Usefulness of cell ratios and the derived neutrophil-to-lymphocyte ratio in the diagnosis of pediatric acute appendicitis. / Utilidad de los índices celulares y el índice neutrófilo/linfocito derivado en el diagnóstico de la apendicitis aguda pediátrica.

OBJECTIVE: To analyze the accuracy of cell ratios in the diagnosis of pediatric acute appendicitis while introducing a new one -the derived neutrophil-to-lymphocyte ratio (dNLR). MATERIALS AND METHODS: An observational, retrospective study of patients aged 0-15 years old diagnosed with acute appendicitis (AA) and with non-surgical abdominal pain (AP) treated in our institution from 2021 to 2022 was carried out. The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and dNLR were compared between groups. RESULTS: 98 AA patients (30% of whom were female; age: 10 ± 3.3 years) and 97 AP patients (53% of whom were male; age: 9.3 ± 3.7 years) were included. NLR, MLR, PLR, and dNLR values were higher in AA patients than in AP patients: 9.6 IQR (interquartile range) 9.5 vs. 3.3 IQR 5.3: p< 0.0001; 0.7 IQR 0.6 vs. 0.46 IQR 0.7: p< 0.023; 199.8 IQR 163.9 vs. 134.0 IQR 129.2: p< 0.0001; and 5.29 IQR 3.9 vs. 2.39 IQR 2.7; p< 0.0001, respectively. Sensitivity, specificity, positive-negative predictive value, area under the ROC curve, and dNLR cut-off point for AA diagnosis were 70%, 78%, 77-72%, 0.811, and 3.98, respectively. CONCLUSIONS: Cell ratios are useful and cost-effective inflammatory parameters in the diagnosis of pediatric acute appendicitis. The results of this study suggest dNLR has the greatest clinical accuracy.

OBJETIVOS: Analizar la precisión de los índices celulares en el diagnóstico de la apendicitis aguda pediátrica, introduciendo uno nuevo, el índice neutrófilo/linfocito derivado (INLd). MATERIAL Y METODOS: Estudio retrospectivo observacional de los pacientes de 0-15 años diagnosticados de apendicitis aguda (AA) y con dolor abdominal no quirúrgico (DA) tratados en nuestro centro entre 2021-2022. Se comparó el índice neutrófilo/linfocito (INL), índice monocito/linfocito (IML), índice plaqueta/linfocito (IPL) y el INLd entre los grupos. RESULTADOS: Se incluyeron 98 casos con AA (30% mujeres, edad 10 ± 3,3 años) y 97 pacientes con DA (53% hombres, edad 9,3 ± 3,7 años). Los valores de INL, IML, IPL e INLd fueron mayores en pacientes con AA respecto a niños con DA: 9,6 rango intercuartil (RIC) 9,5 vs. 3,3 RIC 5,3: p< 0,0001; 0,7 RIC 0,6 vs. 0,46 RIC 0,7: p< 0,023; 199,8 RIC 163,9 vs. 134,0 RIC 129,2: p< 0,0001; y 5,29 RIC 3,9 vs. 2,39 RIC 2,7: p< 0,0001; respectivamente. La sensibilidad, especificidad, valor predictivo positivo-negativo, área bajo la curva ROC y el punto de corte del INLd para el diagnóstico de AA fue de 70%, 78%, 77-72%, 0,811 y 3,98; respectivamente. CONCLUSIONES: Los índices celulares son parámetros inflamatorios útiles y coste-efectivos que pueden contribuir al diagnóstico de la apendicitis aguda pediátrica. Los resultados de este estudio sugieren que el INLd es el de mayor precisión clínica.

Infrequent associations of cutis marmorata telangiectatica congenita: a two-case report. / Asociaciones infrecuentes de la cutis marmorata telangiectásica congénita: reporte de dos casos.

