Intracellular osteopontin promotes the release of TNF by mast cells to restrain neuroendocrine prostate cancer.

Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer that emerges as tumors become resistant to hormone therapies or, rarely, arises de novo in treatment-naïve patients. The urgent need for effective therapies against NEPC is hampered by the limited knowledge of the biology governing this lethal disease. Based on our prior observations in the TRAMP spontaneous prostate cancer model, in which the genetic depletion of either mast cells (MCs) or the matricellular protein osteopontin (OPN) increases NEPC frequency, we tested the hypothesis that MCs can restrain NEPC through OPN production, using in vitro co-cultures between murine or human tumor cell lines and MCs, and in vivo experiments. We unveiled a role for the intracellular isoform of OPN (iOPN), so far neglected compared to the secreted isoform. Mechanistically, we unraveled that iOPN promotes TNF production in MCs via the TLR2/TLR4-MyD88 axis, specifically triggered by the encounter with NEPC cells. We found that MC-derived TNFin turn, hampered the growth of NEPC. We then identified the protein syndecan-1 (SDC1) as the NEPC-specific TLR2/TLR4 ligand that triggered this pathway. Interrogating published single-cell RNA-sequencing data we validated this mechanism in a different mouse model. Translational relevance of the results was provdied by in silco analyses of available human NEPC datasets, and by immunofluorescence on patient-derived adenocarcinoma and NEPC lesions. Overall, our results show that MCs actively inhibit NEPC, paving the way for innovative MC-based therapies for this fatal tumor. We also highlight SDC1 as a potential biomarker for incipient NEPC.

Combined therapy targeting AR and EZH2 curbs castration-resistant prostate cancer enhancing anti-tumor T-cell response.

Aim: Castration-resistant prostate cancer (CRPC) eventually becomes resistant to androgen receptor pathway inhibitors like enzalutamide. Immunotherapy also fails in CRPC. We propose a new approach to simultaneously revert enzalutamide resistance and rewire anti-tumor immunity. Methods: We investigated in vitro and in subcutaneous and spontaneous mouse models the effects of combining enzalutamide and GSK-126, a drug inhibiting the epigenetic modulator EZH2. Results: Enzalutamide and GSK-126 synergized to reduce CRPC growth, also restraining tumor neuroendocrine differentiation. The anti-tumor activity was lost in immunodeficient mice. Indeed, the combination treatment awoke cytotoxic activity and IFN-γ production of tumor-specific CD8+ T lymphocytes. Conclusion: These results promote the combination of enzalutamide and GSK-126 in CRPC, also offering new avenues for immunotherapy in prostate cancer.

Prostate cancer depends on hormones called androgens for its growth. Therefore, hormonal therapies are commonly used. However, the tumor often does not respond to these treatments and new therapeutic approaches are needed. Here, using cell and mouse models, we have tested a new combination between hormone therapy and a drug that restrains an enzyme regulating gene expression. Our results have shown that this combination therapy not only reduces the growth of the tumor but also stops it from becoming more aggressive. This is really important because aggressive prostate cancer is much harder to treat. We have also found that this approach helps the immune system recognizing and attacking cancer cells. More research is needed to identify the mechanism of action of this treatment. However, our findings suggest that this approach could pave the way for new therapeutic strategies, including using immunotherapy, typically unsuccessful in treating prostate cancer.

Use of COVID-19 Convalescent Plasma for Treatment of Symptomatic SARS-CoV-2 Infection at a Children's Hospital: A Contribution to a Still Inadequate Body of Evidence.

