Emerging Resistance Trends in Viridans Group Streptococci Bloodstream Infections Among Immunocompromised Children Receiving Levofloxacin Prophylaxis.

BACKGROUND: Levofloxacin prophylaxis (LVXp) is often used for patients with underlying leukemia and severe neutropenia to reduce the risk of fever and bacteremia. This study evaluated trends in viridans group streptococci (VGS) antibiotic susceptibilities over time and clinical outcomes of children with VGS bloodstream infections (BSIs) during institutional adoption of LVXp. METHODS: VGS blood culture isolates between 1/1/2010 and 12/31/2021 with susceptibility testing reported were included. Available isolates were re-identified to the species level and additional susceptibility testing was performed. Demographic and clinical data were abstracted from medical records. RESULTS: A total of 264 VGS BSI isolates were identified in immunocompromised (IC, n = 125) and non-immunocompromised subjects, (non-IC, n = 139). IC subjects had lower rates of VGS isolates susceptible (S) to LVX and higher minimum inhibitory concentration (MICs) to LVX (p = 0.004) and ciprofloxacin (p = 0.0005) compared with non-IC subjects. No other evaluated antibiotic had increased MICs in either group. Fifteen of 19 (74%) LVX not susceptible (NS) isolates occurred in IC subjects, 13 represented breakthrough infections. IC subjects had higher rates of VGS-related shock (p = 0.012), need for pressor support (p = 0.039), and longer duration of hospitalization than non-IC subjects (p < 0.001). Clinical outcomes were comparable between subjects with LVX S and NS VGS BSI isolates. CONCLUSIONS: VGS with reduced susceptibility to LVX emerged during institutional adoption of LVXp in high-risk children with immunocompromising conditions, but did not result in significant differences in clinical outcomes. Ongoing surveillance and susceptibility testing are critical in weighing the utility of LVXp against emerging antimicrobial resistance in this high-risk population.

Myeloid-Derived Suppressor Cells and Clinical Outcomes in Children With COVID-19.

Background: Although children with COVID-19 account for fewer hospitalizations than adults, many develop severe disease requiring intensive care treatment. Critical illness due to COVID-19 has been associated with lymphopenia and functional immune suppression. Myeloid-derived suppressor cells (MDSCs) potently suppress T cells and are significantly increased in adults with severe COVID-19. The role of MDSCs in the immune response of children with COVID-19 is unknown. Aims: We hypothesized that children with severe COVID-19 will have expansion of MDSC populations compared to those with milder disease, and that higher proportions of MDSCs will correlate with clinical outcomes. Methods: We conducted a prospective, observational study on a convenience sample of children hospitalized with PCR-confirmed COVID-19 and pre-pandemic, uninfected healthy controls (HC). Blood samples were obtained within 48 h of admission and analyzed for MDSCs, T cells, and natural killer (NK) cells by flow cytometry. Demographic information and clinical outcomes were obtained from the electronic medical record and a dedicated survey built for this study. Results: Fifty children admitted to the hospital were enrolled; 28 diagnosed with symptomatic COVID-19 (10 requiring ICU admission) and 22 detected by universal screening (6 requiring ICU admission). We found that children with severe COVID-19 had a significantly higher percentage of MDSCs than those admitted to the ward and uninfected healthy controls. Increased percentages of MDSCs in peripheral blood mononuclear cells (PBMC) were associated with CD4+ T cell lymphopenia. MDSC expansion was associated with longer hospitalizations and need for respiratory support in children admitted with acute COVID-19. Conclusion: These findings suggest that MDSCs are part of the dysregulated immune responses observed in children with severe COVID-19 and may play a role in disease pathogenesis. Future mechanistic studies are required to further understand the function of MDSCs in the setting of SARS-CoV-2 infection in children.

Corrigendum to: 204. Mucosal Cytokine Profiles in Children with COVID-19.

[This corrects the article DOI: 10.1093/ofid/ofab466.000.].

Renal length z-score for the detection of dysfunction in children with solitary functioning kidney.

AIM: To evaluate whether renal length z-scores predict renal dysfunction in children with a solitary functioning kidney (SFK). METHODS: In a single-centre retrospective cohort of children with SFK, we correlated body mass index z-scores, extracellular volume and lean body mass to renal length z-scores. We grouped these z-scores to other markers of renal dysfunction (proteinuria, hypertension, extracellular volume and abnormal estimated glomerular function rate [eGFR]) and analysed renal length z-score with multivariate analysis, receiver-operated characteristics (ROC) plots and Youden's index to determine an appropriate cut-off. RESULTS: 111 children had a median follow-up 5.08 years, eGFR 80.8 mL/min/1.73 m2 , and age at last follow-up 7.4 (3.8-13.4 years). The median renal length z-scores of those without any renal dysfunction (n = 37, 25.1%) were greater (+3.66, interquartile range 3.02-4.47) than those with renal dysfunction (median 3.11, interquartile range 1.76-4.11, P = .0107, Mann-Whitney test). Using a cut-off of z-score of >+1.911, the odds ratio for having no renal dysfunction was 0.07 (95% CI 0.002-0.459, P = .0010). However, accuracy of the renal length z-score was poor (ROC curve 0.6488). CONCLUSION: In this cohort of children with SKF, using the renal length z-score as a biomarker of renal dysfunction at 7 years of age is not recommended.