INTRODUCTION: Cutis marmorata telangiectatica congenita (CMTC) is a rare capillary malformation characterized by persistent reticular and violaceous erythema. We present two cases of CMTC. CLINICAL OBSERVATION: The first case involved a 13-month-old male with a reticular violaceous macule on the left gluteal region and a brownish papule with Darier's sign on the inner malleolus of the left foot, which was biopsied, revealing > 15 mast cells per field, leading to a diagnosis of CMTC and solitary cutaneous mastocytoma. The second case involved a newborn with a characteristic CMTC lesion without other malformations at birth, who subsequently developed two cutaneous tumors consistent with infantile hemangiomas during follow-up. DISCUSSION: CMTC is a benign condition. However, approximately 50% of cases exhibit associated anomalies. When CMTC is suspected, musculoskeletal, ophthalmological, and cutaneous malformations should be ruled out. To the best of our knowledge, this is the first report of CMTC associated with mastocytoma and one of the few cases associated with infantile hemangioma.

INTRODUCCION: La cutis marmorata telangiectásica congénita (CMTC) es una rara malformación capilar caracterizada por eritema reticular y violáceo persistente. Presentamos dos casos de CMTC. OBSERVACION CLINICA: Un varón de 13 meses presentaba una mácula violácea reticular en glúteo izquierdo y una pápula parduzca con signo de Darier en el maléolo interno del pie izquierdo, que fue biopsiada identificando > 15 mastocitos/campo, con lo cual se diagnosticó de CMTC y mastocitoma cutáneo solitario. El segundo caso, una recién nacida con una lesión característica de CMTC sin otras malformaciones al nacer, que durante el seguimiento desarrolló dos tumoraciones cutáneas compatibles con hemangiomas infantiles. COMENTARIOS: La CMTC es una condición benigna, sin embargo, aproximadamente el 50% de los casos presentan anomalías asociadas. Ante la sospecha de CMTC se deben descartar malformaciones musculoesqueléticas, oftalmológicas y cutáneas. Hasta donde tenemos conocimiento, este es el primer reporte de CMTC asociada con mastocitoma y uno de los pocos con hemangioma infantil.

Single-port transumbilical pediatric cholecystectomy: any benefits for the patient? / Colecistectomía pediátrica por puerto único transumbilical: ¿aporta algo al paciente?

OBJECTIVE: To compare the perioperative results of single-port laparoscopic cholecystectomy (SPLC) with those of laparoscopic cholecystectomy (LC), and to analyze whether there were any differences between both techniques in our patients. MATERIALS AND METHODS: A retrospective, observational analysis was carried out in non-homogeneous groups of patients under 15 years of age undergoing LC and SPLC over a 6-year period. LC was conducted using four ports, while SPLC was performed through an umbilical incision using a wound retractor to which a surgical glove was coupled for the insertion of 3 ports and instruments curved as required. 15 clinical, surgical, and economic variables were compared by means of a univariate and bivariate analysis. RESULTS: 11 patients underwent surgery - 5 through SPLC and 6 through LC. No significant differences were found in terms of mean operating time (SPLC: 144 minutes vs. LC: 139, P= 0.855) or hospital stay, but a slight increase in hospital cost was noted (SPLC: 1,160 € vs. LC: 1,177 €). The cost of LC was 1,322 € vs. 1,367 € for SPLC, with a premium of 44.30 € owing to the use of the wound retractor. None of the patients had perioperative complications, and all of them felt the cosmetic result was excellent. CONCLUSIONS: In our limited experience, the differences between SPLC and LC do not clearly support one or the other. SPLC could provide patients with a better cosmetic result and allow surgeons to improve their skills. However, we believe cholecystectomy is not the most adequate procedure to start a career in single-port laparoscopy because potential complications may be severe.