Data on COVID-19 convalescent plasma (CCP) safety and efficacy in children and young adults are limited. This single-center prospective, open-label trial evaluates CCP safety, neutralizing antibody kinetics, and outcomes in children and young adults with moderate/severe COVID-19 (April 2020-March 2021). A total of 46 subjects received CCP; 43 were included in the safety analysis (SAS); 7.0% < 2 years old, 2.3% 2-<6, 27.9% 6-<12, 39.5% 12-<19, and 23.3% > 19 years old; 28 were included in the antibody kinetic analysis (AbKS); 10.7% < 2 years old, 10.7% 6-<12, 53.8% 12-<19, and 25.0% > 19 years old. No adverse events occurred. The median COVID-19 severity score improved (5.0 pre-CCP to 1.0 by day 7; p < 0.001). A rapid increase in the median percentage of inhibition was observed in AbKS (22.5% (13.0%, 41.5%) pre-infusion to 52% (23.7%, 72%) 24 h post-infusion); a similar increase was observed in nine immune-competent subjects (28% (23%, 35%) to 63% (53%, 72%)). The inhibition percentage increased until day 7 and persisted at 21 and 90 days. CCP is well tolerated in children and young adults, providing rapid and robust increased antibodies. CCP should remain a therapeutic option for this population for whom vaccines are not fully available and given that the safety and efficacy of existing monoclonal antibodies and antiviral agents have not been established.

Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central Nervous System Infections.

BACKGROUND: Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management and in characterizing prognosis. Usual care testing by culture and polymerase chain reaction is often unable to identify a pathogen. We examined the systematic application of metagenomic next-generation sequencing (mNGS) for detecting organisms and transcriptomic analysis of cerebrospinal fluid (CSF) in children with central nervous system (CNS) infections. METHODS: We conducted a prospective multisite study that aimed to enroll all children with a CSF pleocytosis and suspected CNS infection admitted to 1 of 3 tertiary pediatric hospitals during the study timeframe. After usual care testing had been performed, the remaining CSF was sent for mNGS and transcriptomic analysis. RESULTS: We screened 221 and enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 25 (35.7%) subjects by any diagnostic modality. Metagenomic next-generation sequencing of the CSF samples identified a pathogen in 20 (28.6%) subjects, which were also all identified by usual care testing. The median time to result was 38 hours. CONCLUSIONS: Metagenomic sequencing of CSF has the potential to rapidly identify pathogens in children with CNS infections.

Castration-Induced Downregulation of SPARC in Stromal Cells Drives Neuroendocrine Differentiation of Prostate Cancer.

Fatal neuroendocrine differentiation (NED) of castration-resistant prostate cancer is a recurrent mechanism of resistance to androgen deprivation therapies (ADT) and antiandrogen receptor pathway inhibitors (ARPI) in patients. The design of effective therapies for neuroendocrine prostate cancer (NEPC) is complicated by limited knowledge of the molecular mechanisms governing NED. The paucity of acquired genomic alterations and the deregulation of epigenetic and transcription factors suggest a potential contribution from the microenvironment. In this context, whether ADT/ARPI induces stromal cells to release NED-promoting molecules and the underlying molecular networks are unestablished. Here, we utilized transgenic and transplantable mouse models and coculture experiments to unveil a novel tumor-stroma cross-talk that is able to induce NED under the pressure of androgen deprivation. Castration induced upregulation of GRP78 in tumor cells, which triggers miR29-b-mediated downregulation of the matricellular protein SPARC in the nearby stroma. SPARC downregulation enabled stromal cells to release IL6, a known inducer of NED. A drug that targets GRP78 blocked NED in castrated mice. A public, human NEPC gene expression dataset showed that Hspa5 (encoding for GRP78) positively correlates with hallmarks of NED. Finally, prostate cancer specimens from patients developing local NED after ADT showed GRP78 upregulation in tumor cells and SPARC downregulation in the stroma. These results point to GRP78 as a potential therapeutic target and to SPARC downregulation in stromal cells as a potential early biomarker of tumors undergoing NED. SIGNIFICANCE: Tumor-stroma cross-talk promotes neuroendocrine differentiation in prostate cancer in response to hormone therapy via a GRP78/SPARC/IL6 axis, providing potential therapeutic targets and biomarkers for neuroendocrine prostate cancer.

Safety and Antibody Kinetics of COVID-19 Convalescent Plasma for the Treatment of Moderate to Severe Cases of SARS-CoV-2 Infection in Pediatric Patients.

