Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression.

Colorectal cancer (CRC) remains one of the most commonly diagnosed and deadliest types of cancer worldwide. CRC displays a desmoplastic reaction (DR) that has been inversely associated with poor prognosis; less DR is associated with a better prognosis. This reaction generates excessive connective tissue, in which cancer-associated fibroblasts (CAFs) are critical cells that form a part of the tumor microenvironment. CAFs are directly involved in tumorigenesis through different mechanisms. However, their role in immunosuppression in CRC is not well understood, and the precise role of signal transducers and activators of transcription (STATs) in mediating CAF activity in CRC remains unclear. Among the myriad chemical and biological factors that affect CAFs, different cytokines mediate their function by activating STAT signaling pathways. Thus, the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors. Here, we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

Hyperuricemia: an unrecognized risk factor for kidney-related sequelae in children with hemolytic uremic syndrome.

BACKGROUND: Chronic kidney-related sequelae after STEC-HUS occur in 20-40% of patients. Hyperuricemia (HU) may cause acute and chronic toxicity involving the kidneys. We retrospectively assessed if there was an association between the presence of HU during the acute illness and that of kidney-related sequelae in children with STEC-HUS. METHODS: Children with STEC-HUS who had clinical and laboratory data at 2 years of follow-up were included in this case-control study. Univariate and multivariate analyses were performed between patients with (cases) or without (controls) kidney-related sequelae to identify factors associated with outcomes, including different measures of serum uric acid (sUA) (baseline level, peak, and duration of HU). HU was defined as sUA > 8 mg/dL. RESULTS: Of 86 patients included, 77.9% had HU. Patients with sequelae (n = 41) had a higher prevalence of HU (41/41 vs. 26/45, p < 0.01), higher baseline leukocyte count, serum creatinine (sCr), and sUA levels as well as lower sodium than controls. During hospitalization, cases also had higher sCr peak, sUA peak and duration of HU, requirement and duration of dialysis, extrarenal complications, and hypertension. By multivariate analysis, after adjusting for length of dialysis, only duration of HU (p = 0.0005; OR 1.7, 95% CI 1.27-2.36) remained as an independent predictor of sequelae, with a best cutoff of 5.5 days (AUC 0.95, specificity 80%, sensitivity 100%). CONCLUSIONS: The presence of HU is a common finding in children with STEC-HUS and its duration during the acute stage was associated with kidney-related sequelae, regardless of the duration of dialysis. A higher resolution version of the Graphical abstract is available as Supplementary Information.

Erythropoietin in children with hemolytic uremic syndrome: a pilot randomized controlled trial.

BACKGROUND: The efficacy of recombinant human erythropoietin (rHuEPO) in sparing red blood cell (RBC) transfusions in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) is uncertain. METHODS: We conducted a pilot randomized controlled open trial between December 2018 and January 2021. Children were randomized to the intervention (subcutaneous rHuEPO 50 U/kg three times weekly until discharge + RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability) or to the control arm (RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability). Primary outcome was the number of RBC transfusions received during hospitalization. Secondary outcomes were to explore whether baseline EPO levels were adequate to the degree of anemia, to correlate selected acute phase parameters with the number of RBC transfusions, and to assess possible adverse events. RESULTS: Twelve patients per arm were included; they were comparable at recruitment and throughout the disease course. Median number of RBC transfusions was similar between groups (1.5, p = 0.76). Most patients had baseline EPO levels adequate to the degree of anemia, which did not correlate with the number of transfusions (r = 0.19, p = 0.44). Conversely, baseline (r = 0.73, p = 0.032) and maximum lactic dehydrogenase levels (r = 0.78, p = 0.003), creatinine peak (r = 0.71, p = 0.03) and dialysis duration (r = 0.7, p = 0.04) correlated significantly with RBC requirements. No side effects were recorded. CONCLUSION: In children with STEC-HUS, the administration of rHuEPO did not reduce the number of RBC transfusions. Larger studies addressing higher doses and similar severity of kidney failure at rHuEPO initiation (e.g. at start of dialysis) are warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03776851. A higher resolution version of the Graphical abstract is available as Supplementary information.

Uncommon Presentation of Atypical Hemolytic Uremic Syndrome: A Case Report.

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal damage. Its presentation as nephrotic syndrome (NS) during first year of life is uncommon; we describe a child with clinical and laboratory findings of NS whose renal biopsy revealed thrombotic microangiopathy (TMA). A previously healthy 4-month-old male was admitted with severe dehydration, diarrhea and anuria. Laboratory results showed electrolyte disturbances, increased serum creatinine, anemia without schistocytes, thrombocytosis, normal lactic dehydrogenase (LDH) levels, hypoalbuminemia hypercholesterolemia and decreased C3 levels. After rehydration hematuria and massive proteinuria were also documented and an initial diagnosis of NS of the first year was established. Studies seeking for infectious agents were negative. During hospitalization he continued to be oligo-anuric needing dialysis and a renal biopsy was performed, which showed TMA findings. We here considered the diagnosis of aHUS and started plasma infusions as a bridge until starting eculizumab. After two infusions urine output improved leading to discontinuation dialysis. The diagnoses of STEC infection and thrombocytopenic thrombotic purpura were ruled out. Factor B, H, I and properdin levels were normal. Antibodies against CFH negative were negative. Screening for genes causative of aHUS detected a heterozygous variant in CFHR3 of uncertain significance. On day 20, treatment was switched to eculizumab, which induced a progressive remission of the NS. This case outlines the need for a heightened diagnosis suspicion of this already rare disease since early initiation of eculizumab therapy improves its prognosis.

