Efficacy and safety of withholding antimicrobial therapy in children with cancer, fever, and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.

OBJECTIVES: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection. METHODS: Prospective, multicenter, noninferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus, negative for a bacterial pathogen, and had a favourable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with an uneventful resolution, whereas the secondary endpoints were days of fever, days of hospitalization, requirement of antimicrobial treatment readministration, sepsis, paediatric intensive care unit admission, and death. RESULTS: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a respiratory virus as a unique identified microorganism, of which 139 had a favourable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p < 0.001), with similar frequency of uneventful resolution 66/70 (94%) and 66/69 (96%); relative risk, 1.01; (95% CI, 0.93 to 1.09), absolute risk difference 0.01; (95% CI, -0.05 to 0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, paediatric intensive care unit admission, or death were reported. DISCUSSION: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance.

Impact of GAD65 and IA2 autoantibodies on islet allograft survival.

Introduction: Islet transplantation (ITx) shows promise in treating T1D, but the role of islet autoantibodies on graft survival has not been clearly elucidated. We aimed to analyze the effect of GAD65 and IA2 autoantibody status on graft survival and attainment of insulin independence in subjects with T1D who underwent ITx. Method: We conducted a retrospective cohort study on 47 ITx recipients from 2000 to 2018. Islet infusion was performed via intrahepatic portal (n=44) or onto the omentum via laparoscopic approach (n=3). Immunosuppression involved anti-IL2 receptor antibody, anti-TNF, and dual combinations of sirolimus, tacrolimus, or mycophenolate mofetil (Edmonton-like) in 38 subjects (80.9%). T-cell depletion induction with Edmonton-like maintenance was used in 9 subjects (19%). GAD65 and IA2 autoantibodies were assessed pre-transplant and post-transplant (monthly) until graft failure, and categorized as persistently negative, persistently positive, or seroconverters. Graft survival was analyzed using U-Mann-Whitney test, and Quade's nonparametric ANCOVA adjusted for confounders. Kaplan-Meier and Log-Rank tests were employed to analyze attainment of insulin independence. P value <0.05 indicated statistical significance. Results: ITx recipients with persistent autoantibody negativity (n = 21) showed longer graft function (98 [61 - 182] months) than those with persistent autoantibody positivity (n = 18; 38 [13 - 163] months), even after adjusting for immunosuppressive induction protocol (P = 0.027). Seroconverters (n=8) had a median graft survival time of 73 (7.7 - 167) months, which did not significantly differ from the other 2 groups. Subjects with persistently single antibody positivity to GAD65 (n = 8) had shorter graft survival compared to negative islet autoantibody (GAD65/IA2) subjects (n = 21; P = 0.016). Time of graft survival did not differ in subjects with single antibody positivity to IA2. The proportion of insulin independence attainment was similar irrespective of autoantibody status. Conclusion: The persistence of islet autoantibodies, as markers of islet autoimmunity, may represent an underappreciated contributing factor to the failure of transplanted ß cells. Whether induction with T-cell depletion may lead to improved graft survival, independent of islet autoantibody status, could not be evaluated in our cohort. Larger prospective studies are needed to further address the role of islet autoantibody status on islet graft survival.

Infecciones fúngicas invasoras en niños con cáncer y portadores de aplasia medular severa en nueve hospitales de la red PINDA, Chile. 2016-2020 / Invasive fungal infections in children with cancer and severe aplastic anemia in nine hospitals from PINDA Network, Chile. 2016-2020