Coeficiente de difusión aparente en tejido encefálico: valores de normalidad en población colombiana clínicamente sana / Apparent diffusion coefficient in brain tissue: values of normality in clinically healthy colombian population

Resumen Introducción: Las secuencias de difusión en resonancia magnética, incluido el coeficiente de difusión aparente (ADC), representan una herramienta fundamental para el radiólogo en el diagnóstico clínico. Sin embargo, no existe estandarización para las medidas entre los límites normales o un rango de valores normales del ADC. Objetivo: Determinar valores normales del ADC en el tejido encefálico para la población clínica y radiológicamente sana. Métodos: Estudio de corte transversal sobre datos retrospectivos, se midieron valores del ADC para 21 regiones encefálicas (sustancia gris frontal, parietal y temporal, sustancia blanca frontal y parietal, núcleo caudado, putamen, tálamo, cápsula interna, hemisferios cerebelosos bilateralmente y puente del tallo cerebral) en 90 sujetos clínica y radiológicamente sanos, en dos clínicas privadas de Bogotá. Resultados: Valores normales del ADC, en población clínica y radiológicamente sana, en 21 territorios encefálicos, análisis comparativo de los resultados según el sexo y edad de los pacientes, y correlación entre las mediciones realizadas por dos investigadores. Conclusiones: Los hallazgos sirven como referencia para la población colombiana y latinoamericana normal, establecen un punto de comparación para la evaluación de patologías intracraneanas, y abre la posibilidad a desarrollar nuevos proyectos de investigación que busquen determinar valores de ADC en población enferma.

Abstract Introduction: The diffusion sequences in magnetic resonance, including the apparent diffusion coefficient (ADC), represent a fundamental tool for the radiologist in the clinical diagnosis. However, there is no standardization for measurements between normal limits or a range of normal ADC values. Objective: To determine normal ADC values ​​in the brain tissue for the clinical and radiologically healthy population. Methods: Cross-sectional study on retrospective data, ADC values ​​were measured for 21 encephalic regions (frontal gray, parietal and temporal substance, frontal and parietal white matter, caudate nucleus, putamen, thalamus, internal capsule, cerebellar hemispheres bilaterally and bridge of the brainstem) in 90 clinically and radiologically healthy subjects, in two private clinics in Bogotá. Results: Normal ADC values, in a clinical and radiologically healthy population, in 21 encephalic territories, comparative analysis of the results according to the sex and age of the patients, and correlation between the measurements made by two researchers. Conclusions: The findings serve as a reference for the Colombian and normal Latin American population, establish a point of comparison for the evaluation of intracranial pathologies, and open the possibility to develop new research projects that seek to determine ADC values ​​in sick population.

Síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos debido a la carbamazepina: Caso pediátrico / Drug reaction with eosinophilia and systemic symptoms due to carbamazepine: Pediatric case

Entre las reacciones medicamentosas graves en la piel, se encuentran el síndrome de Stevens-Johnson, la necrólisis epidérmica tóxica y el síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos (drug reaction with eosinophilia and systemic symptoms; DRESS, por sus siglas en inglés), que son poco comunes en la población pediátrica (incidencia: 1/1000-10 000 niños), sin embargo, tienen mal pronóstico. El síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos consiste en erupciones cutáneas, alteraciones hematológicas, linfadenopatía y afectación de órganos. Se presenta el caso de un paciente masculino de 12 años que desarrolló esta patología después de iniciar el tratamiento anticonvulsivo con carbamazepina. Se considera que es importante que el personal de la salud tenga conocimiento de esta enfermedad para que sea incluida entre los diagnósticos diferenciales de pacientes con afecciones similares, ya que este síndrome es potencialmente mortal.

Severe skin reactions include Stevens-Johnson Syndrome, toxic epidermal necrolysis and Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, which are uncommon in the pediatric population (incidence 1/1000-10 000 children), but they have bad prognosis. Drug-sensitive Syndrome with eosinophilia and systemic symptoms consists in rash, hematological abnormalities, lymphadenopathy and organ involvement. We report the case of a 12-year-old male patient who developed this pathology after initiating anticonvulsant therapy with carbamazepine. We consider that it is important to be aware of this disease and to include it among the differential diagnoses in patients with similar conditions because this syndrome is life-threatening.

