Pediatric perianal Crohn's disease behavior in the era of biologic therapy. / Comportamiento de la afectación perianal en pacientes pediátricos con enfermedad de Crohn en la era de la terapia biológica.

AIM OF THE STUDY: To describe perianal Crohn's disease behavior and the role of biological therapy in a sample of pediatric patients. METHODS: A retrospective study of pediatric patients with Crohn's disease (CD) treated in our institution from 2017 to 2021, with a minimum follow up period of 6 months, was conducted. Patients were divided whether they had perianal disease (PD) or not. Baseline characteristics, extension of disease, growth failure rate, aggressive pattern rate, use of biological therapy and need for surgery, among other variables, were compared between both groups. Clinical and/or radiological improvement in the last 6 months of follow up was considered good control of PD. RESULTS: Seventy eight pediatric patients with CD were included. Median age at diagnosis was 10.5 years, and median follow up time was 3.8 years. 64.1% patients were male. Of all, 15 (19.2%) had perianal disease, of which 10 had fistulizing findings and 5 had non fistulizing findings. PD was presented at diagnosis in 8 patients, and the rest developed it in a median time of 1 year from diagnosis. PD was associated with growth failure (p = 0.003), use of biological therapies (p = 0.005), and need for second line of biologics (p = 0.005). Most patients (12/15, 80%) had good control of PD with the treatment received. CONCLUSIONS: CD patients with PD seem to need a more aggressive treatment, with biological therapies playing a key role for its handling nowadays. These patients require close nutritional evaluation that ensures proper development and growth.

OBJETIVO DEL ESTUDIO: Describir el comportamiento de la enfermedad de Crohn perianal y el papel de la terapia biológica en una muestra de pacientes pediátricos. METODOS: Estudio retrospectivo de pacientes pediátricos con enfermedad de Crohn (EC) tratados en nuestro centro entre 2017 y 2021, con un seguimiento mínimo de seis meses. Los pacientes se dividieron en función de si tenían enfermedad perianal (EP) o no. Se compararon entre ambos grupos las características iniciales, la extensión de la enfermedad, el índice de retraso en el crecimiento, el índice de patrón agresivo, el empleo de terapia biológica y la necesidad de cirugía, entre otras variables. Se consideró un buen control de la EP una mejoría clínica o radiológica en los 6 últimos meses de seguimiento. RESULTADOS: Se incluyeron 78 pacientes pediátricos con EC. La edad mediana en el momento del diagnóstico fue de 10,5 años, y el tiempo mediano de seguimiento fue de 3,8 años. El 64,1% de los pacientes eran varones. Del total, 15 (19,2%) tenían enfermedad perianal, de los cuales 10 presentaban hallazgos fistulizantes y 5 no fistulizantes. La EP estaba presente en el momento del diagnóstico en 8 pacientes, y el resto la desarrolló en una mediana de 1 año desde el diagnóstico. La EP se asoció con retraso en el crecimiento (p = 0,003), empleo de terapias biológicas (p = 0,005) y necesidad de una segunda línea de terapia biológica (p = 0,005). La mayoría de los pacientes (12/15, 80%) tuvieron un buen control de la EP con el tratamiento recibido. CONCLUSIONES: Los pacientes de EC con EP parecen necesitar un tratamiento más agresivo, en el que las terapias biológicas desempeñan hoy en día un papel fundamental. Estos pacientes precisan de una estrecha evaluación nutricional que garantice su correcto crecimiento y desarrollo.

Comportamiento de la afectación perianal en pacientes pediátricos con enfermedad de Crohn en la era de la terapia biológica / Pediatric perianal Crohn’s disease behavior in the era of biologic therapy

