Adequate control of seizures in a case of lead migration and neuromodulation of the posterior Sylvian junction: A case report.

Background: This report aims to describe the neuromodulation effect on seizure control in a patient with a left hippocampal migrated electrode to the Posterior Sylvian Junction (PSJ) during a follow-up of 17 years. Case Description: We report a case of a female patient with drug-resistant epilepsy who initiated at seven years old and underwent a stereotactic frame-based insertion of a left hippocampal electrode for deep brain stimulation (DBS). Posterior migration of the electrode was identified at PSJ by postoperative magnetic resonance imaging one month after surgery. A consistent seizure reduction (Engel IC) was obtained with 2v-120 uS-145 Hz, contacts 0-3 negative, casing positive DBS parameters and maintained to this day. Patient data were collected from electronic medical records preceded by obtaining an informed consent for research and publication purposes. Stimulation parameter adjustments were confirmed with the digital records of the local device provider (Medtronic). Results: PSJ is a connectivity confluence point of white matter pathways in the posterior quadrant of the hemispheres. White mater DBS could be considered for research as a potential complementary target for neuromodulation of refractory epilepsy.

CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up.

BACKGROUND: Treatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission. METHODS: We evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology-European League against Rheumatism (ACR-EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded. RESULTS: The median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR-EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell-associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization. CONCLUSIONS: In this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.).

Use of electromyographic biofeedback in rehabilitation following anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

BACKGROUND: Rehabilitation following anterior cruciate ligament (ACL) reconstruction surgery is essential to regain functionality and return to previous activity level. Electromyographic biofeedback may be an effective intervention for rehabilitation of patients following ACL surgery. OBJECTIVE: To synthesize the available evidence on the effect of electromyographic biofeedback in the treatment of quadriceps strength following ACL surgery. DESIGN: Systematic review with meta-analysis. DATA SOURCES: PubMed, EMBASE, CENTRAL and Epistemonikos were searched. ELIGIBILITY CRITERIA: Randomized clinical trials with patients undergoing ACL reconstruction surgery comparing biofeedback with a standard rehabilitation control group. DATA EXTRACTION AND DATA SYNTHESIS: Two authors selected articles and performed data extraction. The analysed outcomes were strength, function, pain, knee extension and balance. The risk of bias of individual studies was assessed using the Cochrane Risk of Bias Tool. Results were combined through random-effects meta-analysis, reporting mean differences. RESULTS: Eight articles were included in the qualitative analysis, and four articles were included in the quantitative analysis. The interventions lasted between 4 and 12 weeks. Three studies evaluated the effect of biofeedback on quadriceps strength; of these, two studies showed a significant difference in favour of the biofeedback group. In addition, biofeedback was found to improve knee extension [standardized mean difference - 1.3, 95% confidence interval (CI) - 1.74 to -0.86] and balance (one study). There was no significant difference in Lysholm score (mean difference -6.21, 95% CI -17.51 to 5.08; I2 =59%) or pain between the biofeedback group and the control group. CONCLUSION: Electromyographic biofeedback in knee rehabilitation could be useful following ACL reconstruction surgery. KEY MESSAGES: SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO (CRD42020193768).

The Molecular Role of Polyamines in Age-Related Diseases: An Update.

Polyamines (Pas) are short molecules that exhibit two or three amine groups that are positively charged at a physiological pH. These small molecules are present in high concentrations in a wide variety of organisms and tissues, suggesting that they play an important role in cellular physiology. Polyamines include spermine, spermidine, and putrescine, which play important roles in age-related diseases that have not been completely elucidated. Aging is a natural process, defined as the time-related deterioration of the physiological functions; it is considered a risk factor for degenerative diseases such as cardiovascular, neurodegenerative, and musculoskeletal diseases; arthritis; and even cancer. In this review, we provide a new perspective on the participation of Pas in the cellular and molecular processes related to age-related diseases, focusing our attention on important degenerative diseases such as Alzheimerߣs disease, Parkinsonߣs disease, osteoarthritis, sarcopenia, and osteoporosis. This new perspective leads us to propose that Pas function as novel biomarkers for age-related diseases, with the main purpose of achieving new molecular alternatives for healthier aging.

