Dickson Glerup (streamwedge8)

Background The purpose of this paper is to describe how end-of-life care is managed when life-support limitation is decided in a Pediatric Intensive Care Unit and to analyze the influence of the further development of the Palliative Care Unit. Methods A 15-year retrospective study of children who died after life-support limitation was initiated in a pediatric intensive care unit. Patients were divided into two groups, pre- and post-palliative care unit development. Epidemiological and clinical data, the decision-making process, and the approach were analyzed. Data was obtained from patient medical records. Results One hundred seventy-five patients were included. The main reason for admission was respiratory failure (86/175). A previous pathology was present in 152 patients (61/152 were neurological issues). The medical team and family participated together in the decision-making in 145 cases (82.8%). The family made the request in 10 cases (9 vs. 1, p = 0.019). Withdrawal was the main life-support limitation (113/175), followed by withholding life-sustaining treatments (37/175). Withdrawal was more frequent in the post-palliative group (57.4% vs. 74.3%, p = 0.031). In absolute numbers, respiratory support was the main type of support withdrawn. Conclusions The main cause of life-support limitation was the unfavourable evolution of the underlying pathology. Families were involved in the decision-making process in a high percentage of the cases. The development of the Palliative Care Unit changed life-support limitation in our unit, with differences detected in the type of patient and in the strategy used. Increased confidence among intensivists when providing end-of-life care, and the availability of a Palliative Care Unit may contribute to improvements in the quality of end-of-life care.Background With the recent emergence of immune checkpoint inhibitors, microsatellite instability (MSI) status has become an important biomarker for immune checkpoint blockade therapy. There are growing technical demands for the integration of different genomic alterations profiling including MSI analysis in a single assay for full use of the limited tissues. Methods Tumor and paired control samples from 64 patients with primary colorectal cancer were enrolled in this study, including 14 MSI-high (MSI-H) cases and 50 microsatellite stable (MSS) cases determined by MSI-PCR. All the samples were sequenced by a customized NGS panel covering 2.2 MB. A training dataset of 28 samples was used for selection of microsatellite loci and a novel NGS-based MSI status classifier, USCI-msi, was developed. NGS-based MSI status, single nucleotide variant (SNV) and tumor mutation burden (TMB) were detected for all patients. Most of the patients were also independently detected by immunohistochemistry (IHC) staining. Results A 9-loci model for detecting microsatellite instability was able to correctly predict MSI status with 100% sensitivity and specificity compared with MSI-PCR, and 84.3% overall concordance with IHC staining. Mutations in cancer driver genes (APC, TP53, and KRAS) were dispersed in MSI-H and MSS cases, while BRAF p.V600E and frameshifts in TCF7L2 gene occurred only in MSI-H cases. Mismatch repair (MMR)-related genes are highly mutated in MSI-H samples. Conclusion We established a new NGS-based MSI classifier, USCI-msi, with as few as 9 microsatellite loci for detecting MSI status in CRC cases. This approach possesses 100% sensitivity and specificity, and performed robustly in samples with low tumor purity.Background Sepsis-associated encephalopathy (SAE) increases the mortality of septic patients, but its mechanism remains unclear. The present study aimed to investigate the roles of T lymphocytes, proBDNF, and their interaction in the pathogenesis of SAE. Methods Fear conditioning tests were conducted for cognitive assessment in the lipopolysaccharide (LPS, 5 mg kg-1)-induced septic mice. Meninges and peripheral blood were harvested for flow c