INTRODUCCIÓN: La infección fúngica invasora (IFI) es una causa importante de morbilidad y mortalidad en pacientes oncológicos pediátricos y portadores de aplasia medular (AM) severa. OBJETIVO: Describir la epidemiología de la IFI desde el año 2016 al 2020 en niños con cáncer y AM para evaluar la necesidad de profilaxis antifúngica. MÉTODOS: Estudio retrospectivo, multicéntrico, en pacientes pediátricos con cáncer y AM severa. Se incluyeron IFI probables y probadas. RESULTADOS: Se diagnosticaron 57 casos de IFI, mediana de edad 9 años, 70% probadas y 30% probables. Hubo 42% de infecciones por levaduras y 56% por hongos filamentosos. Los sitios de infección más frecuentes fueron pulmón 38%, sangre 36% y rinosinusal 21%. La frecuencia global fue 5,4%; de ellas 21% en AM severa, 10% en leucemia mieloide aguda (LMA), 6,9% en recaída de LMA, 5,4% en recaída de leucemia linfática aguda (LLA), 3,8% en LLA. Las infecciones por hongos filamentosos predominaron en LMA, recaída de LMA. y AM severa. La mortalidad en pacientes con IFI fue de 11%. CONCLUSIÓN: La frecuencia de IFI concuerda con la literatura médica. Recomendamos profilaxis antifúngica contra hongos filamentosos en pacientes con AM severa, LMA y recaída de LMA. Considerar en recaída de LLA de alto riesgo en etapa de inducción.

BACKGROUND: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in pediatric oncology patients and severe aplastic anemia (SAA). AIM: To describe the epidemiology of IFI from 2016 to 2020 in children with cancer and SAA to assess the indication of antifungal prophylaxis. METHODS: Multicenter, retrospective study of IFIs in pediatric oncology patients and SAA. Probable and proven IFIs were included. RESULTS: Over the 5-year period, 57 IFIs were found, median age 9 years, 70% were proven and 30% were probable. Yeast infections were 42% and mold infections 56%. The most frequent infection sites were lung 38%, blood 36% and rhinosinusal 21%. The total IFI frequency was 5.4%, 21% in SAA, 10% in acute myeloid leukemia (AML), 6.9% in relapsed AML, 5.4% in relapsed acute lymphoblastic leukemia (ALL), 3.8% in ALL. Mold infections were predominant in AML, relapsed AML, and SAA. IFIs mortality was 11%. CONCLUSION: Frequency of IFI was consistent with the literature. We strongly recommend antifungal prophylaxis against mold infections in patients with SAA, AML, and relapsed AML. Would consider in high risk ALL relapse in induction chemotherapy.

Traveling Does More Than Widen One's Horizon: Travel History as Key to Diagnosing Blastomycosis.

This case report highlights the importance of a detailed travel history and the need to revisit the differential diagnosis when there is an unexpected clinical course. A previously healthy 15-year-old male presented to a hospital in Florida with a fever, cough, and shortness of breath. He was seen multiple times at urgent care centers and treated with steroids and antibiotics for community-acquired pneumonia (CAP). The patient's chest X-rays and CT showed necrotizing pneumonia with pleural effusion, which required a chest tube. Despite broadening coverage for possible resistant organisms, his fevers and hypoxia continued. On day 14 of hospitalization, a bronchoscopy was performed, which led to the diagnosis of blastomycosis. History was revisited, and a specific travel history was obtained. The patient had been camping with his father on the Minnesota/Canada border a few months prior to his presentation. Blastomycosis is caused by a dimorphic fungus endemic in certain parts of the United States including areas surrounding the Mississippi and Ohio River valleys, some southeastern states, and areas bordering the Great Lakes. Autochthonous blastomycosis is not seen in Florida. The infection is acquired by inhalation of the organism and is associated with outdoor occupation and recreation. As with other infections with specific endemic distribution, the diagnosis of blastomycosis can be delayed if the epidemiologic link is not established. Questions about travel history need to be very specific as this could be critical in establishing the appropriate differential diagnosis and leading the workup. The patient's lack of improvement despite appropriate antibiotic therapy for CAP led to questioning the working diagnosis, revisiting the history, and expanding the workup, which was critical in this case.

Noise characteristics in spaceflight multichannel EEG.

