Pediatría para la cooperación

La mayor parte de las niñas y niños del planeta nace y muere en lugares carentes de adecuada atención sanitaria, lejos de hospitales y universidades. Hemos querido fusionar el mundo académico, clínico y de la cooperación, sumando ciencia, voluntades e incertidumbres, con la intención de que de esta mezcla pudiera surgir una herramienta útil para quienes se acercan desde el ámbito de la sanidad a la cooperación infantil. Si el recurso más valioso de cada pueblo son las personas y la mayor riqueza es el conocimiento, contribuir a la formación en cuidados sanitarios de la infancia debiera ser la mejor de las inversiones

Addition of terlipressin to initial volume resuscitation in a pediatric model of hemorrhagic shock improves hemodynamics and cerebral perfusion

Hemorrhagic shock is one of the leading causes of mortality and morbidity in pediatric trauma. Current treatment based on volume resuscitation is associated to adverse effects, and it has been proposed that vasopressors may be used in the pharmacological management of trauma. Terlipressin has demonstrated its usefulness in other pediatric critical care scenarios and its long half-life allows its use as a bolus in an outpatient critical settings. The aim of this study was to analyze whether the addition of a dose of terlipressin to the initial volume expansion produces an improvement in hemodynamic and cerebral perfusion at early stages of hemorrhagic shock in an infant animal model. We conducted an experimental randomized animal study with 1-month old pigs. After 30 minutes of hypotension (mean arterial blood pressure [MAP]<45 mmHg) induced by the withdrawal of blood over 30 min, animals were randomized to receive either normal saline (NS) 30 mL/kg (n = 8) or a bolus of 20 mcg/kg of terlipressin plus 30 mL/kg of normal saline (TP) (n = 8). Global hemodynamic and cerebral monitoring parameters, brain damage markers and histology samples were compared. After controlled bleeding, significant decreases were observed in MAP, cardiac index (CI), central venous pressure, global end-diastolic volume index (GEDI), left cardiac output index, SvO(2), intracranial pressure, carotid blood flow, bispectral index (BIS), cerebral perfusion pressure (CPP) and increases in systemic vascular resistance index, heart rate and lactate. After treatment, MAP, GEDI, CI, CPP and BIS remained significantly higher in the TP group. The addition of a dose of terlipressin to initial fluid resuscitation was associated with hemodynamic improvement, intracranial pressure maintenance and better cerebral perfusion, which would mean protection from ischemic injury. Brain monitoring through BIS was able to detect changes caused by hemorrhagic shock and treatment.This work was partially supported by Basque Government Grant (GIU19/026) to VEM and Spanish Society of pediatric critical care (Ruza Grant 2017) to JG

Rescue treatment with terlipressin in children with refractory septic shock: a clinical study

INTRODUCTION: Refractory septic shock has dismal prognosis despite aggressive therapy. The purpose of the present study is to report the effects of terlipressin (TP) as a rescue treatment in children with catecholamine refractory hypotensive septic shock. METHODS: We prospectively registered the children with severe septic shock and hypotension resistant to standard intensive care, including a high dose of catecholamines, who received compassionate therapy with TP in nine pediatric intensive care units in Spain, over a 12-month period. The TP dose was 0.02 mg/kg every four hours. RESULTS: Sixteen children (age range, 1 month–13 years) were included. The cause of sepsis was meningococcal in eight cases, Staphylococcus aureus in two cases, and unknown in six cases. At inclusion the median (range) Pediatric Logistic Organ Dysfunction score was 23.5 (12–52) and the median (range) Pediatric Risk of Mortality score was 24.5 (16–43). All children had been treated with a combination of at least two catecholamines at high dose rates. TP treatment induced a rapid and sustained improvement in the mean arterial blood pressure that allowed reduction of the catecholamine infusion rate after one hour in 14 out of 16 patients. The mean (range) arterial blood pressure 30 minutes after TP administration increased from 50.5 (37–93) to 77 (42–100) mmHg (P < 0.05). The noradrenaline infusion rate 24 hours after TP treatment decreased from 2 (1–4) to 1 (0–2.5) µg/kg/min (P < 0.05). Seven patients survived to the sepsis episode. The causes of death were refractory shock in three cases, withdrawal of therapy in two cases, refractory arrhythmia in three cases, and multiorgan failure in one case. Four of the survivors had sequelae: major amputations (lower limbs and hands) in one case, minor amputations (finger) in two cases, and minor neurological deficit in one case. CONCLUSION: TP is an effective vasopressor agent that could be an alternative or complementary therapy in children with refractory vasodilatory septic shock. The addition of TP to high doses of catecholamines, however, can induce excessive vasoconstriction. Additional studies are needed to define the safety profile and the clinical effectiveness of TP in children with septic shock

