Immune dysregulation and pathophysiology of alcohol consumption and alcoholic liver disease.

Alcoholic liver disease (ALD) is a clinical-pathologic entity caused by the chronic excessive consumption of alcohol. The disease includes a broad spectrum of anomalies at the cellular and tissual level that can cause acute-on-chronic (alcoholic hepatitis) or chronic (fibrosis, cirrhosis, hepatocellular cancer) injury, having a great impact on morbidity and mortality worldwide. Alcohol is metabolized mainly in the liver. During alcohol metabolism, toxic metabolites, such as acetaldehyde and oxygen reactive species, are produced. At the intestinal level, alcohol consumption can cause dysbiosis and alter intestinal permeability, promoting the translocation of bacterial products and causing the production of inflammatory cytokines in the liver, perpetuating local inflammation during the progression of ALD. Different study groups have reported systemic inflammatory response disturbances, but reports containing a compendium of the cytokines and cells involved in the pathophysiology of the disease, from the early stages, are difficult to find. In the present review article, the role of the inflammatory mediators involved in ALD progression are described, from risky patterns of alcohol consumption to advanced stages of the disease, with the aim of understanding the involvement of immune dysregulation in the pathophysiology of ALD.

Preoperative coagulation screening tests in pediatric patients: Clinical relevance and hemorrhagic outcomes of abnormal results.

PURPOSE: Coagulation screening tests in children are still frequently performed in many countries to evaluate bleeding risk. The aim of this study was to assess the management of unexpected prolongations of the activated partial thromboplastin time (APTT) and prothrombine time (PT) in children prior to elective surgery, and the perioperative hemorrhagic outcomes. METHODS: Children with prolonged APTT and/or PT who attended a preoperative anesthesia consultation from January 2013 to December 2018 were included. Patients were grouped according to whether they were referred to a Hematologist or were scheduled to undergo surgery without further investigation. The primary endpoint was to compare perioperative bleeding complications. RESULTS: 1835 children were screened for eligibility. 102 presented abnormal results (5.6%). Of them, 45% were referred to a Hematologist. Significant bleeding disorders were associated with a positive bleeding history, odds ratio of 51 (95% CI 4.8-538.5, P=.0011). No difference in perioperative hemorrhagic outcomes were found between the groups. An additional cost of 181 euros per patient and a preoperative median delay of 43 days was observed in patients referred to Hematology. CONCLUSIONS: Our results suggest that hematology referral has limited value in asymptomatic children with a prolonged APTT and/or PT. Hemorrhagic complications were similar among patients referred and not referred to Hematology. A positive personal or family bleeding history can help identify patients with a higher bleeding risk, thus it should guide the need for coagulation testing and hematology referral. Further efforts should be made to standardize preoperative bleeding assessments tools in children.

Pruebas de coagulación preoperatorias en pacientes pediátricos: relevancia clínica y consecuencias hemorrágicas de los resultados anómalos / Preoperative coagulation screening tests in pediatric patients: Clinical relevance and hemorrhagic outcomes of abnormal results

Objetivo: Las pruebas de evaluación de la coagulación en niños siguen realizándose con frecuencia en muchos países, para evaluar el riesgo de hemorragia. El objetivo de este estudio fue valorar el manejo de la prolongación inesperada del tiempo de tromboplastina parcial activada (APTT) y el tiempo de protrombina (PT) en niños previa a la cirugía electiva, y el riesgo hemorrágico perioperatorio. Métodos: Se incluyó a los niños con APTT y/o PT prolongados que acudieron a consulta de anestesia preoperatoria desde enero del 2013 a diciembre del 2018. Se agrupó a los pacientes en función de si habían sido derivados a Hematología o habían sido programados para cirugía sin pruebas adicionales. El resultado primario fue comparar las complicaciones hemorrágicas perioperatorias. Resultados: Se evaluó para elegibilidad a 1.835 niños. Presentaron resultados anormales 102 de ellos (5,6%) y el 45% fue derivado a Hematología previo a la cirugía. Los trastornos hemorrágicos significativos estuvieron asociados a a una historia hemorrágica (personal y/o familiar) positiva, odds ratio de 51 (IC 95% de 4,8 a 538,5, p = 0,0011). No se encontró diferencia en términos de resultados de hemorragia perioperatoria entre los grupos. Se observó un coste adicional de 181 € por paciente y una mediana de demora preoperatoria de 43 días en los pacientes derivados a Hematología. Conclusiones: Nuestros resultados sugieren que la derivación a Hematología tiene un valor limitado en niños asintomáticos con APTT y/o PT prolongados. Las complicaciones hemorrágicas fueron similares entre los pacientes derivados y los no derivados a Hematología. Una historia familiar positiva de hemorragia puede ayudar a identificar a los pacientes con mayor riesgo de sangrado, por lo que debería guiar la petición de los análisis de coagulación y la derivación a Hematología. Esfuerzos adicionales son necesarios para estandarizar las herramientas preoperatorias de evaluación hemorrágica en niños.(AU)