BACKGROUND: Therapies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its life-threatening respiratory infection coronavirus disease 2019 (COVID-19) have been evaluated, including COVID-19 convalescent plasma (CCP). Multiple large reports of CCP treatment in adults exist. Pediatric data on CCP safety and efficacy are limited. METHODS: Single-center prospective, open-label trial looking at safety, antibody kinetics and outcomes of CCP (10 mL/kg, max 1 unit) treatment for COVID-19 in hospitalized pediatric patients with moderate to severe disease or at high-risk for serious illness. RESULTS: Thirteen patients were enrolled. No infusion-related adverse events occurred. No hematologic or metabolic adverse events were noted during hospitalization or at 3-weeks. Ten patients had clinical improvement by day 7 (WHO eight-category ordinal severity scale for COVID-19). Following CCP, anti-SARS-CoV-2 anti-nucleocapsid IgG increased significantly at 24 hours and high levels were sustained at 7- and 21-days. Transient IgM response was noted. Twelve patients (92.3%) were discharged home, 9 (75%) by day 7 post-CCP. One remained on invasive ventilatory support 42 days after CCP and was eventually discharged to an intermediate care facility. The single patient death was retrospectively confirmed to have had brain death before CCP. CONCLUSION: CCP was well tolerated in pediatric patients, resulted in rapid antibody increase, and did not appear to interfere with immune responses measured at 21 days. More pediatric data are necessary to establish the efficacy of CCP, but our data suggest benefit in moderate to severe COVID-19 when used early. Other immunologic or antiviral interventions may be added as supported by emerging data.

Repurposing of the Antiepileptic Drug Levetiracetam to Restrain Neuroendocrine Prostate Cancer and Inhibit Mast Cell Support to Adenocarcinoma.

A relevant fraction of castration-resistant prostate cancers (CRPC) evolve into fatal neuroendocrine (NEPC) tumors in resistance to androgen deprivation and/or inhibitors of androgen receptor pathway. Therefore, effective drugs against both CRPC and NEPC are needed. We have previously described a dual role of mast cells (MCs) in prostate cancer, being capable to promote adenocarcinoma but also to restrain NEPC. This finding suggests that a molecule targeting both MCs and NEPC cells could be effective against prostate cancer. Using an in silico drug repurposing approach, here we identify the antiepileptic drug levetiracetam as a potential candidate for this purpose. We found that the protein target of levetiracetam, SV2A, is highly expressed by both NEPC cells and MCs infiltrating prostate adenocarcinoma, while it is low or negligible in adenocarcinoma cells. In vitro, levetiracetam inhibited the proliferation of NEPC cells and the degranulation of MCs. In mice bearing subcutaneous tumors levetiracetam was partially active on both NEPC and adenocarcinoma, the latter effect due to the inhibition of MMP9 release by MCs. Notably, in TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice subjected to surgical castration to mimic androgen deprivation therapy, levetiracetam reduced onset and frequency of both high grade prostatic intraepithelial neoplasia, adenocarcinoma and NEPC, thus increasing the number of cured mice showing only signs of tumor regression. Our results demonstrate that levetiracetam can directly restrain NEPC development after androgen deprivation, and that it can also block adenocarcinoma progression through the inhibition of some MCs functions. These findings open the possibility of further testing levetiracetam for the therapy of prostate cancer or of MC-mediated diseases.

¿Limitar la presión de distensión protege contra la lesión pulmonar adquirida por la ventilación mecánica (VALI)? / Does limiting the distension pressure protect against lung injury acquired by mechanical ventilation (VALI)? / A limitação da pressão de distensão protege contra lesão pulmonar adquirida por ventilação mecânica (VALI)?

