Regional moderate hyperthermia for mild-to-moderate COVID-19 (TherMoCoV study): a randomized controlled trial.

Background: To prevent COVID-19 progression, low-cost alternatives that are available to all patients are needed. Diverse forms of thermotherapy have been proposed to prevent progression to severe/critical COVID-19. Objective: The aim of this study is to evaluate the efficacy and safety of local thermotherapy to prevent disease progression in hospitalized adult patients with mild-to-moderate COVID-19. Methods: A multicenter, open-label, parallel-group, randomized, adaptive trial is used to evaluate the efficacy and safety of local thermotherapy to prevent disease progression in hospitalized adult patients with mild-to-moderate COVID-19. Eligible hospitalized adult patients with symptoms of COVID-19 with ≤5 days from symptom onset, meeting criteria for mild or moderate COVID-19, were randomly assigned to the intervention consisting of local thermotherapy via an electric heat pad in the thorax (target temperature range 39.5­42°C) continuously for 90 min, twice daily, for 5 days, or standard care. The main outcome was the proportion of patients who progressed to severe-to-critical COVID-19 or death. Patients were randomized in a 1:1 ratio through a centralized computer-generated sequence of minimization with a random component of 20%. Participants and medical staff were not blinded to the intervention. Results: One-hundred and five participants (thermotherapy n = 54, control n = 51) with a median age of 53 (IQR: 41­64) years were included for analysis after the early cessation of recruitment due to the closure of all temporal COVID-19 units (target sample size = 274). The primary outcome of disease progression occurred in 31.4% (16/51) of patients in the control group vs. 25.9% (14/54) of those receiving thermotherapy (risk difference = 5.5%; 95%CI: −11.8­22.7, p = 0.54). Thermotherapy was well tolerated with a median total duration of thermotherapy of 900 (IQR: 877.5­900) min. Seven (13.7%) patients in the control group and seven (12.9%) in the thermotherapy group had at least one AE (p = 0.9), none of which were causally attributed to the intervention. No statistically significant differences in serum cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-17, and IFN-γ) were observed between day 5 and baseline among groups. Conclusion: Local thermotherapy was safe and well-tolerated. A non-statistically significant lower proportion of patients who experienced disease progression was found in the thermotherapy group compared to standard care. Local thermotherapy could be further studied as a strategy to prevent disease progression in ambulatory settings.Clinical Trial registration: www.clinicaltrials.gov, identifier: NCT04363541.

Lactancia materna y COVID-19 / Breastfeeding and COVID-19

Resumen La pandemia de enfermedad por coronavirus 2019 (COVID-19) ha afectado a todas las dimensiones de la atención en salud, entre ellas el aseguramiento de la lactancia materna exclusiva y su promoción. El riesgo de contagio y las consecuencias de la pandemia han provocado preocupación entre las futuras madres o las que se ya encuentran lactando debido al riesgo de una posible transmisión del virus a través de la leche materna. Aunque aún no se ha detectado el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) activo en la leche materna. El miedo al contagio ha favorecido las políticas de aislamiento madre-hijo. Hasta el momento no existe evidencia de transmisión vertical y el riesgo de transmisión horizontal en el lactante es similar al de la población general. En lactantes con COVID-19 la lactancia materna incluso puede cambiar favorablemente el curso clínico de la enfermedad.

Abstract The COVID-19 pandemic has affected the health attention in all dimensions, one of them, the exclusive breastfeeding assurance and her promotion. The high risk of contagion and the pandemic consequences have raised a number of concerns in future mothers or those who are breastfeeding because of the risk of a possible transmission of the virus through breast milk. Although SARS-CoV2 has no evidence of being active on breast milk, the fear of contagion has favored mother-child isolation policies. At this point, there are no evidence of vertical transmission and the risk of horizontal transmission in the infant is similar to the general population. Breastfeeding in newborn with COVID-19, can even favorably change the clinical course of the disease.

Neurophysiological Mechanisms Related to Pain Management in Bone Tumors.