[Drug reaction with eosinophilia and systemic symptoms due to carbamazepine. Pediatric case]. / Síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos debido a la carbamazepina. Caso pediátrico.

Severe skin reactions include Stevens-Johnson Syndrome, toxic epidermal necrolysis and Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, which are uncommon in the pediatric population (incidence 1/1000- 10 000 children), but they have bad prognosis. Drug-sensitive Syndrome with eosinophilia and systemic symptoms consists in rash, hematological abnormalities, lymphadenopathy and organ involvement. We report the case of a 12-year-old male patient who developed this pathology after initiating anticonvulsant therapy with carbamazepine. We consider that it is important to be aware of this disease and to include it among the differential diagnoses in patients with similar conditions because this syndrome is life-threatening.

Entre las reacciones medicamentosas graves en la piel, se encuentran el síndrome de Stevens-Johnson, la necrólisis epidérmica tóxica y el síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos (drug reaction with eosinophilia and systemic symptoms; DRESS, por sus siglas en inglés), que son poco comunes en la población pediátrica (incidencia: 1/1000- 10 000 niños), sin embargo, tienen mal pronóstico. El síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos consiste en erupciones cutáneas, alteraciones hematológicas, linfadenopatía y afectación de órganos. Se presenta el caso de un paciente masculino de 12 años que desarrolló esta patología después de iniciar el tratamiento anticonvulsivo con carbamazepina. Se considera que es importante que el personal de la salud tenga conocimiento de esta enfermedad para que sea incluida entre los diagnósticos diferenciales de pacientes con afecciones similares, ya que este síndrome es potencialmente mortal.

Detection of insulitis by pancreatic scintigraphy with 99mTc-labeled IL-2 and MRI in patients with LADA (Action LADA 10).

OBJECTIVE: Pancreatic scintigraphy with interleukin-2 radiolabeled with (99m)Tc ((99m)Tc-IL-2) is a technique used to image chronic inflammatory-mediated disorders. We used this method to detect a signal consistent with the presence of insulitis in patients with autoimmune diabetes. Positive and negative controls (patients with pancreatic carcinoma and type 2 diabetes, respectively) also were studied. RESEARCH DESIGN AND METHODS: We examined 25 patients with autoimmune diabetes (16 with recently diagnosed type 1 diabetes, 9 with latent autoimmune diabetes in adults [LADA]), 6 with type 2 diabetes, and 7 with pancreatic carcinoma (the latter two groups were used as negative and positive controls, respectively). All patients underwent (99m)Tc-IL-2 scintigraphy and contrast-enhanced MRI of the pancreas. To validate positive controls, samples were taken from patients with pancreatic carcinoma during surgery for histological and immunohistochemical investigations. RESULTS: Pancreatic accumulation of (99m)Tc-IL-2 was detected in patients with autoimmune diabetes (61% positive) and, notably, in 6 of 9 patients with LADA; semiquantitative evaluation of pancreatic uptake of (99m)Tc-IL-2 showed higher values in patients with autoimmune diabetes (both childhood and LADA) and pancreatic carcinoma than in those with type 2 diabetes (4.45 ± 1.99, 4.79 ± 1.1, and 4.54 ± 1.62 vs. 2.81 ± 0.63; P = 0.06, P = 0.01, and P = 0.04, respectively). In patients with pancreatic carcinoma, pancreatic interleukin-2 receptor expression correlated with pancreatic (99m)Tc-IL-2 uptake (r = 0.8; P = 0.01). In patients with LADA, (99m)Tc-IL-2 uptake inversely correlated with duration of disease (r = 0.7; P = 0.03). CONCLUSIONS: Autoimmune diabetes in adults is associated with increased pancreatic (99m)Tc-IL-2 uptake, indicating the presence of insulitis, particularly within 1 year of the beginning of insulin therapy, similar to type 1 diabetes at diagnosis.

Adenosine monophosphate-activated protein kinase activation protects against sepsis-induced organ injury and inflammation.

