Factores de riesgo de bacteriemia en niños con cáncer y neutropenia febril / Risk factors for bacteremia in children with cancer and febrile neutropenia

La bacteriemia representa una importante causa de morbimortalidad en pacientes oncológicos. Durante el episodio de neutropenia inducida por quimioterapia, un 15%­25% de los pacientes tendrá bacteriemia. Objetivo: identificar factores de riesgo asociados con bacteriemia en pacientes oncológicos pediátricos con neutropenia y fiebre. Material y métodos: estudio de cohorte prospectivo. Se incluyeron pacientes con enfermedades hematooncológicas y neutropenia febril, internados en un hospital pediátrico de alta complejidad entre julio de 2018 y mayo de 2019. Se excluyeron receptores de trasplante de médula ósea. Se compararon las características clínicas según se documentara bacteriemia (B) o no. Resultados: Se incluyeron 160 pacientes (p). Eran varones 93 (58%). La mediana de edad fue 81,5 meses (RIC 36-127,5). La enfermedad de base (EB) más frecuente fue: leucemia linfoblástica aguda (LLA) 88 (55%). Se identificaron 20 (12,5%) pacientes con bacteriemia (B). En el análisis univariado hubo asociación entre B y LMA (p=0,003) y la internación en UCI (p=0,0001). En el modelo multivariado, ajustado por el resto de las variables, se identificaron la LMA (OR 8,24, IC95% 2,5-26,4; p<0,001) y la tiflitis (OR 5,86, IC95% 1,2-27,3; p=0,02) como factores relacionados con bacteriemia. Los principales microorganismos identificados fueron: estreptococos del grupo viridans 6 (30%), Escherichia coli 4 (20%) y estafilococos coagulasa negativos 3 (15%). Quince (75%) fueron bacteriemias secundarias a un foco clínico. El foco más frecuente fue el mucocutáneo (n=7, 35%). En esta cohorte de niños con cáncer y neutropenia febril, los factores asociados con bacteriemia fueron: la LMA, la tiflitis y la internación en UCI (AU)

Bacteremia is an important cause of morbidity and mortality in oncology patients. During an episode of chemotherapy-induced neutropenia, 15%-25% of patients will develop bacteremia. Objective: to identify risk factors associated with bacteremia in pediatric oncology patients with neutropenia and fever. Material and methods: prospective cohort study. Patients with hematology-oncology diseases and febrile neutropenia, admitted to a tertiary-care pediatric hospital between July 2018 and May 2019 were included. Bone marrow transplant recipients were excluded. Clinical characteristics were compared according to whether or not bacteremia was recorded. Results: 160 patients were included of whom 93 (58%) were male. Median age was 81.5 months (IQR 36-127.5). The most common underlying disease was acute lymphoblastic leukemia (ALL) in 88 patients (55%). Twenty (12.5%) patients with bacteremia were identified. In univariate analysis, an association was found between bacteremia and acute myeloid leukemia (AML) (p=0.003) and ICU admission (p=0.0001). In the multivariate model, adjusted for the remaining variables, AML (OR 8.24; 95%CI 2.5-26.4; p<0.001) and typhlitis (OR 5.86; 95%CI 1.2-27.3; p=0.02) were identified as factors related to bacteremia. The main microorganisms identified were viridans group streptococci in 6 (30%), Escherichia coli in 4 (20%), and coagulase negative staphylococci in 3 (15%). In 15 cases (75%), bacteremia was secondary to a clinical focus. The most frequent focus was mucocutaneous (n=7, 35%). In this cohort of children with cancer and febrile neutropenia, the factors associated with bacteremia were AML, typhlitis, and ICU admission (AU)

Características clínicas y evolutivas de niños con infección por SARS-CoV-2 en un hospital de alta complejidad: estudio de cohorte / Clinical and outcome characteristics of children with SARS CoV-2 infection in a tertiary-care hospital: a cohort study

