Clearance of inflammatory cytokines in patients with septic acute kidney injury during renal replacement therapy using the EMiC2 filter (Clic-AKI study)

BACKGROUND: The EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance. METHODS: This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations. RESULTS: Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p < 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period. CONCLUSION: EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal. TRIAL REGISTRATION: NCT03231748, registered on 27th July 2017

Effects of regional citrate anticoagulation on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving continuous renal replacement therapy for acute kidney injury: a prospective study

Background: Regional citrate anticoagulation (RCA) is recommended for continuous renal replacement therapy (CRRT). However, filter life varies and premature filter clotting can occur. The aims of this explorative prospective study were to investigate the effects of RCA on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving CRRT, to compare clotting parameters between systemic and intra-circuit blood samples, and to screen participants for coagulation disorders. We recruited critically ill adult patients admitted to a 30-bedded Intensive care unit in a tertiary care hospital who required CRRT with RCA for acute kidney injury (AKI). Patients with pre-existing thrombotic, bleeding tendencies or a CRRT duration less than 48 h were excluded. We measured coagulation and thrombophilia parameters at baseline. Thrombin generation, D-dimer and platelet function were measured pre-CRRT and at 12, 24, 36, 48 and 72 h after commencing CRRT using blood samples taken from the arterial line and the circuit. Results: At baseline, all eleven patients (mean age 62.4 years, 82% male) had Factor VIII and von Willebrand Factor concentrations above reference range and significantly increased peak thrombin generation. During CRRT, there were no significant changes in systemic maximum peak thrombin generation, time to peak thrombin generation, fibrinogen, D-dimer and platelet function analysis. We observed no significant difference between paired samples taken from the patient's arterial line and the circuit. Conclusions: Critically ill patients with AKI requiring CRRT are hypercoagulable. Citrate used for anticoagulation during CRRT does not affect thrombin generation, D-dimer or platelet function. Systemic clotting parameters reflect intra-circuit results. Trial registration: ClinicalTrials.gov Identifier: NCT02486614. Registered 01 July 2015—Registered after recruitment of first patient. https://clinicaltrials.gov/ct2/show/NCT0248661

Correlates of Poor Health among Orphans and Abandoned Children in Less Wealthy Countries: The Importance of Caregiver Health

BACKGROUND: More than 153 million children worldwide have been orphaned by the loss of one or both parents, and millions more have been abandoned. We investigated relationships between the health of orphaned and abandoned children (OAC) and child, caregiver, and household characteristics among randomly selected OAC in five countries. METHODOLOGY: Using a two-stage random sampling strategy in 6 study areas in Cambodia, Ethiopia, India, Kenya, and Tanzania, the Positive Outcomes for Orphans (POFO) study identified 1,480 community-living OAC ages 6 to 12. Detailed interviews were conducted with 1,305 primary caregivers at baseline and after 6 and 12 months. Multivariable logistic regression models describe associations between the characteristics of children, caregivers, and households and child health outcomes: fair or poor child health; fever, cough, or diarrhea within the past two weeks; illness in the past 6 months; and fair or poor health on at least two assessments. PRINCIPAL FINDINGS: Across the six study areas, 23% of OAC were reported to be in fair or poor health; 19%, 18%, and 2% had fever, cough, or diarrhea, respectively, within the past two weeks; 55% had illnesses within the past 6 months; and 23% were in fair or poor health on at least two assessments. Female gender, suspected HIV infection, experiences of potentially traumatic events, including the loss of both parents, urban residence, eating fewer than 3 meals per day, and low caregiver involvement were associated with poorer child health outcomes. Particularly strong associations were observed between child health measures and the health of their primary caregivers. CONCLUSIONS: Poor caregiver health is a strong signal for poor health of OAC. Strategies to support OAC should target the caregiver-child dyad. Steps to ensure food security, foster gender equality, and prevent and treat traumatic events are needed

Characterisation, expression and ontogeny of interleukin-6 and its receptors in zebrafish (Danio rerio)

10 páginas, 8 figuras, 2 tablasInterleukin-6 (IL-6) is one of the most pleiotropic cytokines due to its importance in both innate and adaptive immune responses and other physiological processes. In this study, we identified the zebrafish (Danio rerio) IL-6 homologue by investigating the synteny between the human (Homo sapiens), the fugu (Takifugu rubripes) and the zebrafish genome. Although zebrafish IL-6 showed a low sequence homology with other IL-6 sequences in other species, it presented a high structural similarity to human IL-6. We also analysed IL-6 expression in several different tissues, along with analysis of the expression of the genes that form the IL-6 receptor complex, IL-6R and gp130. After treatment with bacterial or viral stimuli, zebrafish IL-6 expression was modulated in a manner similar to that of other proinflammatory molecules, such as IL-1β and TNF-α. The expression of IL-6, IL-6R and gp130 was also studied during the ontogeny of zebrafish larvae using quantitative PCR and in situ hybridisation. Our results indicated that the transcripts were detected very early, increased during the first week of life and were predominantly expressed in the head, epidermis and neuromasts of the anterior and posterior lateral line system, suggesting their involvement in the normal development of these tissues.We want to thank the funding from the project CSD2007-00002 “Aquagenomics” of the program Consolider-Ingenio 2010 from the Spanish Ministerio de Ciencia e Innovación. M. Varela gratefully acknowledges the JAE Program, co financed by CSIC and European Social Funds, for a predoctoral grant.Peer reviewe

Using semantically paired images to improve domain adaptation for the semantic segmentation of aerial images

Modern machine learning, especially deep learning, which is used in a variety of applications, requires a lot of labelled data for model training. Having an insufficient amount of training examples leads to models which do not generalize well to new input instances. This is a particular significant problem for tasks involving aerial images: Often training data is only available for a limited geographical area and a narrow time window, thus leading to models which perform poorly in different regions, at different times of day, or during different seasons. Domain adaptation can mitigate this issue by using labelled source domain training examples and unlabeled target domain images to train a model which performs well on both domains. Modern adversarial domain adaptation approaches use unpaired data. We propose using pairs of semantically similar images, i.e., whose segmentations are accurate predictions of each other, for improved model performance. In this paper we show that, as an upper limit based on ground truth, using semantically paired aerial images during training almost always increases model performance with an average improvement of 4.2% accuracy and .036 mean intersection-over-union (mIoU). Using a practical estimate of semantic similarity, we still achieve improvements in more than half of all cases, with average improvements of 2.5% accuracy and .017 mIoU in those cases. © 2020 Copernicus GmbH. All rights reserved