Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology.

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune-driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence-related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging.

Resultados perinatales tras la suplementación de una cohorte de gestantes con vitamina D / Perinatal results after vitamin D supplementation in a pregnant women cohort

INTRODUCCIÓN Y OBJETIVOS: La deficiencia de vitamina D es muy prevalente durante la gestación, siendo cada vez más numerosos los estudios que relacionan esta condición con peores resultados perinatales. El objetivo del presente trabajo es describir los resultados perinatales y el curso del embarazo de una cohorte de gestantes deficitarias en vitamina D durante el primer trimestre del embarazo, suplementándolas con colecalciferol, así como establecer una comparación entre los resultados perinatales de aquellas pacientes con déficit o insuficiencia que lograron niveles normales de vitamina D en el tercer trimestre frente a aquellas que no lo lograron. Como objetivo secundario se describe el curso del embarazo de una cohorte de pacientes que durante el mismo periodo de tiempo del estudio presentaban normovitaminosis al inicio de la gestación. MÉTODOS: La cohorte de 190 pacientes analizada procede de casos consecutivos en la primera consulta de embarazo. Se determinaron los niveles de 25-hidroxivitamina D (25-OH-D) en la analítica del primer trimestre de 190 gestantes diferenciando entre valores normales (>30ng/mL), insuficiencia (30-15 ng/mL) y deficiencia (<15 ng/mL). Las pacientes con insuficiencia se suplementaron con 1000 UI/día de colecalciferol y las pacientes con deficiencia con 2000 UI/día. En el tercer trimestre se determinaron de nuevo los niveles de 25-OH-D en las pacientes suplementadas, suspendiendo la prescripción en caso de haberse normalizado los valores. Se comparan estadísticamente los resultados perinatales entre aquellas pacientes que mejoraron con la suplementación frente a aquellas que no lo hicieron. RESULTADOS: De las 190 pacientes analizadas, un 45% presentaban insuficiencia; un 27,5% deficiencia; y un 27,5% valores normales. De forma global, un 61% de las pacientes suplementadas habían normalizado sus niveles de vitamina D en la analítica del tercer trimestre, suspendiéndose la prescripción. De ese 61% normalizado, un 63% pertenecían al grupo de insuficiencia y un 37% al de deficiencia. Dentro del grupo suplementado con colecalciferol, un 1,4% de las pacientes desarrollaron hipertensión arterial, mientras que un 33% desarrollaron diabetes en el embarazo, de las cuales un 87% la controlaron exclusivamente con dieta y un 13% precisaron insulina. Un 3,6% de las gestaciones cursaron con retraso del crecimiento y la tasa de prematuridad fue igualmente del 3,6%. La tasa de cesáreas fue del 23%, de las cuales un 77% fueron indicadas intraparto y un 23% cesáreas programadas. El peso medio al nacimiento fue 3205g. Dentro del grupo con valores normales de 25-OH-D en el primer trimestre de la gestación, ninguna paciente desarrolló hipertensión arterial, mientras que un 15% presentaron diabetes gestacional controlada con dieta. Un 3,8% de dichas gestaciones cursaron con retrasos del crecimiento y la tasa de prematuridad fue del 1,9%. La tasa de cesáreas fue del 23%, de las cuales un 50% fueron indicadas intraparto y el 50% restante programadas. El peso medio al nacimiento fue de 3280g. En el análisis comparativo de los resultados perinatales entre el grupo de pacientes suplementadas que normalizaron sus cifras de vitamina D y aquellas que no lo hicieron, no se hallan diferencias estadísticamente significativas para ninguno de los parámetros analizados. CONCLUSIONES: La elevada tasa de hipovitaminosis D en la muestra analizada apoya la extensión del cribado y suplementación a todas las embarazadas y no solamente a aquellas con factores de riesgo. Dado que no se observaron diferencias estadísticamente significativas entre los niveles de vitamina D en el tercer trimestre y las variables perinatales estudiadas, podemos concluir que en nuestro estudio la suplementación con vitamina D no se ha comportado como factor protector de eventos obstétricos adversos.