Purpose: Coagulation screening tests in children are still frequently performed in many countries to evaluate bleeding risk. The aim of this study was to assess the management of unexpected prolongations of the activated partial thromboplastin time (APTT) and prothrombine time (PT) in children prior to elective surgery, and the perioperative hemorrhagic outcomes. Methods: Children with prolonged APTT and/or PT who attended a preoperative anesthesia consultation from January 2013 to December 2018 were included. Patients were grouped according to whether they were referred to a Hematologist or were scheduled to undergo surgery without further investigation. The primary endpoint was to compare perioperative bleeding complications. Results: 1835 children were screened for eligibility. 102 presented abnormal results (5.6%). Of them, 45% were referred to a Hematologist. Significant bleeding disorders were associated with a positive bleeding history, odds ratio of 51 (95% CI 4.8 to 538.5, P = 0.0011). No difference in perioperative hemorrhagic outcomes were found between the groups. An additional cost of 181 euros per patient and a preoperative median delay of 43 days was observed in patients referred to Hematology. Conclusions: Our results suggest that hematology referral has limited value in asymptomatic children with a prolonged APTT and/or PT. Hemorrhagic complications were similar among patients referred and not referred to Hematology. A positive personal or family bleeding history can help identify patients with a higher bleeding risk, thus it should guide the need for coagulation testing and hematology referral. Further efforts should be made to standardize preoperative bleeding assessments tools in children.(AU)

Déficit de glucosa-6-fosfato deshidrogenasa asociado a rasgo falciforme: importancia de una buena historia clínica / Glucose-6-phosphate dehydrogenase deficiency associated with sickle cell trait: importance of a good medical history

Introducción: El déficit de glucosa-6-fosfato deshidrogenasa es la alteración enzimática más frecuente a nivel eritrocitario. El debut característico lo constituye un paciente previamente sano en el que se desencadena una crisis hemolítica por determinados fármacos, infecciones o alimentos. En este último contexto es conocido como favismo el cuadro clínico secundario a la ingesta de habas. Caso clínico. Varón de 23 meses que consulta por fiebre, ictericia, palidez y coluria. Como antecedente personal de interés destaca la determinación de un rasgo falciforme en el cribado neonatal. Los resultados de la analítica sanguínea son compatibles con una crisis hemolítica no inmune, por lo que se establece como hipótesis diagnóstica una anemia hemolítica desencadenada por proceso infeccioso en paciente con rasgo falciforme. Puesto que el rasgo falciforme es asintomático, durante el ingreso se amplíó la anamnesis detectándose al menos un episodio de similares características, pero más leve, y al incidir en la dieta familiar se confirmó la ingesta intermitente de habas. Ante la posibilidad de favismo se solicitó análisis genético que confirmó el diagnóstico. Conclusiones. Las complicaciones de las enfermedades de base de cada paciente frecuentemente causan sus patologías, pero no siempre es así. Es fundamental realizar una anamnesis exhaustiva, dado que esta puede ofrecer claves diagnósticas inesperadas.(AU)