Butyrophilin 2a2 (Btn2a2) expression on thymic epithelial cells promotes central T cell tolerance and prevents autoimmune disease.

Butyrophilins are surface receptors belonging to the immunoglobulin superfamily. While several members of the butyrophilin family have been implicated in the development of unconventional T cells, butyrophilin 2a2 (Btn2a2) has been shown to inhibit conventional T cell activation. Here, we demonstrate that in steady state, the primary source of Btn2a2 are thymic epithelial cells (TEC). Absence of Btn2a2 alters thymic T cell maturation and bypasses central tolerance mechanisms. Furthermore, Btn2a2-/- mice develop spontaneous autoimmunity resembling human primary Sjögren's Syndrome (pSS), including formation of tertiary lymphoid structures (TLS) in target organs. Ligation of Btn2a2 on developing thymocytes is associated with reduced TCR signaling and CD5 levels, while absence of Btn2a2 results in increased TCR signaling and CD5 levels. These results define a novel role for Btn2a2 in promoting central tolerance by modulating TCR signaling strength and indicate a potential mechanism of pSS development.

Innovative perspectives in limbic surgery using deep brain stimulation.

Limbic surgery is one of the most attractive and retaken fields of functional neurosurgery in the last two decades. Psychiatric surgery emerged from the incipient work of Moniz and Lima lesioning the prefrontal cortex in agitated patients. Since the onset of stereotactic and functional neurosurgery with Spiegel and Wycis, the treatment of mental diseases gave attention to refractory illnesses mainly with the use of thalamotomies. Neurosis and some psychotic symptoms were treated by them. Several indications when lesioning the brain were included: obsessive-compulsive disorder, depression, and aggressiveness among others with a diversity of targets. The indiscriminately use of anatomical sites without enough scientific evidence, and uncertainly defined criteria for selecting patients merged with a deficiency in ethical aspects, brought a lack of procedures for a long time: only select clinics allowed this surgery around the world from 1950 to the 1990s. In 1999, Nuttin et al. began a new chapter in limbic surgery with the use of Deep Brain Stimulation, based on the experience of pain, Parkinson's disease, and epilepsy. The efforts were focused on different targets to treat depression and obsessive-compulsive disorders. Nevertheless, other diseases were added to use neuromodulation. The goal of this article is to show the new opportunities to treat neuropsychiatric diseases.

Abordando el cuerpo de evidencia: conceptos fundamentales de los overviews / Approaching the body of evidence: Key concepts of Overviews

El aumento de la producción de investigación primaria y de las revisiones de la literatura durante las últimas décadas ha hecho necesario el desarrollo de un nuevo diseño metodológico para sintetizar la evidencia: los overviews. Un overview es un diseño de síntesis de evidencia que toma como unidad de análisis a las revisiones sistemáticas, con el objetivo de extraer y analizar los resultados para una pregunta de interés nueva o más amplia, ayudando así a mejorar los procesos de toma de decisiones informadas. El objetivo de este artículo es introducir al lector a este tipo de resúmenes de evidencia, destacando las diferencias con los otros tipos de síntesis de evidencia, los aspectos metodológicos particulares de los overviews, y los desafíos pendientes. Este artículo es el duodécimo de una serie metodológica colaborativa de revisiones narrativas sobre temáticas de bioestadística y epidemiología clínica.

The increasing production of primary research and literature reviews in the last decades has made it necessary to develop a new methodological design to synthesize the evidence: the overviews. An overview is a type of evidence synthesis that uses systematic reviews as the unit of analysis, with the aim of extracting and analyzing the results for a new or broader research question, helping the shared decision-making processes. The aim of this article is to introduce the reader to this type of evidence summaries, highlighting the differences between overviews and other types of synthesis, the unique methodological aspects of overviews, and future challenges. This is the twelfth article from a collaborative methodological series of narrative reviews about biostatistics and clinical epidemiology.