Sensibilidad diagnóstica de la ampliación de los criterios hematológicos y renales para la definición de síndrome urémico hemolítico / Diagnostic sensitivity of extended renal and hematologic criteria to define hemolytic uremic syndrome

Introducción. La definición habitual de síndrome urémico hemolítico causado por Escherichia coli productora de toxina Shiga (STEC-SUH) se basa en la presencia de anemia, plaquetopenia y elevación de los niveles séricos de creatinina, acompañadas o no de proteinuria y/o hematuria. La definición estricta solo acepta como criterio renal el aumento de la creatinina sérica. La definición amplia mantiene criterios renales flexibles, aunque reemplaza la anemia por hemólisis y acepta la caída brusca del recuento plaquetario como indicador de consumo plaquetario. El objetivo de este estudio fue estimar y comparar la sensibilidad diagnóstica de dichas definiciones en pacientes con STEC-SUH como diagnóstico de egreso hospitalario. Población y métodos. Revisión retrospectiva de las historias clínicas de pacientes con SUH. Se calculó la sensibilidad y el valor predictivo positivo con sus intervalos de confianza 95 % (IC95 %) de las tres definiciones en función del diagnóstico de egreso de STEC-SUH (diagnóstico de referencia). Se utilizó la prueba de McNemar. Resultados. De 208 pacientes, 107 (51,4 %) fueron identificados con la definición estricta, 133 (63,9 %) con la habitual; y 199, con la amplia (95,6 %). La sensibilidad resultó menor para la definición estricta (51,4 %; IC 95 %: 44,8-58,3), intermedia para la habitual (63,9 %; IC 95 %: 56,9-70,4) y mayor para la amplia (95,6 %; IC 95 %: 91,6-97,8); (p < 0,001). Conclusión. Las distintas definiciones de STEC-SUH presentaron diferencias significativas en la sensibilidad diagnóstica. Dado que la definición amplia alcanzó una sensibilidad superior al 95 %, su uso generalizado podría disminuir la demora diagnóstica

Introduction. The usual definition of Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is based on the presence of anemia, thrombocytopenia, and elevated serum creatinine levels, with or without proteinuria and/or hematuria. The strict definition only considers elevated serum creatinine levels as a renal criterion. The extended definition maintains flexible renal criteria, although it replaces anemia with hemolysis and considers a sharp drop in platelet count as an indicator of platelet consumption. The objective of this study was to estimate and compare the diagnostic sensitivity of these definitions in patients with STEC-HUS as hospital discharge diagnosis. Population and methods. Retrospective review of medical records of HUS patients. Sensitivity and positive predictive value, with their corresponding 95 % confidence intervals (CIs), were estimated for the 3 definitions based on a discharge diagnosis of STEC-HUS (reference diagnosis). The McNemar test was used. Results. Out of 208 patients, 107 (51.4 %), 133 (63.9 %), and 199 (95.6 %) were identified with the strict, usual, and extended definition, respectively. Sensitivity was lower for the strict definition (51.4 %; 95 % CI: 44.8-58.3), intermediate for the usual definition (63.9 %; 95 % CI: 56.9-70.4), and higher for the extended one (95.6 %; 95 % CI: 91.6-97.8); (p < 0.001). Conclusion. The different STEC-HUS definitions showed significant differences in diagnostic sensitivity. The extended definition reached a sensitivity above 95 %, so its generalized use may help to reduce diagnostic delays

Nefropatía por inmunoglobulina M: características histopatológicas y clínicas. Serie de casos / Immunoglobulin M nephropathy: histopathological and clinical characteristics. Case series

La nefropatía por inmunoglobulina M (NIgM) es una glomerulopatía idiopática caracterizada por depósitos mesangiales globales y difusos de IgM. Se realizó un estudio retrospectivo de las características clínicas e histopatológicas de los pacientes con NIgM atendidos en nuestro servicio. De 241 biopsias renales, 21 correspondieron a NIgM (8,7 %). Se incluyeron 18 pacientes (14 de sexo femenino, mediana de edad: 3,08 años). Se excluyó a 1 paciente por enfermedad sistémica asociada y a 2 por seguimiento menor a 1 año. Catorce pacientes se manifestaron con síndrome nefrótico (SN) y 4 con proteinuria aislada o asociada a hematuria. En la microscopia óptica, 13 presentaron hiperplasia mesangial, y 5 esclerosis focal y segmentaria. De los pacientes con SN, 7 fueron corticorresistentes, 4 corticodependientes y 3 presentaban recaídas frecuentes. Todos los pacientes con SN y 1 con proteinuria-hematuria recibieron inmunosupresores; los 18 pacientes recibieron, además, antiproteinúricos. Luego de 5,2 años (2-17,5) de seguimiento, 6 pacientes evolucionaron a enfermedad renal crónica

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulopathy characterized by diffuse global mesangial deposits of IgM. We retrospectively studied the clinical and histopathological characteristics of the patients with IgMN seen in our service. Of 241 renal biopsies, 21 corresponded to IgMN (8.7 %). One patient was excluded due to associated systemic disease and 2 due to follow-up less than 1 year, 18 were included (14 girls, median age 3.08 years). Fourteen manifested with nephrotic syndrome (NS) and the remaining with proteinuria (isolated or associated with hematuria). On light microscopy, 13 had hyperplasia with mesangial expansion and 5 had focal and segmental sclerosis. Of the patients with NS, 7 were steroid-resistant, 4 steroid-dependent, and 3 frequent relapsers. All patients with NS and 1 with proteinuria-hematuria received immunosuppressants; the 18 patients also received antiproteinuric drugs. After 5.2 years (2-17.5) of follow-up, 6 patients developed chronic kidney disease.