OBJETIVO: Comparar los resultados perioperatorios de la colecistectomía laparoscópica por puerto único (CLPU) respecto a la colecistectomía laparoscópica (CL) y analizar si, en nuestra casuistica, existen diferencias entre estas tecnicas. MATERIAL Y METODO: Análisis retrospectivo y observacional en grupos no homogeneos de pacientes menores de 15 años sometidos a CL y CLPU durante un periodo de 6 años. La CL se realizó con cuatro puertos y la CLPU mediante una incisión umbilical y colocación de un retractor de heridas al que se acopló un guante quirúrgico, a través del cual se insertaron 3 trócares para el instrumental convenientemente curvado. Se compararon 15 variables clínicas, quirúrgicas y económicas mediante análisis univariado y bivariado. RESULTADOS: Fueron intervenidos 11 pacientes, cinco mediante CLPU y 6 por CL. No hubo diferencias significativas en el tiempo operatorio medio (CLPU: 144 minutos vs. CL: 139, P= 0,855) ni en estancia hospitalaria, aunque sí un ligero aumento del coste hospitalario (CLPU:1.160 €, CL:1.177 €). El coste de la CL fue de 1.322 € frente a 1.367 de la CLPU, con un sobreprecio de +44,30 € debido al uso del retractor de heridas. Ningún paciente presentó complicaciones perioperatorias y todos percibían un resultado cosmético excelente. CONCLUSIONES: Las diferencias entre CLPU y CL, en nuestra reducida experiencia, no justifican decidirse claramente por una u otra técnica. La CLPU podría aportar al paciente un mejor resultado cosmético y al cirujano una mejora de sus habilidades, aunque creemos que la colecistectomía no es la intervención adecuada para iniciarse en laparoscopia por puerto único debido a la gravedad de las posibles complicaciones.

First Reported Case of Malignant Ectomesenchymoma with p.Leu122Arg Mutation in MYOD1 Gene: Extensive Intra- and Extracranial Tumor in a 15-Year-Old Female.

BACKGROUND: Ectomesenchymomas (EMs) are extremely rare neoplasms composed of malignant mesenchymal components and neuroectodermal derivatives. They are described in a wide variety of locations, with the head and neck region being one of the most frequently involved areas. EMs are usually managed as high-risk rhabdomyosarcomas and have similar outcomes. METHODS: We present the case of a 15-year-old female with an EM that arose in the parapharyngeal space and extended into the intracranial space. RESULTS: Histologically, the tumor presented an embryonal rhabdomyosarcomatous mesenchymal component and the neuroectodermal component was constituted by isolated ganglion cells. Next-generation sequencing (NGS) revealed a p.Leu122Arg (c.365 T > G) mutation in the MYOD1 gene, a p.Ala34Gly mutation in the CDKN2A gene, and CDK4 gene amplification. The patient was treated with chemotherapy. She died 17 months after the debut of symptoms. CONCLUSION(S): To our knowledge, this is the first reported case in English literature of an EM with this MYOD1 mutation. We suggest combining PI3K/ATK pathway inhibitors in these cases. NGS should be performed in EMs cases to detect mutations with potential treatment options.

Pediatric thyroidectomy in a "low volume" institution without protocolization: results and future horizons. / Tiroidectomía pediátrica en un centro de "bajo volumen" y sin protocolización: resultados y horizontes.

OBJECTIVE: Pediatric thyroidectomy is an infrequent, complex surgery, with high risk of complications. Complication rates and oncological results of non-protocolized thyroidectomy in a secondary pediatric hospital were compared with those from reference institutions. MATERIALS AND METHODS: A retrospective study of patients under 15 years old undergoing thyroidectomy ± cervical lymphadenectomy by low volume pediatric surgeons (<30 cervical endocrine surgeries annually) in a pediatric hospital from January 2010 to January 2020 was carried out. RESULTS: 11 patients undergoing 12 surgeries (mean age: 9.8 years; 63% female) were analyzed. Thyroid nodules were the main surgical indication (50%), and prevalence of genetic mutations was 45%. 1 patient had transient hypocalcemia, and there were 2 cases of transient recurrent laryngeal nerve neuropraxia (16.6%). No permanent complications were noted. 66.6% of pathological reports showed malignancy. Mean hospital stay was 2.35 days (range: 1.25-5), with an overall complication rate of 25%, similar to that reported by high-volume institutions. After a mean follow-up of 4 years, tumor recurrence has not been observed in any patient. CONCLUSIONS: In our view, an experienced pediatric surgeon specialized in pediatric and neonatal general surgery - even if below the high volume threshold - acquires the skills required in pediatric thyroid surgery without an increase in morbidity and mortality. Perioperative management should be agreed and protocolized by the various specialists involved to improve results.