Abordaje de la enfermedad de Behçet vulvar: comunicación de caso

La enfermedad de Behçet (EB) es un trastorno inflamatorio, multisistémico, recidivante y remitente de etiología desconocida. Una característica clave de la enfermedad es la ulceración orogenital que provoca una morbilidad considerable con gran impacto en la calidad de vida de los pacientes. Su manejo médico consiste en un esquema con colchicina, esteroides o inmunomoduladores. Comunicamos el caso de una paciente con lesiones genitales quien consultó en múltiples ocasiones, recibiendo manejo antibiótico e incluso quirúrgico, con respuesta refractaria a estas intervenciones. Posteriormente, por las características de las lesiones y el comportamiento clínico se sospechó enfermedad de Behçet y se instauró manejo médico con esteroides orales y curaciones con fitoestimulina. Hubo resolución de las úlceras genitales y posteriormente la paciente fue llevada a cirugía para corrección de las sinequias vulvares.

Behçet's disease (BD) is an inflammatory, multisystemic, relapsing-remitting disorder of unknown etiology. A key feature of the disease is orogenital ulceration that causes considerable morbidity with great impact on patient's quality of life. Its medical management consists of a scheme with colchicine, steroids or immunomodulators. We report the case of a patient with genital lesions who consulted on multiple occasions, receiving antibiotics and even surgical management, with refractory response to these interventions. Subsequently, due to the characteristics of the lesion and clinical behavior, Behçet's disease was suspected and medical management with oral steroids and cures with phytostimulin was initiated. The genital ulcers were resolved, and the patient was subsequently taken to surgery for correction of the vulvar synechiae.

Neuropathic Pain and Positive Sensory Symptoms in Brachial Plexus Neuropathy: An Exploratory Study of Outcomes after Surgical Decompression and Proposal of a New Sensory Frequency of Symptoms Scale.

BACKGROUND: There are no articles that aim to evaluate the specific role of surgical decompression on the recovery of pain and positive sensory symptoms (PSS) in patients with brachial plexus neuropathy (BPN), as well as the relationship between pain and frequency of sensory manifestations. METHODS: A prospective before and after study was performed, considering the pain intensity through the visual analogue scale (VAS), and the frequency of PSS through a proposed new scale: Sensory Frequency of Symptoms Scale (SFSS). To compare the patients before and after the intervention, a paired T-test, a Wilcoxon signed-rank test, and Cohen's D test were made, coupled with a Spearman analysis in order to establish the relationship between pain and PSS. RESULTS: Sixteen patients were included in the study, the clinical evaluation showed changes in pain according with VAS, going from a mean preoperative state of 8.19 to 1.31 after surgery, showing significant changes (84%, p < 0.00006, Δ = 2.776). Within the PSS, a significant decrease was observed in paresthesias (74%, p < 0.0001, Δ = 1.645), dysesthesias (80%, p < 0.002, Δ = 1.453), and allodynia (70%, p = 0.031, Δ = 0.635). Conversely, the preoperative correlation analysis between pain and dysesthesias/allodynia showed a low and non-significant relationship (R < 0.4, p > 0.05). CONCLUSIONS: Surgical decompression is an effective technique for the relief of pain and sensory manifestations in adult patients with BPN of compressive origin. No relationship was observed between pain and dysesthesias/allodynia. Therefore, during clinical evaluation, they should be considered as independent manifestations, highlighting the need to validate new scales.

Hallazgos histopatológicos pulmonares asociados a COVID-19. Una revisión sistemática y meta-análisis / Histopathological findings in lungs of COVID-19 infected subjects. A systematic review and meta-analysis

El COVID-19 es una nueva enfermedad que requería resultados prontos provenientes de la investigación. Un abordaje para la comprensión de su fisiopatología es conocer el daño a nivel histopatológico que genera en los pulmones de los afectados. Objetivo. Proveer un resumen riguroso de la evidencia disponible sobre los hallazgos histopatológicos pulmonares en pacientes con COVID-19. Se desarrolló una revisión sistemática con metaanálisis de proporciones. Se incluyeron estudios primarios de cualquier diseño que tuvieran datos primarios de hallazgos histopatológicos de pulmones en pacientes COVID-19. Se excluyeron revisiones y guías. Las fuentes de información fueron el repositorio centralizado Living OVerview of Evidence, PubMed/Medline, LitCovid, la base de datos COVID-19 de la Organización Mundial de la Salud, y medRxiv hasta el 3 de abril 2021. La evaluación del riesgo de sesgos se realizó utilizando las herramientas del Instituto Joanna Briggs para series de casos y reportes de casos. Se extrajo cada dato de hallazgo pulmonar histopatológico. Se calcularon las frecuencias encontradas y los datos de los hallazgos más frecuentes fueron resumidas en metaanálisis usando el método de efectos aleatorios de Der Simmonian-Liard. Se midió la heterogeneidad. Los criterios de inclusión fueron cumplidos por 69 artículos sumando 594 sujetos. Presentaron bajo riesgo de sesgos 35 artículos. El metaanálisis de proporciones mostro daño alveolar difuso en 0,62 (IC 95 % 0,51-0,72), I2 59 % (p < 0,01), en su fase temprana (85,14 %). Conclusión. El daño alveolar difuso temprano fue el hallazgo histopatológico más frecuente en muestras pulmonares de pacientes con COVID-19