Obesity Parameters, Physical Activity, And Physical Fitness are Correlated With Serum Dipeptidyl Peptidase IV Activity In A Healthy Population

Objective: To determine whether obesity, physical fitness, and physical activity parameters are associated with the enzymatic activity of serum dipeptidyl peptidase IV (sDPPIV) in a sample of healthy women and men. Design and methods: We have correlated parameters of obesity, physical fitness, and physical activity with sDPPIV activity in 374 healthy subjects (age: 60.7 +/- 6.9 years, body mass index: 26.1 +/- 4.1 kg/m(2)). Enzymatic activity was analyzed using spectrofluorimetry, body composition was assessed by impedanciometry, physical fitness data were obtained using the Senior Fitness Test, and physical activity data were collected by accelerometer. Pearson' s partial correlation analysis was applied to determine the relationship between DPPIV activity and the rest of parameters and significantly correlated variables were introduced into linear regression models to predict DPPIV. Results: Serum DPPIV activity was negatively associated with obesity parameters such as body mass (r = -0.112), body mass index (BMI) (r = -0.147), waist circumference (r = -0.164), waist-to-hip ratio (-0.104), and percentage of fat mass (r = -0.185). Serum DPPIV activity was positively associated with cardiovascular fitness (r = 0.138), total amount of physical activity (r = 0.153), and time spent doing light exercise (r = 0.184). Regression models revealed sex differences in enzyme activity with overall activity higher in women than in men (beta = 0.437, p < 0.001). Further, percent fat mass was an independent negative predictor of DPPIV activity (beta = -0.184, p = 0.001). Serum DPPIV activity was positively predicted based on the amount of time spent doing light physical activity (beta = 0.167, p = 0.001). Conclusion: Our results demonstrate that sDPPIV activity is positively associated with healthier parameters regarding fatness, fitness and physical activity.This work was supported by the Basque Government (GIC12/173: IT811-13) and the University of the Basque Country (UPV/EHU: PPG17/40)

Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients

Purpose: Prognostic and predictive biomarkers to cyclindependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA ( ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy. Experimental Design: Correlative blood samples were collected at baseline [cycle 1-day 1 (C1D1)] and prior to treatment [cycle 1-day 15 (C1D15)]. Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A prespecified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model. Results: 201 patients were profiled at baseline, with ctDNA detection associated with worse progression-free survival (PFS)/ overall survival (OS). Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n = 120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms. Conclusions: We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with hormone receptor-positive/HER2-negative metastatic breast cancer harboring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted

Diseño y puesta en marcha del curso MOOC: “Diversidad afectivo-sexual y por identidad de género en la Universidad”

Memoria ID-125. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2019-2020

Critically short telomeres and toxicity of chemotherapy in early breast cancer

Cumulative toxicity from weekly paclitaxel (myalgia, peripheral neuropathy, fatigue) compromises long-term administration. Preclinical data suggest that the burden of critically short telomeres ( 21.9% CSTs) had 2-fold higher number of neuropathy (P = 0.04) or fatigue (P = 0.019) episodes and >3-fold higher number of myalgia episodes (P = 0.005). The average telomere length was unrelated to the incidence of side effects.The percentage of CSTs, but not the average telomere size, is associated with weekly paclitaxel-derived toxicity.This work was supported by the Fondo de Investigación Sanitaria [FIS PI10/00288 and FIS PI13/00430]; AECC Scientific Foundation [Beca de Retorno-2010, to MQF]; Spanish Ministry of Economy and Competitiveness Projects [SAF2013-45111-R]; Madrid Regional Government Projects [S2010/BMD- 2303]; AXA Research Found; Fundación Botin; AVON Spain; and Boehringer-Ingelheim Spain.S

Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain

Background Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia. Methods A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared. Results Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5-11.8) vs 3.4 years (IQR 0.4-9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5-8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group. Conclusions MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients

Nuevas dimensiones de la docencia sobre Derecho y factor religioso: interdisciplinariedad y cooperación internacional

Depto. de Derecho Internacional, Eclesiástico y Filosofía del DerechoFac. de DerechoFALSEsubmitte

Incidencia y pronóstico del ictus minor y ataque isquémico transitorio de alto riesgo en Nordictus: estudio IMMINENT