OBJETIVOS: La tiroidectomía pediátrica es una intervención infrecuente, compleja y con un riesgo elevado de complicaciones. Se evalúa la tasa de complicaciones y resultados oncológicos de la tiroidectomía no protocolizada en un hospital infantil de segundo nivel en comparación con los centros de referencia. MATERIAL Y METODOS: Estudio retrospectivo de los pacientes menores de 15 años sometidos a tiroidectomía ± disección ganglionar cervical por cirujanos pediátricos de bajo volumen (< 30 cirugías endocrinas cervicales/año) entre enero de 2010 y enero de 2020 en un hospital infantil. RESULTADOS: Se analizaron once pacientes sometidos a 12 procedimientos quirúrgicos (edad media 9,8 años, 63% niñas). Los nódulos tiroideos fueron la principal indicación quirúrgica (50%) y la prevalencia de mutaciones genéticas en la serie fue del 45%. Un paciente presentó hipocalcemia transitoria y hubo 2 casos de neuropraxia transitoria del nervio laríngeo recurrente (16,6%). No hubo complicaciones permanentes. El 66,6% de los informes anatomopatológicos mostraron malignidad. La estancia hospitalaria media fue de 2,35 días (rango 1,25-5) con una tasa global de complicaciones del 25%, similar a la reportada por centros de alto volumen. Después de un seguimiento medio de 4 años, ningún paciente ha presentado recidiva tumoral. CONCLUSIONES: Sugerimos que un cirujano infantil con experiencia en cirugía pediátrica general y neonatal, a pesar de no superar el umbral de alto volumen, adquiere las facultades para realizar la cirugía tiroidea pediátrica sin aumento de morbilidad y mortalidad. El manejo perioperatorio debe ser consensuado entre los diversos especialistas involucrados y protocolizado para mejorar los resultados.

Current status of precision medicine in pediatric oncology in Spain: a consensus report by the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

The study analyzes the current status of personalized medicine in pediatric oncology in Spain. It gathers national data on the tumor molecular studies and genomic sequencing carried out at diagnosis and at relapse, the centers that perform these studies, the technology used and the interpretation and clinical applicability of the results. Current challenges and future directions to achieve a coordinated national personalized medicine strategy in pediatric oncology are also discussed. Next generation sequencing-based (NGS) gene panels are the technology used in the majority of centers and financial limitations are the main reason for not incorporating these studies into routine care. Nowadays, the application of precision medicine in pediatric oncology is a reality in a great number of Spanish centers. However, its implementation is uneven and lacks standardization of protocols; therefore, national coordination to overcome the inequalities is required. Collaborative work within the Personalized Medicine Group of SEHOP is an adequate framework for encouraging a step forward in the effort to move precision medicine into the national healthcare system.

A phase I/II dose-escalation multi-center study to evaluate the safety of infusion of natural killer cells or memory T cells as adoptive therapy in coronavirus pneumonia and/or lymphopenia: RELEASE study protocol.

BACKGROUND: Moderate/severe cases of COVID-19 present a dysregulated immune system with T cell lymphopenia and a hyper-inflammatory state. This is a study protocol of an open-label, multi-center, double-arm, randomized, dose-finding phase I/II clinical trial to evaluate the safety, tolerability, alloreactivity, and efficacy of the administration of allogeneic memory T cells and natural killer (NK) cells in COVID-19 patients with lymphopenia and/or pneumonia. The aim of the study is to determine the safety and the efficacy of the recommended phase 2 dose (RP2D) of this treatment for patients with moderate/severe COVID-19. METHODS: In the phase I trial, 18 patients with COVID-19-related pneumonia and/or lymphopenia with no oxygen requirement or with an oxygen need of ≤ 2.5 liters per minute (lpm) in nasal cannula will be assigned to two arms, based on the biology of the donor and the patient. Treatment of arm A consists of the administration of escalating doses of memory T cells, plus standard of care (SoC). Treatment of arm B consists of the administration of escalating doses of NK cells, plus SoC. In the phase II trial, a total of 182 patients with COVID-19-related pneumonia and/or lymphopenia requiring or not oxygen supplementation but without mechanical ventilation will be allocated to arm A or B, considering HLA typing. Within each arm, they will be randomized in a 1:1 ratio. In arm A, patients will receive SoC or RP2D for memory T cells plus the SoC. In arm B, patients will receive SoC or RP2D for NK cells plus the SoC. DISCUSSION: We hypothesized that SARS-CoV-2-specific memory T-lymphocytes obtained from convalescent donors recovered from COVID-19 can be used as a passive cell immunotherapy to treat pneumonia and lymphopenia in moderate/severe patients. The lymphopenia induced by COVID-19 constitutes a therapeutic window that may facilitate donor engraftment and viral protection until recovery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04578210 . First Posted : October 8, 2020.