COVID-19 is a new disease that required prompt results from research. An approach to understanding its pathophysiology is to know the damage at the histopathological level that it generates in the lungs of those affected. Aim. To provide a rigorous summary of the available evidence on pulmonary histopathological findings in patients with COVID-19. A systematic review with meta-analysis of proportions was developed. Primary studies of any design that had primary data on lung histopathology findings in COVID-19 patients were included. Reviews and guidelines were excluded. The sources of information were the Living OVerview of Evidence centralized repository, PubMed/Medline, LitCovid, the World Health Organization COVID-19 database, and medRxiv up to April 3, 2021. The risk of bias assessment was performed using the Joanna Briggs Institute tools for case series and case reports. Each histopathological pulmonary finding data was extracted. The frequencies found were calculated and the data of the most frequent findings were summarized in meta-analyses using the Der Simmonian-Liard random effects method. Heterogeneity was measured. The inclusion criteria were met by 69 articles totaling 594 subjects. Thirty-five articles presented low risk of bias. The meta-analysis of proportions showed diffuse alveolar damage in 0.62 (95% CI 0.51-0.72), I2 59% (p < 0.01), in its early phase (85.14%). Conclution. Early diffuse alveolar damage was the most frequent histopathological finding in lung samples from patients with COVID-19

Satisfactory clinical outcomes with autologous matrix-induced chondrogenesis in the treatment of grade IV chondral injuries of the knee.

OBJECTIVE: The research aims to evaluate short- and medium-term outcomes of patients treated using autologous matrix-induced chondrogenesis (AMIC) with a hyaluronic acid scaffold (Hyalofast, Anika Therapeutics, MA, USA) in grade IV chondral lesions according to the Outerbridge classification in the knee. METHODS: This is a multicentre, non-randomized, retrospective study conducted between 2017 and 2022. To determine the clinical outcome of the patients, the follow-up was done with the subjective International Knee Documentation Committee (IKDC) score, pre-surgery, and with a follow-up at 12, 24, and 32 months. RESULTS: Fifty patients (28 female) with a mean age of 45.9 ± 12.7 years were recruited. The mean size of the lesion was 3.5 cm2, and the injuries located in the patella (30%) and trochlear groove (24%) were the most frequent. The total IKDC clinical score significantly increased from baseline to the 32 months of follow-up with a mean difference of 36.4 (95% CI, 29.1-43.7, p < 0.001). Besides, there was a statistically significant improvement in all categories of the IKDC (symptoms, sports activities, function, and activity of daily living) compared between pre-surgery and 24 and 32 months of follow-up. The patients younger than 45 years presented better clinical outcomes than older ones with a difference between medians of 10.40 (95% CI, 1.10-11.50, p = 0.0247), and a negative correlation was found between the 32-month IKDC score and the age. In addition, no statistically significant difference was found when comparing the last results of the IKDC between patients with and without associated surgical procedures or between patients with single and several lesions, neither nor between men and women. The level of satisfaction with the procedure of all the patients, on a score of 1-10, was on average 8 ± 1.5. CONCLUSION: Results of this study indicate that patients who underwent the AMIC procedure with hyaluronic acid scaffold for the treatment of grade IV chondral lesions in the knee presented satisfactory results throughout the follow-up. LEVEL OF EVIDENCE: Level IV.