INTRODUCTION AND OBJECTIVES: Vitamin D deficiency is highly prevalent during pregnancy, with an increasing number of studies linking this condition with worse perinatal outcomes. The objective of this present work is to describe the perinatal results and the course of pregnancy in a cohort of pregnant women deficient in vitamin D during the first trimester of pregnancy, supplementing them with cholecalciferol, as well as to establish a comparison between perinatal results of those patients with deficiencnieve or insufficiency who achieved normal levels of vitamin D in the third trimester compared to those who did not. As a secondary objective, the course of pregnancy is described in a cohort of patients who presented normal levels at the beginning of gestation during the same period of time of the study. METHODS: The cohort of 190 patients analyzed comes from consecutive cases in the first pregnancy visit. The levels of 25-hydroxyvitamin D (25-OH-D) were determined in the analysis of the first trimester of 190 pregnant women, differentiating between normal values (> 30ng / mL), insufficiency (30-15 ng / mL) and deficiency (<15 ng / mL). Patients with insufficiency were supplemented with 1000 IU/day of cholecalciferol and patients with deficiency with 2000 IU/day. In the third trimester, the 25-OH-D levels were determined again in the supplemented patients, suspending the prescription if the values had normalized. Perinatal outcomes are statistically compared between those patients who improved with supplementation versus those who did not. RESULTS: Of the 190 patients analyzed, 45% had insufficiency; 27.5% deficiency; and 27.5% normal values. Overall, 61% of the supplemented patients had normalized their vitamin D levels in the third trimester analysis, suspending the prescription. Within that 61% normalized, 63% belonged to the insufficiency group and 37% to the deficiency group. In the group supplemented with cholecalciferol, 1.4% of the patients developed arterial hypertension, while 33% developed diabetes in pregnancy, of which 87% controlled it exclusively with diet and 13% required insulin. 3.6% of pregnancies had intrauterine growth restriction and the prematurity rate was also 3.6%. The caesarean section rate was 23%, of which 77% were indicated intrapartum and 23% scheduled caesarean sections. The mean weight at birth was 3205g. Within the group with normal 25-OH-D values in the first trimester of pregnancy, no patient developed hypertension, while 15% had diet-controlled gestational diabetes. 3.8% of these pregnancies had intrauterine growth restriction and the prematurity rate was 1.9%. The cesarean section rate was 23%, of which 50% were indicated intrapartum and the remaining 50% scheduled. The mean weight at birth was 3280g. In the comparative analysis of the perinatal results between the group of supplemented patients who normalized their vitamin D levels and those who did not, no statistically significant differences were found for any of the parameters analyzed. CONCLUSIONS: The high rate of hypovitaminosis D in the analyzed sample supports the extension of screening and supplementation to all pregnant women and not only to those with risk factors. Since no statistically significant differences were observed between vitamin D levels in the third trimester and the perinatal outcomes studied, we can conclude that in our study vitamin D supplementation has not behaved as a protective factor against adverse obstetric events.

Detection of volatile organic compounds using flexible gas sensing devices based on tungsten oxide nanostructures functionalized with Au and Pt nanoparticles.

Flexible gas sensor devices are fabricated and optimized by integrating directly, via a single-step vapor-phase deposition method, highly crystalline tungsten oxide nanostructures functionalized with either gold or platinum nanoparticles. Gas tests of these devices show significant improvements with respect to flexible gas sensors based on non-functionalized structures, including greater responses to various volatile organic compounds (ethanol, acetone, methanol and toluene) and better selectivity towards ethanol and methanol, as demonstrate results for the sensors based on platinum-functionalized structures. The method presented here, which includes the fabrication of the whole flexible gas sensing device and the integration of functional nanostructures without the use of transfer methods, provides a simpler, faster and inexpensive method for the fabrication of highly functional flexible microsystems for gas sensing.

[Giant cell tumour of bone: a series of 97 cases with a mean follow-up of 12 years]. / Tumor de células gigantes óseo. Noventa y siete casos con seguimiento medio de 12 años.

PURPOSE: To describe our series of patients with giant cell tumour of bone with a long-term follow-up to show the results obtained with our treatment protocol. MATERIAL AND METHODS: A total of 97 histologically confirmed giant cell tumour of bone were treated in our center between 1982 and 2009. The mean follow-up period was 12 years (2-27 years). The treatment received was determined by the radiological grade based on the Campanacci classification. The series consisted of 53 women (54.6%) and 44 men (54.4%) with a median age of 34.16 years (15-71 years). The data collected was focused on the clinical presentation, location, phase, extension, recurrences, and complications. RESULTS: The treatment most used in Campanacci grades i and ii was intralesional excision with high velocity drilling and filling with a graft. In grades iii that could not be treated with the aforementioned method, it was decided to perform en bloc resection. An overall recurrence rate of around 25.8% was observed. Seven cases (7.2%) presented with a recurrence of the malignancy. The death rate at the end of follow-up was 2.1% (2 cases). CONCLUSIONS: Curettage with a high-velocity drill and a bone graft in giant cell tumour of bone Campanacci grades i and ii obtain good results after long-term follow-up. Some grade iii giant cell tumour of bone that cannot be treated with this therapeutic option require en bloc resection and reconstruction.

Characterization of an array of Love-wave gas sensors developed using electrospinning technique to deposit nanofibers as sensitive layers.

The electrospinning technique has allowed that very different materials are deposited as sensitive layers on Love-wave devices forming a low cost and successful sensor array. Their excellent sensitivity, good linearity and short response time are reported in this paper. Several materials have been used to produce the nanofibers: polymers as Polyvinyl alcohol (PVA), Polyvinylpyrrolidone (PVP) and Polystirene (PS); composites with polymers as PVA+SnCl4; combined polymers as PS+Poly(styrene-alt-maleic anhydride) (PS+PSMA) and metal oxides (SnO2). In order to test the array, well-known chemical warfare agent simulants (CWAs) have been chosen among the volatile organic compounds due to their importance in the security field. Very low concentrations of these compounds have been detected by the array, such as 0.2 ppm of DMMP, a simulant of sarin nerve gas, and 1 ppm of DPGME, a simulant of nitrogen mustard. Additionally, the CWA simulants used in the experiment have been discriminated and classified using pattern recognition techniques, such as principal component analysis and artificial neural networks.