Phase I dose-escalation single centre clinical trial to evaluate the safety of infusion of memory T cells as adoptive therapy in COVID-19 (RELEASE).

BACKGROUND: Effective treatments are still needed to reduce the severity of symptoms, time of hospitalization, and mortality of COVID-19. SARS-CoV-2 specific memory T-lymphocytes obtained from convalescent donors recovered can be used as passive cell immunotherapy. METHODS: Between September and November 2020 a phase 1, dose-escalation, single centre clinical trial was conducted to evaluate the safety and feasibility of the infusion of CD45RA- memory T cells containing SARS-CoV-2 specific T cells as adoptive cell therapy against moderate/severe cases of COVID-19. Nine participants with pneumonia and/or lymphopenia and with at least one human leukocyte antigen (HLA) match with the donor were infused. The first three subjects received the lowest dose (1 × 105 cells/kg), the next three received the intermediate dose (5 × 105 cells/kg) and the last three received the highest dose (1 × 106 cells/kg) of CD45RA- memory T cells. Clinicaltrials.gov registration: NCT04578210. FINDINGS: All participants' clinical status measured by National Early Warning Score (NEWS) and 7-category point ordinal scales showed improvement six days after infusion. No serious adverse events were reported. Inflammatory parameters were stabilised post-infusion and the participants showed lymphocyte recovery two weeks after the procedure. Donor microchimerism was observed at least for three weeks after infusion in all patients. INTERPRETATION: This study provides preliminary evidence supporting the idea that treatment of COVID-19 patients with moderate/severe symptoms using convalescent CD45RA- memory T cells is feasible and safe. FUNDING: Clinical Trial supported by Spanish Clinical Research Network PT17/0017/0013. Co-funded by European Regional Development Fund/European Social Fund. CRIS CANCER Foundation Grant to AP-M and Agencia Valenciana de Innovación Grant AVI-GVA COVID-19-68 to BS.

Abdominal hernia repair using the Rives-Stoppa technique: an abdominal reconstruction. / Eventroplastia abdominal con técnica de Rives-Stoppa: reconstruyendo un abdomen.

INTRODUCTION: Retromuscular mesh hernia repair using Rives-Stoppa technique has demonstrated the best results when it comes to repairing large midline hernias. We present the first pediatric case successfully treated with this technique. CLINICAL CASE: This is the case of a 9-year-old male patient with hernia following urgent midline laparotomy. Basic repair principles included opening of the hernia sac and adhesiolysis, longitudinal incision on the posterior sheath of the rectus muscle and division of the retromuscular space, closure of the posterior sheath, placement of a mesh on this plane in the brand-new retromuscular space, and tension-free closure of the anterior musculo-aponeurotic flap, thus reconstructing the midline. No recurrences have been noted after a 2-year follow-up. DISCUSSION: Rives-Stoppa technique allows for a more anatomical layered reconstruction, which helps restore the anatomical and physiological properties of the abdominal wall. In our view, this could be a useful alternative for pediatric hernia treatment.

INTRODUCCION: La eventroplastia con malla retromuscular de Rives-Stoppa ha demostrado en adultos tener los mejores resultados en la reparación de las grandes eventraciones de la línea media. Presentamos el primer caso pediátrico tratado exitosamente con esta técnica. CASO CLINICO: Varón de 9 años con eventración tras laparotomía media urgente. Los principios básicos de la corrección fueron: apertura del saco herniario y adhesiolisis, incisión longitudinal sobre la vaina posterior del músculo recto y tallado del espacio retromuscular, cierre de la vaina posterior, colocación de una malla sobre este plano alojándola en el espacio retromuscular creado y cierre sin tensión del colgajo musculo-aponeurótico anterior, reconstruyendo así la línea media. No recidiva tras 2 años de seguimiento. COMENTARIOS: La técnica de Rives-Stoppa implica una reconstrucción por planos más anatómica que restaura las propiedades anatomofisiológicas de la pared abdominal. Consideramos que puede ser una alternativa útil en el tratamiento de las eventraciones pediátricas.