Objetivo del estudio: Describir el comportamiento de la enfermedad de Crohn perianal y el papel de la terapia biológica en una muestra de pacientes pediátricos. Métodos: Estudio retrospectivo de pacientes pediátricos con enfermedad de Crohn (EC) tratados en nuestro centro entre 2017 y 2021, con un seguimiento mínimo de seis meses. Los pacientes se dividieron en función de si tenían enfermedad perianal (EP) o no. Se compararon entre ambos grupos las características iniciales, la extensión de la enfermedad, el índice de retraso en el crecimiento, el índice de patrón agresivo, el empleo de terapia biológica y la necesidad de cirugía, entre otras variables. Se consideró un buen control de la EP una mejoría clínica o radiológica en los 6 últimos meses de seguimiento. Resultados: Se incluyeron 78 pacientes pediátricos con EC. La edad mediana en el momento del diagnóstico fue de 10,5 años, y el tiempo mediano de seguimiento fue de 3,8 años. El 64,1% de los pacientes eran varones. Del total, 15 (19,2%) tenían enfermedad perianal, de los cuales 10 presentaban hallazgos fistulizantes y 5 no fistulizantes. La EP estaba presente en el momento del diagnóstico en 8 pacientes, y el resto la desarrolló en una mediana de 1 año desde el diagnóstico. La EP se asoció con retraso en el crecimiento (p = 0,003), empleo de terapias biológicas (p = 0,005) y necesidad de una segunda línea de terapia biológica (p = 0,005). La mayoría de los pacientes (12/15, 80%) tuvieron un buen control de la EP con el tratamiento recibido. Conclusiones: Los pacientes de EC con EP parecen necesitar un tratamiento más agresivo, en el que las terapias biológicas desempeñan hoy en día un papel fundamental. Estos pacientes precisan de una estrecha evaluación nutricional que garantice su correcto crecimiento y desarrollo.(AU)

Aim of the study: To describe perianal Crohn’s disease behavior and the role of biological therapy in a sample of pediatric patients. Methods: A retrospective study of pediatric patients with Crohn’s disease (CD) treated in our institution from 2017 to 2021, with a minimum follow up period of 6 months, was conducted. Patients were divided whether they had perianal disease (PD) or not. Baseline characteristics, extension of disease, growth failure rate, aggressive pattern rate, use of biological therapy and need for surgery, among other variables, were compared between both groups. Clinical and/or radiological improvement in the last 6 months of follow up was considered good control of PD. Results: Seventy eight pediatric patients with CD were included. Median age at diagnosis was 10.5 years, and median follow up time was 3.8 years. 64.1% patients were male. Of all, 15 (19.2%) had perianal disease, of which 10 had fistulizing findings and 5 had non fistulizing findings. PD was presented at diagnosis in 8 patients, and the rest developed it in a median time of 1 year from diagnosis. PD was associated with growth failure (p = 0.003), use of biological therapies (p = 0.005), and need for second line of biologics (p = 0.005). Most patients (12/15, 80%) had good control of PD with the treatment received. Conclusions: CD patients with PD seem to need a more aggressive treatment, with biological therapies playing a key role for its handling nowadays. These patients require close nutritional evaluation that ensures proper development and growth.(AU)

Ghrelin treatment leads to dendritic spine remodeling in hippocampal neurons and increases the expression of specific BDNF-mRNA species.

Ghrelin (Gr) is an orexigenic peptide that acts via its specific receptor, GHSR-1a distributed throughout the brain, being mainly enriched in pituitary, cortex and hippocampus (Hp) modulating a variety of brain functions. Behavioral, electrophysiological and biochemical evidence indicated that Gr modulates the excitability and the synaptic plasticity in Hp. The present experiments were designed in order to extend the knowledge about the Gr effect upon structural synaptic plasticity since morphological and quantitative changes in spine density after Gr administration were analyzed "in vitro" and "in vivo". The results show that Gr administered to hippocampal cultures or stereotactically injected in vivo to Thy-1 mice increases the density of dendritic spines (DS) being the mushroom type highly increased in secondary and tertiary extensions. Spines classified as thin type were increased particularly in primary extensions. Furthermore, we show that Gr enhances selectively the expression of BDNF-mRNA species.

Nasal high flow oxygen in acute respiratory failure.