Introduction. Glucose-6-phosphate dehydrogenase deficiency is the most common enzymatic alteration at the erythrocyte level. The characteristic onset is a previously healthy patient in whom a hemolytic crisis is triggered by certain drugs, infections or foods. In this latter context, the clinical condition secondary to the ingestion of broad beans is known as favism. Clinical case. A 23-month-old male presented with fever, jaundice and choluria. As a personal history of interest, the determination of a sickle cell trait in neonatal screening stands out. The blood test results are compatible with a non-immune hemolytic crisis, so the diagnostic hypothesis is established as a hemolytic anemia triggered by an infectious process in a patient with sickle cell trait. During their stay in the ward, the anamnesis is expanded, detecting at least one episode with similar but milder characteristics and by influencing the family diet, the intermittent intake of beans at least once a month is confirmed. Given the possibility of favism, genetic analysis is requested to confirm the diagnosis. Conclusions. The complications of each patient’s underlying diseases often cause their pathologies, but this is not always the case. It is essential to carry out an exhaustive anamnesis, since this can offer unexpected.(AU)

Percepción de las competencias docentes en ciencias de la actividad física y el deporte / Perception of Teaching Competences in Sciences of Physical Activity and Sports

Se pretende analizar las mejoras significativas en la percepción de las competencias docentes en Educación Física. Se lleva a cabo una intervención basada en el Modelo de Autoeficacia docente de Bandura (1986) y el estatuto del co-sujeto Not (1987), en la asignatura de Procesos de Enseñanza-Aprendizaje curso 2018-2019 (Grado de Ciencias de la Actividad Física y del Deporte, UCLM). Se utiliza un método descriptivo, cuantitativo, correlacional y de carácter transversal, participan 104 estudiantes (74 chicos y 30 chicas). Se hallan expectativas de logro, sin distinción de sexo, en el desempeño de las competencias docentes: potencial creativo con apoyo institucional, dominio técnico didáctico y personalidad activa con capacidad didáctica metacognitiva. Se llega a la conclusión de que es posible modificar las perspectivas de actuación en la acción docente dando prioridad a la evolución personal y profesional de los futuros docentes, independientemente del sexo y del rol que ejerce la sociedad. Línea pionera de investigación en la que se necesita profundizar. (AU)

The aim is to analyze the significant improvements in the perception of the teaching competences in Physical Education. An intervention is carried out based on the Model of Teacher Self-efficacy of Bandura (1986) and the status of co-subject Not (1987), in the subject of Teaching-Learning Processes course 2018-2019 (Degree of Physics Activity and Sports Sciences, UCLM). A descriptive, quantitative, correlational and cross-sectional method is used, involving 104 students (74 boys and 30 girls). There are expectations of achievement, without distinction of sex, in the performance of teaching competences: creative potential with institutional support, didactic technical mastery and active personality with metacognitive didactic ability. So it is possible to modify the perspectives in the teaching action of future teachers, giving priority to the personal and professional evolution, regardless of sex and the role played by society. New line of research in which it is necessary to deepen. (AU)

Risk of misclassification during diagnosis of malnutrition in retroperitoneal sarcoma patients.

BACKGROUND: Retroperitoneal sarcoma (RPS) is a rare tumour that can reach exceptionally large size at diagnosis and affects body weight with its volume. We investigated the risk of nutritional status misclassification based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in RPS patients. METHODS: We retrospectively analyzed the baseline data of patients with primary RPS including anthropometry, Malnutrition Universal Screening Tool (MUST) score and skeletal muscle index (SMI) calculated on preoperative CT scan. Phenotypic GLIM criteria considered were non-volitional weight loss, low-BMI and low muscle mass. MUST score, being inclusive of weight loss, was chosen as its surrogate. Reduced muscle mass was defined with SMI cut-offs <38.5-52.4 cm2/m2 for female and male respectively. RESULTS: From 2018 to 2020, 100 consecutive patients (male/female: 48/52) were included. Median age was 61 (48-68) years, median BMI 24.6 (21.5-27.4) kg/m2. Seven patients (7%) reported MUST score ≥2 and 80 (80%) score 0. Five patients (5%) were underweight, 44 (44%) overweight and obese. Sixty patients (60%) presented low SMI, of those 56 (93%) were normal or overweight, and 46 (77%) not at nutritional risk according to the MUST score. Both underweight BMI and MUST score ≥2 were not correlated with low SMI (p = 0.406, p = 0.612, respectively). No relevant discrepancy was found in the postoperative course of patients with low or normal muscle mass, although SMI was able to better characterize nutritional risk in the proportion of patents with high-grade liposarcoma and predicted worst overall survival. CONCLUSION: GLIM criteria are a useful tool for diagnosis of malnutrition. However, our analysis suggests that phenotypic criteria are not interchangeable with each other. An altered body composition is often hidden in patients with retroperitoneal sarcoma and the use of weight-based classification does not seem to be appropriate, enhancing the role of mass muscle measurement to prevent misdetections of malnourished patient.