The paediatric cancer clinical research landscape in Spain: a 13-year multicentre experience of the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

PURPOSE: Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. METHODS: Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007-2013 and 2014-2020. RESULTS: Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2 months (IQR 0-6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. CONCLUSIONS: The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barriers to accessing new drugs for all ranges of age and cancer diseases remain. Additionally, opportunities to improve academic research are still required in Spain.

[Cranio-facial-cervical and subglottic hemangioma with respiratory symptoms. A therapeutic emergency].

We describe the case of a 41-day-old infant with a left craniofacial cervical and subglottic hemangioma with respira-tory symptoms. Although infantile hemangiomas are occasional benign vascular tumors that appear predominantly on the skin, 1-2% of patients may have airway lesions that can sometimes cause potentially life-threatening respiratory condi-tions. The decision was made to immediately commence treatment with propranolol, without waiting to complete the exten-sion and syndromic diagnoses. There was a positive clinical response and respiratory symptoms dissipated in twelve hours. Early treatment with beta-blockers is essential for children with hemangiomas whose location causes symptoms or significant functional changes: in some cases it may be a matter of urgency.

SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell Therapy.

Syndrome coronavirus 2 (SARS-CoV-2) pandemic is causing a second outbreak significantly delaying the hope for the virus' complete eradication. In the absence of effective vaccines, we need effective treatments with low adverse effects that can treat hospitalized patients with COVID-19 disease. In this study, we determined the existence of SARS-CoV-2-specific T cells within CD45RA- memory T cells in the blood of convalescent donors. Memory T cells can respond quickly to infection and provide long-term immune protection to reduce the severity of COVID-19 symptoms. Also, CD45RA- memory T cells confer protection from other pathogens encountered by the donors throughout their life. It is of vital importance to resolve other secondary infections that usually develop in patients hospitalized with COVID-19. We found SARS-CoV-2-specific memory T cells in all of the CD45RA- subsets (CD3+, CD4+, and CD8+) and in the central memory and effector memory subpopulations. The procedure for obtaining these cells is feasible, easy to implement for small-scale manufacture, quick and cost-effective, involves minimal manipulation, and has no GMP requirements. This biobank of specific SARS-CoV-2 memory T cells would be immediately available "off-the-shelf" to treat moderate/severe cases of COVID-19, thereby increasing the therapeutic options available for these patients.

Genetic predisposition to fetal and neonatal cancer.

BACKGROUND: Neonatal tumors represent an extremely rare and heterogeneous disease with an unknown etiology. Due to its early onset, it has been proposed that genetic factors could play a critical role; however, germline genetic analysis is not usually performed in neonatal cancer patients PATIENTS AND METHODS: To improve the identification of cancer genetic predisposition syndromes, we retrospectively review clinical characteristics in 45 patients with confirmed tumor diagnosis before 28 days of age, and we carried out germline genetic analysis in 20 patients using next-generation sequencing and directed sequencing. RESULTS: The genetic studies did not find any germline mutation except patients diagnosed with bilateral retinoblastoma who harbored RB1 germline mutations. CONCLUSIONS: Our results suggest that genetic factors have almost no higher impact in most neonatal tumors. However, since the heterogeneity of the tumors and the small sample size analyzed, we recommend complementary and centralized germline studies to discard the early onset as an additional criterion to take into account to improve the identification of cancer genetic predisposition syndromes in neonates.

Challenges in early phase clinical trials for childhood cancer during the COVID-19 pandemic: a report from the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

PURPOSE: The COVID-19 pandemic has forced healthcare stakeholders towards challenging decisions. We analyse the impact of the pandemic on the conduct of phase I-II trials for paediatric cancer during the first month of state of alarm in Spain. METHODS: A questionnaire was sent to all five ITCC-accredited Spanish Paediatric Oncology Early Phase Clinical Trial Units, including questions about impact on staff activities, recruitment, patient care, supply of investigational products, and legal aspects. RESULTS: All units suffered personnel shortages and difficulties in enrolling patients, treatment continuity, or performing trial assessments. Monitoring activity was frequently postponed (73%), and 49% of on-going trials interrupted recruitment. Only two patients could be recruited during this period (75% reduction in the expected rate). CONCLUSIONS: The COVID-19 crisis has significantly impacted clinical research practice and access to innovation for children with cancer. Structural and functional changes are under way to better cope with the expected future restrictions.

