Impact of sex, MHC, and age of recipients on the therapeutic effect of transferred leukocytes from cancer-resistant SR/CR mice

<p>Abstract</p> <p>Background</p> <p>Spontaneous Regression/Complete Resistant (SR/CR) mice are resistant to cancer through a mechanism that is mediated entirely by leukocytes of innate immunity. Transfer of leukocytes from SR/CR mice can confer cancer resistance in wild-type (WT) recipients in both preventative and therapeutic settings. In the current studies, we investigated factors that may impact the efficacy and functionality of SR/CR donor leukocytes in recipients.</p> <p>Results</p> <p>In sex-mismatched transfers, functionality of female donor leukocytes was not affected in male recipients. In contrast, male donor leukocytes were greatly affected in the female recipients. In MHC-mismatches, recipients of different MHC backgrounds, or mice of different strains, showed a greater negative impact on donor leukocytes than sex-mismatches. The negative effects of sex-mismatch and MHC-mismatch on donor leukocytes were additive. Old donor leukocytes performed worse than young donor leukocytes in all settings including in young recipients. Young recipients were not able to revive the declining function of old donor leukocytes. However, the function of young donor leukocytes declined gradually in old recipients, suggesting that an aged environment may contain factors that are deleterious to cellular functions. The irradiation of donor leukocytes prior to transfers had a profound suppressive effect on donor leukocyte functions, possibly as a result of impaired transcription. The cryopreserving of donor leukocytes in liquid nitrogen had no apparent effect on donor leukocyte functions, except for a small loss of cell number after revival from freezing.</p> <p>Conclusion</p> <p>Despite the functional suppression of donor leukocytes in sex- and MHC-mismatched recipients, as well as old recipients, there was a therapeutic time period during the initial few weeks during which donor leukocytes were functional before their eventual rejection or functional decline. The eventual rejection of donor leukocytes will likely prevent donor leukocyte engraftment which would help minimize the risk of transfusion-associated graft-versus-host disease. Therefore, using leukocytes from healthy donors with high anti-cancer activity may be a feasible therapeutic concept for treating malignant diseases.</p

CpG-ODN and MPLA Prevent Mortality in a Murine Model of Post-Hemorrhage-Staphyloccocus aureus Pneumonia

Infections are the most frequent cause of complications in trauma patients. Post-traumatic immune suppression (IS) exposes patients to pneumonia (PN). The main pathogen involved in PN is Methicillin Susceptible Staphylococcus aureus (MSSA). Dendritic cells () may be centrally involved in the IS. We assessed the consequences of hemorrhage on pneumonia outcomes and investigated its consequences on DCs functions. A murine model of hemorrhagic shock with a subsequent MSSA pneumonia was used. Hemorrhage decreased the survival rate of infected mice, increased systemic dissemination of sepsis and worsened inflammatory lung lesions. The mRNA expression of Tumor Necrosis Factor-alpha (TNF-α), Interferon-beta (IFN-β) and Interleukin (IL)-12p40 were mitigated for hemorrhaged-mice. The effects of hemorrhage on subsequent PN were apparent on the pDCs phenotype (reduced MHC class II, CD80, and CD86 molecule membrane expression). In addition, hemorrhage dramatically decreased CD8+ cDCs- and CD8- cDCs-induced allogeneic T-cell proliferation during PN compared with mice that did not undergo hemorrhage. In conclusion, hemorrhage increased morbidity and mortality associated with PN; induced severe phenotypic disturbances of the pDCs subset and functional alterations of the cDCs subset. After hemorrhage, a preventive treatment with CpG-ODN or Monophosphoryl Lipid A increased transcriptional activity in DCs (TNF-α, IFN-β and IL-12p40) and decreased mortality of post-hemorrhage MSSA pneumonia