[The snapping scapula as a sympton of a tumor in the scapulothoracic region]. / El chasquido escapular como síntoma de un tumor de la región escapulotorácica.

INTRODUCTION: The snapping scapula syndrome is a grating sensation located in the scapulothoracic region that appears with movement.This sign is occasionally related to tumors. OBJECTIVE: To show the high incidence of this relationship (clinical sign-tumor), and to be aware of it when performing a differential diagnosis. MATERIAL AND METHOD: Retrospective study of the elastofibromas dorsi (ED) and scapular osteochondromas (SO), which may have presented with the sign under study in our center over the last 17 years (1993-2009). Thirty-seven ED and 6 SO were identified. The series was divided into group A (ED) and group B (SO). Mean follow-up was 7 years. The cohorts are made up of 23 women and 4 men with a mean age of 57 years (42-78) in group A, there were 2 women and 4 men with a mean age of 20 years (11-28) in group B. Action was taken to identify the initial medical sign at diagnosis, the treatment carried out, and the outcome. RESULTS: Around 21% of these tumors are reported to be associated with physical activity. The initial symptom was a painful mass in 81% of the patients, followed by a scapular snapping or clicking in 30 out of the 43 patients (70%). The treatment of choice was resection in both groups. A noticeable improvement in terms of pain was seen (VAS 7.5 preoperatively, 2.8 postoperatively). CONCLUSION: The presence of snapping scapula has a strong relationship to tumors of the scapulothoracic region. Therefore it is important to be aware of this.

[Elastofibroma dorsi: a 7-year follow-up of 37 cases and a review of the literature]. / Elastofibroma dorsi: 7 años de seguimiento de 37 casos y revisión de la literatura.

BACKGROUND: Elastofibroma dorsi (ED) is an infrequent benign, slow growing, soft tissue tumour that is usually located in the scapular zone. MATERIAL AND METHODS: A series of 37 ED patients diagnosed and treated in our hospital between August 1993 and November 2009 were retrospectively reviewed. The average follow up was 7 years. Ten of them presented bilaterally. The male/female ratio was 4:3, and the mean age was 57 years. An MRI was performed, and the diagnosis confirmed by histopathology. Seven cases were treated conservatively. The clinical results were evaluated using a visual analogue score (VAS) for pain and a comparison of the range of movement during follow up. RESULTS: Some 18% of the patients worked or practiced sports that called for the use of the affected limb. The 40% of the patients required a post-operative transfusion was required by 40% of the patients, due to having a haemoglobin <8 g/d. The VAS improved from 6 to 2 after the surgery. The range of movement improved on an average of 40. The complications included an infection, 1 hyperalgesic scar, 8 haematomas and 3 seromas, which were resolved in the follow up without incidence. All the patients were free of illness after a mean follow-up of 85 months. CONCLUSIONS: Good results were achieved with a long follow-up. Based on these results and a literature review of the current state of this pathology, an algorithm for its diagnosis and treatment is suggested.

Elastofibroma dorsi as a cause of shoulder pain or snapping scapula.

Elastofibroma dorsi is a benign soft tissue tumor, not well-known because of its low incidence, located in the chest wall in the subscapular area. In 10 patients with elastofibroma dorsi, the clinical symptoms were snapping scapula or shoulder pain. In three of the patients, the previous diagnosis was shoulder impingement, and the patients were treated without success. The clinical diagnosis was confirmed by magnetic resonance imaging. Surgical treatment resolved the symptoms in all patients. This tumor should be considered in the differential diagnosis of snapping scapula or shoulder impingement.

Osteoid osteoma of the coracoid process.

Osteoid osteoma is a small, benign, and painful tumor most commonly affecting the extra-articular portions of the long bones, especially the femur or tibia. Osteoid osteoma of the coracoid process is so rare that we have found only three previously reported cases in the international literature. We describe our experience in managing a case of osteoid osteoma in this unusual location.

[Adenomatous degeneration in a prepuberal patient with generalized juvenile polyposis and angiomas of the oral mucosa]. / Degeneración adenomatosa en una paciente prepuberal afecta de poliposis juvenil generalizada y angiomas en mucosa oral.

The authors present a 12 year old patient affected by a juvenile polyposis syndrome. They describe the clinic and the complementary tests carried out, especially the findings of the digestive fibroendoscopy which allowed multiple polyps in the duodenum, colon and rectum to be shown, confirmed by an anatomopathological study. Two years afterwards, a total colectomy and ileoproctostomy was carried out. In the operative piece included numerous hamartomatous polyps with adenomatous isolated foci. A subsequent endoscopic exploration showed numerous polyps in anus and rectal stump. The adenomatous transformation and recidivation of her polyposis require close vigilance and a follow-up of this female patient in view of the possibility of the precocious development of a colorectal carcinoma.