BACKGROUND: Primary and metastatic bone tumor incidence has increased in the previous years. Pain is a common symptom and is one of the most important related factors to the decrease of quality of life in patients with bone tumor. Different pain management strategies are not completely effective and many patients afflicted by cancer pain cannot be controlled properly. In this sense, we need to elucidate the neurophysiology of cancer-induced pain, contemplating other components such as inflammation, neuropathies and cognitive components regarding bone tumors, and thus pave the way for novel therapeutic approaches in this field. AIM: This study aims to identify the neurophysiology of the mechanisms related to pain management in bone tumors. METHODS: Advanced searches were performed in scientific databases: PubMed, ProQuest, EBSCO, and the Science Citation index to get information about the neurophysiology mechanisms related to pain management in bone tumors. RESULTS: The central and peripheral mechanisms that promote bone cancer pain are poorly understood. Studies have shown that bone cancer could be related to neurochemicals produced by tumor and inflammatory cells, coupled with peripheral sensitization due to nerve compression and injury caused by tumor growth. The activity of mesolimbic dopaminergic neurons, substance P, cysteine/ glutamate antiporter, and other neurochemical dynamics brings us putative strategies to suggest better and efficient treatments against pain in cancer patients. CONCLUSION: Cancer-induced bone pain could include neuropathic and inflammatory pain, but with different modifications to the periphery tissue, nerves and neurochemical changes in different neurological levels. In this sense, we explore opportunity areas in pharmacological and nonpharmacological pain management, according to pain-involved mechanisms in this study.

Factores asociados a muerte en niños con COVID-19 en México / Mortality risk factors in Mexican children with COVID-19

Resumen Introducción: Se informa que la mayoría de los niños afectados por SARS-CoV-2 cursan asintomáticos y que en ellos la mortalidad por COVID-19 es baja; en México se desconoce la información al respecto en este grupo de la población. Objetivo: Evaluar los factores de riesgo asociados a mortalidad en niños mexicanos con COVID-19. Método: Análisis secundario de la base de datos de la Dirección General de Epidemiología. Se incluyeron niños menores de 19 años, en quienes se confirmó SARS-CoV-2 mediante RT-PCR. Resultados: Se incluyeron 1443 niños. La mediana de edad fue de ocho años; 3.3 % ingresó a la unidad de cuidados intensivos, 1.8 % requirió ventilación mecánica asistida y la mortalidad fue de 1.9 %. En los modelos multivariados, el desarrollo de neumonía constituyó el principal factor de riesgo de mortalidad, con razón de momios (RM) de 6.45 (IC 95 % 1.99, 20.89); los pacientes que requirieron intubación tuvieron RM de 8.75 (IC 95 % 3.23, 23.7). Conclusiones: Los niños con COVID 19 tienen alta mortalidad en México, por lo que en ellos se debe procurar evitar la neumonía, especialmente en los menores de cuatro años, con riesgo cardiovascular o inmunosupresión.

Abstract Introduction: Most children affected by SARS-CoV-2 are reported to be asymptomatic, and COVID-19-related mortality in them is low; in Mexico, there is a lack of information on the subject in this population group. Objective: To assess the risk factors associated with mortality in Mexican children with COVID-19. Method: Secondary analysis of the General Directorate of Epidemiology database. Children younger than 19 years, in whom SARS-CoV-2 infection was confirmed by RT-PCR, were included. Results: 1443 children were included. Median age was eight years; 3.3 % were admitted to the intensive care unit, 1.8 % required assisted mechanical ventilation, and mortality was 1.9 %. In multivariate models, the development of pneumonia was the main risk factor for mortality, with an odds ratio (OR) of 6.45 (95 % CI 1.99, 20.89); patients who required intubation had an OR of 8.75 (95 % CI 3.23, 23.7). Conclusions: Children with COVID-19 exhibit high mortality in Mexico, and avoiding pneumonia should therefore be tried in them, especially in children younger than four years with cardiovascular risk or immunosuppression.

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery.

BACKGROUND: Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery. METHODS: A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed. RESULTS: Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 µg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (ß = -27 µg/kg, p = 0.028; R2 model = 0.90) for shorter duration (ß = -9 days, p = 0.003; R2 model = 0.94). No differences in fentanyl or ketorolac were detected. CONCLUSIONS: Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects.

Beneficial Effects of Enteral Docosahexaenoic Acid on the Markers of Inflammation and Clinical Outcomes of Neonates Undergoing Cardiovascular Surgery: An Intervention Study.