Pyometra-associated insulin resistance assessment by insulin binding assay and tyrosine kinase activity evaluation in canine muscle tissue.

Diestrus is associated with insulin resistance in bitches and pyometra can further impair insulin sensitivity. This study aimed to compare insulin sensitivity, insulin binding, and tyrosine kinase activity in bitches in anestrus, diestrus, or with pyometra. Patients submitted to elective ovariohysterectomy were divided into anestrus (n = 11) or diestrus (n = 13) according to reproductive history, vaginal cytology, and uterine histology. The group pyometra (n = 8) included bitches diagnosed with the disease based on clinical presentation and abdominal ultrasound findings and further confirmed by uterine histopathology. All patients were submitted to an intravenous glucose tolerance test (IVGTT) before ovariohysterectomy, and rectus abdominis muscle samples were collected during surgery for plasmatic membrane suspension preparation. Muscle-membranes were submitted to cold saturation insulin binding assay for dissociation constant (Kd) and maximum binding capacity (Bmax) determination, as well as exogenous substrate Poly (Glu: Tyr 4:1) phosphorylation assay for basal tyrosine kinase evaluation. Bitches with pyometra showed higher basal insulin (P < 0.001) and higher area under the curve (AUC) for insulin (P = 0.01) and glucose (P < 0.001) response during the IVGTT in comparison with bitches in anestrus or diestrus. Diestrus (P < 0.0001) and pyometra (P = 0.001) were associated with reduced tyrosine kinase activity in comparison with anestrus. No differences were documented in Kd and Bmax results for the low-affinity/high-capacity insulin receptors; however, high-affinity/low-capacity insulin receptors showed higher Kd and Bmax results in bitches in diestrus or with pyometra (P < 0.05) in comparison with anestrus. Despite the pyometra group showed the highest Kd values (P < 0.01), its Bmax results did not differ from the diestrus group (P > 0.05). Diestrus' higher Kd values and reduced tyrosine kinase activity in muscle tissue were compensated by increased total insulin binding capacity. Absent differences in IVGTT results between diestrus and anestrus bitches corroborate this finding. However, in bitches with pyometra, the highest Kd values were not compensated by increased total insulin binding capacity. This finding was associated with insulin resistance and glucose intolerance in IVGTT results. Moreover, pyometra resolution restored insulin sensitivity and glucose tolerance. These features can play a key role in pyometra-associated CDM, as well as in diabetic remission after pyometra resolution.

Ecophysiological Performance of Proteaceae Species From Southern South America Growing on Substrates Derived From Young Volcanic Materials.

Southern South American Proteaceae thrive on young volcanic substrates, which are extremely low in plant-available phosphorus (P). Most Proteaceae exhibit a nutrient-acquisition strategy based on the release of carboxylates from specialized roots, named cluster roots (CR). Some Proteaceae colonize young volcanic substrates which has been related to CR functioning. However, physiological functioning of other Proteaceae on recent volcanic substrates is unknown. We conducted an experiment with seedlings of five Proteaceae (Gevuina avellana, Embothrium coccineum, Lomatia hirsuta, L. ferruginea, and L. dentata) grown in three volcanic materials. Two of them are substrates with very low nutrient concentrations, collected from the most recent deposits of the volcanoes Choshuenco and Calbuco (Chile). The other volcanic material corresponds to a developed soil that exhibits a high nutrient availability. We assessed morphological responses (i.e., height, biomass, and CR formation), seed and leaf macronutrient and micronutrient concentrations and carboxylates exuded by roots. The results show that G. avellana was less affected by nutrient availability of the volcanic substrate, probably because it had a greater nutrient content in its seeds and produced large CR exuding carboxylates that supported their initial growth. Embothrium coccineum exhibited greater total plant height and leaf P concentration than Lomatia species. In general, in all species leaf macronutrient concentrations were reduced on nutrient-poor volcanic substrates, while leaf micronutrient concentrations were highly variable depending on species and volcanic material. We conclude that Proteaceae from temperate rainforests differ in their capacity to grow and acquire nutrients from young and nutrient-poor volcanic substrates. The greater seed nutrient content, low nutrient requirements (only for G. avellana) and ability to mobilize nutrients help explain why G. avellana and E. coccineum are better colonizers of recent volcanic substrates than Lomatia species.