The cognitive performance of the crew has a major impact on mission safety and success in space flight. Monitoring of cognitive performance during long-duration space flight therefore is of paramount importance and can be performed using compact state-of-the-art mobile EEG. However, signal quality of EEG may be compromised due to the vicinity to various electronic devices and constant movements. We compare noise characteristics between in-flight extraterrestrial microgravity and ground-level terrestrial electroencephalography (EEG) recordings. EEG data recordings from either aboard International Space Station (ISS) or on earth's surface, utilizing three EEG amplifiers and two electrode types, were compared. In-flight recordings showed noise level of an order of magnitude lower when compared to pre- and post-flight ground-level recordings with the same EEG system. Noise levels between ground-level recordings with actively shielded cables, and in-flight recordings without shielded cables, were similar. Furthermore, noise level characteristics of shielded ground-level EEG recordings, using wet and dry electrodes, and in-flight EEG recordings were similar. Actively shielded mobile dry EEG systems will support neuroscientific research and neurocognitive monitoring during spaceflight, especially during long-duration space missions.

Manejo de los episodios de neutropenia febril en niños con cáncer: consenso de la Sociedad Latinoamericana de Infectología Pediátrica 2021 / Management of episodes of febrile neutropenia in children with cancer: consensus of the Latin American Society of Pediatric Infectious Diseases 2021

Resumen El Comité de Infecciones en el Niño Inmunocomprometido de la Sociedad Latinoamericana de Infectología Pediátrica, entrega este documento de Consenso, llamado "Manejo de los episodios de neutropenia febril en niños con cáncer. Consenso de la Sociedad Latinoamericana de Infectología Pediátrica 2021". El documento contiene recomendaciones sobre aspectos de prevención, predicción, diagnóstico, tratamiento y pronóstico de los episodios de fiebre y neutropenia, incluyendo recomendaciones específicas sobre: Análisis de ingreso; evaluación, ajustes y duración de terapias antimicrobianas; diagnóstico y manejo de infección fúngica invasora; análisis de los principales focos clínicos de infección; condiciones ambientales necesarias para hospitales que atienden niños con cáncer y quimioprofilaxis. Se ha puesto especial énfasis en entregar las mejores recomendaciones para optimizar el manejo de los episodios de fiebre y neutropenia en niños con cáncer, buscando la equidad y la excelencia a través de todos los centros que atienden estos pacientes en América Latina.

Abstract The Committee for Infections in Immunocompromised Children of Sociedad Latinoamericana de Infectología Pediátrica, presents this Consensus document, titled "Management of episodes of febrile neutropenia in children with cancer. Consensus of the Sociedad Latinoamericana de Infectología Pediátrica 2021". The document includes recommendations on prevention, prediction, diagnosis, treatment and prognosis of episodes of fever and neutropenia, including specific recommendations on: Analysis at admission; evaluation, adjustments and duration of antimicrobial therapies; diagnosis and management of invasive fungal infection; analysis of the main clinical source of infections; environmental conditions necessary for hospitals caring for children with cancer and chemoprophylaxis. Special emphasis has been placed on providing the best recommendations to optimize the management of episodes of fever and neutropenia in children with cancer, with equity and excellence through all the centers that treat these patients in Latin America.

Cytokine and chemokine profiles in episodes of persistent high-risk febrile neutropenia in children with cancer.