BACKGROUND: Neonates undergoing surgery are at risk for uncontrolled inflammatory response and adverse clinical outcomes. Docosahexaenoic acid (DHA) ameliorates inflammation, improving clinical outcomes. However, its effect has not been evaluated in neonates undergoing surgery. We evaluated the effect of DHA on markers of inflammation and clinical outcomes in neonates undergoing surgery. METHODS: A double-blind clinical trial evaluated the effect of enteral DHA (DHA group) versus sunflower oil (SO group) perioperatively administered in neonates scheduled for cardiovascular surgery. Inflammation was evaluated by percentage of cells+ for cytokines and CD69 in mononuclear cells at baseline, 24 h and 7 days post surgery. Clinical outcomes measured were sepsis, organ dysfunctions (ODs), length of stay in intensive care and bleeding. Repeated measures analysis of variance and logistic regression were applied. RESULTS: Sixteen neonates received DHA and 18 received SO. Cells+ from neonates in the DHA group showed an early increase in receptor antagonist of interleukin (IL)-1+ (IL-1ra+) and IL-10+ and a late decrease in IL-6+. IL-1ß+ and IL-10+ changes were different between groups. After adjusting for confounders, less cells from DHA group were IL-1ß+, IL-6+, IL-1ra+ and IL-10+. DHA group presented less sepsis, ODs and shorter stay, but no difference in CD69+CD4+ cells or bleeding between groups. CONCLUSIONS: Administration of enteral DHA ameliorates markers of inflammation and improves clinical outcomes in surgical neonates.

Inflammatory Response in Preterm and Very Preterm Newborns with Sepsis.

The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation.

Relación médico-paciente con cáncer / Physician-patient relationship in cancer patients

Es conocido que en el terreno de la salud, el adecuado establecimiento de la relación médico-paciente favorece la intervención profesional oportuna, mejorando la evolución en el proceso de la enfermedad que da motivo al establecimiento de tal vínculo. Esta relación también ha cambiado, favoreciendo la participación activa del paciente en la toma de decisiones sobre su cuidado y salud, así como el compromiso ético en los profesionales de la salud con relación a la actualización de sus conocimientos, remarcando la importancia de la comunicación entre ambas partes. El paciente con cáncer y su familia cursan por un proceso peculiar, debido a la representación social y mental de esta enfermedad, así como por la toma de decisiones, y se hace evidente en ellos una especial vulnerabilidad durante el curso del padecimiento. El médico debe desarrollar su habilidad para la comunicación de malas noticias, asumiendo un rol ético, profesional y humanitario.

It is a well known fact in the health circle that establishing an adequate rapport with the patient facilitates timely interventions, which in turn can improve the course of the disease. The physician-patient relationship has evolved in order to favor an active participation of the patient in the decision-making process concerning his health and self-care, as well as promoting a more ethical commitment of the health professional through motivating knowledge updating and emphazising the importance of developing communication skills. Cancer patients and their families are particularly vulnerable, since they experience a difficult process due to the social and mental representations of cancer, and the tough decisions they have to make in relation to the disease. The health professional has to develop communication skills to deliver bad news from an ethical, professional and human point of view.

Retinopatía del prematuro: controversias en el uso de antiangiogénicos intraoculares / Retinopathy of prematurity: controversies in the usage of intraocular antiangiogenics

El aumento en la sobrevida de los recién nacidos prematuros, las características del cuidado neonatal y la escasez de programas para la prevención, detección y tratamiento de la retinopatía del prematuro provocan que esta enfermedad sea la principal causa de ceguera infantil prevenible en México. El advenimiento de agentes antiangiogénicos de uso oncológico, y su uso -no autorizado, aunque con buenos resultados- en el tratamiento de enfermedades vaso proliferativas en la retina del paciente adulto, así como la presencia de reportes anecdóticos en la literatura y series de casos con serias fallas metodológicas han sugerido su utilización en el tratamiento de la retinopatía del prematuro. Desafortunadamente, estos agentes, utilizados indiscriminadamente, presentan absorción sistémica y causan efectos secundarios en el organismo del paciente prematuro. Además, no existen estudios de seguimiento a largo plazo que garanticen la seguridad de su uso en esta población. El presente artículo describe la situación en nuestro país y advierte sobre los riesgos de estos medicamentos en la población de pacientes prematuros.