BACKGROUND: Mortality in sepsis is most often attributed to the development of multiple organ failure. In sepsis, inflammation-mediated endothelial activation, defined as a proinflammatory and procoagulant state of the endothelial cells, has been associated with severity of disease. Thus, the objective of this study was to test the hypothesis that adenosine monophosphate-activated protein kinase (AMPK) activation limits inflammation and endothelium activation to protect against organ injury in sepsis. 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), which is an adenosine monophosphate analog, has been used to upregulate activity of AMPK. Compound C is a cell-permeable pyrrazolopyrimidine compound that inhibits AMPK activity. METHODS: Wild-type mice underwent cecal ligation and puncture (CLP) or sham surgery. Mice were randomized to vehicle, AICAR, or compound C. Mouse kidney endothelial cells were used for in vitro experiments. Renal and liver function were determined by serum cystatin C, blood urea nitrogen (BUN), creatinine, and alanine aminotransferase. Serum cytokines were measured by enzyme-linked immunosorbent assay. Microvascular injury was determined using Evans blue dye and electron microscopy. Immunohistochemistry was used to measure protein levels of phospho-AMPK (p-AMPK), microtubule-associated protein 1A/1B-light chain 3 (LC3), and intracellular adhesion molecule. LC3 levels were used as a measure of autophagosome formation. RESULTS: AICAR decreased liver and kidney injury induced by CLP and minimized cytokine elevation in vivo and in vitro. CLP increased renal and hepatic phosphorylation of AMPK and autophagic signaling as determined by LC3. Inhibition of AMPK with compound C prevented CLP-induced autophagy and exacerbated tissue injury. Additionally, CLP led to endothelial injury as determined by electron microscopy and Evans blue dye extravasation, and AICAR limited this injury. Furthermore, AICAR limited CLP and lipopolysaccharide (LPS)-induced upregulation of intracellular adhesion molecule in vivo and in vitro and decreased LPS-induced neutrophil adhesion in vitro. CONCLUSIONS: In this model, activation of AMPK was protective, and AICAR minimized organ injury by decreasing inflammatory cytokines and endothelial activation. These data suggest that AMPK signaling influences sepsis or LPS-induced endothelial activation and organ injury.

Imaging of ß-cell mass and insulitis in insulin-dependent (Type 1) diabetes mellitus.

Insulin-dependent (type 1) diabetes mellitus is a metabolic disease with a complex multifactorial etiology and a poorly understood pathogenesis. Genetic and environmental factors cause an autoimmune reaction against pancreatic ß-cells, called insulitis, confirmed in pancreatic samples obtained at autopsy. The possibility to noninvasively quantify ß-cell mass in vivo would provide important biological insights and facilitate aspects of diagnosis and therapy, including follow-up of islet cell transplantation. Moreover, the availability of a noninvasive tool to quantify the extent and severity of pancreatic insulitis could be useful for understanding the natural history of human insulin-dependent (type 1) diabetes mellitus, to early diagnose children at risk to develop overt diabetes, and to select patients to be treated with immunotherapies aimed at blocking the insulitis and monitoring the efficacy of these therapies. In this review, we outline the imaging techniques currently available for in vivo, noninvasive detection of ß-cell mass and insulitis. These imaging techniques include magnetic resonance imaging, ultrasound, computed tomography, bioluminescence and fluorescence imaging, and the nuclear medicine techniques positron emission tomography and single-photon emission computed tomography. Several approaches and radiopharmaceuticals for imaging ß-cells and lymphocytic insulitis are reviewed in detail.

Frecuencia de factores de riesgo cardiovascular en pacientes hipertensos en un hospital de segundo nivel / Frequency of cardiovascular risk factors in patients with hypertension

Objetivo: determinar la frecuencia de exposición a cuatro factores de riesgo cardiovascular en los pacientes adscritosa un programa de control de hipertensión arterial en un hospital de segundo nivel del departamento de Risaralda. Metodología: se evaluaron 133 pacientes que asistían al programa de control de la hipertensión. Como instrumento se utilizó la prueba de adhesión Martin-Bayarre-Grau (testmbg), el índice de masa corporal y la medida de la presión arterial. Resultados: 80% de los pacientes eran mujeres; las cifras de presión arterial promedio fueron de 141 y 86mm Hg, sistólica y diastólica respectivamente. El 74% presentósobrepeso y obesidad. Solo el 42,1% de los pacientes presentó adherencia total al tratamiento antihipertensivo.El 100% de los pacientes presentó al menos uno de los riesgos cardiovasculares evaluados. Conclusiones: la alta frecuencia de exposición de riesgos cardiovasculares es un indicador de la falta de adherencia terapéutica. Es necesario un grupo interdisciplinario que garantice el entendimiento de la enfermedad por parte del paciente y elaboreestrategias para mejorar la adherencia.

Objective: to determine the frequency of exposure to four cardiovascular risk factors in patients from a hypertensioncontrol program. This program belongs to a second level hospital located in Risaralda, Colombia. Methodology: a total of 133 patients from a hypertension control program were assessed. The Martin-Bayarre-Grau test (MBG test), the body mass index, and the blood pressure measurements were used as instruments for measuring adherence to treatment. Results:80% of the patients were female. The average systolic and diastolic arterial pressure values were 141 and 86 mmHg respectively. 74% of the patients exhibited overweight and obesity, and only 42.1% of the patients showed complete adherence to the antihypertensive therapy. Additionally,100% of the patients had at least one of the assessed cardiovascularrisks. Conclusions: high frequency of exposure to cardiovascular risks is an indicator of the lack of treatmentadherence. An interdisciplinary team is needed to ensure that patients understand their disease and to develop strategies to improve adherence.