BACKGROUND: In children with cancer and persistent high-risk febrile neutropenia (HRFN), cytokines/chemokines profiles can guide the differentiation of febrile neutropenia (FN) due to infections and episodes of unknown origin (FN-UO). METHODS: A prospective, multicenter study in Santiago, Chile included patients ≤ 18 years with cancer and HRFN. Clinical and microbiological studies were performed according to validated protocols. Serum levels of 38 cytokines/chemokines were determined on day 4 of persistent HRFN. We performed comparisons between i) HRFN episodes with a detected etiological agent (FN-DEA) and FN-UO, and ii) bacterial versus viral infections. ROC curves were used to assess the discriminatory power of the analytes. RESULTS: 110 HRFN episodes were enrolled (median age 8 years, 53% female). Eighty-four patients were FN-DEA: 44 bacterial, 32 viral, and 8 fungal infections. Twenty-six cases were categorized as FN-UO. Both groups presented similar clinical and laboratory characteristics. Nineteen out of 38 analytes had higher concentrations in the FN-DEA versus FN-UO group. G-CSF, IL-6, and Flt-3L showed the highest discriminatory power to detect infection (AUC 0.763, 0.741, 0.701). Serum levels of G-CSF differentiated bacterial infections and IP-10 viral agents. A combination of G-CSF, IL-6, Flt-3L, and IP-10 showed an AUC of 0.839, 75% sensitivity, and 81% specificity. CONCLUSION: A specific immune response is present on day four of persistent HRFN in children with cancer. We propose a combined measure of serum concentrations of G-CSF, IL-6, IP-10, and Flt-3L, in order to predict the presence of an infectious agent as compared to an episode of FN with unknown origin.

Crucial contribution of the universities to SARS-CoV-2 surveillance in Ecuador: Lessons for developing countries.

COVID-19 pandemic has challenged public health systems worldwide, particularly affecting developing countries in Latin America like Ecuador. In this report, we exposed the fundamental role of the Ecuadorian universities to improve COVID-19 surveillance in the country, with an overall contribution over 15% of the total SARS-CoV-2 RT-PCR tests done. We highlight the role of our university during the first semester of the COVID-19 pandemic, contributing to a massive free SARS-CoV-2 testing up to almost 10% of the total diagnosis completed in the country, mainly focus on underserved urban, rural and indigenous communities. Finally, we described our contribution to a high quality and low-cost SARS-CoV-2 RT-PCR diagnostic in Ecuador.

[Management of episodes of febrile neutropenia in children with cancer. Consensus of the Latin American Society of Pediatric Infectious Diseases 2021]. / Manejo de los episodios de neutropenia febril en niños con cáncer. Consenso de la Sociedad Latinoamericana de Infectología Pediátrica 2021.

The Committee for Infections in Immunocompromised Children of Sociedad Latinoamericana de Infectología Pediátrica, presents this Consensus document, titled "Management of episodes of febrile neutropenia in children with cancer. Consensus of the Sociedad Latinoamericana de Infectología Pediátrica 2021". The document includes recommendations on prevention, prediction, diagnosis, treatment and prognosis of episodes of fever and neutropenia, including specific recommendations on: Analysis at admission; evaluation, adjustments and duration of antimicrobial therapies; diagnosis and management of invasive fungal infection; analysis of the main clinical source of infections; environmental conditions necessary for hospitals caring for children with cancer and chemoprophylaxis. Special emphasis has been placed on providing the best recommendations to optimize the management of episodes of fever and neutropenia in children with cancer, with equity and excellence through all the centers that treat these patients in Latin America.

Usefulness of serum galactomannan in initiating and modifying antifungal therapy in children with cancer and persistent high-risk febrile neutropenia.