Oral care practices in intensive care units: a survey of 59 European ICUs

Objective: To explore the type and frequency of oral care practices in European ICUs and the attitudes, beliefs, and knowledge of health care workers. Design: An anonymous questionnaire was distributed to representatives of European ICUs. Results were obtained from 59 ICUs (one questionnaire per ICU) in seven countries 91% of respondents were registered nurses. Measurements and results: Of the respondents 77% reported that they had received adequate training on providing oral care; most (93%) also expressed the desire to learn more about oral care. Oral care was perceived to be high priority in mechanically ventilated patients (88%). Cleaning the oral cavity was considered difficult by 68%, and unpleasant as well as difficult by 32%. In 37% of cases respondents felt that despite their efforts oral health worsens over time in intubated patients. Oral care practices are carried out once daily (20%), twice (31%) or three times (37%). Oral care consists principally of mouth washes (88%), mostly performed with chlorhexidine (61%). Foam swabs (22%) and moisture agents (42%) are used less frequently as well as manual toothbrushes (41%) although the literature indicates that these are more effective for thorough cleaning of the oral cavity. Electric toothbrushes were never used. Conclusions: In European ICUs oral care is considered very important. It is experienced as a task that is difficult to perform, and that does not necessarily succeed in ensuring oral health in patients with prolonged intubation. Oral care consists primarily of mouth washes. The use of toothbrushes should be given more attention

Centers for Disease Control and Prevention guidelines for preventing central venous catheter-related infection: Results of a knowledge test among 3405 European intensive care nurses

OBJECTIVE:: To determine European intensive care unit (ICU) nurses&apos; knowledge of guidelines for preventing central venous catheter-related infection from the Centers for Disease Control and Prevention. DESIGN:: Multicountry survey (October 2006-March 2007). SETTING:: Twenty-two European countries. PARTICIPANTS:: ICU nurses. MEASUREMENTS AND MAIN RESULTS:: Using a validated multiple-choice test, knowledge of ten recommendations for central venous catheter-related infection prevention was evaluated (one point per question) and assessed in relation to participants&apos; gender, ICU experience, number of ICU beds, and acquisition of a specialized ICU qualification. We collected 3405 questionnaires (70.9% response rate); mean test score was 44.4%. Fifty-six percent knew that central venous catheters should be replaced on indication only, and 74% knew this also concerns replacement over a guidewire. Replacing pressure transducers and tubing every 4 days, and using coated devices in patients requiring a central venous catheter &gt;5 days in settings with high infection rates only were recognized as recommended by 53% and 31%, respectively. Central venous catheters dressings in general are known to be changed on indication and at least once weekly by 43%, and 26% recognized that both polyurethane and gauze dressings are recommended. Only 14% checked 2% aqueous chlorhexidine as the recommended disinfection solution; 30% knew antibiotic ointments are not recommended because they trigger resistance. Replacing administration sets within 24 hrs after administering lipid emulsions was recognized as recommended by 90%, but only 26% knew sets should be replaced every 96 hrs when administering neither lipid emulsions nor blood products. Professional seniority and number of ICU beds showed to be independently associated with better test scores. CONCLUSIONS:: Opportunities exist to optimize knowledge of central venous catheter-related infection prevention among European ICU nurses. We recommend including central venous catheter-related infection prevention guidelines in educational curricula and continuing refresher education programs. © 2008 by the Society of Critical Care Medicine and Lippincott Williams &amp; Wilkins

Evidence-based guidelines for the prevention of ventilator-associated pneumonia: results of a knowledge test among European intensive care nurses

As part of a needs analysis preceding the development of an e-learning platform on infection prevention, European intensive care unit (ICU) nurses were subjected to a knowledge test on evidence-based guidelines for preventing ventilator-associated pneumonia (VAP). A validated multiple-choice questionnaire was distributed to 22 European countries between October 2006 and March 2007. Demographics included nationality, gender, ICU experience, number of ICU beds and acquisition of a specialised degree in intensive care. We collected 3329 questionnaires (response rate 69.1%). The average score was 45.1%. Fifty-five percent of respondents knew that the oral route is recommended for intubation; 35% knew that ventilator circuits should be changed for each new patient; 38% knew that heat and moisture exchangers were the recommended humidifier type, but only 21% knew that these should be changed once weekly; closed suctioning systems were recommended by 46%, and 18% knew that these must be changed for each new patient only; 51% and 57%, respectively, recognised that subglottic drainage and kinetic beds reduce VAP incidence. Most (85%) knew that semi-recumbent positioning prevents VAP. Professional seniority and number of ICU beds were shown to be independently associated with better test scores. Further research may determine whether low scores are related to a lack of knowledge, deficiencies in training, differences in what is regarded as good practice, and/or a lack of consistent policy. (C) 2008 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved