Equipo multidisciplinar de cirugía radioguiada: Alternativa de cambio al paradigma actual / Multidisciplinary radio-guided surgery team: Alternative to change the current paradigm

IntroducciónAnte el aumento constante de la demanda asistencial de exploraciones relacionadas con cirugía radioguiada (CRG), nuestro hospital adoptó incluir en el equipo de CRG nuevos perfiles profesionales con el fin de reducir parcialmente el tiempo de dedicación de los médicos nucleares a esta tarea.Objetivos: Analizar el proceso de incorporación de los perfiles de Técnico Superior en Imagen para el Diagnóstico (TSID) y Enfermera Referente de Ganglio Centinela (ERGC), evaluando su despliegue en los procedimientos ligados a la técnica. Material y métodos: Análisis de la actividad de CRG durante el periodo 2018-2022, centrándolo en los procedimientos prequirúrgicos y quirúrgicos relativos a cáncer de mama (CaM) y melanoma maligno (MM), por ser aquellas patologías en las que se concentró la transferencia de competencias asistenciales. Evolución cronológica de las competencias asumidas por los diferentes perfiles durante su integración en el equipo de CRG. Resultados: La actividad asistencial de CRG durante el periodo analizado experimentó un incremento del 109%. CaM y MM son las patologías que aglutinaron con diferencia una mayor demanda asistencial. La transferencia de competencias en estas dos patologías se ha producido de manera progresiva, asumiendo en 2022 el 74% (460/622) de la fase de administración el ERGC y el 64% (333/519) de las cirugías el TSID. Conclusiones: La creación de un equipo multidisciplinar de CRG, que incluye distintos perfiles profesionales (MN, ERGC y TSID), es una eficaz estrategia para dar respuesta al incremento de la complejidad y número de todos los procedimientos relacionados con la CRG.(AU)

Introduction: Given the constant increase in the healthcare demand for examinations related to radio-guided surgery (RGS), our hospital adopted new professional profiles in the RGS team, in order to partially reduce the time spent by nuclear medicine physicians on this task. Aim: To analyze the process of incorporating the profiles of Superior Diagnostic Imaging Technician (TSID) and Sentinel Node Referent Nurse (ERGC), evaluating their deployment in the procedures linked to the technique. Material and methods: Analysis of RGS activity during the period 2018-2022, focusing on pre-surgical and surgical procedures related to breast cancer (BC) and malignant melanoma (MM), as they are those pathologies on which the transfer of care competencies was concentrated. Chronological evolution of the competencies assumed by the different profiles during their integration into the RGS team. Results: RGS's healthcare activity during the analyzed period experienced an increase of 109%. BC and MM were the pathologies that accounted for by far the greatest demand for care. The transfer of competencies in these two pathologies occurred in a progressive and staggered manner, with 74% (460/622) of the administration phase being carried out by the ERGC and 64% (333/519) of the surgeries by the TSID in 2022. Conclusions: The creation of a multidisciplinary RGS team that includes different professional profiles (NM, ERGC and TSID) is an effective strategy to respond to the increase in the complexity and number of all procedures related to RGS.(AU)

Protein-Protein Binding Kinetics by Biolayer Interferometry.

The specific kinetics and thermodynamics of protein-protein interactions underlie the molecular mechanisms of cellular functions; hence the characterization of these interaction parameters is central to the quantitative understanding of physiological and pathological processes. Many methods have been developed to study protein-protein interactions, which differ in various features including the interaction detection principle, the sensitivity, whether the method operates in vivo, in vitro, or in silico, the temperature control, the use of labels, immobilization, the amount of sample required, the number of measurements that can be accomplished simultaneously, or the cost. Bio-Layer Interferometry (BLI) is a label-free biophysical method to measure the kinetics of protein-protein interactions. Label-free interaction assays are a broad family of methods that do not require protein modifications (other than immobilization) or labels such as fusions with fluorescent proteins or transactivating domains or chemical modifications like biotinylation or reaction with radionuclides. Besides BLI, other label-free techniques that are widely used for determining protein-protein interactions include surface plasmon resonance (SPR), thermophoresis, and isothermal titration calorimetry (ITC), among others.

X-Ray Crystallography for Macromolecular Complexes.

X-ray crystallography has for most of the last century been the standard technique to determine the high-resolution structure of biological macromolecules, including multi-subunit protein-protein and protein-nucleic acids as large as the ribosome and viruses. As such, the successful application of X-ray crystallography to many biological problems revolutionized biology and biomedicine by solving the structures of small molecules and vitamins, peptides and proteins, DNA and RNA molecules, and many complexes-affording a detailed knowledge of the structures that clarified biological and chemical mechanisms, conformational changes, interactions, catalysis and the biological processes underlying DNA replication, translation, and protein synthesis. Now reaching well into the first quarter of the twenty-first century, X-ray crystallography shares the structural biology stage with cryo-electron microscopy and other innovative structure determination methods, as relevant and central to our understanding of biological function and structure as ever. In this chapter, we provide an overview of modern X-ray crystallography and how it interfaces with other mainstream structural biology techniques, with an emphasis on macromolecular complexes.

Multidisciplinary radio-guided surgery team: Alternative to change the current paradigm.

INTRODUCTION: Given the constant increase in the healthcare demand for examinations related to radio-guided surgery (RGS), our hospital adopted new professional profiles in the RGS team, in order to partially reduce the time spent by nuclear medicine physicians on this task. AIM: To analyze the process of incorporating the profiles of Diagnostic Imaging Technician (DIT) and Sentinel Node Referent Nurse (SNRN), evaluating their deployment in the procedures linked to the technique. MATERIAL AND METHODS: Analysis of RGS activity during the period 2018-2022, focusing on pre-surgical and surgical procedures related to breast cancer (BC) and malignant melanoma (MM), as they are those pathologies on which the transfer of care competencies was concentrated. Chronological evolution of the competencies assumed by the different profiles during their integration into the RGS team. RESULTS: RGS's healthcare activity during the analyzed period experienced an increase of 109%. BC and MM were the pathologies that accounted for by far the greatest demand for care. The transfer of competencies in these two pathologies occurred in a progressive and staggered manner, with 74% (460/622) of the administration phase being carried out by the SNRN and 64% (333/519) of the surgeries by the DIT in 2022. CONCLUSIONS: The creation of a multidisciplinary RGS team that includes different professional profiles (nuclear medicine physician [MN], ERGC and TSID) is an effective strategy to respond to the increase in the complexity and number of all procedures related to RGS.

[Antibiotic stewardship programs in the Spanish emergency services: PROA-URG Study]. / Programas de optimización del uso de antimicrobianos en los servicios de urgencias españoles: Estudio PROA-URG.

OBJECTIVE: Antimicrobial stewardship programs (ASP) have become a key tool in the adaptation of these drugs to the health system. The information available on the application and indicators used in these programs in emergency departments is scarce. The objective of this study is to know the extent of ASP implementation in the emergency departments, as well as the use of antimicrobials in these units. METHODS: Multicenter retrospective study. An invitation was sent to all participants of the REDFASTER-SEFH emergency pharmacist working group. A questionnaire was used consisting of 21 items, answered by a team made up of a pharmacist, emergency room specialist, infectious disease specialist and microbiologist. RESULTS: Eighteen hospitals completed the survey. Fourteen (77.8%) had an ASP manager. The DDD value per 1000 admissions ranged between 36.5 and 400.5 (median: 100.4 [IQR:57.2-157.3]). Both carbapenem and macrolide group presented wide variability in use. Six (33.3%) hospitals had an annual report on the specific resistance profile for urine and blood cultures. The percentage of multi-drug resistant strains in urine cultures was 12.5% and in blood cultures 12.2%. The percentage of adequacy in the bacteremia treatment was 81.0% (IQR:74.6-85.0%), while in urinary tract infections was 78.0% (IQR:71.5-88.0). CONCLUSIONS: Despite the existence of ASP members in emergency services, as well as the training activity and local guidelines is common. knowledge of the use of antimicrobials and resistances is limited. Future activities must be aimed at improving information about the ASP results in these units.

Decoding anaphylatoxins: unveiling the molecular mechanisms of complement receptor activation and signaling.

Recent advances in cryo-electron microscopy (Cryo-EM) have revolutionized our understanding of the complement C5a/C3a receptors that are crucial in inflammation. A recent report by Yadav et al. has elucidated the activation, ligand binding, selectivity, and signaling bias of these receptors, thereby enhancing structure-guided drug discovery. This paves the way for more effective anti-inflammatory therapies that target these receptors with unprecedented precision.

C4BP(ß-)-mediated immunomodulation attenuates inflammation in DSS-induced murine colitis and in myeloid cells from IBD patients.

The most recent and promising therapeutic strategies for inflammatory bowel disease (IBD) have engaged biologics targeting single effector components involved in major steps of the immune-inflammatory processes, such as tumor necrosis factor, interleukins or integrins. Nevertheless, these molecules have not yet met expectations regarding efficacy and safety, resulting in a significant percentage of refractory or relapsing patients. Thus, novel treatment options are urgently needed. The minor isoform of the complement inhibitor C4b-binding protein, C4BP(ß-), has been shown to confer a robust anti-inflammatory and immunomodulatory phenotype over inflammatory myeloid cells. Here we show that C4BP(ß-)-mediated immunomodulation can significantly attenuate the histopathological traits and preserve the intestinal epithelial integrity in dextran sulfate sodium (DSS)-induced murine colitis. C4BP(ß-) downregulated inflammatory transcripts, notably those related to neutrophil activity, mitigated circulating inflammatory effector cytokines and chemokines such as CXCL13, key in generating ectopic lymphoid structures, and, overall, prevented inflammatory immune cell infiltration in the colon of colitic mice. PRP6-HO7, a recombinant curtailed analogue with only immunomodulatory activity, achieved a similar outcome as C4BP(ß-), indicating that the therapeutic effect is not due to the complement inhibitory activity. Furthermore, both C4BP(ß-) and PRP6-HO7 significantly reduced, with comparable efficacy, the intrinsic and TLR-induced inflammatory markers in myeloid cells from both ulcerative colitis and Crohn's disease patients, regardless of their medication. Thus, the pleiotropic anti-inflammatory and immunomodulatory activity of PRP6-HO7, able to "reprogram" myeloid cells from the complex inflammatory bowel environment and to restore immune homeostasis, might constitute a promising therapeutic option for IBD.

Thymic atrophy induced by Plasmodium berghei ANKA and Plasmodium yoelii 17XL infection.

The thymus is the anatomical site where T cells undergo a complex process of differentiation, proliferation, selection, and elimination of autorreactive cells which involves molecular signals in different intrathymic environment. However, the immunological functions of the thymus can be compromised upon exposure to different infections, affecting thymocyte populations. In this work, we investigated the impact of malaria parasites on the thymus by using C57BL/6 mice infected with Plasmodium berghei ANKA and Plasmodium yoelii 17XL; these lethal infection models represent the most severe complications, cerebral malaria, and anemia respectively. Data showed a reduction in the thymic weight and cellularity involving different T cell maturation stages, mainly CD4-CD8- and CD4+CD8+ thymocytes, as well as an increased presence of apoptotic cells, leading to significant thymic cortex reduction. Thymus atrophy showed no association with elevated serum cytokines levels, although increased glucocorticoid levels did. The severity of thymic damage in both models reached the same extend although it occurs at different stages of infection, showing that thymic atrophy does not depend on parasitemia level but on the specific host-parasite interaction.

Two-dimensional filtering in the Fourier domain of transient grating coherent artifacts in time-resolved spectroscopy.

Removal of coherent artifacts is important in the analysis of time and wavelength resolved spectroscopy data. By taking advantage of the strong correlation between spectra acquired sequentially in time, artifact removal can be formulated as a 2D problem for improved effectiveness. This paper proposes a 2D method to remove transient grating coherent artifacts from femtosecond time-resolved spectroscopy data based on filtering in the Fourier domain, leading to better estimation of the material parameters from the measured data. The method is simple, intuitive, and light on computation resources. The effectiveness of the method is demonstrated with experimental data acquired from a bare gold film with and without coherent artifacts using mutually parallel and perpendicular pump/probe polarizations, as well as with more complex samples (nanostructured gold film on a glass substrate and rhodamine fluorophores in solution). The proposed method is expected to be applicable to coherent artifact removal in other types of time and wavelength-resolved spectroscopy data.

Structural biology of complement receptors.

The complement system plays crucial roles in a wide breadth of immune and inflammatory processes and is frequently cited as an etiological or aggravating factor in many human diseases, from asthma to cancer. Complement receptors encompass at least eight proteins from four structural classes, orchestrating complement-mediated humoral and cellular effector responses and coordinating the complex cross-talk between innate and adaptive immunity. The progressive increase in understanding of the structural features of the main complement factors, activated proteolytic fragments, and their assemblies have spurred a renewed interest in deciphering their receptor complexes. In this review, we describe what is currently known about the structural biology of the complement receptors and their complexes with natural agonists and pharmacological antagonists. We highlight the fundamental concepts and the gray areas where issues and problems have been identified, including current research gaps. We seek to offer guidance into the structural biology of the complement system as structural information underlies fundamental and therapeutic research endeavors. Finally, we also indicate what we believe are potential developments in the field.

