-operatorio, 43,5% refirieron no sentir dolor, 29% sintieron dolor leve, 20,2% dolor moderado y 7,3% dolor severo. El 16,7% refirió nauseas o vómitos en el pos-operatorio. El 84,1% de los pacientes refirieron que fueron evaluados por un anestesista, 73,9% consideró esclarecidas sus preocupaciones y 45,7% afirmaron que les fue explicado el tipo de anestesia que se realizaría. Conclusiones: Verificamos que los pacientes presentan niveles altos de satisfacción con el acto anestésico. Los factores que se pueden encontrar relacionados con esa satisfacción son la información de los pacientes relativamente al plan anestésico, el esclarecimiento de sus preocupaciones, el nivel de dolor, así como las náuseas y vómitos en el post-operatorio.Objectives: Patient satisfaction is a subjective and complex concept because it depends on several factors. Some depend on the patient, such as age, sex and educational level, and other caregiving. This study aims to evaluate the degree of satisfaction of patients undergoing surgical procedures requiring general anaesthesia and identify factors that have a direct relationship with this satisfaction. Methods: Questionnaires were performed on patients undergoing general anaesthesia for three consecutive months. After obtaining informed consent, the questions and answers were recorded by an external element to the team that gave anaesthetic patient care, between 12-36 hours after the anaesthetic act. The questionnaire consists of 16 questions related to the pre-operative, intra-operative and post-operative period. Results: Most patients surveyed (68.1 %) were very satisfied with their anaesthesia. As for post-operative pain, 43.5 % reported no pain, 29 % felt slight pain, moderate pain 20.2 % and 7.3 % severe pain. 16.7 % reported nausea or vomiting in the postoperative period. 84.1 % of patients reported that they were assessed by an anaesthetist, 73.9 % believe their concerns are clarified and 45.7 % said it was explained to them the type of anaesthesia that would be done. Conclusions: We verified that patients have high levels of satisfaction with the anaesthesia. Factors that could be related to the satisfaction are patient information relative to the anaesthetic plan, clarify concerns, pain, and nausea and vomiting

Portable flow multiplexing device for continuous, in situ biodetection of environmental contaminants

A compact, low-cost and low-powered device was developed and arranged for multiplexed biodetection of sea water contaminants from continuous flow mode. Electronics, mechanics and fluidics were designed to guarantee identical functional liquid flow through eight parallel sensor microchambers during a predetermined time period providing 8 values at the same time. The accuracy and repeatability of the device was tested in-lab, achieving a deviation of less than 10% when measuring the same analyte in all the chambers. The experimental results obtained with our device were finally compared with those measured in continuous flux by a commercial potentiostat SP150 (Bio-Logic Science Instruments), obtaining identical results, which validated the proposed device

Mechanical behavior of single-layer ceramized zirconia abutments for dental implant prosthetic rehabilitation

Objectives: This study was undertaken to characterize the mechanical response of bare (as-received) and single- layer ceramized zirconia abutments with both internal and external connections that have been developed to enhan - ced aesthetic restorations. Material and Methods: Sixteen zirconia implant abutments (ZiReal Post®, Biomet 3i, USA) with internal and ex - ternal connections have been analyzed. Half of the specimens were coated with a 0.5mm-thick layer of a low-fusing fluroapatite ceramic. Mechanical tests were carried out under static (constant cross-head speed of 1mm/min until fracture) and dynamic (between 100 and 400N at a frequency of 1Hz) loading conditions. The failure location was identified by electron microscopy. The removal torque of the retaining screws after testing was also evaluated. Results: The average fracture strength was above 300N for all the abutments, regardless of connection geometry and coating. In most of the cases (94%), failure occurred by abutment fracture. No significant differences were observed either in fatigue behavior and removal torque between the different abutment groups. Conclusions: Mechanical behavior of Zireal zirconia abutments is independent of the type of internal/external connection and the presence/absence of ceramic coating. This may be clinically valuable in dental rehabilitation to improve the aesthetic outcome of zirconia-based dental implant systems

