Critical Care Nurses Inadequately Assess SAPS II Scores of Very Ill Patients in Real Life

Background. Reliable ICU severity scores have been achieved by various healthcare workers but nothing is known regarding the accuracy in real life of severity scores registered by untrained nurses. Methods. In this retrospective multicentre audit, three reviewers independently reassessed 120 SAPS II scores. Correlation and agreement of the sum-scores/variables among reviewers and between nurses and the reviewers' gold standard were assessed globally and for tertiles. Bland and Altman (gold standard—nurses) of sum scores and regression of the difference were determined. A logistic regression model identifying risk factors for erroneous assessments was calculated. Results. Correlation for sum scores among reviewers was almost perfect (mean ICC = 0.985). The mean (±SD) nurse-registered SAPS II sum score was 40.3 ± 20.2 versus 44.2 ± 24.9 of the gold standard (P < 0.002 for difference) with a lower ICC (0.81). Bland and Altman assay was +3.8 ± 27.0 with a significant regression between the difference and the gold standard, indicating overall an overestimation (underestimation) of lower (higher; >32 points) scores. The lowest agreement was found in high SAPS II tertiles for haemodynamics (k = 0.45–0.51). Conclusions. In real life, nurse-registered SAPS II scores of very ill patients are inaccurate. Accuracy of scores was not associated with nurses' characteristics

Dynamics of the Apple Fruit Microbiome after Harvest and Implications for Fruit Quality

The contribution of the apple microbiome to the production chain of apple was so far largely unknown. Here, we describe the apple fruit microbiome and influences on its composition by parameters such as storage season, storage duration, storage technology, apple variety, and plant protection schemes. A combined culturing and metabarcoding approach revealed significant differences in the abundance, composition, and diversity of the apple fruit microbiome. We showed that relatively few genera contribute a large portion of the microbiome on fruit and that the fruit microbiome changes during the storage season depending on the storage conditions. In addition, we show that the plant protection regime has an influence on the diversity of the fruit microbiome and on the dynamics of pathogenic fungal genera during the storage season. For the genus Neofabraea, the quantitative results from the metabarcoding approach were validated with real-time PCR. In conclusion, we identified key parameters determining the composition and temporal changes of the apple fruit microbiome, and the main abiotic driving factors of microbiome diversity on apple fruit were characterized

Predictors of positive blood cultures in critically ill patients: a retrospective evaluation

Aim To identify predictors of bacteremia in critically ill patients, to evaluate the impact of blood cultures on the outcome, and to define conditions for breakthrough bacteremia despite concurrent antibiotic treatment. Methods A descriptive retrospective study was performed over a two-year period (2007-2008) in the medico-surgical Intensive Care Unit (ICU) of the San Giovanni Hospital in Bellinzona, Switzerland. Results Forty-five out of 231 patients (19.5%) had positive blood cultures. Predictors of positive blood cultures were elevated procalcitonin levels (>2 μg/L, P < 0.001), higher severity scores (Simplified Acute Physiology Score II>43, P = 0.014; Sequential Organ Failure Assessment >4.0, P < 0.001), and liver failure (P = 0.028). Patients with bacteremia had longer hospital stays (31 vs 21 days, P = 0.058), but their mortality was not different from patients without bacteremia. Fever (t > 38.5°C) only showed a trend toward a higher rate of blood culture positivity (P = 0.053). The rate of positive blood cultures was not affected by concurrent antibiotic therapy. Conclusions The prediction of positive blood culture results still remains a very difficult task. In our analysis, blood cultures were positive in 20% of ICU patients whose blood was cultured, and positive findings increased with elevated procalcitonin levels, liver failure, and higher severity scores. Blood cultures drawn >4 days after the start of antibiotic therapy and >5 days after surgery could detect pathogens responsible for a new infection complication

High tumor mutational burden (TMB) identifies a microsatellite stable pancreatic cancer subset with prolonged survival and strong anti-tumor immunity.