Thermo-humidified nasal high flow (NHF) oxygen therapy is increasingly used in the management of respiratory failure. This therapy has recently gained attention as an alternative non-invasive respiratory support in several clinical scenarios, including acute and chronic settings. NHF enhances the patient's comfort and tolerance when compared with standard oxygen by supplying a heated and humidified mixture of air and oxygen at flows up to 60L/min. It can be delivered through different devices. Although few studies have compared the clinical effects of different NHF systems, the purpose of this paper is to describe the major benefits of NHF and to provide a quick guide on how to implement this therapy in daily practice. We have also included a brief description of the most frequently used NHF systems.

Acute abdomen in COVID-19 disease: the pediatric surgeon's standpoint. / Abdomen agudo en la enfermedad COVID-19. El punto de vista del cirujano pediátrico.

OBJECTIVE: To describe our experience in the diagnostic and therapeutic management of patients with acute abdomen as the main manifestation of SARS-CoV-2 infection. MATERIAL AND METHODS: A descriptive study of patients with clinical signs of acute abdomen diagnosed with COVID-19 and admitted at out healthcare facility from April 1 to May 10, 2020 was carried out. Clinical records were reviewed for data collection purposes. RESULTS: A series of 14 patients (9 male and 5 female) with a median age of 9.5 years was analyzed. All patients had abdominal pain. There were 11 patients with fever, 9 patients with vomit or diarrhea, and 9 patients with clinically suspected surgical pathology (acute appendicitis or peritonitis). Increased acute phase reactants and coagulation disorders were a common characteristic at blood tests. An abdominal ultrasonography was carried out in all patients, and a CT-scan was performed in 4 patients, which demonstrated inflammatory signs in the terminal ileum, the ileocecal valve and the ascending colon, as well as gallbladder edema. Conservative management was decided upon in all patients except one, and eight patients required intensive care admission for support treatment. CONCLUSIONS: Gastrointestinal symptoms can be the primary manifestation of the new coronavirus infection, which simulates an acute abdomen with a potentially unfavorable evolution. For an accurate diagnosis to be achieved, a good clinical record and a comprehensive physical exploration, as well as complementary tests in search of characteristic findings of COVID-19, should be carried out.

OBJETIVOS: Describir nuestra experiencia en el manejo diagnóstico y terapéutico de los pacientes que han presentado abdomen agudo como principal manifestación de la infección por SARS-Cov-2. MATERIAL Y METODOS: Estudio descriptivo de los pacientes ingresados con clínica inicial de abdomen agudo que fueron diagnosticados de COVID-19 entre el 1 de abril y el 10 de mayo de 2020. Se ha realizado la revisión de historias clínicas para la recogida de datos. RESULTADOS: Describimos una serie de 14 pacientes (9 varones y 5 mujeres) con una mediana de edad de 9,5 años. Todos ellos consultaron por dolor abdominal acompañado de fiebre en 11 y vómitos o diarrea en 9, y la sospecha clínica inicial fue de patología quirúrgica (apendicitis aguda o peritonitis) en 9. En la analítica sanguínea se encontró como característica común elevación de reactantes de fase aguda y alteraciones de coagulación. Se realizó ecografía abdominal a todos los pacientes y tomografía computarizada en cuatro observándose signos inflamatorios en íleon terminal, válvula ileocecal, colon ascendente y edema de vesícula biliar. Se optó por un manejo conservador en todos los pacientes menos uno y ocho pacientes precisaron ingreso en cuidados intensivos para tratamiento de soporte. CONCLUSIONES: La infección por el nuevo coronavirus puede producir síntomas gastrointestinales como principal manifestación, simulando un abdomen agudo que en algunos casos puede evolucionar de forma desfavorable. Para el diagnóstico es preciso realizar una buena historia clínica y exploración física, así como pruebas complementarias en busca de hallazgos característicos de COVID-19.

A comparison between electrospinning and rotary-jet spinning to produce PCL fibers with low bacteria colonization.