The structure of Leptospira interrogans GAPDH sheds light into an immunoevasion factor that can target the anaphylatoxin C5a of innate immunity.

Leptospirosis is a neglected worldwide zoonosis involving farm animals and domestic pets caused by the Gram-negative spirochete Leptospira interrogans. This bacterium deploys a variety of immune evasive mechanisms, some of them targeted at the complement system of the host's innate immunity. In this work, we have solved the X-ray crystallographic structure of L. interrogans glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to 2.37-Å resolution, a glycolytic enzyme that has been shown to exhibit moonlighting functions that potentiate infectivity and immune evasion in various pathogenic organisms. Besides, we have characterized the enzyme's kinetic parameters toward the cognate substrates and have proven that the two natural products anacardic acid and curcumin are able to inhibit L. interrogans GAPDH at micromolar concentration through a noncompetitive inhibition modality. Furthermore, we have established that L. interrogans GAPDH can interact with the anaphylatoxin C5a of human innate immunity in vitro using bio-layer interferometry and a short-range cross-linking reagent that tethers free thiol groups in protein complexes. To shed light into the interaction between L. interrogans GAPDH and C5a, we have also carried out cross-link guided protein-protein docking. These results suggest that L. interrogans could be placed in the growing list of bacterial pathogens that exploit glycolytic enzymes as extracellular immune evasive factors. Analysis of the docking results indicates a low affinity interaction that is consistent with previous evidence, including known binding modes of other α-helical proteins with GAPDH. These findings allow us to propose L. interrogans GAPDH as a potential immune evasive factor targeting the complement system.

Pneumonitis After Concurrent Chemoradiation and Immune Checkpoint Inhibition in Patients with Locally Advanced Non-small Cell Lung Cancer.

AIMS: Pneumonitis is a common and potentially deadly complication of combined chemoradiation and immune checkpoint inhibition (CRT-ICI) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). In this study we sought to identify the risk factors for pneumonitis with CRT-ICI therapy in LA-NSCLC cases and determine its impact on survival. MATERIALS AND METHODS: We conducted a retrospective chart review of 140 patients with LA-NSCLC who underwent curative-intent CRT-ICI with durvalumab between 2018 and 2021. Pneumonitis was diagnosed by a multidisciplinary team of clinical experts. We used multivariable cause-specific hazard models to identify risk factors associated with grade ≥2 pneumonitis. We constructed multivariable Cox proportional hazard models to investigate the impact of pneumonitis on all-cause mortality. RESULTS: The median age of the cohort was 67 years; most patients were current or former smokers (86%). The cumulative incidence of grade ≥2 pneumonitis was 23%. Among survivors, 25/28 patients had persistent parenchymal scarring. In multivariable analyses, the mean lung dose (hazard ratio 1.14 per Gy, 95% confidence interval 1.03-1.25) and interstitial lung disease (hazard ratio 3.8, 95% confidence interval 1.3-11.0) increased the risk for pneumonitis. In adjusted models, grade ≥2 pneumonitis (hazard ratio 2.5, 95% confidence interval 1.0-6.2, P = 0.049) and high-grade (≥3) pneumonitis (hazard ratio 8.3, 95% confidence interval 3.0-23.0, P < 0.001) were associated with higher all-cause mortality. CONCLUSIONS: Risk factors for pneumonitis in LA-NSCLC patients undergoing CRT-ICI include the mean radiation dose to the lung and pre-treatment interstitial lung disease. Although most cases are not fatal, pneumonitis in this setting is associated with markedly increased mortality.

Soluble endoglin reduces thrombus formation and platelet aggregation via interaction with αIIbß3 integrin.