AIM Tumor mutational burden (TMB: somatic mutations per megabase, mut/Mb) predicts the efficacy of immunotherapy. Here, we link TMB levels with the activation of immune pathways and intratumoral immune responses in pancreatic adenocarcinoma (PDAC) to explore immunoarchitectural patterns associated with high TMB. METHODS We assessed TMB in 161 resected, microsatellite stable (MSS) PDACs, including 41 long-term survivors (LTS). Five microsatellite instable (MSI-high) cases were also assessed. Cases were classified into TMB-high (≥10 mut/Mb), TMB-intermediate (>5 < 10 mut/Mb), and TMB-low (≤5 mut/Mb) categories. Tumors additionally underwent mRNA in situ hybridization for immune pathway genes and were immunoprofiled by multiplex immunofluorescence followed by automated image analysis. RESULTS We detected 12 TMB-high, 28 TMB-intermediate, and 121 TMB-low cases. TMB-high tumors comprised ten LTSs (10/41; 24%) and two conventional PDACs (2/120; 1.7%). They exhibited the highest T cell density with significantly increased CD3+CD4+T helper and CD208+dendritic cell (DC) counts, compared to all other cases. CD3+CD8+cytotoxic T cells were significantly closer to tumor cells and T helper cells closer to DCs in TMB-high PDACs. Immune pathways involved in T cell activation, immune cell adhesion/migration, antigen presentation, and cytokine signaling were upregulated in most TMB-high and many TMB-intermediate tumors. ARID1A and ERBB4 alterations were more frequent in TMB-high PDACs. All MSI-high PDACs were TMB-high. CONCLUSIONS TMB-high cases frequently belong to specific PDAC subsets with prolonged survival such as LTSs and MSI-high PDACs. They display strong anti-tumor immune responses fueled by a T helper cell/DC-mediated priming of the cytotoxic T cells. Moreover, they frequently harbor further actionable alterations

Young people from ethnic minority backgrounds : evidence from the Education Maintenance Allowance Pilots Database

This report uses quantitative data collected as part of the evaluation of the Education Maintenance Allowance Pilots to explore comparatively the destinations and achievements of young people from different ethnic minority backgrounds. The report covers two cohorts of young people who finished compulsory education in the summer of 1999 and 2000 respectively and who were interviewed three times at one year intervals, that is, when they were approximately 16, 17 and 18 years of age. It combines data from a random sample of young people in ten EMA pilot areas and 11 control areas Part A of the report focuses on 14,700 young people at the time of their first interview which took place shortly after the end of compulsory education. It compares young people’s school experiences during Years 10 and 11, their qualifications at the end of Year 11, their destinations immediately after compulsory education, the advice they received during Year 11 about these destinations and the reasons they gave for their choice of destination. The final section reflects on the role of EMA on decisions to remain in post-16 education. Data in Part A have been weighted to be representative of all young people in the pilot and control areas. Part B of the report concentrates on 8,300 young people who had taken part in the first three survey interviews. It compares the destinations at ages 17 and 18 of those who initially remained in full-time education at age 16 and then considers the destinations at age 18 of all young people, irrespective of whether they initially remained in education, and explores the relationship between destination, ethnicity and other characteristics known to be associated with remaining in education. The final piece of the analysis explores the relationships between ethnicity, destinations at ages 16, 17 and 18 controlling for certain of these characteristics. Data in Part B have been weighted to be representative of all young people in the pilot and control areas and to take account of differential attrition from the sample between survey interviews

Functional Imaging of Pheochromocytoma with 68Ga-DOTATOC and 68C-HED in a Genetically Defined Rat Model of Multiple Endocrine Neoplasia