Outcomes of spinal cord injury following cervical fracture in ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis (DISH): A prospective cohort study.

INTRODUCTION: The ankylosed spine is prone to increased fractures risk even after minor trauma. The lower cervical spine is most frequently injured, and fractures of the ankylosed spine tend to precipitate spinal cord injury (SCI). The objective of the current study is to assess the incidence, management, and outcomes of patients with ankylosis of the spine sustaining a cervical fracture with associated SCI over a 7-year period. MATERIAL AND METHODS: Prospective cohort study. Patients referred to the institution with a cervical fracture associated with SCI on a background of AS or DISH from 2009 to 2017 were reviewed. Demographics, mechanism of injury, fracture type, neurological level of injury, time to surgery, surgical management, neurological status (AIS), spinal cord independence measure (SCIMIII) scale at admission and discharge, and hospital length of stay. In September 2019 the summative data was analyzed using NDI, VAS, SV-QLI/SCI and length of survival were analyzed for statistical significance. Pathological fractures and dementia were excluded. RESULTS: 1613 patients with traumatic SCI were admitted in this period of whom 37 (12 AS and 25 DISH) met the inclusion criteria (mean age 65 years AS; 67 DISH). Fracture-dislocation was the most frequent fracture type (33% AS patients, 24% DISH patients). C4 was the most common neurological level of injury. SCIMIII score at admission was 1 point and 59 at discharge. AIS at admission was A (50%). At time of discharge no patient had neurologically deteriorated. Post-discharge mortality was 58% in AS patients and 32% in DISH patients (p=0.13). CONCLUSIONS: Both AS and DISH patients have high levels of disability and mortality associated with trauma to the cervical spine. Despite their distinct clinical differences, in this cohort there were no statistically significant differences between AS and DISH patients regarding fracture type, SCIMIII, AIS, hospital stay, mortality, VAS, and SV-QLI/SCI after cervical fracture over 7 years follow-up.

Ajuste escolar, empatía y conectividad con el medio ambiente natural en el marco de la educación ambiental en educación secundaria en España / School adjustment, empathy and connectedness with the natural environment in environmental education in Spanish secondary education

Resumen En investigaciones recientes se ha constatado que la empatía y la conectividad con el medioambiente natural son variables predictoras de la conducta proambiental. Sin embargo, no se han realizado trabajos en los que se analicen las relaciones entre estas dimensiones y el ajuste en la escuela, un escenario en el que tienen lugar gran parte de los programas relacionados con la educación ambiental y cuya finalidad es la de promover conductas proambientales. Con el presente trabajo se pretende analizar las relaciones entre el ajuste escolar, la empatía y la conectividad con el medioambiente natural en función del género. La muestra estuvo constituida por 881 estudiantes (47.2 % chicos), escolarizados en centros de educación secundaria (España), con edades comprendidas entre los 12 y los 17 años (M = 13.67 y SD = 1.32). Se administró una batería de instrumentos para medir el ajuste escolar, la empatía y la conectividad con el medioambiente natural. Se realizó un MANOVA para el análisis de los datos. Los resultados obtenidos mostraron que el ajuste escolar, la empatía y la conectividad se relacionan significativamente y que el género desempeña un rol significativo en estas relaciones. También se observó que chicos y chicas con alto ajuste escolar diferían en empatía emocional, pero no en conectividad. Se discuten los resultados obtenidos y se recomienda la incorporación del ajuste escolar en los estudios y programas relacionados con la educación ambiental.