The Role of Exosomes Derived From Mesenchymal Stromal Cells in Dermatology

This study has been funded by the Carlos III Health Institute of Spain through the PI13/02576 and PI17/02083 projects [cofunded by European Regional Development Fund "A way to make Europe" and Andalusian Regional Government Finance (SAS PI-0458-2016)]. The work of MQ-V was supported by a predoctoral fellowship (BOE 22/10/2019) from the Spanish Ministry of Science, Innovation and Universities. This study is part of her doctoral research in the Biomedicine program at the University of Granada.The skin is the largest organ of the human body and its main functions include providing protection from external harmful agents, regulating body temperature, and homeostatic maintenance. Skin injuries can damage this important barrier and its functions so research focuses on approaches to accelerate wound healing and treat inflammatory skin diseases. Due to their regenerative and immunomodulatory properties, mesenchymal stromal cells (MSCs) have been reported to play a significant role in skin repair and regeneration. However, it seems that the secretome of these cells and exosomes in particular may be responsible for their functions in skin regeneration and the immunomodulation field. The present review aims to gather the available information about the role of MSC-derived exosomes for both in vitro and in vivo models of different skin conditions and to highlight the need for further research in order to overcome any limitations for clinical translation.Carlos III Health Institute of Spain [European Regional Development Fund "A way to make Europe"] PI13/02576 PI17/02083Carlos III Health Institute of Spain [Andalusian Regional Government Finance] PI13/02576 PI17/02083 SAS PI-0458-2016Spanish Ministry of Science, Innovation and Universities BOE 22/10/201

Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models

Simple Summary: Mammalian SWI/SNF complexes regulate gene expression by reorganizing the way DNA is packaged into chromatin. SWI/SNF subunits are recurrently altered in tumors at multiple levels, including DNA mutations as well as alteration of the levels of RNA and protein. Cancer cell lines are often used to study SWI/SNF function, but their patterns of SWI/SNF alterations can be complex. Here, we present a comprehensive characterization of DNA mutations and RNA and protein expression of SWI/SNF members in 38 lung adenocarcinoma (LUAD) cell lines. We show that over 85% of our cell lines harbored at least one alteration in one SWI/SNF subunit. In addition, over 75% of our cell lines lacked expression of at least one SWI/SNF subunit at the protein level. Our catalog will help researchers choose an appropriate cell line model to study SWI/SNF function in LUAD. Abstract: Mammalian SWI/SNF (SWitch/Sucrose Non-Fermentable) complexes are ATP-dependent chromatin remodelers whose subunits have emerged among the most frequently mutated genes in cancer. Studying SWI/SNF function in cancer cell line models has unveiled vulnerabilities in SWI/SNF-mutant tumors that can lead to the discovery of new therapeutic drugs. However, choosing an appropriate cancer cell line model for SWI/SNF functional studies can be challenging because SWI/SNF subunits are frequently altered in cancer by various mechanisms, including genetic alterations and post-transcriptional mechanisms. In this work, we combined genomic, transcriptomic, and proteomic approaches to study the mutational status and the expression levels of the SWI/SNF subunits in a panel of 38 lung adenocarcinoma (LUAD) cell lines. We found that the SWI/SNF complex was mutated in more than 76% of our LUAD cell lines and there was a high variability in the expression of the di erent SWI/SNF subunits. These results underline the importance of the SWI/SNF complex as a tumor suppressor in LUAD and the di culties in defining altered and unaltered cell models for the SWI/SNF complex. These findings will assist researchers in choosing the most suitable cellular models for their studies of SWI/SNF to bring all of its potential to the development of novel therapeutic applications.Ministry of Economy of Spain SAF2015-67919-RJunta de Andalucía CS2016-3 P12-BIO1655 PIGE-0440-2019 Pl-0245-2017 PI-0135-2020University of Granada PPJIA2019-0 B-CTS-126-UGR18International Association for the Study of Lung Cancer (IASLC)Spanish Association for Cancer Research (LAB-AECC)PhD "La Caixa Foundation" LCF/BQ/DE15/10360019"Fundacion Benefica Anticancer Santa Candida y San Francisco Javier" predoctoral fellowshipEuropean Commission 837897Spanish Ministry of Education, Culture and Sports FPU fellowship FPU17/00067 FPU17/01258 FPU18/03709PhD FPI-fellowship BES-2013-064596Fundación Científica de la Asociación Española Contra el Cáncer GCB14-2170Fundación Ramon ArecesInstituto de Salud Carlos III-Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional `Una manera de hacer Europa' (FEDER) PI19/0009