Rats affected by the MENX multitumor syndrome develop pheochromocytoma (100%). Pheochromocytomas are uncommon tumors and animal models are scarce, hence the interest in MENX rats to identify and preclinically evaluate novel targeted therapies. A prerequisite for such studies is a sensitive and noninvasive detection of MENXassociated pheochromocytoma. We performed positron emission tomography (PET) to determine whether rat pheochromocytomas are detected by tracers used in clinical practice, such as 68Ga-DOTATOC (somatostatin analogue) or 11C-Hydroxyephedrine (HED), a norepinephrine analogue. We analyzed four affected and three unaffected rats. The PET scan findings were correlated to histopathology and immunophenotype of the tumors, their proliferative index, and the expression of genes coding for somatostatin receptors or the norepinephrine transporter. We observed that mean 68Ga-DOTATOC standard uptake value (SUV) in adrenals of affected animals was 23.3 ± 3.9, significantly higher than in control rats (15.4 ± 7.9; P = .03). The increase in mean tumor-to-liver ratio of 11C-HED in the MENX-affected animals (1.6 ± 0.5) compared to controls (0.7 ± 0.1) was even more significant (P = .0016). In a unique animal model, functional imaging depicting two pathways important in pheochromocytoma biology discriminated affected animals from controls, thus providing the basis for future preclinical work with MENX rats

Dissemination of patient blood management practices in Swiss intensive care units: a cross-sectional survey

BACKGROUND Patient blood management (PBM) promotes the routine detection and treatment of anaemia before surgery, optimising the management of bleeding disorders, thus minimising iatrogenic blood loss and pre-empting allogeneic blood utilisation. PBM programmes have expanded from the elective surgical setting to nonsurgical patients, including those in intensive care units (ICUs), but their dissemination in a whole country is unknown. METHODS We performed a cross-sectional, anonymous survey (10 October 2018 to 13 March 2019) of all ordinary medical members of the Swiss Society of Intensive Care Medicine and the registered ICU nurses from the 77 certified adult Swiss ICUs. We analysed PBM-related interventions adopted in Swiss ICUs and related them to the spread of PBM in Swiss hospitals. We explored blood test ordering policies, blood-sparing strategies and red blood cell-related transfusion practices in ICUs. RESULTS A total of 115 medical doctors and 624 nurses (response rates 27% and 30%, respectively) completed the surveys. Hospitals had implemented a PBM programme according to 42% of physicians, more commonly in Switzerland's German-speaking regions (Odds Ratio [OR] 3.39, 95% confidence interval [CI] 1.23-9.35; p = 0.018) and in hospitals with more than 500 beds (OR 3.91, 95% CI 1.48-10.4; p = 0.006). The PBM programmes targeted the detection and correction of anaemia before surgery (79%), minimising perioperative blood loss (94%) and optimising anaemia tolerance (98%). Laboratory tests were ordered in 70.4% by the intensivist during morning rounds; the nurses performed arterial blood gas analyses autonomously in 48.4%. Blood-sparing techniques were used by only 42.1% of nurses (263 of 624, missing: 6) and 47.0% of physicians (54 of 115). Approximately 60% of respondents used an ICU-specific transfusion guideline. The reported haemoglobin threshold for the nonbleeding ICU population was 70 g/l and, therefore, was at the lower limit of current guidelines. CONCLUSIONS Based on this survey, the estimated proportion of the intensivists working in hospitals with a PBM initiative is 42%, with significant variability between regions and hospitals of various sizes. The risk of iatrogenic anaemia is relevant due to liberal blood sample collection practices and the underuse of blood-sparing techniques. The reported transfusion threshold suggests excellent adherence to current international ICU-specific transfusion guidelines

European Neuroendocrine Tumour Society (ENETS) 2023 guidance paper for nonfunctioning pancreatic neuroendocrine tumours.

This ENETS guidance paper for well-differentiated nonfunctioning pancreatic neuroendocrine tumours (NF-Pan-NET) has been developed by a multidisciplinary working group, and provides up-to-date and practical advice on the management of these tumours. Using the extensive experience of centres treating patients with NF-Pan-NEN, the authors of this guidance paper discuss 10 troublesome questions in everyday clinical practice. Our many years of experience in this field are still being verified in the light of the results of new clinical, which set new ways of proceeding in NEN. The treatment of NF-Pan-NEN still requires a decision of a multidisciplinary team of specialists in the field of neuroendocrine neoplasms