Surgical Infection Society Guidelines for Vaccination after Traumatic Injury

Background: Recommendations for vaccination of injured patients against infection are evolving. Newly-recognized infections, safety considerations, changing epidemiology, and redefinition of patient groups at risk are factors that may influence vaccine development priorities and recommendations for immunization. However, recommendations must often be formulated based on incomplete data, forcing reliance on expert opinion to address some crucial questions. These guidelines provide evidence-based recommendations for the prevention or treatment of infectious morbidity and mortality after traumatic injury, such as soft tissue wounds, human or animal bites, or after splenectomy. Methods: A panel of experts conducted a thorough review of published literature, as well as information posted on the internet at the websites of the U.S. Centers for Disease Control and Prevention, among others. MEDLINE was searched for the period 1966–2004 using relevant terms including anthrax, rabies, tetanus, tetanus toxoid, and splenectomy, in combination with vaccine and immunization. The Cochrane database was searched also. Reference lists were cross-referenced for additional relevant citations. All published reports were analyzed for quality and graded, with the strength of the recommendation proportionate to the quality of the supporting evidence. Results: Recommendations are provided for pre- and post-exposure prophylaxis of rabies and anthrax. For tetanus prophylaxis, recommendations are provided for prophylaxis of acute wounds stratified y age and prior immunization status, and for immunization of persons at high risk. After splenectomy, it is recommended that all persons ages 2–64 years receive 23- valent pneumococcal vaccine and meningococcal vaccine, with Haemophilus influenzae type B vaccine administered to high-risk patients as well (all are Grade D recommendations). Vaccination should be given two weeks before elective splenectomy (Grade C), or two weeks after emergency splenectomy (Grade D). A booster dose of pneumococcal vaccine is recommended after five years (Grade D); no re- vaccination recommendation is made for meningococcal or Haemophilus influenzae type B vaccine. Recommendations for prophylaxis of splenectomized children under the age of five years are also provided. Conclusion: There are limited data on the use of vaccines after injury. This document brings together a disparate literature of variable quality into a discussion of the infectious risks after injury relevant to vaccine administration, a summary of safety and adverse effects of vaccines, and evidence-based recommendations for vaccination

Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern

INTRODUCTION: Following trauma and systemic inflammatory response syndrome (SIRS), the typical response is an elevation of the total complete blood count (CBC) and a reduction of the lymphocyte count. This leukocytosis typically returns to normal within 48 hours. The persistence of a leukocytosis following trauma is associated with adverse outcomes. Although lymphocyte anergy and dysfunction following trauma is associated with increased risk for infection and sepsis, there is a paucity of data regarding the impact of a persistence of a low lymphocyte count in trauma patients. METHODS: This is a retrospective review of prospectively collected data from trauma patients collected over the 5 years of September 2003 to September 2008. Patients were included if the injury severity score (ISS) was >/=15, and they survived at least 3 days. Demographic data, mechanism and injury severity score, mortality, and length of stay were collected from the medical record. Laboratory values for the first 4 hospital days were collected. Leukocyte, neutrophil and lymphocyte counts were extracted from the daily complete blood count (CBC). Patients were then grouped based on response (elevation/depression) of each component of the CBC, and their return, or failure thereof, to normal. Proportional hazards regression with time-varying covariates as well as Kaplan-Meier curves were used to predict risk of death, time to death and time to healthy discharge based on fluctuations of the individual components of the CBC. RESULTS: There were 2448 patients admitted over the 5 years included in the analysis. When adjusting for age, gender and ISS the relative risk of death was elevated with a persistent leukocytosis (2.501 (95% CI = 1.477-4.235)) or failure to normalize lymphopenia (1.639 (95% CI = 10.17-2.643)) within the first 4 days following admission. Similar results were seen when Kaplan-Meier curves were created. Persistent lymphopenia was associated with shortest time to death. Paradoxically in survivors persistent lymphopenia was associated with the shortest time to discharge. CONCLUSIONS: Persistently abnormal CBC responses are associated with a higher mortality following trauma. This is the first report noting that a failure to normalize lymphopenia in severely injured patients is associated with significantly higher mortality