[Abstract] Background. Our primary aim was to investigate the incidence of non-cardioembolic minor acute ischemic stroke (AIS) and high-risk transient ischemic attack (TIA) and to identify predictors of stroke recurrence/death and severe bleeding. We also evaluated the rates of TIA, major vascular events, therapeutic management and predictors of poor functional outcome at 3 months in these patients. Methods. We retrospectively reviewed data from all stroke patients evaluated at the emergency department of 19 hospitals belonging to the NORDICTUS stroke network between July and December 2019. Consecutive patients with non-cardioembolic minor AIS (NIHSS ≤5) and high-risk TIA (ABCD2 ≥6 or ipsilateral stenosis ≥50%) were included. We recorded clinical, neuroimaging and therapeutic variables. Follow-up was performed at 30 and 90 days. Functional prognosis was assessed with the modified Rankin scale score (mRS). Results. Of 8275 patients, 1679 (20%) fulfilled IMMINENT criteria (1524 AIS/155 TIA), resulting in a global incidence of 48/100,000 inhabitants per-year. Recurrent stroke/death occurred in 73 (4.3%) patients. Extracranial ipsilateral stenosis (>50%): HR 1.999 (95% CI: 1.115–3.585, p = 0.020) and lack of hyperacute cerebral arterial assessment: HR 1.631 (95% CI: 1.009–2.636, p = 0.046) were associated with recurrent stroke/death at 90 days. Intracranial stenosis was associated with poor prognosis (p = 0.044). Reperfusion therapy was given to 147 (9%) and urgent double antiplatelet therapy (DAPT) to 320 (21%) patients. Conclusion. Twenty percent of our stroke patients presented as non-cardioembolic high-risk TIA or minor AIS. Extracranial ipsilateral stenosis and lack of hyperacute cerebral arterial assessment were predictors of stroke recurrence/death; intracranial stenosis was associated with poor outcome. Despite current recommendations there was a low penetrance of DAPT.[Resumen] Introducción. Nuestro objetivo principal fue investigar la incidencia de ictus minor no cardioembólico y ataque isquémico transitorio (AIT) de alto riesgo, además de identificar predictores de recurrencia de ictus/muerte y sangrado grave. Evaluamos los porcentajes de AIT, eventos vasculares mayores, manejo terapéutico y predictores de mal pronóstico funcional. Métodos. Estudio retrospectivo de todos los pacientes con ictus evaluados en urgencias de 19 hospitales de la RED NORDICTUS entre julio-diciembre de 2019. Se incluyeron pacientes consecutivos con ictus minor no cardioembólico (National Institute of Health Stroke Scale [NIHSS] ≤ 5) y AIT de alto riesgo (ABCD2 ≥ 6 o estenosis ipsilateral ≥ 50%). Registramos variables clínicas, de neuroimagen y terapéuticas. Se realizó seguimiento a los 30 y 90 días. El pronóstico funcional se determinó mediante la escala de Rankin modificada (mRS). Resultados. De 8.275 pacientes, 1.679 (20%) cumplieron criterios del estudio IMMINENT (1.524 ictus/155 AIT), la incidencia global fue 48/100.000 h habitantes-año. Hubo recurrencias de ictus/muerte en 73 (4,3%) pacientes. La estenosis extracraneal ipsilateral (>50%): HR 1.999 (IC 95%: 1.115-3.585); p = 0,020 y la ausencia de estudio cerebrovascular hiperagudo: HR 1.631 (IC 95%: 1.009-2.636); p = 0.046, fueron predictores de ictus/muerte a 90 días. La estenosis intracraneal se asoció a mal pronóstico (p = 0,044). Se administró terapia de reperfusión a 147 (9%) y doble antiagregación a 320 (21%) pacientes. Conclusión. Un 20% de los pacientes se presentó como ictus minor o AIT de alto riesgo. La estenosis extracraneal ipsilateral y la ausencia de estudio neurovascular hiperagudo fueron predictores de ictus/muerte; la estenosis intracraneal se asoció con mal pronóstico. A pesar de las recomendaciones actuales hay baja penetrancia de doble antiagregación.This study was sponsored by AstraZeneca, funder had no involvement in the analysis or interpretation of the data, or the writing of the manuscript. MER-A was funded by the Instituto de Salud Carlos III (ISCIII) JR19/00020, co-funded by ERDF/ESF, “A way to make Europe”/“Investing in your future”). Investigators of this study belong to the RETICS-RICORS ICTUS financed by ISCIII (RD21/0006/0005-RD21/0006/0016-RD21/0006/0017-RD21/0006/0020-RD21/0006/0022).Instituto de Salud Carlos III; JR19/0002