BACKGROUND: Invasive fungal disease is a major cause of morbidity and mortality in children with cancer and high-risk febrile neutropenia (HRFN). Repeated serum galactomannan (sGM) measurements have been described as an effective tool to guide therapy in adults under suspicion of invasive aspergillosis. However, the utility of this approach has not been reported in paediatric population. OBJECTIVES: To evaluate the usefulness of sGM measurements in initiating and modifying antifungal therapy (AFT) in children with cancer and persistent HRFN. PATIENTS/METHODS: Nested case-control study in children with cancer and persistent HRFN episodes, between July 2013 and January 2019. Patients were classified as cases and controls depending on if they received AFT or not, respectively. Through odds ratio analysis, we assessed the role of sGM positivity in the AFT initiation decision. Then, we analysed the group of patients that initiated AFT, and compared those who had AFT modifications and those who did not, analysing different sGM kinetics thresholds. RESULTS: A total of 191 episodes from children with persistent HRFN were enrolled, of which 107 received AFT and 84 did not. The median age was 7 years (IQR 4-12), 52% were male and 89% had a haematologic malignancy as underlying disease. Positive sGM was not associated with AFT initiation (OR 0.99, 95% CI 0.43-2.33, P = .99). A difference threshold in sGM Δ ≥ 0.3 sGM was significantly associated with AFT modification (OR 5.07, 95% CI 1.02- 25.70, P = .04). CONCLUSIONS: Our results suggest the utility of serial sGM sampling during AFT in children with persistent HRFN.

A report of congenital adrenal hyperplasia due to 17α-hydroxylase deficiency in two 46,XX sisters.

Congenital adrenal hyperplasia (CAH) is a group of rare orphan disorders caused by mutations in seven different enzymes that impair cortisol biosynthesis. The 17α-hydroxylase deficiency (17OHD) is one of the less common forms of CAH, corresponding to approximately 1% of the cases, with an estimated annual incidence of 1 in 50,000 newborns. Cases description - two phenotypically female Ecuadorian sisters, both with primary amenorrhea, absence of secondary sexual characteristics, and osteoporosis. High blood pressure was present in the older sister. Hypergonadotropic hypogonadism profile was observed: decreased cortisol and dehydroepiandrosterone sulfate (DHEAS), increased adrenocorticotropic hormone (ACTH) and normal levels of 17-hydroxyprogesterone, extremely high deoxycorticosterone (DOC) levels, and a tomography showed bilateral adrenal hyperplasia in both sisters. Consanguinity was evident in their ancestors. Furthermore, in the exon 7, the variant c.1216T > C, p.Trp406Arg was detected in homozygosis in the CYP17A1 gene of both sisters. We report a homozygous missense mutation in the CYP17A1 gene causing 17OHD in two sisters from Loja, Ecuador. According to the authors, this is the first time such deficiency and mutation are described in two members of the same family in Ecuador.

[Consensus of infectious complications in patients treated with selected biological therapies: first Part]. / Consenso sobre riesgo de complicaciones infecciosas en pacientes usuarios de medicamentos biológicos seleccionados. Parte I.

The use of biological therapies has meant a great improvement in the management of several conditions like autoimmune, neoplastic or others diseases. Although its use has implied significant improvements in the prognosis of these diseases, it is not exempt from complications: infectious diseases as one of them. The objective of this consensus was to evaluate, from an infectious viewpoint, the safeness of the most frequently used biological therapies and give recommendations for the prevention of infections in patients treated with these drugs. These recommendations were based on the highest quality evidence available for the selected biologics. The consensus counts of two manuscripts. This first part details the risks of developing infectious complications depending on the type of biological used for a certain pathology. This evaluation included a broad search in MEDLINE and Epistemonikos of systematic reviews and meta-analyzes of controlled clinical trials and casecontrol examining post-treatment infections with anti-TNF alpha, anti-CD20, anti-CD52, CTLA4-Ig and anti-integrins. The research was complemented by a review of: multicentre cohorts of biological users, the MMWR of the CDC, Atlanta, U.S.A., and national registers and scientific societies in which infectious complications derived from the use of biological therapies were mentioned.