Diagnostic sensitivity of extended renal and hematologic criteria to define hemolytic uremic syndrome. / Sensibilidad diagnóstica de la ampliación de los criterios hematológicos y renales para la definición de síndrome urémico hemolítico.

INTRODUCTION: The usual definition of Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is based on the presence of anemia, thrombocytopenia, and elevated serum creatinine levels, with or without proteinuria and/or hematuria. The strict definition only considers elevated serum creatinine levels as a renal criterion. The extended definition maintains flexible renal criteria, although it replaces anemia with hemolysis and considers a sharp drop in platelet count as an indicator of platelet consumption. The objective of this study was to estimate and compare the diagnostic sensitivity of these definitions in patients with STEC-HUS as hospital discharge diagnosis. POPULATION AND METHODS: Retrospective review of medical records of HUS patients. Sensitivity and positive predictive value, with their corresponding 95% confidence intervals (CIs), were estimated for the 3 definitions based on a discharge diagnosis of STEC-HUS (reference diagnosis). The McNemar test was used. RESULTS: Out of 208 patients, 107 (51.4%), 133 (63.9%), and 199 (95.6%) were identified with the strict, usual, and extended definition, respectively. Sensitivity was lower for the strict definition (51.4%; 95% CI: 44.8-58.3), intermediate for the usual definition (63.9%; 95% CI: 56.9-70.4), and higher for the extended one (95.6%; 95% CI: 91.6-97.8); (p< 0.001). CONCLUSION: The different STEC-HUS definitions showed significant differences in diagnostic sensitivity. The extended definition reached a sensitivity above 95%, so its generalized use may help to reduce diagnostic delays.

Introducción. La definición habitual de síndrome urémico hemolítico causado por Escherichia coli productora de toxina Shiga (STEC-SUH) se basa en la presencia de anemia, plaquetopenia y elevación de los niveles séricos de creatinina, acompañadas o no de proteinuria y/o hematuria. La definición estricta solo acepta como criterio renal el aumento de la creatinina sérica. La definición amplia mantiene criterios renales flexibles, aunque reemplaza la anemia por hemólisis y acepta la caída brusca del recuento plaquetario como indicador de consumo plaquetario. El objetivo de este estudio fue estimar y comparar la sensibilidad diagnóstica de dichas definiciones en pacientes con STECSUH como diagnóstico de egreso hospitalario. Población y métodos. Revisión retrospectiva de las historias clínicas de pacientes con SUH. Se calculó la sensibilidad y el valor predictivo positivo con sus intervalos de confianza 95% (IC95%) de las tres definiciones en función del diagnóstico de egreso de STEC-SUH (diagnóstico de referencia). Se utilizó la prueba de McNemar. Resultados. De 208 pacientes, 107 (51,4%) fueron identificados con la definición estricta, 133 (63,9%) con la habitual; y 199, con la amplia (95,6%). La sensibilidad resultó menor para la definición estricta (51,4%; IC 95%: 44,8-58,3), intermedia para la habitual (63,9%; IC 95%: 56,9- 70,4) y mayor para la amplia (95,6%; IC 95%: 91,6-97,8); (p< 0,001). Conclusión. Las distintas definiciones de STECSUH presentaron diferencias significativas en la sensibilidad diagnóstica. Dado que la definición amplia alcanzó una sensibilidad superior al 95%, su uso generalizado podría disminuir la demora diagnóstica.

[Immunoglobulin M nephropathy: histopathological and clinical characteristics. Case series]. / Nefropatía por inmunoglobulina M: características histopatológicas y clínicas. Serie de casos.

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulopathy characterized by diffuse global mesangial deposits of IgM. We retrospectively studied the clinical and histopathological characteristics of the patients with IgMN seen in our service. Of 241 renal biopsies, 21 corresponded to IgMN (8.7 %). One patient was excluded due to associated systemic disease and 2 due to follow-up less than 1 year, 18 were included (14 girls, median age 3.08 years). Fourteen manifested with nephrotic syndrome (NS) and the remaining with proteinuria (isolated or associated with hematuria). On Nefropatía por inmunoglobulina M: características histopatológicas y clínicas. Serie de casos Immunoglobulin M nephropathy: histopathological and clinical characteristics. Case series light microscopy, 13 had hyperplasia with mesangial expansion and 5 had focal and segmental sclerosis. Of the patients with NS, 7 were steroid-resistant, 4 steroid-dependent, and 3 frequent relapsers. All patients with NS and 1 with proteinuria-hematuria received immunosuppressants; the 18 patients also received antiproteinuric drugs. After 5.2 years (2-17.5) of follow-up, 6 patients developed chronic kidney disease.

La nefropatía por inmunoglobulina M (NIgM) es una glomerulopatía idiopática caracterizada por depósitos mesangiales globales y difusos de IgM. Se realizó un estudio retrospectivo de las características clínicas e histopatológicas de los pacientes con NIgM atendidos en nuestro servicio. De 241 biopsias renales, 21 correspondieron a NIgM (8,7 %). Se incluyeron 18 pacientes (14 de sexo femenino, mediana de edad: 3,08 años). Se excluyó a 1 paciente por enfermedad sistémica asociada y a 2 por seguimiento menor a 1 año. Catorce pacientes se manifestaron con síndrome nefrótico (SN) y 4 con proteinuria aislada o asociada a hematuria. En la microscopia óptica, 13 presentaron hiperplasia mesangial, y 5 esclerosis focal y segmentaria. De los pacientes con SN, 7 fueron corticorresistentes, 4 corticodependientes y 3 presentaban recaídas frecuentes. Todos los pacientes con SN y 1 con proteinuria-hematuria recibieron inmunosupresores; los 18 pacientes recibieron, además, antiproteinúricos. Luego de 5,2 años (2-17,5) de seguimiento, 6 pacientes evolucionaron a enfermedad renal crónica.

Hemolytic uremic syndrome due to Shiga toxin­producing Escherichia coli and hypocomplementemia with favorable response to eculizumab: a case report / [Síndrome urémico hemolítico por Escherichia Coli e hipocomplementemia con respuesta favorable a eculizumab: comunicación de un caso]

Introduction: Neurologic involvement in hemolytic uremic syndrome related to Shiga toxin­producing Escherichia coli (STEC-HUS) is the main cause of death. In last years has been demonstrated that activation of complement alternative pathway also contributes to organ damage. This finding led to the recognition of decreased C3 levels at admission as a marker of poor prognosis as well as the evaluation of the use of eculizumab in cases with neurologic compromise. Objective: to report a patient with STEC-HUS and hypocomplementemia with neurological involvement treated with eculizumab. Clinical case: A 17-month-old male was admitted due to seizures and anuria for last 24 h with a history of 48 h of bloody diarrhea. He presented a laboratory profile compatible with STEC-HUS and severe hyponatremia, results of brain tomography were normal. Also there was complement activation: C3 73 mg/dl (normal > 90 mg/dL) and C5b-9 778.9 ng/ml (normal 135.8-385.3 ng/ml). Initial treatment includes normal saline solution and anticonvulsants drugs, sodium correction and peritoneal dialysis. On third day of hospitalization, because of progression of the neurologic involvement a dose of eculizumab (300 mg) was given, showing at 24 h a markedly neurologic improvement along with and increasing platelet count and a descending lactic dehydrogenase levels. He was discharged after 14 days in a good condition. Later a STEC O157:H7 infection was confirmed and he also normalized the C3 level. Conclusion: This case shows that decreased C3 level at admission was associated to neurologic involvement and suggests that eculizumab might be a favorable therapeutic option.

Introducción: En compromiso neurológico en el síndrome urémico hemolítico producido por Eschericha coli productor de Shiga toxina (STEC-SUH) es la primera causa de mortalidad. En los últimos años se ha demostrado que también contribuye al daño de órgano la activación de la vía alterna del complemento. Este hallazgo dio lugar al reconocimiento del descenso de C3 como marcador de mal pronóstico así como a la evaluación del uso de eculizumab ante compromiso neurológico severo. Objetivo: Comunicar un paciente con STEC-SUH e hipocomplementemia con compromiso neurológico tratado con eculizumab. Caso clínico: Varón de 17 meses que ingresa por síndrome convulsivo y 24 horas de anuria con antecedente de diarrea con sangre de 48 horas de evolución. Presentaba al ingreso laboratorio compatible con STEC-HUS e hiponatremia severa, con tomografía de cerebro normal. Además presentaba activación del complemento: C3 73 mg/dl (normal > 90 mg/dL) y C5b-9 778,9 ng/ml (normal 135,8-385,3 ng/ml). Se administró solución fisiológica y anticonvulsivantes, se corrigió la natremia y comenzó diálisis peritoneal. Al tercer día, por progresión del compromiso neurológico, se administró eculizumab (300 mg) experimentando una notable recuperación neurológica a las 24 horas junto a aumento de plaquetas y descenso de láctico deshidrogenasa. El paciente fue dado de alta luego de 14 días en buen estado general. Posteriormente se confirmó aislamiento de STEC O157:H7 y normalización de C3. Conclusión: este caso demuestra que el descenso de C3 al ingreso se asoció con daño neurológico y sugiere que la administración de eculizumab podría ser una alternativa terapéutica favorable.

Prodromal Phase of Hemolytic Uremic Syndrome Related to Shiga Toxin-Producing Escherichia coli: The Wasted Time.

OBJECTIVES: This study aimed to evaluate practice patterns during prodromal phase of hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS). METHODS: Trajectories of children from first symptoms until STEC-HUS admitted consecutively at our center (period 2000-2017) were retrospectively reviewed. Early recommended practices include identification of STEC infections, antibiotics and antiperistaltic avoidance, and administration of anticipatory intravenous fluids; therefore, implementation and changes over time (before and after 2011) of such interventions were assessed. In addition, early management was correlated with acute disease outcomes. RESULTS: Of 172 patients, 98 (57%) had early consults, 75 of them visit the pediatric emergency department. Those seen with watery diarrhea (n = 74) were managed as outpatients, whereas 27 of the 45 assisted with bloody diarrhea were hospitalized for diagnosis other than STEC-HUS. Stool cultures were performed in 13.4% (23/172), 18% (31/172) received antibiotics, and 12.8% (22/172) received endovenous fluids; none received antiperistaltic agents. Shiga toxin-producing E. coli infection was proven in 4% (7/172) before HUS. Rate of cultured patients and treated with intravenous fluids remained unchanged over time (P = 0.13 and P = 0.48, respectively), whereas antibiotic prescription decreased from 42.8% to 16.6% (P = 0.005). Main acute outcomes (need for dialysis, pancreatic compromise, central nervous system involvement, and death) were similar (P > 0.05) regardless of whether they received antibiotics or intravenous fluids. CONCLUSIONS: During the diarrheal phase, 57% of patients consulted; three-quarters of them consulted to the pediatric emergency department. Shiga toxin-producing E. coli detection was poor, antibiotic use remained high, and anticipatory volume expansion was underused. These findings outline the critical need to improve the early management of STEC-HUS.

