Human Flt3L Generates Dendritic Cells from Canine Peripheral Blood Precursors: Implications for a Dog Glioma Clinical Trial

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and carries a dismal prognosis. We have developed a conditional cytotoxic/immunotherapeutic approach using adenoviral vectors (Ads) encoding the immunostimulatory cytokine, human soluble fms-like tyrosine kinase 3 ligand (hsFlt3L) and the conditional cytotoxic molecule, i.e., Herpes Simplex Type 1- thymide kinase (TK). This therapy triggers an anti-tumor immune response that leads to tumor regression and anti-tumor immunological memory in intracranial rodent cancer models. We aim to test the efficacy of this immunotherapy in dogs bearing spontaneous GBM. In view of the controversy regarding the effect of human cytokines on dog immune cells, and considering that the efficacy of this treatment depends on hsFlt3L-stimulated dendritic cells (DCs), in the present work we tested the ability of Ad-encoded hsFlt3L to generate DCs from dog peripheral blood and compared its effects with canine IL-4 and GM-CSF.Our results demonstrate that hsFlT3L expressed form an Ad vector, generated DCs from peripheral blood cultures with very similar morphological and phenotypic characteristics to canine IL-4 and GM-CSF-cultured DCs. These include phagocytic activity and expression of CD11c, MHCII, CD80 and CD14. Maturation of DCs cultured under both conditions resulted in increased secretion of IL-6, TNF-alpha and IFN-gamma. Importantly, hsFlt3L-derived antigen presenting cells showed allostimulatory potential highlighting their ability to present antigen to T cells and elicit their proliferation.These results demonstrate that hsFlt3L induces the proliferation of canine DCs and support its use in upcoming clinical trials for canine GBM. Our data further support the translation of hsFlt3L to be used for dendritic cells' vaccination and gene therapeutic approaches from rodent models to canine patients and its future implementation in human clinical trials

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

A survey of asylum seekers\u27 general practice service utilisation and morbidity patterns

To compare Irish asylum seekers to other General Medical Scheme (GMS) patients possessing Irish citizenship in terms of their utilisation of GP services, morbidity patterns and consultation outcomes. A retrospective 1 year study on patient records in two Galway City practices was performed. All asylum seekers who were patients of the two practices were compared with two controls each from a population of GMS patients with Irish citizenship matched for age, sex, and GMS status. Demographic information was recorded. For each consultation over the 12 months the diagnosis using the ICPC coding system1 and consultation outcomes were recorded. Data was collected on 171 asylum seekers and 342 Irish citizens. The majority of asylum seekers registered in the two practices were from Nigeria (43.9%). The age of cases ranged from 1 month to 60 years of age with a median of 26. 45.8% were female and 54% male. The mean number of visits per asylum seeker per year was 5.16 (SD 3.12) whereas the mean for Irish Citizens was 2.31(SD 2.33) (p = 0.0001). Asylum seekers had a significantly higher likelihood of being assigned diagnoses in the disease systems of psychiatry, dermatology, neurology, musculoskeletal disease, urology, respiratory, ENT, Obstetrics and Gynaecology and gastroenterology. Asylum seekers were five times more likely to be diagnosed with psychiatric illness than Irish citizens. Specifically they had a significantly higher chance of being diagnosed with anxiety (odds ratio =3.17[95% CI 1.1, 8.68]). Overall, the frequency of prescription as a consultation outcome was higher for asylum seekers. Asylum seekers were prescribed more antibiotics and psychiatric medications but Irish GMS had higher prescription rates for drugs outside of these categories. Referral rates were higher in the asylum seeker group. Asylum seekers attended the GP more frequently than their Irish counterparts. They were more likely to be diagnosed with psychological problems than the Irish. Studies have shown a strong link between psychological illness and being a frequent attender in general practice2, 3. This could explain the higher than average frequency of attendance in this group. They were more likely to be prescribed antibiotics and psychiatric medications. This study provides the first quantitative data to inform debate regarding the appropriate supply of resources to Irish practices with significant numbers of asylum seekers

A survey of asylum seekers' general practice service utilisation and morbidity patterns

To compare Irish asylum seekers to other General Medical Scheme (GMS) patients possessing Irish citizenship in terms of their utilisation of GP services, morbidity patterns and consultation outcomes. A retrospective 1 year study on patient records in two Galway City practices was performed. All asylum seekers who were patients of the two practices were compared with two controls each from a population of GMS patients with Irish citizenship matched for age, sex, and GMS status. Demographic information was recorded. For each consultation over the 12 months the diagnosis using the ICPC coding system1 and consultation outcomes were recorded. Data was collected on 171 asylum seekers and 342 Irish citizens. The majority of asylum seekers registered in the two practices were from Nigeria (43.9%). The age of cases ranged from 1 month to 60 years of age with a median of 26. 45.8% were female and 54% male. The mean number of visits per asylum seeker per year was 5.16 (SD 3.12) whereas the mean for Irish Citizens was 2.31(SD 2.33) (p = 0.0001). Asylum seekers had a significantly higher likelihood of being assigned diagnoses in the disease systems of psychiatry, dermatology, neurology, musculoskeletal disease, urology, respiratory, ENT, Obstetrics and Gynaecology and gastroenterology. Asylum seekers were five times more likely to be diagnosed with psychiatric illness than Irish citizens. Specifically they had a significantly higher chance of being diagnosed with anxiety (odds ratio =3.17[95% CI 1.1, 8.68]). Overall, the frequency of prescription as a consultation outcome was higher for asylum seekers. Asylum seekers were prescribed more antibiotics and psychiatric medications but Irish GMS had higher prescription rates for drugs outside of these categories. Referral rates were higher in the asylum seeker group. Asylum seekers attended the GP more frequently than their Irish counterparts. They were more likely to be diagnosed with psychological problems than the Irish. Studies have shown a strong link between psychological illness and being a frequent attender in general practice2, 3. This could explain the higher than average frequency of attendance in this group. They were more likely to be prescribed antibiotics and psychiatric medications. This study provides the first quantitative data to inform debate regarding the appropriate supply of resources to Irish practices with significant numbers of asylum seekers