Consenso sobre riesgo de complicaciones infecciosas en pacientes usuarios de medicamentos biológicos seleccionados. Parte I / Consensus of infectious complications in patients treated with selected biological therapies: first Part

Resumen La incorporación de terapias biológicas ha significado un gran avance en el manejo de diversas patologías de origen autoinmune, neoplásico u otros. Si bien su uso ha implicado mejoras significativas en el pronóstico de estas enfermedades, no está exento de complicaciones, entre estas, las infecciosas. El objetivo de este consenso fue evaluar el perfil de seguridad, desde la mirada infectológica, de las terapias biológicas de uso más frecuente y dar recomendaciones para la prevención de infecciones en pacientes tratados con ellas, basándose en la evidencia de mayor calidad disponible para los biológicos seleccionados. El consenso cuenta de dos manuscritos. Esta primera parte detalla los riesgos de desarrollar complicaciones infecciosas dependiendo del tipo de biológico utilizado para determinada patología. La revisión incluyó búsqueda amplia en MEDLINE y Epistemonikos de revisiones sistemáticas y meta-análisis de estudios clínicos controlados y caso/control que examinaban infecciones posteriores al tratamiento con anti-TNF alfa, anti-CD20, anti-CD52, CTLA4-Ig y anti-integrinas. Esta búsqueda se complementó con revisión de cohortes multicéntricas de usuarios de biológicos, del MMWR del CDC, Atlanta, E.U.A. y de registros nacionales y/o de sociedades científicas en la que se hiciera mención a complicaciones infecciosas derivadas del uso de biológicos.

The use of biological therapies has meant a great improvement in the management of several conditions like autoimmune, neoplastic or others diseases. Although its use has implied significant improvements in the prognosis of these diseases, it is not exempt from complications: infectious diseases as one of them. The objective of this consensus was to evaluate, from an infectious viewpoint, the safeness of the most frequently used biological therapies and give recommendations for the prevention of infections in patients treated with these drugs. These recommendations were based on the highest quality evidence available for the selected biologics. The consensus counts of two manuscripts. This first part details the risks of developing infectious complications depending on the type of biological used for a certain pathology. This evaluation included a broad search in MEDLINE and Epistemonikos of systematic reviews and meta-analyzes of controlled clinical trials and casecontrol examining post-treatment infections with anti-TNF alpha, anti-CD20, anti-CD52, CTLA4-Ig and anti-integrins. The research was complemented by a review of: multicentre cohorts of biological users, the MMWR of the CDC, Atlanta, U.S.A., and national registers and scientific societies in which infectious complications derived from the use of biological therapies were mentioned.

Chemometric assessment of soil organic matter storage and quality from humic acid infrared spectra.

The knowledge of biogeochemical mechanisms involved in soil organic carbon (SOC) storage is crucial to control its release to the atmosphere. In particular, the chemical composition of soil organic matter (SOM) plays an important role in the performance of the C storage and resilience in soils. The structural information provided by infrared spectroscopy (IR) of soil humic acid (HA) was used in the assessment of the C storage potential of 35 Spanish soils. Partial least squares (PLS) regression using the intensities of the points of the IR spectra of the HAs (4000-400 cm-1) as descriptors shows that a relationship exists between IR spectral pattern and the SOC content. This was also the case for E4 (humification index based on HA optical density at 465 nm). In addition, the chemical characteristics of the HAs correlated with the SOC levels were identified from digital data treatments of the IR spectra. Additional application of principal component analysis (PCA) and multidimensional scaling (MDS) suggested that bands assigned to carboxyl and amide structures were characteristic in HAs from soils with low C content, whereas HA spectra from soils with high C levels showed a conspicuous band pattern suggesting structural units of lignin from slightly transformed plant residues. The spectral profiles were analyzed in detail by an approach based on digital subtraction of IR spectra obtained by averaging those from HAs extracted from soils in the upper and lower quartiles of the SOC distribution. The results showed that significant relationships exist between the molecular composition of HAs and SOC levels and E4 values in a way in which aromatic, carboxyl and amide groups were predominant in HAs from soils with low SOC content, whereas lignin-derived structures were more characteristic of HAs from soils with high SOC content.

The Current Genomic Landscape of Western South America: Andes, Amazonia, and Pacific Coast.