Program Cell Death Receptor-1-Mediated Invariant Natural Killer T-Cell Control of Peritoneal Macrophage Modulates Survival in Neonatal Sepsis

We have shown that invariant natural killer T (iNKT) cells mediate sepsis-induced end-organ changes and immune responses, including macrophage bacterial phagocytosis, a finding regulated by the check point protein program cell death receptor-1 (PD-1). Furthermore, PD-1 mediates mortality in both adult and neonatal murine sepsis as well as in surgical patients. Given our previous findings, we hypothesize that iNKT cells will also modulate neonatal sepsis survival, and that this effect is regulated in part through PD-1. We utilized a polymicrobial intra-peritoneal cecal slurry (CS) sepsis model in wild type (WT), iNKT−/− or PD-1−/− 5–7 day old neonatal pups. Typically, tissues were harvested at 24 h for various bioassays/histology and, in some cases, survival was assessed for up to 7 days. Interestingly, similar to what we recently reported for PD-1−/− mice following CS, iNKT−/−-deficient animals exhibit a markedly improved survival vs. WT. Histologically, minor alterations in liver architectural, which were noted in WT pups, were attenuated in both iNKT−/− and PD-1−/− pups. Following CS, PECAM-1 expression was unchanged in the WT pups but increased in both iNKT−/− and PD-1−/− pups. In WT, following CS the emergence of a Ly6Clow subpopulation was noted among the influxed peritoneal macrophage population. Conversely, within iNKT−/− pups, there were fewer peritoneal macrophages and a greater percentage of Ly6Chigh macrophages. We show not only a key role for iNKT cells in affecting end-organ damage as well as alterations in phagocytes phenotypes in neonatal sepsis but that this iNKT cell mediated effect is driven by the central checkpoint protein PD-1

Neutrophil–Endothelial Interactions Mediate Angiopoietin-2–Associated Pulmonary Endothelial Cell Dysfunction in Indirect Acute Lung Injury in Mice

Unresolved inflammation in the lung is thought to elicit loss of endothelial cell (EC) barrier integrity and impaired lung function. We have shown, in a mouse model of shock/sepsis, that neutrophil interactions with resident pulmonary cells appear central to the pathogenesis of indirect acute lung injury (iALI). Normally, EC growth factors angiopoietin (Ang)-1 and Ang-2 maintain vascular homeostasis through tightly regulated interaction with the kinase receptor Tie2 expressed on ECs. Although Ang-1/Tie2 has been shown to promote vessel integrity, stimulating downstream prosurvival/antiinflammatory signaling, Ang-2, released from activated ECs, is reported to promote vessel destabilization. This mechanism of regulation, together with recent clinical findings that plasma Ang-2 levels are significantly elevated in patients who develop acute respiratory distress syndrome, has focused our investigation on the contribution of Ang-2 to the development of iALI. A murine model of hemorrhagic shock–induced priming for the development of iALI after subsequent septic challenge was used in this study. Our findings show that 1 ) Ang-2 is elevated in our experimental model for iALI, 2 ) direct EC/neutrophil interactions contribute significantly to EC Ang-2 release, and 3 ) suppression of Ang-2 significantly decreases inflammatory lung injury, neutrophil influx, and lung and plasma IL-6 and TNF-α. These findings support our hypothesis and suggest that Ang-2 plays a role in the loss of pulmonary EC barrier function in the development of iALI in mice resultant from the sequential insults of hemorrhagic shock and sepsis and that this is mediated by EC interaction with activated neutrophils