Prevalencia de Hipertensión Arterial en una unidad de cuidados intensivos neonatales / Prevalence of Arterial Hypertension in a neonatal intensive care unit

INTRODUCCIÓN: La prevalencia de hipertensión arterial neonatal en las unidades de cuidados intensivos neonatales (UCIN) varía entre el 3 y el 9%, sin embargo, no existe información actualizada de Latinoamérica. OBJETIVO: Estimar la prevalencia de hipertensión arterial y evaluar su asociación con causas previa mente relacionadas con esta condición. PACIENTES Y MÉTODO: Estudio transversal que incluyó a todos los niños internados en una UCIN durante un año, excluidos aquellos trasladados a cirugía cardio vascular. Se registraron variables maternas y neonatales, hipertensión arterial materna, vía de parto, edad gestacional, edad, sexo, peso de nacimiento, Apgar, antecedente de maduración pulmonar con corticoides y cateterismo de vasos umbilicales. Se consignó motivo de ingreso a UCIN, medicamen tos y complicaciones durante la hospitalización. La tensión arterial se registró con oscilómetro au tomatizado considerando hipertensión arterial según tablas para edad gestacional. La prevalencia se expresó como porcentaje (intervalo de confianza 95%, IC95%). La estadística descriptiva se presenta como mediana (rango) o frecuencia de presentación (porcentajes) y se buscó asociación con el Test de Wilcoxon, Chi2 o Fisher según correspondiera (p < 0,05). RESULTADOS: Se reclutaron 169 pacientes (60% sexo masculino). Edad gestacional: 38 semanas (rango 26-42), 38% prematuros. Peso 3.000 g (rango 545-4.950), 32% bajo peso. Ocho pacientes presentaron hipertensión arterial (prevalencia 4,7%, IC95% 2,4-9). La presencia de hipertensión arterial se asoció con prematurez (p = 0,0003), bajo peso (p = 0,01), maduración pulmonar con corticoides (p = 0,002), cateterismo umbilical (p = 0,03), uso de ≥ 2 drogas nefrotóxicas (p = 0,02), tratamiento con cafeína (p = 0,0001), injuria renal aguda (p = 0,02) e hipertensión intracraneal (p = 0,04). Solo un paciente requirió medicación antihiper- tensiva y en todos los casos se normalizó durante el seguimiento. CONCLUSIÓN: La prevalencia de hipertensión arterial neonatal fue de 4,7% y en todos los casos se presentó en niños prematuros con factores previamente reconocidos como asociados a esta condición.

INTRODUCTION: The prevalence of neonatal hypertension in neonatal intensive care units (NICU) ranges between 3 and 9%. However, there is no current data on Latin America. Objective: To estimate the prevalence of neonatal hypertension and to assess its association with causes previously related to this condi tion. PATIENTS AND METHOD: cross-sectional study. All patients admitted to the NICU during one year were included, excluding those transferred to the cardiovascular NICU. The following maternal and neonatal variables were registered: maternal arterial hypertension, type of delivery, gestational age, age, sex, birth weight, Apgar score, history of pulmonary maturation with corticosteroids, and umbilical vessel catheterization as well as the reason for admission to the NICU, medications, and complications during hospitalization. Blood pressure was measured with an automated oscillometric device, defining neonatal hypertension according to standards in gestational age. Prevalence was ex pressed as percentage (confidence interval 95%, CI95%). Descriptive data were reported as median (range) and frequency of presentation (percentage). Finally, we used the Wilcoxon, Chi2 o Fisher exact test to identify factors related to NH as applicable (p < 0.05). RESULTS: 169 patients were in cluded (60% males). Gestational age was 38 weeks (range 26-42 weeks), 38% were preterm. Birth weight was 3000 g (range 545-4950 g) and 32% presented low birth weight. Eight patients presented hypertension during hospitalization (4.7% prevalence, CI95% 2.4-9). The presence of hypertension was associated with prematurity (p = 0.0003), low birth weight (p = 0.01), prenatal corticosteroid treatment (p = 0.002), umbilical catheterization (p = 0.03), administration of ὅ 2 nephrotoxic drugs (p = 0.02), caffeine treatment (p = 0.0001), acute kidney injury (p = 0.02), and intracranial hyper tension (p = 0.04). Only one patient required antihypertensive pharmacologic treatment and in all cases, hypertension was resolved during follow-up. CONCLUSION: Prevalence of neonatal hypertension in our NICU was 4.7% and in all cases occurred in preterm newborns with previously recognized factors associated with this condition.

Rasburicase in hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli: a report of nine cases.

BACKGROUND: Hyperuricemia might induce additional renal damage in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS). A few case reports have shown rasburicase to be effective in decreasing serum uric acid (UA) and improving renal function. However, there is only one report on the use of rasburicase in a child with STEC-HUS, which shows satisfactory results. We describe here the safety and efficacy of rasburicase in nine additional cases. CASE-DIAGNOSIS/TREATMENT: Data from 9 children (5 females, median age 2 years) who received rasburicase were reviewed. At admission, 6 were dehydrated and 3 euvolemic. Dehydrated patients received saline solution and afterwards, as well as for those initially euvolemic, we aimed to keep a neutral fluid balance. Despite this, urine output did not increase. Baseline creatinine was 3.35 mg/dL (1.47-9.1) and UA 11.4 mg/dL (8.3-19.2). A single dose of rasburicase (0.2 mg/kg) was given 6-8 h after admission, which reduced UA levels to 1.8 mg/dL (0.3-5, p = 0.009) on the next day. However, renal parameters worsen and dialysis had to be initiated. Then, while still on dialysis, a UA rebound occurred in all cases reaching a peak of 8.9 mg/dL (4.5-13.8). Just after a steady increase in urine output, a sustained decline in UA levels concomitantly occurred with an improvement in renal function. At discharge, all patients reached normal UA levels. No side effects were recorded. CONCLUSIONS: Administration of rasburicase in children with STEC-HUS was safe but failed to provide any significant benefit despite fall in serum UA levels.