One of the important components in tissue engineering is material structure, providing a model for fixing and the development of cells and tissues, which allows for the transport of nutrients and regulatory molecules to and from cells. The community claims the need for new materials with better properties for use in the clinic. Poly (ε-caprolactone) (PCL) is a biodegradable polymer, semi crystalline, with superior mechanical properties and has attracted an increasing interest due to its usefulness in various biomedical applications. Herein, two different methods (electrospinning versus rotary jet spinning) with different concentrations of PCL produced ultra thin-fibers each with particular characteristics, verified and analyzed by morphology, wettability, thermal and cytotoxicity features and for bacteria colonization. Different PCL scaffold morphologies were found to be dependent on the fabrication method used. All PCL scaffolds showed greater mammalian cell interactions. Most impressively, rotary-jet spun fibers showed that a special rough surface decreased bacteria colonization, emphasizing that no nanoparticle or antibiotic was used; maybe this effect is related with physical (scaffold) and/or biological mechanisms. Thus, this study showed that rotary jet spun fibers possess a special topography compared to electrospun fibers to reduce bacteria colonization and present no cytotoxicity when in contact with mammalian cells.

Peripheral blood tumor-infiltrating lymphocytes in a neuroblastoma model. / Linfocitos infiltrantes de tumor en sangre periférica en un modelo de neuroblastoma.

OBJECTIVE: To detect tumor-infiltrating lymphocytes (TILs) in the peripheral blood (PB) of a preclinical neuroblastoma model. MATERIALS AND METHODS: Two types of preclinical models - immunodeficient mice and immunocompetent mice - were generated by injecting a cell suspension of neuroblastoma cell line NB36769 with MYCN gene (TH-MYCN+) overexpression. Spleen, tumor, and peripheral blood were studied using flow cytometry to detect PD-1+ T-cells. TCR-ß immunosequencing was performed in matched samples (tumor and peripheral blood). RESULTS: Most PB T-cells of immunodeficient mice were CD4 (control: 83.1%; tumor: 86.1%), with a small proportion of PD-1+ T-cells (control: 0.4%; tumor: 0.3%). However, the percentage of PD-1+ T-cells in the spleen was higher (control: 6.5%; tumor: 6.2%), and it was expressed in the CD4+ subset only. Regarding the TCR repertoire of immunocompetent mice, the proportion of the 10 most frequent sequences was significantly higher in tumors (11.09% ± 2.83%) than in the peripheral blood (1.59% ± 0.59%) (p=0.024). These findings are suggestive of clonotype enrichment within the tumor. 9 out of the 10 most frequent tumor clones were identified in the matched peripheral blood sample in 2 mice, and 6 out of 10 in one mouse. In addition, TILs with shared sequences from different animals were found. CONCLUSIONS: Our results in terms of immunophenotype and clonality suggest the presence of PB T-cells which could include TILs in a preclinical neuroblastoma model.

OBJETIVO: Comprobar la existencia de linfocitos T que incluyen linfocitos infiltrantes de tumor (TILs) en la sangre periférica (SP) de un modelo preclínico de neuroblastoma. MATERIAL Y METODOS: Utilizamos un modelo en ratones inmunodeficientes y otro en inmunocompetentes mediante inyección de suspensiones de la línea tumoral NB36769 con mutación de MYCN (TH-MYCN+). Se realizaron análisis por citometría de flujo (bazo, SP y tumor) y secuenciación del TCR-ß en el ADN de muestras pareadas de tumor y SP. RESULTADOS: En los ratones inmunodeficientes el componente principal en SP fue CD4: 83,1% (control) y 86,1% (tumor), siendo PD-1+ el 0,4 y el 0,3%. En el bazo obtuvimos un mayor porcentaje de linfocitos T PD-1+ que en SP, siendo similar en el control (6,5%) y en el ratón con tumor (6,2%), en subpoblación CD4+ exclusivamente. En los ratones inmunocompetentes observamos que la proporción de los 10 clones más frecuentes en los tumores constituía el 11,09% ± 2,83% del repertorio del TCR, mientras en SP representaba el 1,59% ± 0,59% (p= 0,024). Estos resultados sugieren un enriquecimiento de clonotipos dentro del tumor. De los 10 clones más frecuentes en las muestras tumorales, localizamos 9 también en la SP en dos ratones y 6 en el tercero. Además, encontramos secuencias compartidas por TILs de animales diferentes. CONCLUSIONES: Nuestros resultados de inmunofenotipo y clonalidad apuntan a la existencia de linfocitos en SP que podrían contener TILs en un modelo experimental de neuroblastoma.