Introducción: Las infecciones por SARS-CoV-2 representan un problema de salud pública a nivel mundial. En los niños se reporta menor incidencia y cuadros clínicos más leves. Se realizó el presente estudio con el objetivo de describir las características clínicas y evolutivas de los niños con diagnóstico de infección por SARS CoV-2 en el Hospital Juan P. Garrahan. Material y métodos: estudio de cohorte prospectivo. Se incluyeron todos los pacientes con diagnóstico confirmado por PCR de COVID-19 desde 20.4.20 hasta el 3.07.21 y con seguimiento en el hospital de Pediatría Juan P. Garrahan. Resultados: n: 1644. Eran varones 836 (51%). La mediana de edad fue 75 meses (RIC 22- 143). Tenían alguna enfermedad de base previa al diagnóstico de COVID-19: 884 pacientes (53,7%), la más frecuente fue la enfermedad oncohematológica. Estaban asintomáticos 423 pacientes (25,7%). De los pacientes sintomáticos, 1071 (65,1%) presentaron cuadro leve, 5 (0,3%) moderado, 69 (4,2%) grave y 76 (4,6%) crítico. La fiebre fue el hallazgo más frecuente n: 782; (47,5%). Se internaron 900 pacientes (54,7%), 33 en UCI (2%). Fallecieron 7 pacientes (0,4%), todos ellos con comorbilidades graves. Conclusiones: En este estudio de cohorte de niños con infección por SARS-CoV-2 confirmada, predominaron los pacientes con enfermedad de base y las formas leves de COVID-19. El ingreso a UCI fue menor al 2%. Fallecieron 7 pacientes (0.4%) todos ellos con comorbilidades y coinfecciones (AU)

Introduction: SARS-CoV-2 infections represent a worldwide public health problem. A lower incidence and milder clinical pictures are reported in children. The aim of this study was to describe clinical and outcome characteristics of children diagnosed with SARS-CoV-2 infection at Hospital de Pediatría Juan P. Garrahan. Methods: A prospective cohort study was conducted. All patients with a PCR-confirmed diagnosis of COVID-19 seen between 20.4.20 and 3.07.21 and followed-up at Hospital de Pediatría Juan P. Garrahan were included. Results: n: 1644; 836 males (51%) were male. Median age was 75 months (IQR, 22-143). Overall, 884 patients (53.7%) had an underlying disease prior to COVID-19 diagnosis, most frequently hematologic/ oncologic disease. 423 patients (25.7%) were asymptomatic. Of the symptomatic patients, 1071 (65.1%) had mild, 5 (0.3%) moderate, 69 (4.2%) severe, and 76 (4.6%) critical disease. Fever was the most frequent finding (n: 782; 47.5%). A total of 900 patients (54.7%) were admitted, 33 of whom to the ICU (2%). Seven patients (0.4%) died, all with severe comorbidities. Conclusions: In this cohort study of children with confirmed SARSCoV-2 infection, patients with underlying disease and mild forms of COVID-19 predominated. ICU admission occurred in less than 2%. Seven patients (0.4%) died, all of them with comorbidities and coinfections. (AU)

Epidemiología de COVID-19 / Epidemiology of COVID-19

El 31 de diciembre de 2019, en el estado de Wuhan, al sur de China, se notificaron los primeros casos de una enfermedad nueva que se denominó COVID-19. Se identificó al virus SARS-CoV-2 como el agente etiológico. Esta enfermedad fue declarada pandemia por la OMS en marzo 2020. El objetivo de este trabajo es describir la epidemiología de la COVID-19 y las características particulares de los niños con esta enfermedad. El SARS-CoV-2 es un virus ARN que pertenece a la familia Coronaviridae. Su trasmisión es principalmente interhumana a través de pequeñas gotitas respiratorias y también mediante aerosoles. En la clínica puede presentarse de forma asintomática o con un cuadro grave de distrés respiratorio. Puede haber manifestaciones cutáneas, gastrointestinales y/o cardiovasculares entre otras. En los niños se describió un síndrome inflamatorio denominado síndrome inflamatorio multisistémico asociado a SARS-CoV-2 (SIMS). La evidencia sobre el rol de los niños en la transmisión de la enfermedad es creciente. En la Argentina, desde el inicio de la pandemia hasta junio 2021, se notificaron más de 4 000 000 de casos confirmados de COVID-19 y, 90 000 personas fallecidas. Las infecciones por SARS-CoV-2 representan un desafío sanitario global. El rol de los niños como dispersores de la enfermedad y su real carga de enfermedad continúan en estudio (AU)