[Prevalence of Arterial Hypertension in a neonatal intensive care unit]. / Prevalencia de Hipertensión Arterial en una unidad de cuidados intensivos neonatales.

INTRODUCTION: The prevalence of neonatal hypertension in neonatal intensive care units (NICU) ranges between 3 and 9%. However, there is no current data on Latin America. OBJECTIVE: To estimate the prevalence of neonatal hypertension and to assess its association with causes previously related to this condi tion. PATIENTS AND METHOD: cross-sectional study. All patients admitted to the NICU during one year were included, excluding those transferred to the cardiovascular NICU. The following maternal and neonatal variables were registered: maternal arterial hypertension, type of delivery, gestational age, age, sex, birth weight, Apgar score, history of pulmonary maturation with corticosteroids, and umbilical vessel catheterization as well as the reason for admission to the NICU, medications, and complications during hospitalization. Blood pressure was measured with an automated oscillometric device, defining neonatal hypertension according to standards in gestational age. Prevalence was ex pressed as percentage (confidence interval 95%, CI95%). Descriptive data were reported as median (range) and frequency of presentation (percentage). Finally, we used the Wilcoxon, Chi2 o Fisher exact test to identify factors related to NH as applicable (p < 0.05). RESULTS: 169 patients were in cluded (60% males). Gestational age was 38 weeks (range 26-42 weeks), 38% were preterm. Birth weight was 3000 g (range 545-4950 g) and 32% presented low birth weight. Eight patients presented hypertension during hospitalization (4.7% prevalence, CI95% 2.4-9). The presence of hypertension was associated with prematurity (p = 0.0003), low birth weight (p = 0.01), prenatal corticosteroid treatment (p = 0.002), umbilical catheterization (p = 0.03), administration of ὅ 2 nephrotoxic drugs (p = 0.02), caffeine treatment (p = 0.0001), acute kidney injury (p = 0.02), and intracranial hyper tension (p = 0.04). Only one patient required antihypertensive pharmacologic treatment and in all cases, hypertension was resolved during follow-up. CONCLUSION: Prevalence of neonatal hypertension in our NICU was 4.7% and in all cases occurred in preterm newborns with previously recognized factors associated with this condition.

Correction to: C3 levels and acute outcomes in Shiga toxin-related hemolytic uremic syndrome.

Due to an unfortunate error during the processing of the article, the spelling of the second author name was incorrect.

C3 levels and acute outcomes in Shiga toxin-related hemolytic uremic syndrome.

BACKGROUND: The correlation between complement activation and severity of hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) has been examined in few studies, with conflicting results. We investigated whether C3 levels on admission are associated with worse acute outcomes. METHODS: Demographic, clinical, and laboratory variables were compared between dialyzed and non-dialyzed patients and between those with or without extrarenal complications. Univariate and multivariate analyses were performed; odds ratio (OR) and 95% confidence interval (95%CI) were calculated. C3 concentrations were correlated with dialysis length (Spearman test) and ROC curves with area under the curves (AUC) were calculated to identify C3 concentrations able to discriminate patients with dialysis requirements and complicated course. RESULTS: Among 49 children, 33 had normal and 16 had decreased C3 concentrations. Higher hemoglobin, lactic dehydrogenase, urea and creatinine and lower albumin, sodium, and C3 and C4 concentrations at admission were associated with dialysis requirement; only creatinine remained significant (p = 0.03, OR 2.1, 95%CI 1.34-2.7) by multivariate analysis. Patients with a complicated course presented higher leukocyte count, hemoglobin and lactic dehydrogenase and lower albumin, sodium, and C3 and C4. In the multivariate analysis, leukocyte count (p = 0.02, OR 2.6, 95%CI 1.4-4.3) and C3 concentration (p = 0.039, OR 1.7, 95%CI 1.1-2.73) were independently associated with a complicated disease. C3 levels correlated with dialysis length (r = - 0.42, p = 0.002); nevertheless, they were unable to discriminate dialysis requirement (AUC = 0.25, 95%CI 0.11-0.38) and extrarenal complications (AUC = 0.24, 95%CI 0.11-0.4). CONCLUSIONS: Our study suggests that decreased C3 levels at admission are associated with a more complicated STEC-HUS episode.