The increase in survival rates among preterm infants, characteristics of neonatal care for such infants and a lack of suitable programs for preventing, detecting and treating retinopathy of prematurity (ROP) are factors that have made this disease the main cause of preventable blindness among children in Mexico. The advent of antiangiogenic agents in cancer treatment and their off-label use with favorable results in the treatment of proliferative vessel disease of the retina among adult patients, as well as anecdotal reports in the literature and a series of cases showing serious methodological flaws, have prompted their use in the treatment of retinopathy of prematurity. Unfortunately, these agents used indiscriminately in our country have a systemic absorption and secondary effects on the preterm patient's body. There are no long-term monitoring studies that guarantee their safe use in this segment of the population. This article describes the situation in our country and warns of the risks posed by the use of this type of drug on the preterm infant population.

Interleukin-1 receptor antagonist gene polymorphism increases susceptibility to septic shock in children with acute lymphoblastic leukemia.

BACKGROUND: Interleukin-1 receptor antagonist polymorphism (ILRN) 2 (ILRN*2) has been associated with a poor outcome in septic patients because of an elevated production of anti-inflammatory cytokines. In >70% of patients, morbidity and mortality in childhood acute lymphoblastic leukemia is caused by infections. The aim of this study was to determine the association between this polymorphism and the frequency of septic shock from the time of diagnosis until completion of treatment. METHODS: This cohort study was conducted in 57 consecutive children with acute lymphoblastic leukemia. At the end of follow-up, children were stratified according to their IL1RN polymorphism (ILRN*1/ILRN*2), evaluating the impact of genotype on the severity of febrile neutropenic events during their treatment. RESULTS: Overall survival was 80% at 55 months after treatment. The average number of febrile neutropenic events in this cohort was 2.82 per patient. Genotype distribution was 50.9% for homozygote IL-1RN*1, 38.6% for heterozygote ILRN*1/ILRN*2 and 10.5% for homozygote IL-1RN*2. The risk of presenting septic shock for homozygote IL1RN*2/IL1RN*2 and heterozygote ILRN*1/ILRN*2 patients was significantly greater (odds ratio, 45; P = 0.001) adjusted for age, gender, risk of leukemia and presence of pathogenic bacteria. Genotype IL-1RN*2 is associated with the risk of development of septic shock in children with acute lymphoblastic leukemia. Further research in larger population-based studies is needed to replicate these findings. CONCLUSIONS: This information would allow us to identify more predictive factors in this group of acute lymphoblastic leukemia patients in whom this information is lacking to establish an earlier and more aggressive approach.

Tumor necrosis factor -308 and lymphotoxin +252 polymorphisms in Mexican children with Kawasaki disease and coronary aneurysms.

BACKGROUND AND AIMS: The Mexican population has a distinct capacity for the expression of tumor necrosis factor (TNF), a cytokine that plays a cardinal role in Kawasaki disease (KD), particularly in those who develop coronary aneurysms. It is important to identify, in Mexican pediatric patients, the association of the frequency of TNF. This study determined the association of TNF -308 and lymphotoxin-alpha (LTA) +252 polymorphisms in Mexican pediatric patients with KD and coronary aneurysms (CA). METHODS: We conducted a cross-sectional, analytical study in 48 children with KD, 22 with CA. Control samples were obtained from 61 aged-matched children. We took a peripheral blood sample and extracted genomic DNA from all children participating in the study. Using restriction factor length polymorphism-polymerase chain reaction (RFLP-PCR), we performed determination of TNF -308 and LTA +252. RESULTS: There was no difference in frequency between the study groups for genotype LTA +252 (OR 0.37, 95% CI, 0.06-2, p = 0.44) or between groups for KD with or without coronary aneurysms for both polymorphisms. In subjects with KD, we did not observe the heterozygous genotype of TNF -308, the difference being significant (OR 12, 95% CI, 4.8-30.4, p = 0.0001) using the χ(2) test with the continuity correction on comparison with the control group. CONCLUSIONS: Comparative analysis by group did not show a significant difference in the frequency of the alleles and genotypes between KD with CA vs. KD without CA vs. controls, for both TNF -308 and LTA +252.

Activity of hydroxyurea against Leishmania mexicana.