Studies of Native South American genetic diversity have helped to shed light on the peopling and differentiation of the continent, but available data are sparse for the major ecogeographic domains. These include the Pacific Coast, a potential early migration route; the Andes, home to the most expansive complex societies and to one of the most widely spoken indigenous language families of the continent (Quechua); and Amazonia, with its understudied population structure and rich cultural diversity. Here, we explore the genetic structure of 176 individuals from these three domains, genotyped with the Affymetrix Human Origins array. We infer multiple sources of ancestry within the Native American ancestry component; one with clear predominance on the Coast and in the Andes, and at least two distinct substrates in neighboring Amazonia, including a previously undetected ancestry characteristic of northern Ecuador and Colombia. Amazonian populations are also involved in recent gene-flow with each other and across ecogeographic domains, which does not accord with the traditional view of small, isolated groups. Long-distance genetic connections between speakers of the same language family suggest that indigenous languages here were spread not by cultural contact alone. Finally, Native American populations admixed with post-Columbian European and African sources at different times, with few cases of prolonged isolation. With our results we emphasize the importance of including understudied regions of the continent in high-resolution genetic studies, and we illustrate the potential of SNP chip arrays for informative regional-scale analysis.

Efficacy of pre-emptive versus empirical antifungal therapy in children with cancer and high-risk febrile neutropenia: a randomized clinical trial.

Objectives: To compare the efficacy of pre-emptive versus empirical antifungal therapy in children with cancer, fever and neutropenia. Methods: This was a prospective, multicentre, randomized clinical trial. Children presenting with persistent high-risk febrile neutropenia at five hospitals in Santiago, Chile, were randomized to empirical or pre-emptive antifungal therapy. The pre-emptive group received antifungal therapy only if the persistent high-risk febrile neutropenia was accompanied by clinical, laboratory, imaging or microbiological pre-defined criteria. The primary endpoint was overall mortality at day 30 of follow-up. Secondary endpoints included invasive fungal disease (IFD)-related mortality, number of days of fever, days of hospitalization and use of antifungal drugs, percentage of children developing IFD, requiring modification of initial treatment strategy and need for ICU. The trial was registered with Registro Brasileiro de Ensaios Clínicos (ReBEC) under trial number RBR-3m9d74. Results: A total of 149 children were randomized, 73 to empirical therapy and 76 to pre-emptive therapy. Thirty-two out of 76 (42%) children in the pre-emptive group received antifungal therapy. The median duration of antifungal therapy was 11 days in the empirical arm and 6 days in the pre-emptive arm (P < 0.001), with similar overall mortality (8% in the empirical arm and 5% in the pre-emptive arm, P = 0.47). IFD-related mortality was the same in both groups (3%, P = 0.97), as were the percentage of children with IFD (12%, P = 0.92) and the number of days of fever (9, P = 0.76). The number of days of hospitalization was 19 in the empirical arm and 17 in the pre-emptive arm (P = 0.15) and the need for ICU was 25% in the empirical arm and 20% in the pre-emptive arm (P = 0.47). Conclusions: Pre-emptive antifungal therapy was as effective as empirical antifungal therapy in children with cancer, fever and neutropenia, significantly reducing the use of antifungal drugs.

Multi-Target Strategy for Pan/Foot-and-Mouth Disease Virus (FMDV) Detection: A Combination of Sequences Analysis, in Silico Predictions and Laboratory Diagnostic Evaluation.