Spiritual well-being and quality of life are impaired in chronic urticaria.

SUMMARY: Background. Patients with chronic urticaria (CU) often report an impaired quality of life (QoL). Although a positive effect of addressing spirituality in health care has been proved in several chronic diseases, its potential role in CU has received no attention. Objective. We aim to evaluate spirituality and QoL in CU subjects. Methods. In a single-centre observational study, 100 CU subjects were investigated using Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12) scale, Chronic Urticaria Quality of life Questionnaire (CU-Q2oL) and Urticaria Control Test (UCT). Results. Of 100 subjects, 82 were female and 18 were male. It was observed that subjects with poorly controlled CU presented FACIT Sp-12 meaning/peace (p = 0.004) significantly lower, and CU-Q2oL (p less than 0.0001) significantly higher (worst QoL) than subjects with controlled CU. There was no difference in the FACIT Sp-12 faith (p = 0.43) between groups. There was moderate direct correlation between FACIT Sp-12 faith and FACIT Sp-12 meaning/peace (r = 0.483; p less than 0.0001; n = 100). There was a significant strong inverse correlation between the CU-Q2oL and the UCT (r = - 0.762; p less than 0.0001; n = 100). No correlation was found between the FACIT Sp-12 faith and CU-Q2oL, neither with UCT. Conclusions. No study has ever investigated the role of spirituality in managing patients with urticaria. Our findings support the impact of poorly controlled urticaria in spiritual well-being and QoL. Therefore, clinicians should pay more attention to spirituality among CU patients. We suggest that urticaria guidelines should include specific recommendations on spirituality assessment.

Impacto clínico del estroncio y del zinc en los procesos de regeneración ósea y del cartílago, aproximación desde la biología hacia la clínica. Revisión de literatura / Clinical impact of strontium and zinc on bone and cartilage regeneration processes, an approach from biology to the clinic. Literature review

Muchos trastornos sistémicos como la artritis o la osteoporosis son patologías responsables de las alteraciones crónicas de la articulación temporomandibular, creando así un problema a largo plazo que afectan la calidad de vida de aquellas personas que las padecen. Actualmente no existe tratamiento curativo para dichas patologías, aunque sí de tipo paliativo, que en muchas ocasiones tienen efectos secundarios en el tiempo o una limitación en su efectividad y eficacia, por lo que se hace necesario buscar alternativas con la implementación de terapias regenerativas para el tratamiento de aquellas enfermedades que afectan el sistema musculoesquelético. En muchos estudios se discute sobre el papel fundamental que cumple el zinc y el estroncio en la génesis de tejido tanto cartilaginoso como óseo, así como la relevancia de incorporarlos con diversos biomateriales en procedimientos de regeneración, sin embargo, este tema no es claro aún y requieren más aten- ción por parte del clínico. El objetivo de este artículo es determinar la función cumplen el zinc y el estroncio en los procesos de regeneración del hueso y el cartílago desde una visión molecular y celular aplicada a la práctica clínica, con el fin de obtener nuevas alternativas en el tratamiento de diversas patologías y alteraciones musculoesqueléticas que mejoren las condiciones de salud oral de los pacientes, además de, contar con la revisión que nos aproxime a comprender los mecanismos de acción de diferentes moléculas que incorporadas a los biomateriales compatibles con el tejido duro y blando mejoren las condiciones biológicas para la regeneración.