Leishmania mexicana is a protozoan parasite that causes a disease in humans with frequent relapses after treatment. It is also highly resistant to the currently available drugs. For this reason, there is an urgent need for more effective antileishmanial drugs. Hydroxyurea, an anticancer drug, is toxic to replicating eukaryotic cells and has been proven to be effective in arresting the Leishmania major cell cycle. In this study, hydroxyurea was tested in an in vitro model of intracellular Leishmania infection in macrophages. The parasite density in infected macrophages was measured by microscopy after incubation for various times and treatment with hydroxyurea at different concentrations. Viable parasites that could be transformed into promastigotes by shifting the temperature to 26 degrees C were counted every other day after the replacement of hydroxyurea with fresh medium. Meglumine antimoniate, the standard drug treatment for Leishmania mexicana, was used as a reference drug under the same experimental conditions. Hydroxyurea completely eliminated Leishmania parasites when it was used at a dosage of 10 or 100 microg/ml. Differences in the length of treatment needed to achieve elimination were as follows: the 10-microg/ml doses required 9 days, while 3 days was sufficient when 100 microg/ml was used. Hydroxyurea had a 50% effective dose of 0.015 microg/ml in vitro, which was observed on day 6 after exposure. Hydroxyurea is highly effective in killing intracellular amastigotes in vitro.

Utilidad de las citocinas en el diagnóstico de sepsis neonatal: medicina basada en evidencias / Diagnostic usefulness of cytokines in neonatal sepsis

La medición de citocinas pro-inflamatorias, como IL-1, TNFa y la IL-6 en plasma de neonatos con infección, ha sido objeto de controversia en cuanto a su consistencia diagnóstica, tal vez debido a las diferentes técnicas utilizadas y a la gran variedad de criterios de inclusión de los grupos de estudio. Sin embargo, muchos informes coinciden en que su incremento refleja la magnitud del proceso inflamatorio durante la infección. Con base en estudios sobre el tema publicados en los últimos 5 años y que se pueden consultar en bases de datos como Medline, se puede considerar que los incrementos de IL-1, TNFa, IL-6, IL-8 y proteína C reactiva son de utilidad en el apoyo diagnóstico y pronóstico de la sepsis neonatal. Las combinaciones aumentan la potencia de la sensibilidad, especificidad y valores predictivos, siendo las determinaciones en suero o plasma de IL-6 y proteína C reactiva las más útiles hasta el momento. La ventaja de utilizar estos indicadores de inflamación es que pueden fortalecer de manera temprana y en pocas horas la impresión clínica del médico tratante y agilizar el establecimiento de una terapéutica antimicrobiana oportuna. Otras citocinas se consideran ya como verdaderas alternativas de tratamiento adyuvante en la sepsis neonatal, tal es el caso de los factores estimulantes de colonias, superando ampliamente las expectativas que en su momento tuvieron los antagonistas, inhibidores y anticuerpos anti-citocinas o anticuerpos anti-endotoxina, que en grandes series de estudios multicéntricos demostraron poca utilidad clínica en humanos, a pesar de los resultados previos tan promisorios en modelos animales y en pacientes con choque séptico.

Antígenos de Giardia lamblia que son reconocidos por anticuerpos de lecha materna / Antigens of Giarda lamblia that are recognized by antibodies from human milk

Existen evidencias de que anticuerpos específicos participan en la eliminación del parásito Giardia lamblia, como lo indican los mayores índices de giardiosis en pacientes con deficiencias de IgA, y la protección contra esta parasitosis que la leche de animales inmunizados confiere a las crías. Con el fin de identificar los antígenos de este protozoario que son reconocidos por los anticuerpos presentes en las secreciones, se cuantificaron por ELISA las IgG e IgA anti-giardia en 104 leches maternas colectadas en el Departamento de Nutrición del Hospital del Niño, de Villahermosa, Tabasco; se determinó el sitio de reconocimiento en el trofozoíto por inmunofluorescencia indirecta (IFI) y se identificó el peso molecular relativo (PMr) de las proteínas de G. lamblia reconocidas por inmuno-electrotransferencia (Western-blot). En la prueba de ELISA, 89 por ciento de las muestras tuvo anticuerpos de clase IgA por arriba del punto de corte y hubo una estrecha correlación entre los niveles de IgA e IgG en la leche. En la IFI se observó que la membrana del trofozoíto reaccionó con intensidad a los anticuerpos anti-giardia de las muestras de leche estudiadas, algunas de las cuales tiñeron intensamente al disco suctor. Los antígenos identificados por Western-blot fueron 27 bandas con PMr de 26 a 185 kDa. Las seis bandas reconocidas con mayor frecuencia fueron las de 135, 127, 123, 112, 84 y 75 kDa. Otras con menor intensidad y frecuencia correspondieron a 185, 45, 42, 36 y 26 kDa. Se observaron dos patrones de bandas: múltiple, únicas (84 o_ 75 kDa). Este estudio identificó el peso molecular y la localización de las proteínas de G. lamblia hacia las que están dirigidos los anticuerpos secretorios específicos de la leche humana y que pudieran ser de importancia en la prevención y eliminación de la giardiosis