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed animals that causes severe economic losses. The disease is characterized by a vesicular condition and it cannot be differentiated from other vesicular diseases. Therefore, laboratory confirmation of any suspected FMD case is compulsory. Despite viral isolation in cell cultures has been considered for many years as the gold standard for FMD diagnosis, the advantages of real-time reverse transcription polymerase chain reaction (rRT-PCR) technology have motivated its use directly in clinical specimens for FMD diagnosis. The current work was aimed to develop and validate a molecular multi-check strategy using rRT-PCR (mMulti-rRT-PCR) based on SYBR-Green I for pan/foot-and-mouth disease virus (pan/FMDV) diagnosis. From in silico approaches, different primer pairs previously reported were selected and modified to reduce the likelihood of viral escape as well as potential failures in the pan/FMDV detection. The analytical parameters were evaluated using a high number of representative viral strains. The repeatability of the assay and its performance on field samples were also assessed. The mMulti-rRT-PCR was able to detect emergent FMDV strains that circulated in South America between the years 2006-2010 and on which the single rRT-PCRs failed when they were applied independently. The results obtained here showed that the proposed system is an accurate and rapid diagnosis method for sensitive and specific detection of FMDV. Thus, a validated mMulti-rRT-PCR assay based on SYBR-Green I detection coupled to melting curves resolution for pan/FMDV diagnosis on clinical samples is proposed. This study also highlights the need to incorporate the multi-target detection principle in the diagnosis of highly variable agents, specially, of those listed by OIE like FMDV.

[Microorganisms isolated from blood cultures in children with cancer and high-risk febrile neutropenia from five hospitals in Santiago, Chile, 2012-2015]. / Microorganismos aislados de hemocultivos en niños con cáncer y neutropenia febril de alto riesgo en cinco hospitales de Santiago, Chile, período 2012-2015.

BACKGROUND: Microorganisms isolated from blood cultures (BC) in patients with febrile neutropenia (NF) vary over time, requiring systematic monitoring to guide appropriate empirical therapy. AIM: To identify microorganisms isolated from BC and their antimicrobial resistance profile in children with cancer and high risk NF. METHOD: Prospective, multicenter study. The analysis included episodes of high-risk FN with positive BC in children under 18 years of age treated in five hospitals in Santiago, Chile, 2012-2015. RESULTS: A total of 206 microorganisms were analyzed in 185 episodes of high-risk FN. The main isolates were Gram negative bacilli (46.6%) and Gram positive cocci (45.1%) and the most frequent microorganisms were Escherichia coli (22.8%), coagulase negative Staphylococcus (18.0%) and Klebsiella spp. (16.5%). Escherichia coli and Klebsiella spp showed 4.2% and 67.6% resistance to third generation cephalosporins (cefotaxime/ceftriaxone), 10.6% and 40.6% resistance to fluoroquinolones (ciprofloxacin) and 2.1% and 26.5% to amikacin, respectively. Coagulase negative Staphylococcus and Staphylococcus aureus had 86.4% and 22.2% resistance to oxacillin, Streptococcus viridans group had 71% resistance to penicillin. DISCUSSION: This study updates the etiology and resistance profile of microorganisms isolated in BC from children with cancer and high risk FN, an essential tool for the adequate management of these patients.

Genetic diversity of the HLA system in human populations from the Sierra (Andean), Oriente (Amazonian) and Costa (Coastal) regions of Ecuador.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in a total of 1101 Ecuadorian individuals from three regions of the country, the Coastal region, the Andean region, and the Amazonian region, to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent HLA haplotypes with significant linkage disequilibrium in those populations are HLA-A*24∼B*35∼DRB1*04∼DQB1*03:02, A*02∼B*35∼DRB1*04∼DQB1*03:02, A*24∼B*35∼DRB1*14∼DQB1*03:01, A*02∼B*35∼DRB1*14∼DQB1*03:01 and A*02∼B*40:02∼DRB1*04∼DQB1*03:02. The only non-Native American haplotype with frequency >1% shared by all groups was A*29∼B*44∼DRB1*07∼DQB1*02. Admixture estimates obtained by a maximum likelihood method using HLA-B as genetic estimator revealed that the main genetic components for this sample of mixed-ancestry Ecuadorians are Native American (ranging from 52.86% to 63.83%) and European (from 28.95% to 46.54%), while an African genetic component was only apparent in the Coastal region (18.19%). Our findings provide a starting point for the study of population immunogenetics of Ecuadorian populations.