BACKGROUND: The circulating form of human endoglin (sEng) is a cleavage product of membrane-bound endoglin present on endothelial cells. Because sEng encompasses an RGD motif involved in integrin binding, we hypothesized that sEng would be able to bind integrin αIIbß3, thereby compromising platelet binding to fibrinogen and thrombus stability. METHODS: In vitro human platelet aggregation, thrombus retraction, and secretion-competition assays were performed in the presence of sEng. Surface plasmon resonance (SPR) binding and computational (docking) analyses were carried out to evaluate protein-protein interactions. A transgenic mouse overexpressing human sEng (hsEng+) was used to measure bleeding/rebleeding, prothrombin time (PT), blood stream, and embolus formation after FeCl3-induced injury of the carotid artery. RESULTS: Under flow conditions, supplementation of human whole blood with sEng led to a smaller thrombus size. sEng inhibited platelet aggregation and thrombus retraction, interfering with fibrinogen binding, but did not affect platelet activation. SPR binding studies demonstrated that the specific interaction between αIIbß3 and sEng and molecular modeling showed a good fitting between αIIbß3 and sEng structures involving the endoglin RGD motif, suggesting the possible formation of a highly stable αIIbß3/sEng. hsEng+ mice showed increased bleeding time and number of rebleedings compared to wild-type mice. No differences in PT were denoted between genotypes. After FeCl3 injury, the number of released emboli in hsEng+ mice was higher and the occlusion was slower compared to controls. CONCLUSIONS: Our results demonstrate that sEng interferes with thrombus formation and stabilization, likely via its binding to platelet αIIbß3, suggesting its involvement in primary hemostasis control.

Impact of gingivitis on oral health-related quality of life in 12-year-old schoolchildren of Quito, Ecuador.

PURPOSE: Evaluate the impact of gingivitis on oral health-related quality of life (OHRQoL) amongst 12-year-old schoolchildren from Quito, Ecuador. METHODS: We evaluated 998 school children using the Community Periodontal Index for gingival bleeding and calculus. OHRQoL was assessed with the Child Perceptions Questionnaire 11-14 (CPQ11-14) questionnaire. RESULTS: Of the 998 schoolchildren, 93% had gingival bleeding and 73% had dental calculus. Schoolchildren with more than one sextant with gingival bleeding had 1.18 times higher mean CPQ11-14 (RR 1.18, 95% CI 1.11-1.27) than those with none or just one affected sextant. Male schoolchildren presented a 15% lower mean Child Perceptions Questionnaire (CPQ) (RT 0.85; 95% CI 0.76-0.96). Children whose parents had incomplete secondary education had a 15% lower mean CPQ (RT 0.85; 95% CI 0.77-0.94). Bleeding in more than one sextant was significantly associated with worse quality of life in the emotional well-being (RT 1.40, 95% CI 1.03-1.90) and social well-being domains (RT 1.76, 95% CI 1.32-2.34). CONCLUSION: Gingival bleeding negatively impacted the OHRQoL of 12-year-old Ecuadorian schoolchildren living in Quito.

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)

Paraplejia funcional que imita una mielopatía aguda durante el embarazo: reporte de un caso

Introducción: Los trastornos funcionales son un reto clínico en la atención de pacientes con déficits neurológicos. Pueden generar manifestaciones clínicas típicas y gran discapacidad. Para su diagnóstico se requiere de una alta sospecha inicial asociado a una batería de examen físico completa. Hallazgos clínicos: Presentamos el caso de una paciente indígena embarazada de 19 años, con pérdida de la fuerza en sus extremidades inferiores, un nivel sensitivo y pérdida del control de los esfínteres. Luego de una evolución estacionaria con estudios imagenológicos e infectocontagiosos dentro de la normalidad. Se sospechó el diagnóstico de un trastorno neurológico funcional por lo que se realizó la prueba del Spinal Injuries Center (SIC) el cual fue positivo. Tratamiento y evolución: Realizamos una intervención multidisciplinar, incluyendo el servicio de rehabilitación, neurología, psiquiatría y psicología. Se utilizaron intervenciones con movimientos articulares, fortalecimiento muscular, estimulación eléctrica y psicoterapia. Posteriormente se obtuvo la recuperación completa de la paciente antes del alta hospitalaria, con la exigencia de seguimiento ambulatorio, además de una inserción satisfactoria en las actividades sociales y familiares. Conclusiones: Este caso refleja la importancia de un análisis neurológico detallado, el conocimiento de diferentes herramientas de semiología y el reto diagnóstico de los trastornos funcionales en neurológicos. La intervención de un equipo multidisciplinar favorece abordajes multidimensionales y resultados clínicos favorables.

