Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

A global research priority agenda to advance public health responses to fatty liver disease

Background & aims An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. Methods Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. Results The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of ‘agree’ responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement (‘agree’ + ‘somewhat agree’); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% ‘agree’), 13 priorities had 90% combined agreement. Conclusions Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community’s efforts to advance and accelerate responses to this widespread and fast-growing public health threat. Impact and implications An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat

Effect of ant predation and abiotic factors on the mortality of medfly larvae, Ceratitis capitata, in the Argan forest of Western Morocco

The Argan Argania spinosa (L.) Skeels (Ericales: Sapotaceae) is an endemic and emblematic tree growing in the centre and the southwest of Morocco. Argan fruits are frequently infested by the Mediterranean fruit fly Ceratitis capitata Wied (Diptera: Tephritidae). To date, no control program has been undertaken in the Argan forest. This research is the first investigation of natural mortality factors of C. capitata larvae in the Argan forest. The study was conducted at two localities near the city of Essaouira with different climatic conditions. Observations were conducted using 260 late instar larvae which were individually deposited on the ground, under fruiting host trees, where they naturally fall to find a suitable pupation site. Overall, 42% of the larvae died before being able to burrow into the ground, irrespectively of the location. Larval survival and their likelihood of burrowing decreased with increasing ground temperature, as 53% of all the larvae deaths occurred at temperatures over 48 degrees C. However, at lower ground temperature, predation by ants and spiders accounted for 47% of all mortality. Four species of ants carried out 94% of the captures. Monomorium subopacum Mayr (Hymenoptera: Formicidae), which frequently forages under Argan trees, was by far the most efficient predator, due to a powerful sting that rapidly immobilizes the prey. Our results suggest that the burrowing performance of larvae is constrained by high thermal conditions and the presence of ant predators at lower temperatures.Peer Reviewe

Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs.

Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering (p < 0.01). IAPCs produced more PTN than MK (p < 0.01). NAS TLRs and iAPCs had differential abilities to induce the production of MK, which was induced in monocytes and pDCs by all NAS TLRs (p < 0.05) and in MDDCs by TLRs 7/8 (p < 0.05). TLR4 induced a stronger MK production than NAS TLRs (p ≤ 0.05). Monocytes produced higher levels of PTN after differentiation to macrophages and MDDCs (p < 0.05). The production of MK and PTN differs among iAPCs, with a higher production of PTN and a selective induction of MK production by NAS TLR. This highlights the potentially important role of iAPCs in angiogenesis, tumors, infections, and autoimmunity through the differential production of MK and PTN upon TLR triggering

Human macrophages and monocyte-derived dendritic cells stimulate the proliferation of endothelial cells through midkine production.

The cytokine midkine (MK) is a growth factor that is involved in different physiological processes including tissue repair, inflammation, the development of different types of cancer and the proliferation of endothelial cells. The production of MK by primary human macrophages and monocyte-derived dendritic cells (MDDCs) was never described. We investigated whether MK is produced by primary human monocytes, macrophages and MDDCs and the capacity of macrophages and MDDCs to modulate the proliferation of endothelial cells through MK production. The TLR stimulation of human monocytes, macrophages and MDDCs induced an average of ≈200-fold increase in MK mRNA and the production of an average of 78.2, 62, 179 pg/ml MK by monocytes, macrophages and MDDCs respectively (p < 0.05). MK production was supported by its detection in CD11c+ cells, CLEC4C+ cells and CD68+ cells in biopsies of human tonsils showing reactive lymphoid follicular hyperplasia. JSH-23, which selectively inhibits NF-κB activity, decreased the TLR-induced production of MK in PMBCs, macrophages and MDDCs compared to the control (p < 0.05). The inhibition of MK production by macrophages and MDDCs using anti-MK siRNA decreased the capacity of their supernatants to stimulate the proliferation of endothelial cells (p = 0.01 and 0.04 respectively). This is the first study demonstrating that the cytokine MK is produced by primary human macrophages and MDDCs upon TLR triggering, and that these cells can stimulate endothelial cell proliferation through MK production. Our results also suggest that NF-κB plays a potential role in the production of MK in macrophages and MDDCs upon TLR stimulation. The production of MK by macrophages and MDDCs and the fact that these cells can enhance the proliferation of endothelial cells by producing MK are novel immunological phenomena that have potentially important therapeutic implications