Obesity and Pulmonary Complications in Critically Injured Adults

Naglasak ovog istraživanja stavljen je na učeničku percepciju suvremene vizualne umjetnosti i postizanje kvalitete osobe u nastavi Likovne kulture. Korelacija između te dvije odrednice jasna je ako uzmemo u obzir da se većina djela suvremene vizualne umjetnosti bavi pitanjem pojedinca i društva, a samim su time primjena i poučavanje suvremenih umjetničkih praksi u osnovnim školama poželjne kao metode za samoostvarenje učenika. No, prema postojećem Nastavnom planu i programu za likovnu kulturu u osnovnim školama, učenici se u nastavi Likovne kulture minimalno susreću sa suvremenim tendencijama u umjetnosti. Naglaska na refleksiju likovnog djela gotovo da nema, kao niti praktične izvedbe likovnih radova u suvremenim medijima. Ovim radom istražuje se što je kvaliteta osobe, kako su je definirali pojedini psiholozi i filozofi te koja je veza razvoja kvalitete osobe i umjetnosti, tj. kreativnosti i vizualne kulture. Istraživanjem se nastojalo ustanoviti koji čimbenici utječu na razvoj intrapersonalne inteligencije kod učenika, čiji je razvoj neophodan za samoaktualizaciju osobe i kako bi nastava Likovne kulture mogla doprinijeti njenom razvoju. Analizirajući odnos umjetnosti i života, zapanjujući je nesrazmjer poučavanja suvremene umjetnosti i umjetnosti prethodnih razdoblja. Primjenjujući prakse suvremene umjetnosti učenici doista neposredno uče o sebi i svijetu i na taj način ih se priprema za konkretne probleme s kojima bi se mogli susresti u budućnosti te bi se nesrazmjer trebao smanjiti. Prilikom istraživanja pokušalo se odgovoriti na sljedeća pitanja: Kako se intrapersonalna inteligencija učenika može poticati u nastavi Likovne kulture? Kako nastava Likovne kulture može doprinijeti samoostvarenju učenika? Kako suvremena vizualna umjetnost utječe na postizanje kvalitete osobe? Kako učenici promišljaju odnos vizualne umjetnosti i života? Dobivenim rezultatima istraživanja odgovorilo se na istraživačka pitanja. Uključivanjem suvremene vizualne umjetnosti u nastavu, učenici se upoznaju s aktualnim zbivanjima u umjetnosti, a drugačijim pristupima i poticanjima konceptualnog mišljenja omogućuje se kvalitetniji razvoj osobnosti na putu prema samoaktualizaciji.The focus of this research is students' perceptions of contemporary art and the achievement of a person's quality through the process of teaching fine arts. Considering that most contemporary artworks deal with the issue of the individual and society teaching, practicing contemporary art in primary schools is desirable as a method for self-realization. However, according to the existing curriculum for elementary schools, in the fine arts classes, students are minimally confronted with contemporary art. There is almost no encouragement of reflection about fine art, as neither practical implementation through contemporary media. This treatise explores what is the quality of the person, as defined by psychologists and philosophers, and correlation between the development of a person's quality and fine art, creativity, and visual culture. The research is trying to define factors of achieving intrapersonal intelligence, which development is necessary for the self-actualization of person, and how to process teaching of fine arts can contribute to that development. Analyzing the relationship between art and life, the astonishing disparity between teaching contemporary art and art of previous periods is staggering, Through contemporary art practices, students can learn directly about themselves and the world, thus preparing them for the specific problems they might confront in the future. This research appoint the following questions: Which is the way to encourage intrapersonal intelligence in the process of teaching fine arts? How the teaching of fine arts can contribute to self-realization? How contemporary visual art can affect on person's quality of life? Which is students opinion of the relationship between visual art and life? Incorporating contemporary art into the process of teaching, students become familiarized with current developments in the arts. Also, different approaches and encouraging conceptual thinking can support the development of personality in the process of self-actualization

A Novel Role for Programmed Cell Death Receptor Ligand-1 in Sepsis-Induced Intestinal Dysfunction

