B cells enhance early innate immune responses during bacterial sepsis

Type I interferon–responsive B cells provide early protection against bacterial sepsis

Type I interferon signaling in hematopoietic cells is required for survival in mouse polymicrobial sepsis by regulating CXCL10

Type I interferon (IFN) α/β is critical for host defense. During endotoxicosis or highly lethal bacterial infections where systemic inflammation predominates, mice deficient in IFN-α/β receptor (IFNAR) display decreased systemic inflammation and improved outcome. However, human sepsis mortality often occurs during a prolonged period of immunosuppression and not from exaggerated inflammation. We used a low lethality cecal ligation and puncture (CLP) model of sepsis to determine the role of type I IFNs in host defense during sepsis. Despite increased endotoxin resistance, IFNAR−/− and chimeric mice lacking IFNAR in hematopoietic cells display increased mortality to CLP. This was not associated with an altered early systemic inflammatory response, except for decreased CXCL10 production. IFNAR−/− mice display persistently elevated peritoneal bacterial counts compared with wild-type mice, reduced peritoneal neutrophil recruitment, and recruitment of neutrophils with poor phagocytic function despite normal to enhanced adaptive immune function during sepsis. Importantly, CXCL10 treatment of IFNAR−/− mice improves survival and decreases peritoneal bacterial loads, and CXCL10 increases mouse and human neutrophil phagocytosis. Using a low lethality sepsis model, we identify a critical role of type I IFN–dependent CXCL10 in host defense during polymicrobial sepsis by increasing neutrophil recruitment and function

A genomic storm in critically injured humans

Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes

“Pulling the plug”—Management of meconium plug syndrome in neonates

Background: The significance of meconium plug syndrome (MPS) is unclear but has been associated with Hirschsprung\u27s disease and magnesium tocolysis. We reviewed our experience to attempt to identify any potential association with these conditions and to review our outcomes.Methods: Using the International Classification of Diseases, Ninth revision, code for meconium obstruction, patient charts were identified during the 1998-2008 period. A total of 61 cases of MPS were found, after excluding 7 of meconium ileus. Data regarding the hospital course and outcomes were collected and analyzed.Results: Approximately 30% of patients had spontaneous resolution of the meconium plug without any treatment. Of those patients requiring treatment, contrast barium enema was used, with 97% success. Only 2 patients required surgical intervention owing to worsening distension and subsequent peritonitis. When we stratified the patients according to gestational age of \u3e36 and \u3c36 \u3ewk, contrast barium enemas were performed 2.2 ± 1.8 versus 8.6 ± 7.8 d after birth (P = 0.003), respectively, and the lower gestational age patients had a longer length of stay. Contrast barium enema was still successful in 94% of patients with a gestational age of 16% of the cases, and Hirschsprung\u27s disease was only found in 3.2% of patients.Conclusions: Patients with MPS have excellent outcomes, independent of gestational age. Contrast barium enema remains the initial diagnostic and treatment of choice for patients with MPS. Also, although previous reports have shown a link between magnesium tocolysis and Hirschsprung\u27s disease with MPS, our experience suggests otherwise

Delayed emergency myelopoiesis following polymicrobial sepsis in neonates

Neonates have increased susceptibility to infection, which leads to increased mortality. Whether or not this as a result of implicit deficits in neonatal innate immune function or recapitulation of innate immune effector cell populations following infection is unknown. Here, we examine the process of emergency myelopoiesis whereby the host repopulates peripheral myeloid cells lost following the initial infectious insult. As early inflammatory responses are often dependent upon NF-κB and type I IFN signaling, we also examined whether the absence of MyD88, TRIF or MyD88 and TRIF signaling altered the myelopoietic response in neonates to polymicrobial sepsis. Following neonatal polymicrobial septic challenge, hematopoietic stem cell (HSC) expansion in bone marrow and the spleen were both attenuated and delayed in neonates compared with adults. Similar reductions in other precursors were observed in neonates. Similar to adult studies, the expansion of progenitor stem cell populations was also seen in the absence of MyD88 and/or TRIF signaling. Overall, neonates have impaired emergency myelopoiesis in response to sepsis compared with young adults. Despite reports that this expansion may be related to TLR signaling, our data suggest that other factors may be important, as TRIF(−/−) and MyD88(−/−) neonatal HSCs are still able to expand in response to polymicrobial neonatal sepsis

Equestrian injuries in children

Purpose: Equestrian activities are regarded by some as high-risk sports, and our recent experience suggested this to be true. We undertook this study to review our experience with pediatric equestrian injuries.Methods: After institutional review board approval, we reviewed emergency department and hospital admissions for children 0 to 18 years, with equestrian trauma, over an 11-year period.Results: There were 164 encounters with 135 girls and 29 boys. Most injuries (82%) occurred after falling or being thrown from the animal, and only 12% occurred during jumping or rodeo competitions. The remaining injuries were secondary to being trampled, kicked, or trapped under the animal. Eighty-seven children required hospital admission. Lacerations and contusions (58%) or orthopedic injuries (31%) were most common in the emergency department cohort. In the admission cohort, injury sites included orthopedic (34%), head (23%), abdomen (21%), and chest (11%). Multiple injuries occurred in 13%. A significant number of children required surgical interventions, including 19 orthopedic procedures, 4 laparotomies, 3 facial reconstructions, and 2 craniotomies. The average length of stay was nearly 4 days, with 60% of the children requiring intensive care admission. There were no deaths. One child was discharged to rehab, the rest were sent home.Conclusions: In our experience, more than one third of the children admitted after sustaining injuries in horse-related sports required surgical interventions. Children participating in equestrian activities are at risk for substantial injury, and pediatric care providers must maintain a high index of suspicion when evaluating these children

Pediatric segmental Caroli disease: A case report and review of the literature

Introduction: Caroli disease is a rare congenital disorder causing nonobstructive segmental dilatation of intrahepatic bile ducts. Caroli disease can affect the liver diffusely or be confined to a single segment or lobe, although localized Caroli disease is extremely uncommon. We present a rare case of an 8-year-old child with incidentally found Caroli disease limited to two hepatic segments who was treated with partial hepatectomy, as well as a review of the literature regarding the presentation, diagnosis, and management of Caroli disease in children and adults. Case Presentation: Our patient is an 8-year-old male with an incidentally found multiloculated cystic liver mass referred to our institution for further management. Due to its heterogeneous nature and lack of evidence of direct communication with the biliary system, our differential diagnosis included hepatic teratoma, mesenchymal hamartoma, and undifferentiated embryonal sarcoma. A decision was made to resect the lesion both for definitive diagnosis and to mitigate the risk of malignant transformation of this lesion. At the time of surgery, the mass was observed to occupy portions of liver segments 6 and 7, necessitating a formal right hepatectomy and cholecystectomy. The patient tolerated the procedure well, was extubated in the operating room, and recovered in the ICU in stable condition without further complications and was seen in clinic for follow-up without further postoperative concerns. Conclusion: Though rare, Caroli disease can present as an asymptomatic focal heterogeneous mass in children. Pediatric patients with segmental Caroli disease can be treated with partial hepatectomy safely