Many systemic disorders such as arthritis or osteoporosis are pathologies responsible of temporomandibular joint chronic dysfunctions, thus creating a long-term problem that affects life ́s quality of those who suffer from them. Currently there is no curative treatment for these pathologies, although there is a palliative treatment, which in many cases have side effects over time or a limitation in their effectiveness and efficacy, so it is necessary to look for alternatives with the implementation of regenerative therapies for treatment of those diseases that affect musculoskeletal system. In many studies the fundamental role of zinc and strontium in genesis of both cartilaginous and bone tissue is discussed, as well as the relevance of incorporating them with various biomaterials in regeneration procedures, however, this issue is not clear yet and requires more attention from the clinician. The objective of this article is to determine function of zinc and strontium in regeneration processes of bone and cartilage from a molecular and cellular perspective applied to clinical practice, in order to obtain new alternatives in the treatment of various pathologies and musculoskeletal alterations that improve the oral health conditions of patients. In addition, this review brings us closer to understanding the mechanisms of action of different molecules that when incorporated into biomaterials compatible with hard and soft tissue improve the biological conditions for the regeneration.

A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study.

BACKGROUND: Bromelain (Brom) and Acetylcysteine (Ac) have synergistic activity resulting in dissolution of tumour-produced mucin both in vitro and in vivo. The aim of this study was to determine whether treatment of mucinous peritoneal tumour with BromAc can be performed with an acceptable safety profile and to conduct a preliminary assessment of efficacy in a clinical setting. METHODS: Under radiological guidance, a drain was inserted into the tumour mass or intraperitoneally. Each patient could have more than one tumour site treated. Brom 20-60 mg and Ac 1·5-2 g was administered in 5% glucose. At 24 h, the patient was assessed for symptoms including treatment-related adverse events (AEs) and the drain was aspirated. The volume of tumour removed was measured. A repeat dose via the drain was given in most patients. All patients that received at least one dose of BromAc were included in the safety and response analysis. FINDINGS: Between March 2018 and July 2019, 20 patients with mucinous tumours were treated with BromAc. Seventeen (85%) of patients had at least one treatment-emergent AE. The most frequent treatment-related AEs were CRP rise (n = 16, 80%), WCC rise (n = 11, 55%), fever (n = 7, 35%, grade I) and pain (n = 6, 30%, grade II/III). Serious treatment-related AEs accounted for 12·5% of all AEs. There were no anaphylactic reactions. There were no deaths due to treatment-related AEs. An objective response to treatment was seen in 73·2% of treated sites. CONCLUSION: Based on these preliminary results and our preclinical data, injection of BromAc into mucinous tumours had a manageable safety profile. Considerable mucolytic activity was seen by volume of mucin extracted and radiological appearance. These results support further investigation of BromAC for patients with inoperable mucinous tumours and may provide a new and minimally invasive treatment for these patients.

Nutritional status and body composition assessment in patients with a new diagnosis of advanced solid tumour: Exploratory comparison of computed tomography and bioelectrical impedance analysis.

OBJECTIVE: Low skeletal muscle is a common characteristic of cancer-related malnutrition and a predictor of poorer prognosis in oncological patients. In this study we evaluated nutritional status and altered body composition using computed tomography (CT) and bioelectrical impedance analysis (BIA) in newly diagnosed patients. Our purpose was to compare the results of two available techniques to assess body composition suggested by the guidelines and some diagnostic criteria to identify malnutrition. METHODS: In a prospective study, patients with a new diagnosis of advanced solid tumour were enrolled and evaluated before starting first-line chemotherapy. Anthropometric, body composition and systemic inflammation measurements were collected and cut-off points from literature data were used for results classification. Malnutrition was expressed as weight loss (WL) in the previous 6 months >10% and underweight body mass index (BMI). Altered body composition was assessed as low index both skeletal muscle (SMI) derived by CT and fat-free mass by BIA (FFMI). Descriptive statistic was presented. Several statistical correlation analyses were performed. RESULTS: 67 patients were assessed: 40M/27F; average age 59 ± 13 years and BMI 23 ± 4; 43 (64%) upper gastrointestinal, 12 lung, 9 colorectal, 3 other cancers. Fourty-five (67%) were malnourished with WL criteria but only 8 (12%) resulted underweight. From analysis of CT images and BIA, 49 (73%) and 10 (15%) patients respectively reported lower cut-off point. Overall, 35 (52%) had both sarcopenia and WL > 10%. CONCLUSIONS: Our results suggest that prevalence data of malnutrition expressed as WL are more in agreement with those of sarcopenia recognised using CT than BIA method. Further studies are required to confirm these findings and to identify the best and easiest methods for monitoring BC during nutritional intervention and oncological therapies.