O-065 Multicenter investigation into presentation, management and outcome of infectious intracranial aneurysms

Introduction Infectious intracranial aneurysms (IIAs) are rare complications of infective endocarditis or systemic infection. To date, data are limited regarding management as well as long-term outcomes of patients with ruptured or unruptured IIAs. We explored, at multicenter level, the presentation, technical and clinical outcomes of patients with IIAs management by conservative or surgical intervention. Methods This is a multicenter retrospective study of patients presenting with IIAs between January 2016 and December 2022 at seven tertiary care centers in the United States. Medical record, procedure notes, and imaging findings were reviewed for demographics, aneurysm features, management and clinical and technical outcomes. Patients were managed either via sole medical management (MM) which included antibiotics and serial imaging, endovascular embolization and antibiotics, or open microsurgery and antibiotics. Technical outcome include aneurysm obliteration at follow-up vascular imaging, and primary clinical outcome was the modified Rankin Score (mRS) at 90 days dichotomized into good outcome (mRS 0-2) and poor outcome (mRS 3-6). Results A total of 66 patients with 116 IIAs (Age: 42+/-17, 67% Males) were treated at all sites during the study period. Comorbid IE was present in 67%, and 12% had a Left Ventricular Assist Device. IIAs presented with rupture in 73% of cases, were discovered during stroke workup in 9%, or were incidentally discovered in 18%. Most IIAs (64%) were diagnosed with a cerebral angiogram, 30% with MR angiography, and 6% with CT angiography. Multiple aneurysms were detected in 36% of subjects. Aneurysms predominantly involved the M3/4 segment (62%), followed by M2 (9%), and A2/3 (8%) while 11% involved the posterior circulation (7% in P2/3). The average size of aneurysms was 4.2 mm +/- 3.5; 73% were less than 5mm in size while 7% were above 10 mm. Primary medical management was used in 63% of IIAs, of which 43% failed medical management with progression of aneurysm or rupture/re-rupture with average time to fail of 24+/- 23 days (42% within 2 weeks). Endovascular treatment was used in 22% of cases as primary treatment (36% as both primary and rescue of failed medical management), whereas open microsurgery was used as primary treatment in 14% of cases (21% as both primary and rescue of failed medical management). Recurrence or progression was noted in 12% of the endovascular group, and 4% of microsurgery group with average follow-up of 200 days. The overall 1-year mortality rate was 21%, and 48% had a mRS 0-2 at 90 days. Multivariate model for prediction of failure of MM, aneurysms with larger size (aOR=1.5,p=0.002) and posterior circulation aneurysms (aOR=6.9,p=0.001) were independent predictor of antibiotic failure. On multivariate logistic regression controlling for demographics, comorbidities, aneurysm size, location and morphology, and treatment group, predictors of 1-year mortality included failed medical management (aOR=6.1,p=.005), age (aOR=1.07,p<0.001), and black race (aOR=3.95,p=0.03). Conclusion Patients with IIAs are at high risk of aneurysm rupture or re-hemorrhage despite treatment with antibiotics. Antibiotic failure occurred in 43% of medically treated patients, and failure was associated with 6 times higher odds of mortality in 1 year. Disclosures A. Alawieh: None. L. Dimisko: None. Y. Zohdy: None. H. Saad: None. S. Newman: None. J. Grossberg: None. C. Cawley: None. G. Pradilla: None. C. Fox: None. C. Perez-Vaga: None. J. Burkhardt: None. M. Salem: None. P. Jabbour: None. K. El Naamani: None. R. Schmidt: None. M. Gooch: None. R. Starke: None. A. Abdelsalam: None. V. Lu: None. M. Levitt: None. A. Spiotta: None. V. Hertzberg: None. D. Barrow: None. B. Howard: None