Impacto del componente hiperclorémico de la acidosis metabólica en el estado de hidratación y en el tratamiento de la cetoacidosis diabética / Impact of the hyperchloremic component of metabolic acidosis on the patient's hydration status and the treatment of diabetic ketoacidosis

Introducción. La cetoacidosis diabética (CAD) se caracteriza por acidosis metabólica (AM) con anión restante (AR) elevado, aunque, ocasionalmente, puede presentar hipercloremia. Se postuló que la presencia de hipercloremia inicial podría reflejar un mejor estado de hidratación; sin embargo, su prevalencia y su impacto en el tratamiento de la CAD se desconoce. Objetivos. Determinar la prevalencia de AM con componente hiperclorémico previo al inicio del tratamiento y evaluar si su presencia se asocia con mejor estado de hidratación y con menor tiempo de salida de la CAD, en comparación con los pacientes con AR elevado exclusivo. Pacientes y métodos. Se agruparon los pacientes internados con CAD (período entre enero de 2014 y junio de 2016) según presentaran, al ingresar, AM con AR elevado exclusivo o con hipercloremia y se compararon sus variables clínicas, de laboratorio y la respuesta al tratamiento. Resultados. Se incluyeron 40 pacientes -amp;#91;17 varones, mediana de edad: 14,5 años (2,4-18)-amp;#93;, 22 con AM con componente hiperclorémico (prevalencia de 55%) y 18 con AR elevado exclusivo. La presencia de hipercloremia no se asoció con mejor estado de hidratación (porcentaje de déficit de peso en ambos grupos: 4,9%; p= 0,81) ni con una respuesta terapéutica más rápida (con componente hiperclorémico: 9,5 horas; con AR elevado exclusivo: 11 horas; p= 0,64). Conclusiones. En niños con CAD, la prevalencia de AM con componente hiperclorémico fue del 55% y no se asoció con un mejor estado de hidratación ni con una salida más temprana de la descompensación metabólica.

Introduction. Diabetic ketoacidosis (DKA) is characterized by metabolic acidosis (MA) with a high anion gap (AG), although, occasionally, it can present with hyperchloremia. It has been postulated that the early presence of hyperchloremia could reflect a better hydration status; however, its prevalence and impact on DKA treatment remain unknown. Objectives. To determine the prevalence of the hyperchloremic component in MA prior to treatment and to assess whether it is associated with a better hydration status and a shorter recovery time from DKA compared to patients with high AG only. Patients and Methods. Patients hospitalized with DKA (between January 2014 and June 2016) were grouped according to whether they were admitted with MA with high AG only. or with hyperchloremia, and clinical and laboratory outcome measures and response to treatment were compared. Results. Forty patients (17 males, median age: 14.5 years -amp;#91;2.4-18-amp;#93;) were included; 22 with hyperchloremic metabolic acidosis (prevalence of 55%) and 18 with metabolic acidosis with high AG only. The presence of hyperchloremia was not associated with a better hydration status (weight loss percentage in both groups: 4.9%; p= 0.81) nor with a faster treatment response (MA with a hyperchloremic component: 9.5 hours; MA with high AG only: 11 hours; p= 0.64). Conclusions. The prevalence of MA with a hyperchloremic component among children with DKA was 55% and was not associated with a better hydration status nor with a faster recovery from the metabolic decompensation.

Impact of the hyperchloremic component of metabolic acidosis on the patient's hydration status and the treatment of diabetic ketoacidosis. / Impacto del componente hiperclorémico de la acidosis metabólica en el estado de hidratación y en el tratamiento de la cetoacidosis diabética.

INTRODUCTION: Diabetic ketoacidosis (DKA) is characterized by metabolic acidosis (MA) with a high anion gap (AG), although, occasionally, it can present with hyperchloremia. It has been postulated that the early presence of hyperchloremia could reflect a better hydration status; however, its prevalence and impact on DKA treatment remain unknown. determine the prevalence of the hyperchloremic component in MA prior to treatment and to assess whether it is associated with a better hydration status and a shorter recovery time from DKA compared to patients with high AG only. Patients and Methods. Patients hospitalized with DKA (between January 2014 and June 2016) were grouped according to whether they were admitted with MA with high AG only. or with hyperchloremia, and clinical and laboratory outcome measures and response to treatment were compared. RESULTS: Forty patients (17 males, median age: 14.5 years [2.4-18]) were included; 22 with hyperchloremic metabolic acidosis (prevalence of 55%) and 18 with metabolic acidosis with high AG only. The presence of hyperchloremia was not associated with a better hydration status (weight loss percentage in both groups: 4.9%; p= 0.81) nor with a faster treatment response (MA with a hyperchloremic component: 9.5 hours; MA with high AG only: 11 hours; p= 0.64). CONCLUSIONS: The prevalence of MA with a hyperchloremic component among children with DKA was 55% and was not associated with a better hydration status nor with a faster recovery from the metabolic decompensation.

Introducción. La cetoacidosis diabética (CAD) se caracteriza por acidosis metabólica (AM) con anión restante (AR) elevado, aunque, ocasionalmente, puede presentar hipercloremia. Se postuló que la presencia de hipercloremia inicial podría reflejar un mejor estado de hidratación; sin embargo, su prevalencia y su impacto en el tratamiento de la CAD se desconoce. Objetivos. Determinar la prevalencia de AM con componente hiperclorémico previo al inicio del tratamiento y evaluar si su presencia se asocia con mejor estado de hidratación y con menor tiempo de salida de la CAD, en comparación con los pacientes con AR elevado exclusivo. Pacientes y métodos. Se agruparon los pacientes internados con CAD (período entre enero de 2014 y junio de 2016) según presentaran, al ingresar, AM con AR elevado exclusivo o con hipercloremia y se compararon sus variables clínicas, de laboratorio y la respuesta al tratamiento. Resultados. Se incluyeron 40 pacientes [17 varones, mediana de edad: 14,5 años (2,4-18)], 22 con AM con componente hiperclorémico (prevalencia de 55%) y 18 con AR elevado exclusivo. La presencia de hipercloremia no se asoció con mejor estado de hidratación (porcentaje de déficit de peso en ambos grupos: 4,9%; p= 0,81) ni con una respuesta terapéutica más rápida (con componente hiperclorémico: 9,5 horas; con AR elevado exclusivo: 11 horas; p= 0,64). Conclusiones. En niños con CAD, la prevalencia de AM con componente hiperclorémico fue del 55% y no se asoció con un mejor estado de hidratación ni con una salida más temprana de la descompensación metabólica.