Abstract Studies imply that intestinal barrier dysfunction is a key contributor to morbid events associated with sepsis. Recently, the co-inhibitory molecule programmed death-ligand1 (PD-L1) has been shown to be involved in the regulation of intestinal immune tolerance and/or inflammation. Our previous studies showed that PD-L1 gene deficiency reduced sepsis-induced intestinal injury morphologically. However, it is not known how PD-L1 expression impacts intestinal barrier dysfunction during sepsis. Here we tested the hypothesis that PD-L1 expressed on intestinal epithelial cells (IECs) has a role in sepsis-induced intestinal barrier dysfunction. To address this, C57BL/6 or PD-L1 gene knockout mice were subjected to experimental sepsis and PD-L1 expression, intestinal permeability and tissue cytokine levels were assessed. Subsequently, septic or nonseptic colonic samples (assigned by pathology report) were immunohistochemically stained for PD-L1 in a blinded fashion. Finally, human Caco2 cells were used for in vitro studies. The results demonstrated that PD-L1 was constitutively expressed and sepsis significantly upregulates PD-L1 in IECs from C57BL/6 mice. Concurrently, we observed increased PD-L1 expression in colon tissue samples from septic patients. PD-L1 gene deficiency reduced ileal permeability and tissue levels of IL-6, TNF-α and MCP-1, and prevented ileal tight junction protein loss compared with WT after sepsis. Comparatively, while Caco2 cell monolayers also responded to inflammatory cytokine stimulation with elevated PD-L1 expression, increased monolayer permeability and altered/decreased monolayer tight junction protein morphology/expression, these changes were reversed by PD-L1 blocking antibody. Together these data indicate that ligation of PD-L1 plays a novel role in mediating the pathophysiology of sepsis-induced intestinal barrier dysfunction

Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS)

Abstract Background Acute respiratory distress syndrome (ARDS) remains a common organ dysfunction in the critically ill patient. Mechanisms for its development have focused on immune mediated causes, aspects of our understanding are not complete, and we lack biomarkers. Design, setting, and subjects Blood and bronchial alveolar lavage fluid (BAL) from humans (n = 10–13) with ARDS and controls (n = 5–10) as well as a murine model of ARDS (n = 5–6) with controls (n = 6–7) were studied. Methods ARDS was induced in mice by hemorrhagic shock (day 1) followed by poly-microbial sepsis (day 2). Samples were then collected on the third day after the animals were euthanized. Ex vivo experiments used splenocytes from animals with ARDS cultured with and without soluble programmed death receptor-1 (sPD-1). Results Levels of sPD-1 are increased in both the serum (11,429.3 pg/mL(SD 2133.3) vs. 8061.4(SD 4187.8), p = 0.036) and bronchial alveolar lavage (BAL) fluid (6,311.1 pg/mL(SD 3758.0) vs. 90.7 pg/mL(SD 202.8), p = 0.002) of humans with ARDS. Similar results are seen in the serum (9396.1 pg/mL(SD 1546.0) vs. 3464.5 pg/mL(SD 2511.8), p = 0.001) and BAL fluid (2891.7 pg/mL(SD 868.1) vs. 1385.9 pg/mL(SD 927.8), p = 0.012) of mice. sPD-1 levels in murine blood (AUC = 1(1–1), p = 0.006), murine BAL fluid (AUC = 0.905(0.717–1.093), p = 0.015), and human BAL (AUC = 1(1–1), p = 0.001) fluid predicted ARDS. To assess the importance of sPD-1 in ARDS, ex vivo experiments were undertaken. BAL fluid from mice with ARDS dampens the TNF-α production compared to cells cultured with BAL lacking sPD-1 (2.7 pg/mL(SD 3.8) vs. 52.38 pg/mL(SD 25.1), p = 0.002). Conclusions This suggests sPD-1 is elevated in critical illness and may represent a potential biomarker for ARDS. In addition, sPD-1 has an anti-inflammatory mechanism in conditions of marked stress and aids in the resolution of severe inflammation. sPD-1 could be used to not only diagnose ARDS, but may be a potential therapy