Dysregulated monocyte-derived macrophage response to Group B Streptococcus in newborns.

Introduction: Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading pathogen of neonatal sepsis. The host-pathogen interactions underlying the progression to life-threatening infection in newborns are incompletely understood. Macrophages are first line in host defenses against GBS, contributing to the initiation, amplification, and termination of immune responses. The goal of this study was to compare the response of newborn and adult monocyte-derived macrophages (MDMs) to GBS. Methods: Monocytes from umbilical cord blood of healthy term newborns and from peripheral blood of healthy adult subjects were cultured with M-CSF to induce MDMs. M-CSF-MDMs, GM-CSF- and IFNγ-activated MDMs were exposed to GBS COH1, a reference strain for neonatal sepsis. Results: GBS induced a greater release of IL-1ß, IL-6, IL-10, IL-12p70 and IL-23 in newborn compared to adult MDMs, while IL-18, IL-21, IL-22, TNF, RANTES/CCL5, MCP-1/CCL2 and IL-8/CXCL8 were released at similar levels. MDM responses to GBS were strongly influenced by conditions of activation and were distinct from those to synthetic bacterial lipopeptides and lipopolysaccharides. Under similar conditions of opsonization, newborn MDMs phagocytosed and killed GBS as efficiently as adult MDMs. Discussion: Altogether, the production of excessive levels of Th1- (IL-12p70), Th17-related (IL-1ß, IL-6, IL-23) and anti-inflammatory (IL-10) cytokines is consistent with a dysregulated response to GBS in newborns. The high responsiveness of newborn MDMs may play a role in the progression of GBS infection in newborns, possibly contributing to the development of life-threatening organ dysfunction.

Obesity as a Risk Factor for Venous Thromboembolism Recurrence: A Systematic Review.

Background and Objectives: Venous thromboembolism (VTE) encompasses Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE). The duration of anticoagulant therapy following a VTE event partly relies on the risk of recurrent VTE which depends on the clinical setting where VTE occurred and the VTE risk factors present. Obesity is considered a minor risk factor and studies in the literature have provided conflicting results on whether obesity influences the development of recurrences. The aim of the present study is to assess the effect of obesity on VTE recurrence in patients that suffered from a previous VTE event. Materials and Methods: We conducted systematic research for English language studies in Medline, Scopus and ProQuest databases in order to identify publications that assess the risk of VTE recurrence in obesity. Inclusion criteria were: 1. Diagnosis of VTE, 2. Definition of obesity as a body mass index ≥30 kg/m2, 3. Report of the risk of obesity on VTE recurrence, 4. Adult human population. We did not include case reports, review studies or studies that assessed other forms of thrombosis and/or used other definitions of obesity. We used the Newcastle-Ottawa scale to address the quality of the studies. Results: Twenty studies were included in the analysis, of which 11 where prospective cohort studies, 6 were retrospective cohort studies, 1 was a cross-sectional study, and 2 were post-hoc analysis of randomized clinical trials. Obesity was significantly associated with recurrences in 9 studies and in 3 of them the association was significant only in females. Conclusions: There is heterogeneity between the studies both in their design and results, therefore the effect of obesity on VTE recurrence cannot be adequately estimated. Future randomized clinical studies with appropriately selected population are needed in order to streamline the effect of obesity on VTE recurrence.

Late-onset cardiomyopathy among survivors of childhood lymphoma treated with anthracyclines: a systematic review.

Medical advances in pediatric oncology have led to increases in survival but the long-term adverse effects of treatment in childhood cancer survivors have not yet been examined in depth. In this systematic review, we aimed to study the prevalence and risk factors of late-onset cardiomyopathy (LOCM) among survivors of childhood lymphoma treated with anthracyclines. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines we searched Pubmed/Medline, abstracted data and rated studies on quality regarding late-onset (>1 year following treatment) cardiotoxicity of anthracyclines in survivors of childhood lymphoma. Across 22 identified studies, the prevalence of anthracycline-induced LOCM among survivors of childhood lymphoma ranges from 0 to 40%. Anthracycline dose, administration and dose of mediastinal radiation, patient's age and era of diagnosis and evaluation, follow-up duration as well as disease relapse have been reported as risk factors for LOCM, whereas administration of dexrazoxane seems to act protectively. There was significant between-study heterogeneity with regards to lymphoma subtypes, follow-up duration, definition of outcomes, and anthracycline-based treatment protocols. The rates of anthracycline-induced LOCM among survivors of childhood lymphoma are high and dependent on study design. Future studies should explore whether modifying risk factors and suggested supportive care could decrease its prevalence among childhood lymphoma survivors. Until then, lifelong follow-up of these patients aiming to determinate the earliest signs of cardiac dysfunction is the most important measure towards primordial prevention of LOCM.

Season of birth and primary central nervous system tumors: a systematic review of the literature with critical appraisal of underlying mechanisms.

PURPOSE: Season of birth has been considered a proxy of seasonally varying exposures around perinatal period, potentially implicated in the etiology of several health outcomes, including malignancies. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we have systematically reviewed published literature on the association of birth seasonality with risk of central nervous system tumors in children and adults. RESULTS: Seventeen eligible studies using various methodologies were identified, encompassing 20,523 cases. Eight of 10 studies in children versus four of eight in adults showed some statistically significant associations between birth seasonality and central nervous system tumor or tumor subtype occurrence, pointing to a clustering of births mostly in fall and winter months, albeit no consistent pattern was identified by histologic subtype. A plethora of perinatal factors might underlie or confound the associations, such as variations in birth weight, maternal diet during pregnancy, perinatal vitamin D levels, pesticides, infectious agents, immune system maturity, and epigenetic modifications. CONCLUSIONS: Inherent methodological weaknesses of to-date published individual investigations, including mainly underpowered size to explore the hypothesis by histological subtype, call for more elegant concerted actions using primary data of large datasets taking also into account the interplay between the potential underlying etiologic factors.