Angiopoietin Level Trajectories in Toddlers With Severe Sepsis and Septic Shock and Their Effect on Capillary Endothelium.

OBJECTIVE: Angiopoietins are postulated diagnostic biomarkers in children and adults with severe sepsis and septic shock. The diagnostic value of angiopoietins in children less than 5 years old has not been established, nor has their effect on permeability in the capillary microvasculature. We aim to determine if levels of angiopoietin-1 or -2 (angpt-1, -2) are diagnostic for severe sepsis/shock in young children and whether they affect the permeability of cultured human dermal microvascular endothelial cells (HDMEC). DESIGN: Prospective observational study of children < 5 years old. Patients were classified as non-systemic inflammatory response syndrome (SIRS), SIRS/sepsis and severe sepsis/septic shock. SETTING: Tertiary care pediatric hospitals. PATIENTS: Critically ill children. INTERVENTIONS: None. MEASUREMENTS: Plasma angpt-1 and -2 levels were measured with enzyme-linked immunoassays. Expression of angpt-2 in endothelial cells was assessed with quantitative polymerase chain reaction. Permeability changes in cultured HDMECs were assessed with transendothelial electrical resistance measurements. RESULTS: Angpt-1 levels were significantly higher in younger children compared with levels found in previous study of older children across disease severity (all P < 0.001). Angpt-2 was significantly higher in this cohort with severe sepsis/septic shock compared with children without SIRS and SIRS/sepsis (all P < 0.003). Angpt-2/1 ratio was also elevated in children with severe sepsis/septic shock but an order of magnitude less than older children (P < 0.02, P = 0.002). Angpt-1 and -2 did not affect basal HDMEC permeability or modulate leak in isolation or in the presence of tumor necrosis factor (TNF). CONCLUSIONS: Angpt-2 levels and the angpt-2/1 ratio are appropriate diagnostic biomarkers of severe sepsis/septic shock in children less than 5 years old. Neither angpt-1 nor -2 affects basal HDMEC permeability alone or modulates TNF induced capillary leak.

IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells.

IL-21 is a type I cytokine that influences the function of T cells, NK cells, and B cells. In this study, we report that IL-21 plays a major role in stimulating the differentiation of human B cells. When human B cells were stimulated through the BCR, IL-21 induced minimal proliferation, IgD down-modulation, and small numbers of plasma cells. In contrast, after CD40 engagement, IL-21 induced extensive proliferation, class switch recombination (CSR), and plasma cell differentiation. Upon cross-linking both BCR and CD40, IL-21 induced the largest numbers of plasma cells. IL-21 drove both postswitch memory cells as well as poorly responsive naive cord blood B cells to differentiate into plasma cells. The effect of IL-21 was more potent than the combination of IL-2 and IL-10, especially when responsiveness of cord blood B cells was examined. IL-21 costimulation potently induced the expression of both B lymphocyte-induced maturation protein-1 (BLIMP-1) and activation-induced cytidine deaminase as well as the production of large amounts of IgG from B cells. Despite the induction of activation-induced cytidine deaminase and CSR, IL-21 did not induce somatic hypermutation. Finally, IL-2 enhanced the effects of IL-21, whereas IL-4 inhibited IL-21-induced plasma cell differentiation. Taken together, our data show that IL-21 plays a central role in CSR and plasma cell differentiation during T cell-dependent B cell responses.

Central slip tenotomy for the treatment of chronic mallet finger: an anatomic study.

PURPOSE: Tenotomy of the central slip, described by Fowler, can clinically improve chronic distal interphalangeal joint (DIP) extensor lag secondary to mallet finger (terminal tendon disruption). The goal of this study is to evaluate the potential of central slip tenotomy to restore DIP joint extension. METHODS: A mallet deformity was reproduced in 15 fresh-frozen cadaver fingers after the extensor tendon insertion was sectioned over the DIP joint. A suture anchor inserted at the terminal insertion was then secured to the extensor tendon over the middle phalanx to reconstruct the extensor mechanism. A 500-g weight attached to the proximal extensor tendon applied extensor tension. Central slip tenotomy was then performed. DIP extensor lags before and after tenotomy were recorded. RESULTS: After sectioning of the terminal tendon over the DIP joint the average amount of extensor tendon lag produced was 45 degrees. After central slip tenotomy was performed the average amount of extensor lag correction was 36 degrees (range, 30 degrees-46 degrees). CONCLUSIONS: Several clinical studies have shown that central slip tenotomy is an effective treatment for chronic mallet finger but may not fully restore DIP joint extension. Our data suggest that patients with a pre-existing extensor lag of greater than 36 degrees may not achieve full extension from central slip tenotomy, although extensor lags of up to 46 degrees may be corrected.