Resumen: El incremento en la presión de las vías respiratorias causa lesión de la membrana alveolar proponiendo el barotrauma como causa de lesión pulmonar adquirida por el ventilador (VALI), esta afección se presenta de forma frecuente, lo que conduce a entender mejor el papel desempeñado por los ajustes del ventilador mecánico, la fisiopatología pulmonar subyacente y su interacción. En la última década se ha dado relevancia al término presión de distensión (PD), que surge del cálculo del delta de presión (∆P = Vt/CRS). La PD representa los cambios dinámicos de la presión que se genera en la vía aérea en cada ciclo ventilatorio. Aunque se instalen medidas de protección pulmonar de manera inicial, existen diversas condiciones que modifican las propiedades elásticas, tales como reanimación hídrica y el balance positivo de líquidos, procesos infecciosos agregados, etc. Sin embargo, aun cuando se cumplan estas medidas de protección puede haber distensión pulmonar excesiva, por lo que la monitorización de la PD puede ser una herramienta útil para determinar de manera sistemática los cambios en la rigidez pulmonar, estableciendo intervenciones. En ausencia de ensayos que usen PD como objetivo al establecer el ventilador, se sugiere que se utilice como complemento y no como un sustituto de parámetros de protección pulmonar.

Abstract: The increase in airway pressure causes injury in the alveolar membrane by proposing barotrauma as the cause of ventilator-acquired Lung Injury (VALI), this condition occurs frequently, which leads to a better understanding of the roles played by the mechanical ventilator settings, underlying lung pathophysiology and their interaction. In the last decade, the term pressure of distension (PD) has emerged, arising from the calculation of the pressure delta (ΔP = Vt/CRS). The PD represents the dynamic changes of the pressure that is generated in the airway in each ventilatory cycle. Although pulmonary protection measures are initially installed, there are several conditions that modify elastic properties, such as fluid resuscitation and positive fluid balance, aggregated infectious processes, etc. However, even if these protective measures are met, excessive pulmonary distention may occur, so PD monitoring may be a useful tool for systematically determining changes in pulmonary stiffness by establishing interventions. In the absence of assays using PD as a target when establishing the ventilator, it is suggested that it be used as a complement and not as a substitute for pulmonary protection parameters.

Resumo: O aumento da pressão das vias aéreas causa lesão da membrana alveolar, propondo o barotrauma como causa de Lesão Pulmonar Adquirida pelo Ventilador (VALI), esta condição ocorre com frequência, o que leva a uma melhor compreensão dos papéis desempenhados pelos ajustes do ventilador mecânico, a fisiopatologia pulmonar subjacente e sua interação. Na última década, o termo pressão de distensão (PD) tem recebido relevância decorrente do cálculo do delta de pressão (ΔP = Vt/CRS). A DP representa as mudanças dinâmicas da pressão gerada na via aérea em cada ciclo ventilatório. Embora as medidas de proteção pulmonar sejam instaladas inicialmente, existem várias condições que modificam as propriedades elásticas, tais como ressuscitação hídrica e balanço hídrico positivo, processos infecciosos agregados, etc. No entanto, mesmo que essas medidas de proteção sejam atendidas, pode haver distensão pulmonar excessiva, de modo que a monitorização da DP possa ser uma ferramenta útil para determinar sistematicamente as mudanças na rigidez pulmonar, estabelecendo intervenções. Na ausência de ensaios que utilizem a PD como objetivo no estabelecimento do ventilador, sugere-se que seja utilizado como complemento e não como substituto dos parâmetros de proteção pulmonar.

The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis.

The assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium spp. and were dominated by Enterobacteriaceae, Enterococcus, and Staphylococcus organisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA] R2 = 0.48, P < 0.001), while clinical status (health, NEC, or late-onset sepsis) and overlapping times in the neonatal intensive care unit (NICU) did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (PERMANOVA R2 = 0.43, P < 0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05, P < 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage.IMPORTANCE Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from 32 preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found that both the preterm infant microbiome and the metabolome were personalized and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangle the health consequences of the preterm infant microbiome.

Cross-Talk between Myeloid-Derived Suppressor Cells and Mast Cells Mediates Tumor-Specific Immunosuppression in Prostate Cancer.