Abstract In recent research it has been observed that empathy and connectedness with the natural environment are relevant predictive variables of pro-environmental behaviour. However, no work has been done in which the relationships between these dimensions and the adjustment in the school are analysed, a context in which most of the programs related to environmental education, whose purpose is to promote pro-environmental behaviours, take place. The general aim of this paper is to analyse the relationships between school adjustment, empathy and connectedness with the natural environment according to gender. School adjustment is defined as the adolescent's ability to adapt to this context and includes aspects such as academic performance, adaptation to school rules, respect for the teacher as an authority figure, the student's attitude towards school and participation in school activities. Empathy is conceptualized as the awareness of the emotions and cognitions of others, and it is important in the school context for the promotion of coexistence and prevention of aggressive behaviors. Like empathy with people, empathy with the natural environment is a social-emotional process. It is a process that focuses on the ability to feel and understand everything related to that medium. In this line, an essential aspect of empathy is its influence on the attitudes and behaviors of people in general and towards the natural environment. An aspect related to empathy is connectedness which refers to the identification of human beings with the natural environment and the relationships they establish with it. In such a way that to study the connection with nature is to try to understand how people build their relationships and identify themselves with it. Connectedness to the natural environment is related in a negative sense to selfish beliefs and attitudes and in a positive sense to the development of attitudes towards the natural environment and ecological behavior in general. These aspects are taken into account in this work. The sample was composed of 881 students (47.2 % boys), enrolled in secondary education (Spain), aged between 12 and 17 (M = 13.67 y SD = 1.32). A battery of instruments to measure school adjustment, empathy and connectedness with the natural environment was administered. A MANOVA was used for data analysis. The results showed that the school adjustment, empathy and connectedness were significantly related and that gender had a significant role in these relationships. It was also observed that boys and girls with high school adjustment differed in emotional empathy, but not in connectedness. Results obtained are discussed and the inclusion of the school adjustment in the studies and programs related to environmental education is recommended. These results raise the idea that school adjustment, connectedness and empathy should be the subject of further analysis because their results would help to incorporate new ideas and proposals into education and intervention programs regarding the natural environment. It was expected that environmental connectedness in adolescents had the same sign as their connectedness with school, family, etc. because many studies have observed that girls have greater connectedness in these scenarios than boys; however, this result deserves a greater exploration regarding gender and its relationships with other connectedness It is recommended that the results presented be considered in future environmental education programs, mainly aimed at students and their families. All this will benefit these educational programs and interventions aimed at enhancing respect and awareness of the natural environment. In short, the promotion of pro-environmental behaviors should be defended through environmental education that seeks to ensure the health and well-being of all citizens.

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a life-threatening autoimmune disease characterized by adaptive immune system activation, formation of double-stranded DNA autoantibodies and organ inflammation. Five patients with SLE (four women and one man) with a median (range) age of 22 (6) years, median (range) disease duration of 4 (8) years and active disease (median (range) SLE disease activity index Systemic Lupus Erythematosus Disease Activity Index: 16 (8)) refractory to several immunosuppressive drug treatments were enrolled in a compassionate-use chimeric antigen receptor (CAR) T cell program. Autologous T cells from patients with SLE were transduced with a lentiviral anti-CD19 CAR vector, expanded and reinfused at a dose of 1 × 106 CAR T cells per kg body weight into the patients after lymphodepletion with fludarabine and cyclophosphamide. CAR T cells expanded in vivo, led to deep depletion of B cells, improvement of clinical symptoms and normalization of laboratory parameters including seroconversion of anti-double-stranded DNA antibodies. Remission of SLE according to DORIS criteria was achieved in all five patients after 3 months and the median (range) Systemic Lupus Erythematosus Disease Activity Index score after 3 months was 0 (2). Drug-free remission was maintained during longer follow-up (median (range) of 8 (12) months after CAR T cell administration) and even after the reappearance of B cells, which was observed after a mean (±s.d.) of 110 ± 32 d after CAR T cell treatment. Reappearing B cells were naïve and showed non-class-switched B cell receptors. CAR T cell treatment was well tolerated with only mild cytokine-release syndrome. These data suggest that CD19 CAR T cell transfer is feasible, tolerable and highly effective in SLE.

Alpha-1 antitrypsin in autoimmune diseases: Roles and therapeutic prospects.

Alpha-1 antitrypsin (A1AT) is a protease inhibitor in the serum. Its primary function is to inhibit the activity of a series of proteases, including proteinase 3, neutrophil elastase, metalloproteases, and cysteine-aspartate proteases. In addition, A1AT also has anti-inflammatory, anti-apoptotic, anti-oxidative stress, anti-viral, and anti-bacterial activities and plays essential roles in the regulation of tissue repair and lymphocyte differentiation and activation. The overactivation of the immune system characterizes the pathogenesis of autoimmune diseases. A1AT treatment shows beneficial effects on patients and animal models with autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. This review summarizes the functions and therapeutic prospects of A1AT in autoimmune diseases.