[Recurrence of uncomplicated intestinal intussusception. Can it be treated as an outpatient?] / Recurrencia de la invaginación intestinal no complicada. ¿Es posible el manejo ambulatorio?

OBJECTIVES: To estimate the recurrence rate of intussusception after successful enema reduction and to analyze the costs of hospital admission with the current management of this pathology. MATERIAL AND METHODS: A retrospective study over 5 years of 97 patients with confirmed diagnosis of intussusception was undertaken. Medical records were evaluated for patient demographic, clinical and radiological data. Patients with enema-reduced intussusception were selected and data respecting to timing and outcome of recurrences, and length of stay were analyzed. Recurrence was defined as a new episode of intussusception within 72 hours of the initial presentation. Costs were calculated using hospital-specific data. RESULTS: During the study period there were 81/97 children with successful enema reduction. Mean length of stay was 35 hours in the conservative treatment group. There were 8 episodes of recurrence, 5 of them within the first 24 hours (6.17%), for an overall recurrence rate of 9.88%. 7 children were treated by repeated enema and only one patient needed surgery for persistent illness. Assuming the overall recurrence rate of 9.88%, it would require hospitalizing 16 patients to identify a single recurrence with a cost of 1,723.75 € per patient. CONCLUSIONS: Given the low recurrence rate for enema-reduced intussusception and the possibility of repeated enema for their treatment in most of recurrences, we strongly advocated for the outpatient management as a safe and cost-effective alternative.

OBJETIVOS: Estimar la tasa de recurrencia en la invaginación intestinal tras reducción con hidroenema. Analizar los costes de estancia hospitalaria según el manejo actual de esta patología. MATERIAL Y METODOS: Estudio retrospectivo de los 97 pacientes con diagnóstico ecográfico de invaginación intestinal en los últimos 5 años. Revisamos datos demográficos, clínicos y ecográficos. Seleccionamos los casos tratados de forma conservadora, analizando las recurrencias, su tratamiento y la estancia hospitalaria. Consideramos recurrencia a un nuevo episodio de invaginación intestinal en las siguientes 72 horas a la reducción. Los costes fueron calculados según los grupos relacionados por diagnóstico en base a datos específicos del centro. RESULTADOS: En los 81/97 (83,5%) pacientes con tratamiento conservador se diagnosticaron 8 episodios de recurrencia, 5 en las primeras 24 horas. En 7 casos se resolvió la recurrencia con hidroenema, mientras que 1 requirió tratamiento quirúrgico por recidivas persistentes. La media de estancia hospitalaria fue de 35 horas en el grupo de tratamiento conservador (81/97 pacientes). La tasa global de recurrencia fue del 9,88%, (6,17% antes de 24 horas), siendo necesario el ingreso de 16 pacientes para el diagnóstico de un caso de recurrencia en las primeras 24 horas. Según estos resultados, y los costes hospitalarios/24 horas, el manejo ambulatorio supondría un ahorro de 1.723,75 €/paciente. CONCLUSIONES: Dado que el riesgo de recurrencia en la invaginación intestinal no complicada es bajo y su tratamiento es conservador en la mayoría de los casos, estaría justificada la implantación de un protocolo de manejo ambulatorio como alternativa segura y costo-efectiva.

Successful treatment of acute severe graft-versus-host-disease in a pancreas-after-kidney transplant recipient: case report.

The development of acute graft-versus-host-disease (GVHD) in recipients of pancreas transplants is a rare and quite often a fatal post-transplantation complication. We present a 38-year-old male with a longstanding history of type 1 diabetes mellitus and end-stage kidney disease, with a living unrelated kidney transplant from his wife for 3 years, who received an enteric-drained 5-antigen HLA-mismatched deceased-donor pancreas. Five weeks after transplantation, he presented with spiking fevers, severe skin rash, diarrhea, pancytopenia, and increasingly abnormal liver function tests. Skin biopsies were consistent with grade 3 acute GVHD. The patient was treated for GVHD with escalated doses of tacrolimus, pulse doses of steroids, and basiliximab. He was discharged after a 4-week hospital stay with complete resolution of his rash, fever, abnormal liver enzymes, and leukopenia. He remained in good health with excellent kidney and pancreas allograft function 3 years later.