Cross-cutting view of current challenges in paediatric solid organ and haematopoietic stem cell transplantation in Europe: the European Reference Network TransplantChild.

The low prevalence of European paediatric transplanted patients and scarcity of resources and expertise led to the need for a multidisciplinary network able to improve the quality of life of paediatric patients and families requiring a solid organ or haematopoietic stem cell transplantation. The European Reference Network (ERN) TransplantChild is one of the 24 ERNs established in a European legal framework to improve the care of patients with rare diseases. ERN TransplantChild is the only ERN focused on both solid organ and haematopoietic stem cell paediatric transplantation, based on the understanding of paediatric transplantation as a complex and highly specialised process where specific complications appear regardless the organ involved, thus linking the skills and knowledge of different organ disciplines. Gathering European centres of expertise in paediatric transplantation will give access to a correct and timely diagnosis, share expertise and knowledge and collect a critical mass of patients and data that increases the speed and value of clinical research outcomes. Therefore, the ERN TransplantChild aims for a paediatric Pan-European, Pan-transplant approach.

[Impaction of button batteries in the esophagus: a potentially fatal surgical emergency in infancy].

With the recent popularization of button batteries, the incidence of cases of children who ingest them has risen. Unlike other foreign bodies, button batteries are more likely to develop severe complications due to the possibility of early injury to the tissues in direct contact with them. We present the case of a 22-month-old boy who ingested a button battery which subsequently became lodged in the cervical esophagus. The endoscopic attempt to remove the battery failed, requiring an open esophagotomy for its extraction. In the postoperative period, he presented an esophagocutaneous fistula that closed spontaneously, and an esophageal stricture that was treated successfully with endoscopic balloon dilations. We reviewed the literature analyzing the recommendations recently outlined and contrasted them with our own protocol for management of ingested foreign bodies. In addition, measures aimed at reducing the risk of button battery ingestion in small children are proposed to the electronics manufacturing industry.

[An infant with intestinal pneumatosis and pneumoperitoneum: the difficult decision not to intervene]. / Un lactante con neumatosis intestinal y neumoperitoneo: la difícil decisión de no intervenir.

Pneumoperitoneum in children may be due to causes that do not require urgent surgery (cardiopulmonary resuscitation manoeuvres, severe respiratory pathology or mechanical ventilation). Surgery in these cases could even worsen the prognosis. We present the case of a male infant, ex-preterm, with a history of necrotizing enterocolitis and ileal perforation at birth, requiring laparotomy and intestinal resection on two occasions and developing a secondary microcolon, due to disuse. At six months, after transitioning to full oral feeding, he presented abdominal distension with extensive intestinal pneumatosis and pneumoperitoneum on radiographs. His general appearance was good with normal intestinal transit and no peritonitis. The patient remained fasting with intravenous antibiotics, nasogastric decompression and parenteral nutrition. The evolution was favourable with oral feeding restarting on the seventh day of admission. The existence of pneumoperitoneum does not always require a laparotomy and global assessment of the patient by an interdisciplinary health team may avoid unnecessary aggressive treatments.

Haploidentical IL-15/41BBL activated and expanded natural killer cell infusion therapy after salvage chemotherapy in children with relapsed and refractory leukemia.

Primary refractory or relapsed pediatric leukemia yield significant morbidity and mortality, with long-term survival rates <40%. Here we present a post-hoc analysis assessing safety and efficacy of infusing activated and expanded Natural Killer cells (NKAE) from haploidentical donors in patients from 2 clinical trials. In total, 18 children, adolescents and young adults with relapse or refractory acute leukemia were treated with two cycles of rescue chemotherapy followed by fresh NKAE cells infusions and low doses of IL-2. The overall response rate, complete remission achievement at the end of the study, was 72% (13 of 18). We infused 52 NKAE cell products containing a median of 6.76 × 106 NK cells/kg (0.7-34.16) and 0.49 × 106 T cells/kg (0-11). All infusions were well tolerated with no graft versus host disease nor other serious adverse events. Among the 14 patients who completed treatment, 4 of them are alive and leukemia-free more than 750 days post-transplant. We conclude that infusion of fresh NKAE cell therapy is feasible and safe in heavily pretreated pediatric population, and should be further investigated in advanced-phase clinical trials as well as a consolidation therapy to decrease relapse in patients with high-risk leukemia. TRIALS REGISTRATION: Registered at www.clinicaltrials.gov as NCT01944982 and NCT02074657.