On December 31, 2019, in the state of Wuhan, southern China, the first cases of a new disease named COVID-19 were reported. The SARS-CoV-2 virus was identified as the etiologic agent. This disease was declared a pandemic by the WHO in March 2020. The aim of this study was to describe the epidemiology of COVID-19 and the particular characteristics of children with this disease. SARS-CoV-2 is an RNA virus belonging to the Coronaviridae family. Its transmission is mainly human-to-human through small respiratory droplets and aerosols. Clinically, it may present asymptomatically or with severe respiratory distress. There may be cutaneous, gastrointestinal and/or cardiovascular manifestations, among others. In children, SARS-CoV-2-associated multisystemic inflammatory syndrome (MIS) has been described. There is growing evidence on the role of children in the transmission of COVID-19. In Argentina, from the onset of the pandemic until June 2021, more than 4 000 000 confirmed cases of COVID-19 and 90 000 deaths have been reported. SARSCoV-2 infections represent a global health challenge. Research on the role of children as disease spreaders and their actual disease burden is ongoing (AU)

Epidemiología de las meningitis bacterianas en niños en un hospital pediátrico: 2011-2016 / Epidemiology of bacterial meningitis in children at a pediatric hospital: 2011-2016

Introducción: Las meningitis bacterianas en niños son causa de importante morbimortalidad. Los principales agentes etiológicos son Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae. En los últimos años, luego de la introducción sucesiva de vacunas conjugadas al calendario nacional de inmunizaciones, se ha visto un cambio en la epidemiología de estas infecciones. Objetivo: Describir las características clínicas, epidemiológicas y evolutivas de los niños hospitalizados con meningitis bacteriana confirmada microbiológicamente entre 2011 y 2016 en un hospital de tercer nivel de complejidad. Materiales y métodos: Cohorte retrospectiva. Se incluyeron niños entre 1 mes de vida y 17 años con cuadro clínico compatible con meningitis bacteriana y cultivo positivo y/o PCR en líquido cefalorraquídeo y/o hemocultivos positivos para Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae b. Se registraron las características demográficas, clínicas y evolutivas hasta los 30 días del egreso. Se utilizó mediana y rango intercuartilo (RIC) para variables continuas y porcentaje para variables categóricas. Se utilizó Stata 10. Resultados: n=65. Edad: mediana de 9 meses (RIC 4-35). Varones: 58% (n=38). Se identificó Neisseria meningitidis en un 48% (n=31), Haemophilus influenzae b en un 26% (n=17) y Streptococcus pneumoniae en un 26% (n=17). El 26% (n=17) de los pacientes presentaba alguna comorbilidad. Tuvieron hemocultivos positivos el 62% (n = 40) de los pacientes y 86% (n=55) de los líquidos cefalorraquídeos. Todos los pacientes recibieron tratamiento antimicrobiano con ceftriaxona tanto como tratamiento empírico como definitivo y 92% (n=60) recibieron corticoides empíricos. La mediana de días de internación fue de 11 (RIC 8-17). El 28% (n=18) requirió cuidados intensivos, y el 8% (n=5) falleció. Durante el período de estudio se observó que la frecuencia de meningitis por Streptococcus pneumoniae disminuyó en el final del estudio (9% en 2016 vs 60% en 2011), mientras que la frecuencia de meningitis por Neisseria meningitidis en 2016 fue mayor que al inicio del período (64% en 2016 vs. 40% en 2011). La frecuencia de identificación de Haemophilus influenzae b se mantuvo estable. Conclusiones: Las meningitis bacterianas confirmadas por Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae b prevalecieron en niños menores de 12 meses. En esta cohorte se observó un predominio de las infecciones por Neisseria meningitidis en los últimos años, y una disminución en la frecuencia de meningitis por Streptococcus pneumoniae en el período post introducción de la vacuna conjugada 13 valente al calendario nacional de inmunizaciones. (AU)