Immunotherapy, including the use of checkpoint inhibitors, is a potent therapeutic approach for some cancers, but has limited success with prostate tumors, in which immune suppression is instigated by the tumor. The immunosuppressive capacity of mast cells, which promote adenocarcinoma development in the prostate, prompted our investigation on whether mast cells promote tolerance to SV40 Large-T antigen, the transforming oncogene in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. The incidence of adenocarcinoma was reduced in the offspring of a cross between TRAMP mice and mast cell-deficient KitWsh mice. TRAMP mice are tolerant to the SV40 Large T antigen, which is otherwise immunogenic in normal syngeneic B6 mice. Genetic ablation of mast cells in TRAMP mice restored their ability to mount a tumor-specific cytotoxic T-cell response. In KitWsh-TRAMP mice, the restored T-cell immunity correlated with the reduced activity of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC), along with their reduced expression of Arg1, Nos2, and Stat3 Having found that CD40L-expressing mast cells can interact in vivo with CD40-expressing PMN-MDSC, we then determined that only KitWsh-TRAMP mice reconstituted with mast cells expressing CD40L could restore PMN-MDSCs suppressive functions, T-cell unresponsiveness and adenocarcinoma development. Thus, mast cells have an immunoregulatory effect on PMN-MDSCs activity through CD40L-CD40 interaction, favoring immunosuppression and tumor onset. In prostate cancer patients, in silico analyses correlated poor clinical outcomes with high expression of genes related to mast cells and PMN-MDSCs. Cancer Immunol Res; 6(5); 552-65. ©2018 AACR.

A promoter-proximal transcript targeted by genetic polymorphism controls E-cadherin silencing in human cancers.

Long noncoding RNAs are emerging players in the epigenetic machinery with key roles in development and diseases. Here we uncover a complex network comprising a promoter-associated noncoding RNA (paRNA), microRNA and epigenetic regulators that controls transcription of the tumour suppressor E-cadherin in epithelial cancers. E-cadherin silencing relies on the formation of a complex between the paRNA and microRNA-guided Argonaute 1 that, together, recruit SUV39H1 and induce repressive chromatin modifications in the gene promoter. A single nucleotide polymorphism (rs16260) linked to increased cancer risk alters the secondary structure of the paRNA, with the risk allele facilitating the assembly of the microRNA-guided Argonaute 1 complex and gene silencing. Collectively, these data demonstrate the role of a paRNA in E-cadherin regulation and the impact of a noncoding genetic variant on its function. Deregulation of paRNA-based epigenetic networks may contribute to cancer and other diseases making them promising targets for drug discovery.

[Children hospitalized with influenza A H1N1. The field of private care during the pandemic in Mexico]. / Hospitalización pediátrica por influenza A H1N1. El ámbito de la atención privada durante la pandemia en México.

BACKGROUND: the pandemic influenza A H1N1 generated a lot of concern about its potential lethality, because the constant death reported by the media. Our objective was to analyze the clinical characteristics and evolution of children hospitalized in private hospital. METHODS: we included all patients hospitalized since April 2009 to March 2010 with influenza A H1N1 confirmed by RT-PCR test. The clinical data, imaging studies and treatment and outcome (hospital stay, PICU admission, and deaths) were analyzed. RESULTS: 50 children were hospitalized 15 less than 3 years old (30 %), 23 from 3 to 5 years (46 %), and 12 older than 5 years (24 %). Any patient required an intensive pediatric care, and there were not deaths. 86 % were admitted for fever, and 40 % with light or moderate respiratory distress symptoms. In 20 patients a radiologic evidence of interstitial infiltration (ten) or pneumonia condensation (four) or airways obstruction (six) were observed. All received oseltamivir treatment and four antibiotic therapies. The median of hospital stay was 48 hours (24 to 72 hours). All were egressed without any complication. CONCLUSIONS: benign evolutions were seeing in the children studied.

