Neutrophil cannibalism – a back up when the macrophage clearance system is insufficient

BACKGROUND: During a lipopolysaccharide-induced lung inflammation, a massive accumulation of neutrophils occurs, which is normally cleared by macrophage phagocytosis following neutrophil apoptosis. However, in cases of extensive apoptosis the normal clearance system may fail, resulting in extensive neutrophil secondary necrosis. The aim of this study was to explore the hypothesis that neutrophils, in areas of the lung with extensive cellular infiltration, contribute to clearance by phagocytosing apoptotic cells and/or cell debris derived from secondary necrosis. METHODS: Intranasal lipopolysaccharide administration was used to induce lung inflammation in mice. The animals were sacrificed at seven time points following administration, bronchoalveolar lavage was performed and tissue samples obtained. Electron microscopy and histochemistry was used to assess neutrophil phagocytosis. RESULTS: Electron microscopic studies revealed that phagocytosing neutrophils was common, at 24 h after LPS administration almost 50% of the total number of neutrophils contained phagosomes, and the engulfed material was mainly derived from other neutrophils. Histochemistry on bronchoalvolar lavage cells further showed phagocytosing neutrophils to be frequently occurring. CONCLUSION: Neutrophils are previously known to phagocytose invading pathogens and harmful particles. However, this study demonstrates that neutrophils are also able to engulf apoptotic neutrophils or cell debris resulting from secondary necrosis of neutrophils. Neutrophils may thereby contribute to clearance and resolution of inflammation, thus acting as a back up system in situations when the macrophage clearance system is insufficient and/or overwhelmed

Effect of Dexamethasone Implant on Subfoveal Choroidal Thickness in Early Period in Vitrectomized Eyes with Diabetic Macular Edema

Aim. To investigate the change in subfoveal choroidal thickness (SFCT) in vitrectomized eyes with intravitreal dexamethasone (IVD) implant injection for the treatment of diabetic macular edema (DME). Method. In this prospective and controlled study, the vitrectomized eyes of diabetic patients were included. The study group (Group 1) was formed by diabetic vitrectomized eyes with DME. The control group (Group 2) was formed by diabetic vitrectomized eyes without DME. Only one intravitreal IVD implant was injected into the eyes in Group 1. In the first, second, and fourth months, choroidal layers were measured by optical coherence tomography and complete ophthalmologic examinations were performed for all cases. Results. Ninety-six eyes of 96 cases were included in the study. There were 48 eyes of 48 different patients in each group. After IVD injection, statistically significant improvement was observed in the best corrected visual acuity in Group 1. The mean SFCT in eyes with DME was statistically significantly thinner (p < 0.01) and thinness became more pronounced during the four-month follow-up period after IVD implant injection (p < 0.01). Conclusion. In the presence of DME in vitrectomized eyes, the thinness of the SFCT may become evident after dexamethasone implant injection

Potential Cost-Effectiveness of RSV Vaccination of Infants and Pregnant Women in Turkey: An Illustration Based on Bursa Data

Worldwide, respiratory syncytial virus (RSV) is considered to be the most important viral cause of respiratory morbidity and mortality among infants and young children. Although no active vaccine is available on the market yet, there are several active vaccine development programs in various stages. To assess whether one of these vaccines might be a future asset for national immunization programs, modeling the costs and benefits of various vaccination strategies is needed.To evaluate the potential cost-effectiveness of RSV vaccination of infants and/or pregnant women in Turkey.A multi-cohort static Markov model with cycles of one month was used to compare the cost-effectiveness of vaccinated cohorts versus non-vaccinated cohorts. The 2014 Turkish birth cohort was divided by twelve to construct twelve monthly birth cohorts of equal size (111,459 new-borns). Model input was based on clinical data from a multicenter prospective study from Bursa, Turkey, combined with figures from the (inter)national literature and publicly available data from the Turkish Statistical Institute (TÜÏK). Incremental cost-effectiveness ratios (ICERs) were expressed in Turkish Lira (TL) per quality-adjusted life year (QALY) gained.Vaccinating infants at 2 and 4 months of age would prevent 145,802 GP visits, 8,201 hospitalizations and 48 deaths during the first year of life, corresponding to a total gain of 1650 QALYs. The discounted ICER was estimated at 51,969 TL (26,220 US dollars in 2013) per QALY gained. Vaccinating both pregnant women and infants would prevent more cases, but was less attractive from a pure economic point of view with a discounted ICER of 61,653 TL (31,106 US dollars in 2013) per QALY. Vaccinating only during pregnancy would result in fewer cases prevented than infant vaccination and a less favorable ICER.RSV vaccination of infants and/or pregnant women has the potential to be cost-effective in Turkey. Although using relatively conservative assumptions, all evaluated strategies remained slightly below the threshold of 3 times the GDP per capita

The progression of maternal RSV antibodies in the offspring

At birth, 41 mothers (83%) tested positive for anti-RSV IgG and all of their babies carried maternal anti-RSV IgG. Anti-RSV IgG positivity dropped to 73% at 1 month, 6% at 3 months, and 2% at 6 months. Between 3 and 6 months, 8% did acquire RSV infection, half of them as acute bronchiolitis and half as non-specific respiratory infection. All of the patients who acquired clinical RSV disease had an antibody concentration of <20 RU/ml which may be the cut off value for protection