Introduction: In children, bacterial meningitis is an important cause of morbidity and mortality. The main etiological agents are Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. Over the last years, the successive introduction of conjugated vaccines in the national immunization calendar has led to a change in the epidemiology of these infections. Objective: To describe the clinical and epidemiological features and outcome of children admitted because of microbiologically confirmed meningitis seen between 2011 and 2016 at a tertiary care hospital. Material and methods: A retrospective cohort study was conducted. Children between 1 month of life and 17 years of age with clinical features compatible with bacterial meningitis and positive cultures and/or PCR in cerebrospinal fluid (CSF) and/or positive blood cultures for Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae b were included. Demographic, clinical, and outcome features were recorded until 30 days after discharge. Median and interquartile range (IQR) were calculated for continuous variables and percentages for categorical variables. The Stata 10 program was used. Results: n=65. Age: median was 9 months (IQR 4-35). Boys: 58% (n=38). Neisseria meningitidis was identified in 48% (n=31), Haemophilus influenzae b in 26% (n=17), and Streptococcus pneumoniae in 26% (n=17). Overall, 26% (n=17) of the patients presented with comorbidities. Positive blood cultures were found in 62% (n = 40) and positive CSF cultures in 86% (n=55) of the patients. All patients received antimicrobial treatment with ceftriaxone both empirically and as final treatment and corticosteroids were empirically started in 92% (n=60). Median hospital stay was 11 days (IQR 8-17). Overall, 28% (n=18) required intensive care and 8% (n=5) of the patients died. The incidence of meningitis due to Streptococcus pneumoniae was observed to diminish at the end of the study period (9% in 2016 vs 60% in 2011), while the incidence of meningitis due to Neisseria meningitidis in 2016 was higher than at the end of the study period (64% in 2016 vs. 40% in 2011). The frequency of identification of Haemophilus influenzae b remained stable. Conclusions: Confirmed bacterial infections due to Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae b were prevalent in infants younger than 12 months of age in this cohort of patients. Infections due to Neisseria meningitidis predominated over the last years and the incidence of meningitis due to Streptococcus pneumoniae diminished after the introduction of the 13 valent conjugated vaccine was introduced in the national immunization calendar.(AU)

Infección por metapneumovirus en pacientes internados en un hospital pediátrico / Metapneumovirus infection in patients in a pediatric hospital

La infección respiratoria es un importante motivo de internación en pediatría. Ultimamente se identificó a los Metapneumovirus como agentes etiológicos de infecciones respiratorias. Se estudiaron 897 niños internados a los cuales se les realizó el estudio de detección de virus respiratorios, incluyendo Metapneumovirus, por inmunofluorescencia indirecta entre noviembre y diciembre de 2009. Se detectaron 55 pacientes con muestras positivas para virus respiratorios en secreciones nasofaringeas: 33 de ellas fueron positivas para Metapneumovirus. Se analizaron las características epidemiológicas, clínicas y evolutivas de niños con Metapneumovirus en forma retrospectiva. La edad media fue de 45 meses (r =0 a 204) y el 60% eran mayores de un año. Diecisiete de los mayores de un año (85%) presentaron comorbilidades. La bronquiolitis fue la forma clínica más frecuente en los menores de un año [9 (69%) y 8 (61%)] requirieron oxígeno. Todos tuvieron buena evolución. Conclusiones: Metapneumovirus fue causa de internación en los menores de un año y en los mayores con enfermedad de base. La presentación clínica fue similar a la producida por otros virus. Se observó su predominio sobre otros virus como causa de infección respiratoria entre noviembre y diciembre de 2009.