Cutaneous reactions to pine processionary caterpillar (Thaumetopoea pityocampa) in pediatric population.

Cutaneous lesions caused by pine processionary caterpillar (Thaumetopoea pityocampa, TP) are frequent in pinewood areas. However, no epidemiological studies have been performed so far in the pediatric population. In this study, we evaluated the relevance of reactions to pine processionary caterpillar in the pediatric population of our environment and determined the possible role of an IgE-mediated mechanism. A questionnaire was developed and given to 1,101 children and adolescents ranging from 3 to 17 years of age from rural areas with large pine forests. A total of 653 questionnaires were answered by the children or their parents. The search for immunoglobulin E (IgE)-mediated cases was based on the presence of a suspected reaction to caterpillar and confirmed by in vivo (skin prick) and in vitro (immunoblotting) tests. Sixty of the 653 people interviewed (9.18%) identified a cutaneous reaction from exposure to the processionary caterpillar. Within this group only four cases (6.7%) were because of an IgE-mediated mechanism. The predominant clinical feature of these patients with allergy to caterpillar was contact urticaria. We present the first study of cutaneous reactions to pine processionary caterpillar in a large pediatric population. This is a frequent pathology in pinery zones and only in a minority of the cases are because of an IgE-mediated allergic mechanism. This fact contrasts with studies in adults, where this percentage is much greater.

Surface-relief gratings and photoinduced birefringence in layer-by-layer films of chitosan and an azopolymer.

Layer-by-layer (LBL) films of chitosan alternated with an azopolymer, PS119, have been used for optical storage and fabrication of surface-relief gratings. The optical properties stem from the trans-cis-trans isomerization cycles undergone by the azochromophore, with a kinetics for writing the birefringence pattern that is much slower than in the spin-coated or cast films of azopolymers. The long writing times, of the order of 100 s, are due to the electrostatic interactions between adjacent chitosan and PS119 layers. Such interactions are also responsible for other features in the LBL films, namely the increase in the amount of adsorbed material when the pH of the preparation solution is decreased and the large residual birefringence after the writing laser is switched off. Gratings could be inscribed with s-polarized but not with p-polarized light, indicating a mass transport process associated with photodegradation.

[Microbial and enzymatic extraction of pectin. A review]. / Revisión: extracción microbiológica y enzimática de pectina.

Great amounts of agroindustrial wastes rich in polysaccharides, such as pectic substances, are produced worldwide. Some of these wastes are used for the production of pectin. Currently, pectin is extracted at industrial scale by physicochemical means, but lately new biotechnological alternatives have been developed. In this review, the principal characteristics of pectic substances and pectic enzymes are described. The traditional physicochemical method for the pectin extraction is described and the new biotechnological (microbial and enzymatic) methods for pectin extraction are discussed and commented as well.

Diltiazem protects against neurotoxicity induced by excitotoxic amino acids on cochlear afferent fibers.

The neurotoxic effects of two glutamate agonists, kainic acid (KA) and monosodium glutamate (MSG), were analyzed in the pigmented rat cochlea. Neural damage occurring after KA or MSG treatments were evidenced by the presence of a majority of swollen fibers in the inner spiral bundle. The use of diltiazem (DI), a Ca2+ L-channel antagonist, to prevent cochlear neural damage induced by glutamate agonists resulted in a significant increase of unswollen afferent nerve fibers. MSG-treated animals, after DI pretreatment, recovered the normal latency of the compound action potential, and only unswollen nerve fibers were observed.

[Massive lower digestive hemorrhage caused by typhoid fever]. / Hemorragia digestiva baja de carácter masivo por fiebre tifoidea.

A case is presented of massive lower intestinal bleeding due to typhoid fever. Because of uncontrollable bleeding, emergency right hemicolectomy and resection of the last 50 cm of the distal ileum was performed after endoscopy and arteriography, both of which were negative. The histology of the lesions typical of this disease is described.