Aaenhemmingsen7575

ntifying opportunities to improve medication and patient safety. We share here our workflow and hope it serves as a guide for other institutions.

This is the first study to report trends of ADRs spontaneously reported at one of the largest healthcare institutions in the Middle East. It shows similar trends to what has been reported by other institutions, with mainly immediate immunological ADRs being the top reported ADRs, which could be explained by the immediate onset which simplifies the temporal association. Every institution should support and maintain an active ADR team, with responsibilities of evaluating incidents, monitoring trends and most importantly identifying opportunities to improve medication and patient safety. We share here our workflow and hope it serves as a guide for other institutions.The underlying molecular mechanisms involved in the pathogenesis of endometrial cancer (EC) are still not well understood. Our goal was to investigate the composition of the endometrial microbiota and the association with inflammatory cytokines in EC. Endometrial microbiota profiles of women with EC (n = 25) and benign uterine lesions (BUL, n = 25) were assessed by 16S ribosomal RNA gene amplicon sequencing. The expression levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-17 (IL-17) mRNA and protein in the endometrial tissues of the two groups were determined by real-time quantitative polymerase chain reaction and Western blot, respectively. There were significant differences in alpha diversity based on the observed operational taxonomic units (P = .002), Pielou evenness (P = .001), and Shannon index (P  less then  .001) between EC and BUL groups. Significant differences were also found in Bray-Curtis (P = .001) and unweighted UniFrac (P = .001) beta diversity measures between the two groups. At the genus level, Micrococcus was more abundant in the EC group. Pseudoramibacter_Eubacterium, Rhodobacter, Vogesella, Bilophila, Rheinheimera, and Megamonas were enriched in the BUL group. There were no differences in IL-8 and IL-17 protein levels between the two groups, except IL-6 protein levels. However, the mRNA expression levels of IL-6, IL-8, and IL-17 were significantly different. Moreover, the relative abundances of Micrococcus was positively correlated with IL-6, and IL-17 mRNA levels. In conclusion, our results suggested that dysbiosis of endometrial microbiota and the inflammatory cytokines were associated with Micrococcus in EC patients, which might be useful for exploration of the mechanism between the endometrial microbiota and inflammatory responses in future studies.Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) represent a unique patient population with specific characteristics and needs. Growing evidences suggest that pediatric-inspired approaches improve the outcome in AYA. These results prompted the design of a pediatric AIEOP-BFM ALL 2000-based regimen - the GIMEMA LAL-1308 protocol - for newly diagnosed AYA (range 18-35 years) with Philadelphia negative (Ph-) ALL. The protocol included minimal residual disease (MRD) analysis at two different time-points (TP), that is, at the end of induction IA and consolidation IB, and a modulation in post-consolidation intensity according to MRD. Seventy-six patients were eligible between September 2010 and October 2014. The regimen was well tolerated, with 2.7% induction deaths and no deaths in the post-consolidation phase. The complete response (CR) rate was 92%; the 48-month overall survival (OS) and disease-free survival (DFS) were 60.3% and 60.4%. Both OS and DFS were significantly better in T-ALL than B-ALL. A molecular MRD less then 10-3 at TP1 was associated with a significantly better OS and DFS (77% vs 39% and 71.9% vs 34.4%, respectively);similar results were documented at TP2 (OS and DFS 74.5% vs 30.6% and 71.5% vs 25.7%, respectively). The LAL-1308 results were compared to those from similar historic AYA populations undergoing the two previous GIMEMA LAL-2000 and LAL-0904 protocols. Both OS and DFS improved significantly compared to the two previous protocols. These results indicate that this pediatric-inspired and MRD-oriented protocol is feasible and effective for Ph- AYA ALL patients, and underline the prognostic value of MRD determinations at specific TPs.Accurate evaluation of tumor response to preoperative chemotherapy is crucial for assigning appropriate patients with colorectal liver metastases (CRLM) to surgery or conservative therapy. However, there is no well-recognized method for predicting pathological response before surgery. Our study constructed and validated a deep learning algorithm using prechemotherapy and postchemotherapy magnetic resonance imaging (MRI) to predict pathological response in CRLM. CRLM patients from center one who had ≤5 lesions and were scheduled to receive preoperative chemotherapy followed by liver resection between January 2013 and November 2016, were included prospectively and chronologically divided into a training cohort (80% of patients) and a testing cohort (20% of patients). Importazole nmr Patients from center two were included January 2017 and December 2018 as an external validation cohort. MRI-based models were constructed to discriminate according to pathology tumor regression grade (TRG) between the response (TRG1/2) and nonresponse (TRG3/4/5) groups at the lesion level. From center one, 155 patients (328 lesions) were included; chronologically, 101 (264 lesions) in the training cohort and 54 (64 lesions) in the testing cohort. The model achieved better accuracy (0.875 vs 0.578) and AUC (0.849 vs 0.615) than RECIST for discriminating response; it also distinguished the survival outcomes after hepatectomy better than the RECIST criteria. Evaluations of the external validation cohort (25 patients, 61 lesions) also showed good ability with an AUC of 0.833. In conclusion, the MRI-based deep learning model provided accurate prediction of pathological tumor response to preoperative chemotherapy in patients with CRLM and may inform individualized treatment.Here we sought metabolic alterations specifically associated with MYCN amplification as nodes to indirectly target the MYCN oncogene. Liquid chromatography-mass spectrometry-based proteomics identified seven proteins consistently correlated with MYCN in proteomes from 49 neuroblastoma biopsies and 13 cell lines. Among these was phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in de novo serine synthesis. MYCN associated with two regions in the PHGDH promoter, supporting transcriptional PHGDH regulation by MYCN. Pulsed stable isotope-resolved metabolomics utilizing 13 C-glucose labeling demonstrated higher de novo serine synthesis in MYCN-amplified cells compared to cells with diploid MYCN. An independence of MYCN-amplified cells from exogenous serine and glycine was demonstrated by serine and glycine starvation, which attenuated nucleotide pools and proliferation only in cells with diploid MYCN but did not diminish these endpoints in MYCN-amplified cells. Proliferation was attenuated in MYCN-amplified cells by CRISPR/Cas9-mediated PHGDH knockout or treatment with PHGDH small molecule inhibitors without affecting cell viability.