Respiratory infection is a common cause for hospital admission in children. Recently, the metapneumovirus has been identified as a causative agent of respiratory infection. Between Novem-ber and December 2009, 897 pediatric inpatients were studied for respiratory viruses, including the metapneumovirus, using indirect immunofluorescence techniques. Of all patients, 55 had positive nasopharyngeal samples for respiratory viruses; 33 were positive for the metapneumovirus. The epidemio-logical and clinical features and outcome of the children with metapneumovirus were retrospectively analyzed. Mean age was 45 months (r = 0 to 204) and 60% was older than one year. Seventeen of the children older than one year (85%) presented with comorbidities. Bronchiolitis was the most com-mon clinical presentation in children younger than one year. Nine (69%) and eight (61%) children, respectively, required oxygen therapy. Outcome was good in all patients. Conclu-sions: Metapneumovirus was the cause of hospital admission in children under one year of age and in children older than one year with an underlying disease. Symptoms were similar to those produced by other viruses. Between November and December 2009, the metapneumovirus was more commonly observed than other viruses as a cause of respiratory infection.

Rhodococcus equi infection in transplant recipients: a case of mistaken identity and review of the literature.

The incidence of Rhodococcus equi infection in solid-organ transplant recipients continues to rise throughout the world. Unfortunately, this opportunistic pathogen is still underestimated and potentially disregarded by physicians and microbiology laboratories due to its morphology on Gram staining. Pulmonary involvement is the most common finding in the immunocompromised host. We report a case of a 63-year-old heart-transplant recipient who presented with increasing fatigue and nonproductive cough for 3 weeks. After full evaluation, a lung abscess was demonstrated by thoracic computerized tomography (CT). Blood and sputum cultures were remarkable for heavy "diphtheroids." Although the Gram-stain result was initially interpreted as a contaminant, a clinical suspicion for Rhodococcus assisted in further investigation. Broncheoalveolar lavage and CT-guided biopsy of the lung abscess revealed heavy growth of diphtheroids. However, further evaluation by a reference laboratory demonstrated mycolic acid staining consistent with R. equi. Surgical drainage and prolonged antibiotic therapy resulted in complete remission of the pneumonia and abscess. This represents the fourth reported case of R. equi infection in a heart transplant recipient. It is imperative that all physicians and laboratory staff consider R. equi when an immunocompromised patient has any type of pneumonia, especially with abscess formation.

Mechanisms of agonist-dependent and -independent desensitization of a recombinant P2Y2 nucleotide receptor.

UTP activates P2Y, receptors in both 1321N1 cell transfectants expressing the P2Y2 receptor and human HT-29 epithelial cells expressing endogenous P2Y, receptors with an EC50 of 0.2-1.0 microM. Pretreatment of these cells with UTP diminished the effectiveness of a second dose of UTP (the IC50 for UTP-induced receptor desensitization was 0.3-1.0 microM for both systems). Desensitization and down-regulation of the P2Y2 nucleotide receptor may limit the effectiveness of UTP as a therapeutic agent. The present studies investigated the phenomenon of P2Y2 receptor desensitization in human 1321N1 astrocytoma cells expressing recombinant wild type and C-terminal truncation mutants of the P2Y2 receptor. In these cells, potent P2Y2 receptor desensitization was observed after a 5 min exposure to UTP. Full receptor responsiveness returned 5-10 min after removal of UTP. Thapsigargin, an inhibitor of Ca2+-ATPase in the endoplasmic reticulum, induced an increase in the intracellular free calcium concentration, [Ca2+]i, after addition of desensitizing concentrations of UTP, indicating that P2Y2 receptor desensitization is not due to depletion of calcium from intracellular stores. Single cell measurements of increases in [Ca2+]i induced by UTP in 1321N1 cell transfectants expressing the P2Y2 receptor indicate that time- and UTP concentration-dependent desensitization occurred uniformly across a cell population. Other results suggest that P2Y2 receptor phosphorylation/dephosphorylation regulate receptor desensitization/resensitization. A 5 min preincubation of 1321N1 cell transfectants with the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), reduced the subsequent response to UTP by about 50%, whereas co-incubation of PMA with UTP caused a greater inhibition in the response. The protein phosphatases-1 and -2A inhibitor, okadaic acid, partially blocked resensitization of the receptor. Furthermore, C-terminal truncation mutants of the P2Y2 receptor that eliminated several potential phosphorylation sites including two for PKC were resistant to UTP-, but not phorbol ester-induced desensitization. Down regulation of protein kinase C isoforms prevented phorbol ester-induced desensitization but had no effect on agonist-induced desensitization of wild type or truncation mutant receptors. These results suggest that phosphorylation of the C-terminus of the P2Y2 receptor by protein kinases other than protein kinase C mediates agonist-induced receptor desensitization. A better understanding of the molecular mechanisms of P2Y2 nucleotide receptor desensitization may help optimize a promising cystic fibrosis pharmacotherapy based on the activation of anion secretion in airway epithelial cells by P2Y, receptor agonists.