FLUKA simulation of target fragmentation in proton therapy.

In proton therapy, secondary fragments are created in nuclear interactions of the beam with the target nuclei. The secondary fragments have low kinetic energies and high atomic numbers as compared to primary protons. Fragments have a high LET and deposit all their energy close to the generation point. For their characteristics, secondary fragments can alter the dose distribution and lead to an increase of RBE for the same delivered physical dose. Moreover, the radiobiological impact of target fragmentation is significant mostly in the region before the Bragg peak, where generally healthy tissues are present, and immediately after Bragg peak. Considering the high biological impact of those particles, especially in the case of healthy tissues or organs at risk, the inclusion of target fragmentation processes in the dose calculation of a treatment planning system can be relevant to improve the treatment accuracy and for this reason it is one of the major tasks of the MoVe IT project. In this study, Monte Carlo simulations were employed to fully characterize the mixed radiation field generated by target fragmentation in proton therapy. The dose averaged LET has been evaluated in case of a Spread Out Bragg Peak (SOBP). Starting from LET distribution, RBE has been evaluated with two different phenomenological models. In order to characterize the mixed radiation field, the production cross section has been evaluated by means of the FLUKA code. The future development of present work is to generate a MC database of fragments fluence to be included in TPS.

Inter-fractional monitoring of [Formula: see text]C ions treatments: results from a clinical trial at the CNAO facility.

The high dose conformity and healthy tissue sparing achievable in Particle Therapy when using C ions calls for safety factors in treatment planning, to prevent the tumor under-dosage related to the possible occurrence of inter-fractional morphological changes during a treatment. This limitation could be overcome by a range monitor, still missing in clinical routine, capable of providing on-line feedback. The Dose Profiler (DP) is a detector developed within the INnovative Solution for In-beam Dosimetry in hadronthErapy (INSIDE) collaboration for the monitoring of carbon ion treatments at the CNAO facility (Centro Nazionale di Adroterapia Oncologica) exploiting the detection of charged secondary fragments that escape from the patient. The DP capability to detect inter-fractional changes is demonstrated by comparing the obtained fragment emission maps in different fractions of the treatments enrolled in the first ever clinical trial of such a monitoring system, performed at CNAO. The case of a CNAO patient that underwent a significant morphological change is presented in detail, focusing on the implications that can be drawn for the achievable inter-fractional monitoring DP sensitivity in real clinical conditions. The results have been cross-checked against a simulation study.

Utilidad del exoma en el estudio de la paraparesia espástica y la atrofia cerebelosa: mutación de novo en el gen KIF1A, una nueva esperanza pronóstica / Usefulness of exome sequencing in the study of spastic paraparesis and cerebellar atrophy: De novo mutation of the KIF1A gene, a new hope in prognosis

No disponible

Outcomes of an enhanced recovery after radical cystectomy program in a prospective multicenter study: compliance and key components for success.

OBJECTIVE: To investigate the effect of an Enhanced Recovery After Surgery (ERAS) program on complications and length of stay (LOS) after radical cystectomy (RC) and to assess if the number and type of components of ERAS play a key role on the decrease of surgical morbidity. MATERIALS AND METHODS: We analyzed the data of 277 patients prospectively recruited in 11 hospitals undergoing RC initially managed according to local practice (Group I) and later within an ERAS program (Group II). Two main outcomes were defined: 90-day complications rate and LOS. As secondary variables we studied 90-day mortality, 30-day readmission and transfusion rate. RESULTS: Patients in Group II had a higher use of ERAS measures (98.6%) than those in Group I (78.2%) (p < 0.05). Patients in Groups I and II experienced similar complications (70.5% vs. 66%, p = 0.42). LOS was not different between Groups I and II (12.5 and 14 days, respectively, p = 0.59). The risk of having any complication decreases for patients having more than 15 ERAS measures adopted [RR = 0.815; 95% confidence interval (CI) 0.667-0.996; p = 0.045]. Avoidance of transfusion and nasogastric tube, prevention of ileus, early ambulation and a fast uptake of a regular diet are independently associated with the absence of complications. CONCLUSIONS: Complications and LOS after RC were not modified by the introduction of an ERAS program. We hypothesize that at least 15 measures should be applied to maximize the benefit of ERAS.