Experiencias en los servicios de salud de epidemiólogos en formación durante la pandemia COVID-19 / Experiences in the health services of epidemiologists in training during the COVID-19 pandemic

Introducción: Aunque existen numerosas evidencias científica sobre la pandemia, el impacto de la COVID-19 en los servicios de salud desde la perspectiva del personal asistencial ha sido poco explorado. Objetivo: Explorar las experiencias en los servicios de salud de epidemiólogos en formación durante la pandemia COVID-19. Métodos: Estudio exploratorio, cualitativo-descriptivo, con herramientas de investigación etnográfica para la toma de datos como la observación, diario de campo y entrevista grupal; así como teoría fundamentada para la construcción de categorías que permitieron comprender el fenómeno de estudio. Para la conformación del grupo focal, participaron siete epidemiólogos en formación de una universidad colombiana, previo consentimiento informado. Se realizó la introducción de la temática, con la posterior aplicación de los instrumentos guía de grupo focal, carteles de consenso, hojas de respuesta y guía de observación. Resultados: Se generó colapso hospitalario y reestructuración emergente de servicios de salud, promoviendo otras estrategias de atención como la telemedicina. Los participantes del estudio experimentaron temor atendiendo pacientes en jornadas estresantes, con desabastecimiento de insumos y medicamentos; fueron estigmatizados, lo que les generó ansiedad y estrés laboral. Sin embargo, aprendieron a clasificar mejor los casos y con el aumento de los pacientes pudieron percibir inequidades que representaron un desafío profesional y humano. Conclusiones: La pandemia de COVID-19 ha sido válida como proceso de aprendizaje con nuevas perspectivas de formación para poder actuar ante eventos sanitarios de interés mundial, con la necesaria aplicación y manejo de protocolos, lo cual puede cambiar el enfoque de la atención en salud y permitir que la epidemiología avance hacia la educación, promoción y prevención(AU)

Introduction: Although there is ample scientific evidence on the pandemic, the impact of COVID-19 on health services from the perspective of healthcare personnel has been little explored. Objective: To explore the experiences in health services of epidemiologists in training during the COVID-19 pandemic. Methods: Exploratory, qualitative-descriptive study, with ethnographic research tools for data collection such as observation, field diary and group interview; as well as grounded theory for the construction of categories that allowed to understand the studied phenomenon. For the formation of the focus group, seven epidemiologists in training from a Colombian university participated, with prior informed consent. The topic was introduced, with the subsequent application of the focus group guide tools, consensus posters, response sheets and an observation guide. Results: Hospital collapse and emerging restructuring of health services were generated, promoting other care strategies such as telemedicine. Study participants experienced fear attending patients on stressful days, with shortages of supplies and medicines; they were stigmatized, which generated anxiety and work stress. However, they learned to better classify cases and with the increase in patients they were able to perceive inequities that represented a professional and human challenge. Conclusions: The COVID-19 pandemic has been valid as a learning process with new training perspectives to be able to act in the face of health events of global interest, with the necessary application and management of protocols, which can change the focus of health care and allow epidemiology to move towards education, promotion and prevention(AU)

Matched linac stereotactic radiotherapy: An assessment of delivery similarity and distributive patient-specific quality assurance feasibility.