Introduction: Functional disorders pose a clinical challenge in the care of patients with neurological deficits. They can generate typical clinical manifestations and great disability. Diagnosis requires a high initial suspicion together with comprehensive physical examination. Clinical Findings: We present the case of a 19-year-old pregnant indigenous patient, with loss of strength in her lower extremities, with a sensitive level and loss of sphincter control. After a stationary evolution with imaging and infectious studies within normal limits, a diagnosis of a functional neurological disorder was suspected; thus, the Spinal Injuries Center (SIC) test was performed, showing positive results. Treatment and evolution: A multidisciplinary intervention was carried out, including the neurology, psychiatry and psychology rehabilitation. Interventions amied towards joint movements, muscle strengthening, electrical stimulation and psychotherapy were used. Eventually, the patient's complete recovery was achieved before hospital discharge, in addition to a satisfactory integration into social and family activities, with a outpatient follow-up requirement. Conclusions: This case reflects the importance of a detailed neurological analysis, knowledge of different semiology tools and the diagnostic challenge of functional neurological disorders. The intervention of a multidisciplinary team favors multidimensional approaches and favorable clinical results.

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Efectos posturales inmediatos de la amplificación mecanoceptiva en niños con disfunciones neuromotrices, valorados mediante una plataforma de presiones Wii Balance Board. Estudio consecutivo no controlado / Immediate postural effects of mechanoceptive amplification in children with neuromotor dysfunctions, assessed by means of a Wii Balance Board pressure platform. Uncontrolled consecutive study

Introducción: Los trastornos neurológicos son una causa frecuente de discapacidad infantil. Las disfunciones neuromotrices se afrontan clínicamente en la actualidad mediante tratamientos ortopédicos, farmacológicos y fisioterápicos. Las vibraciones terapéuticas son estudiadas para conocer sus efectos tróficos y neuromoduladores. Objetivo: Observar los cambios relacionados con el control postural en casos de disfunción neuromotriz infantil después de la aplicación de estímulos vibratorios ecológicos, medidos con una plataforma de fuerzas. Pacientes y métodos: Estudio consecutivo no controlado. Quince sujetos con discapacidad motora y edad media 9±3,4 años fueron valorados en bipedestación estática mediante la plataforma Wii Balance Board antes y después de una única dosis de amplificación mecanoceptiva (AM). Se analizaron variables del centro de presiones: posición media, excursión media, amplitud y recorrido. Resultados: La posición media conjunta del centro de presiones pre-AM se encontraba más alejada del centro anatómico en el eje frontal que en el sagital de manera estadísticamente significativa (p=0,041) y mostraron recorridos mediolaterales del centro de presiones significativamente más largos (p=0,001) que los anteroposteriores. Post-AM hubo aumentos significativos para la variables excursión media total (p=0,015), amplitud en eje frontal (p=0,010), y recorrido tanto en el total (p=0,005) como en los parciales de ambos ejes frontal (p=0,006) y sagital (p=0,004). A la observación, la posición sagital media conjunta se retrasó mientras que la posición frontal media conjunta se aproximó hacia el centro, con elevada correlación entre reubicación y excursión y entre amplitud y recorrido. Conclusión: Los sujetos obtuvieron un reequilibrio postural tendente hacia la posteriorización y hacia el miembro inferior estimulado después de la AM. (AU)

Introduction: Neurological disorders are a common cause of child disability. Neuromotor dysfunctions are currently being clinically faced through orthopedic, pharmacological and physiotherapeutic treatments. Therapeutic vibrations are studied to know their trophic and neuromodulator effects. Objective: To observe the changes related to postural control in cases of infantile neuromotor dysfunction after the application of ecological vibratory stimuli, measured with a force platform. Patients and methods: Consecutive uncontrolled study. 15 subjects with motor disabilities and a mean age of 9±3.4 years were assessed in static standing using the Wii Balance Board platform before and after a single dose of mechanoceptive amplification (AM). Variables of the center of pressures were analyzed: mean position, mean excursion, amplitude and path length. Results: The pre-MA center of pressures mean position of the ensemble was further from the anatomical center on the frontal axis than on the sagittal axis in a statistically significant way (p=.041) and subjects showed significantly longer mediolateral path lengths of the center of pressures (p=.001) than the anteroposterior path lengths. Post-AM there were significant increases for the total mean excursion variable (p=.015), for the amplitude on the frontal axis (p=.010), and for the path length both in the total (p=.005) as in the partials of axes frontal (p=.006) and sagittal (p=.004). At the observational level, the mean sagittal position of the ensemble was posteriorized while the mean frontal position of the ensemble approached toward the center, with a high correlation between relocation/excursion and amplitude/path length. Conclusion: The subjects obtained a postural rebalancing tending toward posteriorization and toward the stimulated lower limb after MA. (AU)