Introducción: la pandemia de influenza A H1N1 en México generó gran preocupación por su potencial alta letalidad. El objetivo de esta investigación fue analizar las características y evolución de los pacientes pediátricos atendidos en un hospital privado. Métodos: se incluyeron todos los casos hospitalizados de abril de 2009 a marzo de 2010 con diagnóstico confirmado de influenza A H1N1 por medio de RT-PCR. Se analizaron los datos clínicos, radiológicos y tratamiento de los pacientes. Se determinaron días de estancia, muerte y necesidad de cuidados intensivos. Resultados: fueron hospitalizados 50 niños, 15 menores de tres años de edad (30 %), 23 de tres a cinco años (46 %) y 12 mayores de cinco años (24 %). Ninguno ameritó cuidados en terapia intensiva y no hubo defunciones; 86 % ingresó por fiebre y 40 % con dificultad respiratoria de leve a moderada. En 10 hubo evidencia radiológica de neumonía intersticial, en cuatro de condensación pulmonar y en seis de obstrucción aérea. Todos fueron tratados con oseltamivir y cuatro con antibióticos. La estancia media hospitalaria fue de 48 horas. Todos se egresaron sin complicaciones. Conclusiones: la evolución de los pacientes hospitalizados fue benigna.

Streptococcus pneumoniae serotypes isolated from the middle ear of Mexican children diagnosed with acute otitis media.

OBJECTIVE: The aim of this study was to identify the etiology and the serotypes of S. pneumoniae (Sp) in Mexican children with acute otitis media (AOM). MATERIALS AND METHODS: The study includessamples frompatientsdiagnosed with AOM at the Federico Gomez Children's Hospital of Mexico (2002-2003),with positive culture for Sp bacteriologically confirmed in middle ear fluid obtained by tympanocentesis. All Sp were serotyped. A total of 138 samples from 135 children with AOM were included. RESULTS: Sp was isolated in 72 samples from 70 children. Sixty (85.7%) were previously healthy and 10 (14.3%) were immunocompromised. The most common serotypes were 6B and 19F (16.67%), and 6 A, 14 and 23F (15.27%). CONCLUSION: The distribution of serotypes among the children with AOM in the study is similar to that reported in developing cities, and 63.9% of the isolated serotypes are found to be included in the 7-Valent Pneumococcal Conjugate Vaccine (PCV), 68.1% in the 10-Valent PCV and 83.3% in 13-Valent PCV.

Streptococcus pneumoniae serotypes isolated from the middle ear of Mexican children diagnosed with acute otitis media / Serotipificación de Streptococcus pneumoniae aislados de líquido de oído medio en niños mexicanos con diagnóstico de otitis media aguda

OBJECTIVE: The aim of this study was to identify the etiology and the serotypes of S. pneumoniae (Sp) in Mexican children with acute otitis media (AOM). MATERIALS AND METHODS: The study includessamples frompatientsdiagnosed with AOM at the Federico Gomez Children's Hospital of Mexico (2002-2003),with positive culture for Sp bacteriologically confirmed in middle ear fluid obtained by tympanocentesis. All Sp were serotyped. A total of 138 samples from 135 children with AOM were included. RESULTS: Sp was isolated in 72 samples from 70 children. Sixty (85.7 percent) were previously healthy and 10 (14.3 percent) were immunocompromised. The most common serotypes were 6B and 19F (16.67 percent), and 6 A, 14 and 23F (15.27 percent). CONCLUSION: The distribution of serotypes among the children with AOM in the study is similar to that reported in developing cities, and 63.9 percent of the isolated serotypes are found to be included in the 7-Valent Pneumococcal Conjugate Vaccine (PCV), 68.1 percent in the 10-Valent PCV and 83.3 percent in 13-Valent PCV.

OBJETIVO: Conocer la etiología y serotipos de S. pneumoniae (Sp) en niños mexicanos, con otitis media aguda (OMA). MATERIAL Y MÉTODOS: Se incluyeron las muestras de pacientes con OMA del Hospital Infantil de México Federico Gómez (2002-2003), con cultivo positivo para Sp, (bacteriológicamente confirmados en el líquido del oído medio obtenido por timpanocentesis). Todos los Sp. fueron serotipificados. Se incluyeron 138 muestras de 135 niños con OMA. RESULTADOS: Sp. se aisló en 72 muestras de 70 niños: 60 (85.7 por ciento) eran previamente sanos y 10 (14.3 por ciento) eran inmunocomprometidos. Los serotipos más frecuentes fueron 6B y 19F (16.67 por ciento), y 6 A, 14 y 23F (15.27 por ciento). CONCLUSIONES: La distribución de los serotipos en niños con otitis media aguda fue similar a la reportada en ciudades en desarrollo y se observó que 63.9 por ciento de los serotipos aislados están incluidos en la vacuna conjugada 7-valente, 68.1 por ciento en la 10-valente y 83.3 por ciento en la 13-valente.