Matching multiple linacs to common baseline data allows patients to be treated, and patient-specific quality assurance (PSQA) to be completed on any linac. Stereotactic body radiotherapy (SBRT) requires higher levels of accuracy and quality assurance than routine radiotherapy. The achieved linac matching must therefore be evaluated before distributive treatment or PSQA models can be implemented safely. This investigation aimed to propose metrics for defining linacs to be matched for SBRT deliveries, assess 12 linacs against these criteria, and determine if a distributive PSQA model could be implemented by reviewing the rates of false PSQA results. Ten SBRT spine plans were delivered by 12 matched Elekta linacs and measured using one of seven SRS MapCHECK devices. For gamma criteria of (3%, 2 mm), 96.9% of equivalent location detectors, showed a range of gamma ≤ 1.0 and 99.9% showed a standard deviation of ≤ 0.5. For criteria of (3%,1 mm) and (2%,1 mm), these ranges decreased to 92.1% and 80.2% while the standard deviations decreased to 99.3% and 95.7%, respectively. The dose differences showed that 43.6%, 82.7%, and 91.4% of detectors had a dose range of ≤ 3.0%, ≤ 5.0%, and ≤ 6.0%, respectively. Standard deviations of dose differences were 1.5%, 2.5%, and 3.0% for 94.1%, 98.3%, and 99.5% of detectors, respectively. For the fleet of linacs, distributive PSQA yielded false results for 0.0%, 17.7%, and 33.0% of plans, equivalent to 1.2%, 3.5%, and 9.4% of detectors when using gamma criteria of (3%,2 mm), (3%,1 mm), or (2%,1 mm), respectively. These linacs could be considered matched for SBRT treatments and implement a distributive PSQA model when gamma analysis was completed with a criterion of (3%, 2 mm). For stricter criterion of (3%,1 mm) or (2%,1 mm), they did not meet the proposed metrics.

Reducing ExacTrac intrafraction imaging uncertainty for prostate stereotactic body radiotherapy using a pre-treatment CBCT.

This study evaluated the intrafractional auto-matching uncertainties of prostate-implanted fiducial markers when using the ExacTrac v6.5 (Brainlab, Feldkirchen, Germany) X-ray stereoscopic system. A customised phantom with 3 implanted gold seeds was initially positioned at the isocentre using a cone beam CT (CBCT) prior to intrafractional imaging. Progressive offsets were applied to the phantom in all six directions (3 translational, 3 rotational) of 0 mm, 1 mm, 2 mm, 0°, 1° and 2°. Subsequently, the ability of the ExacTrac image-matching functions to detect and correct these offsets was tested. For comparison, this procedure was repeated, but without a CBCT for pre-treatment positioning. The auto-matching uncertainties when a CBCT was introduced into the workflow were significantly reduced, and overall, the auto-matching statistics using the implanted marker (seeds) matching function was found to be more precise than the bony anatomy function in-phantom. The total standard deviations for the translational shifts using the implanted marker and bony anatomy functions respectively were 0.1 mm and 0.3 mm vertically, 0.1 mm and 0.3 mm longitudinally, and 0.1 mm and 0.4 mm laterally. The standard deviations for the rotational shifts using the implanted marker and bony anatomy matching functions respectively were 0.2° and 1.2° for the yaw (angle vert), 0.3° and 1.1° for the pitch (angle long), and 0.2° and 1.2° for the roll (angle lat) directions. The reduced uncertainties from introducing a CBCT for initial localisation resulted in decreased probability of inhibits due to false positives during treatment.

Corrigendum: Low Dose Radiation Therapy Induces Long-Lasting Reduction of Pain and Immune Modulations in the Peripheral Blood - Interim Analysis of the IMMO-LDRT01 Trial.

[This corrects the article DOI: 10.3389/fimmu.2021.740742.].

Ascitis masiva secundaria a preeclampsia severa: reporte de caso / Massive ascitis secondary to severe preeclampsia: case report

RESUMEN La preeclampsia es una patología con múltiples implicaciones y causa de morbimortalidad materno perinatal. Aunque su frecuencia es baja, la ascitis es un signo clínico a tener en cuenta. Reportamos el caso de un embarazo de 33,1 semanas con preeclampsia severa, en quien durante la cesárea se observó ascitis que evolucionó a ascitis masiva al segundo día postoperatorio, y requirió manejo invasivo (drenaje por pig tail) y traslado a UCI por 6 días. Necesitó nitroprusiato durante 2 días por persistencia de la crisis hipertensiva, con mejoría progresiva y egreso de la clínica a los 12 días.

ABSTRACT Preeclampsia is a pathology with multiple implications and a cause of maternal and perinatal morbidity and mortality. Although its frequency is low, ascites is a clinical sign to be taken into account. We report the case of a 33.1-week pregnant woman with severe preeclampsia, in whom ascites was observed during cesarean section and evolved to massive ascites on the second postoperative day, requiring invasive management (pig tail drainage) and transfer to the ICU for 6 days. She needed nitroprusside for 2 days due to persistent hypertensive crisis, with progressive improvement and discharge from the clinic after 12 days.