[Dose-effect of the administration of ferrous fumarate in aged persons with iron deficiency]. / Dosis efecto de la administración de fumarato ferroso en personas ancianas con deficiencia de hierro.

BACKGROUND: Anemia is the most prevalent hematological problem in elderly persons, affecting 14% of the males and 6% of the females of the population over 60 years of age in Mexico City. OBJECTIVE: To determine the effect produced by the prolonged administration of ferrous fumarate in elderly persons with iron deficiency. METHOD: In a population of 178 subjects, aged between 65 to 100 years, iron deficiency was diagnosed in 51 (28.6%), who had serum iron concentrations below 80 micrograms/dL for men and 60 micrograms/dL for women, but only 21 patients (11.8%), accepted to participated in the study. The response to a 6 months oral administration of ferrous fumarate were studied with a daily oral dose of 5 mg/kg of elemental iron. The patients were classified in 3 groups according to the abnormal parameters of iron metabolism (group 1 = 10.9% anemia, group 2 = 28.0% and group 3 = 63.0% anemia). RESULTS: The efficacy of treatment was evaluated by quantification of the changes occurred in serum iron concentrations, hemoglobin, ferritin and transferrin saturation index, at 0, 30, 90 and 180 days of treatment. This study showed that the treatment of oral ferrous fumarate in elderly patients with iron deficiency, produces a quantifiable improvement in measures of iron parameters within 6 months. CONCLUSIONS: The results of this study suggest the usefulness of prolonged treatment with ferrous fumarate in elderly patients with iron deficiency, to avoid therapeutic failure as a consequence of non-compliance as is common in elderly patients.

DNA binding-independent anti-proliferative action of benzazolo[3,2-alpha]quinolinium DNA intercalators.

The proposed mechanism of action of the antineoplastic drug 3-nitrobenzothiazolo[3,2-alpha]quinolinium chloride (NBQ-2) involves its interaction with DNA by intercalation and inhibition of topoisomerase II activity by arresting the enzyme in a covalent cleavage complex. In an attempt to identify some structural determinants for activity and develop a molecular structure/cytotoxicity correlation, four new structural analogs of the antitumor NBQ-2 were prepared and their cytotoxic activity and DNA binding properties were investigated. The cytotoxic activity was evaluated against six different human tumor cell lines: U937, K-562, HL-60, HT-29, HeLa, and A431. The results showed that these new drugs elicit pronounced cytotoxic effects against U937, K-562, HL-60 and A431 while HeLa and HT-29 were less sensitive to the new drugs. This apparent selectivity was different to that of m-AMSA, a drug currently used for cancer treatment. Since the interaction of NBQ-2 to DNA by intercalation has been proposed as the initial step leading to its antineoplastic activity, DNA binding and changes in DNA contour length induced by the new NBQ-2 structural analogs were also investigated using calf thymus and human DNA. The drug, 7-(1-propenyl)-3-nitrobenzimidazolo[3,2-alpha]quinolinium chloride (NBQ-59) was the most cytotoxic agent of the analog series (IC50 = 16 microM for HL-60 cells), however, it demonstrated the weakest binding to DNA (Kint = 0.9 x 10[5] M-1 for calf thymus DNA). NBQ-59 was also found to be a poor intercalator into the DNA double helix. Therefore, our results suggest that DNA binding is not the primary mechanism of drug action for this family of compounds. In addition structural determinants important for cytotoxicity of the benzazolo quinolinium chlorides were suggested by our results. In particular, the nitro group in the 3 position does not seem to be necessary for bioactivity, while substitutions in the benzazolo moiety have striking effects on the biological activity of the drugs.