Invasive pneumococcal disease in a third level pediatric hospital in Mexico City: epidemiology and mortality risk factors.

OBJECTIVE: To assess the epidemiologic characteristics of invasive pneumococcal diseases (IPD) among a population in a pediatric hospital in Mexico City and analyze mortality-related risk factors, serotype distribution and antibiotic susceptibility related to S.pneumoniae. MATERIAL AND METHODS: We performed a retrospective review of IPD cases at a third level pediatric hospital between 1997-2004. RESULTS: A total of 156 patients were included. The mortality rate was 27.5% and was associated with six pneumococcal serotypes: 14, 6B, 23F, 6A, 19F and 19A. There was no relationship between mortality and antimicrobial susceptibility pattern. A total of 28.2% of isolates were resistant to penicillin and 24.6% were resistant to cefotaxime. A statistically significant relationship was observed between mortality and previous underlying disease (CI 95%; 2.5-18.3; p< 0.05) using a multivariate logistic regression model. CONCLUSIONS: Our outcomes show that IPD mortality in our population is closely related to underlying disease and to six serotypes, five of which are included in the 7-valent pneumococcal conjugate vaccine.

Invasive pneumococcal disease in a third level pediatric hospital in Mexico City: epidemiology and mortality risk factors / Enfermedad neumocócica invasora en un hospital pediátrico de tercer nivel en la Ciudad de México: características epidemiológicas y factores de riesgo asociados con mortalidad

Objective. To assess the epidemiologic characteristics of invasive pneumococcal diseases (IPD) among a population in a pediatric hospital in Mexico City and analyze mortality-related risk factors, serotype distribution and antibiotic susceptibility related to S.pneumoniae. Material and Methods. We performed a retrospective review of IPD cases at a third level pediatric hospital between 1997-2004. Results. A total of 156 patients were included. The mortality rate was 27.5 percent and was associated with six pneumococcal serotypes: 14, 6B, 23F, 6A, 19F and 19A. There was no relationship between mortality and antimicrobial susceptibility pattern. A total of 28.2 percent of isolates were resistant to penicillin and 24.6 percent were resistant to cefotaxime. A statistically significant relationship was observed between mortality and previous underlying disease (CI 95 percent; 2.5-18.3; p< 0.05) using a multivariate logistic regression model. Conclusions. Our outcomes show that IPD mortality in our population is closely related to underlying disease and to six serotypes, five of which are included in the 7-valent pneumococcal conjugate vaccine.

Objetivo. Conocer la epidemiología de la enfermedad neumocócica invasora (ENI) en un hospital pediátrico y analizar los factores de riesgo relacionados con la mortalidad, la distribución de serotipos y el patrón de susceptibilidad de S. pneumoniae. Material y métodos. Revisión retrospectiva de los casos de ENI en un hospital pediátrico de tercer nivel, entre 1997 y 2004. Resultados. En 156 pacientes la mortalidad fue de 27.5 por ciento. Los serotipos de neumococo más frecuentemente relacionados con la mortalidad fueron: 14, 6B, 23F, 6A, 19F y 19A; no hubo relación de mortalidad con la resistencia a antibióticos. El 28.2 por ciento mostró resistencia a penicilina y 24.6 por ciento a cefotaxima. A través del modelo multivariado, se encontró una relación estadísticamente significativa entre la mortalidad y enfermedad previa (IC 95 por ciento; 2.5-18.3; p<0.05). Conclusiones. La mortalidad asociada a la ENI tuvo relación significativa con antecedente de una enfermedad previa y con seis serotipos, cinco incluidos en la vacuna neumocócica conjugada 7-valente.