Blood urea nitrogen to serum creatinine ratio as a prognostic factor in diarrhea-associated hemolytic uremic syndrome: a validation study.

Identifying those children with complicated forms of diarrhea-associated hemolytic uremic syndrome (D+HUS) on admission can optimize their management. Recently, the blood urea nitrogen to serum creatinine ratio (BCR) at admission has been proposed as a novel and accurate predictor of complicated clinical outcome in D+HUS; therefore, we performed this retrospective study aimed to validate such observation in a larger series of patients. A complicated course was defined as developing one or more of the following: severe neurological or bowel injury, pancreatitis, cardiac or pulmonary involvement, hemodynamic instability, hemorrhage, and death. Data from 161 children were reviewed, 50 of them with a complicated disease including five deaths. Those with worse evolution presented a lower admission BCR than those with good outcome (22.5 vs. 30.8; p = 0.005). BCR at admission showed a limited ability to identify children at risk of a complicated course, with an AUC of 0.63 (95% CI 0.58-0.71) and an optimal cutoff point of ≤ 26.7, which achieves a sensitivity of 70% (95% CI 55.2-81.7) and a specificity of 56.7% (95% CI 47-66). CONCLUSION: In this validation study, the BCR at admission provided a limited value to predict severe forms of D+HUS. What is Known: • BCR at admission has been proposed as an accurate predictor of complicated clinical course in children with D+HUS. What is New: • In a larger series of children with D+HUS, we were unable to confirm the usefulness of the admission BCR to early identify those at risk of complicated forms of the disease. • Further research is warranted to improve the optimal detection of these high-risk patients.

Diagnosis of vesicoureteral reflux according to the 1999 and 2011 guidelines of the Subcommittee on Urinary Tract Infection of the American Academy of Pediatrics.

INTRODUCTION: In 1999, the American Academy of Pediatrics (AAP) recommended perform a renal ultrasonography and avoiding cystourethrography to all infants between 2 and 24 months of age after their first urinary tract infection (UTI). In 2011, the AAP restricted voiding cystourethrography to children with a pathological ultrasonography, recurrent and/ or atypical infections. Our objective was to compare, in patients with vesicoureteral reflux (VUR) and normal renal ultrasonography, the prevalence of a relevant pathology as if patients had been studied as per the 1999 guidelines (for first UTI) or the 2011 guidelines (for recurrent and/or atypical UTI). POPULATION AND METHODS: We conducted a retrospective analysis of patients with UTI, aged between 2 and 24 months old, seen at our department between January 2010 and August 2014 and who had a normal renal ultrasonography and VUR. A relevant pathology was defined as a finding of grade III VUR or higher and/or pathological renal scintigraphy. RESULTS: Forty-five patients (31 girls) were included and were grouped as if they had been treated as per the 1999 or 2011 guidelines. The prevalence of a relevant pathology among patients studied as per the 1999 guidelines (9 out of 24 cases, 3 with atypical UTI) or as per the 2011 guidelines (11 out of 21 cases) was similar (37.5% versus 52%, respectively; p= 0.31). Six patients (25%) with a relevant pathology diagnosed as per the 1999 guidelines would not have been identified in a timely manner with the 2011 version. CONCLUSIONS: The prevalence of a relevant pathology identified in children with VUR and normal renal ultrasonography was similar with both guidelines. However, considering the present guidelines, one out of four patients would have been exposed to a delayed or potentially missed diagnosis if recurrence would have been expected to complete the assessment.

INTRODUCCIÓN: En 1999, la Academia Americana de Pediatría recomendó realizar una ecografía renal y una cistouretrografía miccional a todos los niños de entre 2 y 24 meses con un primer episodio de infección del tracto urinario (ITU). En 2011, limitó la cistouretrografía miccional a aquellos con ecografía patológic infecciones recurrentes y/o atípicas. Nuestro objetivo fue comparar, en pacientes con reflujo vesicoureteral (RVU) y ecografía renal normal, la prevalencia de patología relevante según hubieran sido estudiados con las guías de 1999 (en la primera ITU) o de 2011 (ante ITU recurrente y/o atípica). POBLACIÓN Y MÉTODOS: Estudiamos retrospectivamente pacientes con ITU de entre 2 y 24 meses atendidos entre enero de 2010 y agosto de 2014 con ecografía renal normal y RVU. Consideramos patología relevante al hallazgo de RVU > grado III y/o centellograma renal patológico. RESULTADOS: Incluimos 45 pacientes (31 niñas), que fueron agrupados según hubieran sido estudiados con las guías de 1999 o de 2011. La prevalencia de patología relevante entre los estudiados con las guías de 1999 (9 de 24 casos, 3 con ITU atípica) o de 2011 (11 de 21 casos) fue comparable (37,5% vs. 52%, respectivamente; p= 0,31). Seis pacientes (25%) con patología relevante diagnosticados con las guías de 1999 no se hubieran identificado oportunamente con las de 2011. CONCLUSIONES: La prevalencia de patología relevante identificada en niños con RVU y ecografía renal normal con ambas guías fue comparable. Sin embargo, con las guías actuales, uno de cada cuatro pacientes hubiera estado expuesto a la demora o eventual pérdida diagnóstica si se hubiera esperado la recurrencia para completar la evaluación.