Amniotic fluid interleukin-6 and the risk of Early-Onset sepsis among preterm infants

Background. High concentrations of interleukin-6 (IL-6) have been demonstrated in amniotic fluid (AF) from women with intra-amniotic infection. Recent studies have reported that IL-6 levels in AF were related to a increase in neonatal morbidity; moreover, higher Il-6 plasma levels have been observed in neonates with sepsis. Methods. A cohort study was carried out at the National Institute of Perinatology in Mexico City. Inclusion criteria were the following: 1) preterm singleton pregnancy; 2) intact membranes at time of enrollment, and 3) written informed consent. Women with other complications of pregnancy were excluded. Newborn sepsis during the first 72 h was defined as early-onset sepsis. Amniotic fluid was obtained at the moment of delivery. Amniotic fluid Il-6 (Af IL-6) was determined by enzyme-linked immunoassays. Results. Ninety-three women met the criteria for enrolment in the study and 31 (33 percent) of their newborns had early-onset neonatal sepsis. The mean AF IL-6 in mothers of septic newborns was 5779 ñ 2804 pg/ml compared to 729 ñ 382 pg/ml in mothers with noninfected neonates (p<0.001). AF IL-6 concentrations higher than 1250 pg/ml were significantly associated with early-onset sepsis (OR 33.3: 95 percent CI 9.4-117.3) (p< 0.001). Gestational age under 32 weeks was also associated with neonatal sepsis (OR 2.56; 95 percent CI 1.2-9) (p = 0.002). Women whose infants developed neonatal sepsis had a higher frequency of clinical choriamnionitis (p = 0.02). Conclusions. IL-6 determination in AF may be a useful indicator to identifity neonates with higher risk of in utero bacterial infection

Avances y promesas en la inmunoterapia de sepsis neonatal / Advances and promises in immunotherpy for neonatal sepsis

La sepsis neonatal es una infección sistémica en el primer mes de vida que, según su gravedad, presenta las 4 fases del síndrome de respuesta inflamatoria sistémica (SRIS) que caracteriza a esta enfermedad en los adultos. El uso de antibióticos sigue siendo el pilar en su tratamiento; sin embargo, la morbi-letalidad de la sepsis neonatal no ha disminuido significativamente y la aparición de cepas resistentes es alarmante, lo cual plantea la necesidad de alternativas terapéuticas. En esta búsqueda, se pretende regular la respuesta inflamatoria a la infección a través de 3 grandes grupos de citocinas: interleucinas, interferones y los factores de crecimiento, algunas de las cuales se comportan como pro-inflamatorias, y otras como anti-inflamatorias al neutralizar, bloquear o inhibir a las pro-inflamatorias. Hasta ahora, los 2 mayores avances en la terapia auxiliar de sepsis neonatales son la inmunoglobulina para uso intravenoso (IgIV), que tiene su principal indicación en los neonatos prematuros y de bajo peso, y los factores estimulantes de colonias de granulocitos y de macrófagos (G-CSF y GM-CSF), indicados en neonatos pretérmino o a término con neutropenia por sepsis. Una actitud de extrema reserva entre muchos médicos ha postergado de manera poco justificable su aplicación clínica. En fases preliminares de investigación se encuentran los antagonistas naturales de la endotoxina bacteriana, como la BPI, proteína producida por los granulocitos, y las inmunoadhesinas, moléculas híbridas de inmunoglubulina y un receptor específico que bloquean la unión de citocinas pro-inflamatorias con sus receptores celulares, modulando así la respuesta inflamatoria a la infección