[Postural deformities of the skull. Advantages of protocolization in its treatment]. / Deformidades craneales posturales. Ventajas de la protocolización en su tratamiento.

INTRODUCTION: Since 2007, we have examined in our medical practice children with cranial deformities. The increasing demand and lack of professionals dedicated to it has forced us to assume the treatment of this disease. We present our experience. MATERIAL AND METHODS: Retrospective study of patients with cranial deformities treated from 2010 to 2015. We collected data as age at the first visit and at discharge, sequential measurements of the skull and cranial index, type of treatment prescribed (postural, orthosis or both) and consultation requested to other specialties. In the first stage (2010-2012), each surgeon prescribed the treatment he considered appropriate. Since November 2012 a protocol has been implemented, it includes guideline sheets for the surgeon and parents with information on postural therapy and graphs to record the measurements. RESULTS: We have treated 261 patients. Two were diagnosed with craniosynostosis. From the rest, only 151 possessed complete quantitative data and were included in the study with 105 men and 46 women and a mean age of 5.8 months (± 1.9 months). There were 23 pure brachycephaly, 126 mixed forms and 2 pure plagiocephaly. A significant disparity between observers' measurements was noticed. All patients underwent a protocolized postural treatment. In 36 patients who did not improve with postural treatment, cranial orthosis was prescribed with good response: 66.8% became mild forms. Those who maintained only postural treatment also improved to milder forms in 64.4%. CONCLUSIONS: The implementation of a protocol has enabled us to unify the care and follow-up of these patients. Cranial measurement techniques should be more precise and reproducible. Good postural treatment and empathy with the family reduce the use of orthosis in carefully selected cases.

INTRODUCCION: Desde 2007 hemos valorado en consulta a niños con deformidades craneales. La creciente demanda y la falta de profesionales dedicados nos obligaron a asumir el tratamiento de esta patología. Presentamos nuestra experiencia. MATERIAL Y METODOS: Estudio descriptivo retrospectivo de los enfermos con deformidades craneales atendidos desde 2010 a 2015. Recopilamos datos sobre edad en la primera visita y al alta, medidas secuenciales del cráneo, tipo de tratamiento prescrito (postural, ortesis o ambos) e interconsulta a otras especialidades. En la primera etapa (2010-2012), cada cirujano prescribía el tratamiento que consideraba oportuno. Desde noviembre de 2012 se implementó un protocolo que incluye una hoja de actuación para el cirujano y otra para los padres con información sobre medidas posturales y gráficas para anotar las mediciones. RESULTADOS: Hemos atendido a 261 pacientes afectos de deformidades craneales. Dos fueron diagnosticados de craneosinostosis. Del resto, solo 151 disponían de datos cuantitativos completos y se incluyeron en el estudio. Fueron 105 varones y 46 mujeres con edad media de 5,8 meses (± 1,9 meses). Veintitrés presentaban una braquicefalia pura, 126 formas mixtas y 2 presentaban plagiocefalia pura. Existía una importante disparidad entre observadores en la toma de medidas. Todos fueron sometidos a un tratamiento postural protocolizado. En 36 enfermos que no mejoraban se pautó ortesis craneal con buena respuesta: 66,8% pasaron a formas más leves. Los que se mantuvieron solo con tratamiento postural también mejoraron evolucionando a formas más leves en el 64,4%. CONCLUSIONES: La introducción de un protocolo asistencial nos ha permitido unificar la atención y el seguimiento de estos enfermos. Las técnicas de medición craneal deben ser más precisas y reproducibles. Un buen tratamiento postural y empatía con la familia reducen la utilización de ortesis a casos muy seleccionados.