The role of subclonal TP53 mutations, defined by a variant allele frequency of <20%, has not been addressed in acute myeloid leukemia yet. We, therefore, analyzed their prognostic value in a cohort of 1,537 patients with newly diagnosed disease, prospectively treated within three trials of the “German-Austrian Acute Myeloid Leukemia Study Group”. Mutational analysis was performed by targeted deep sequencing and patients with TP53 mutations were categorized by their variant allele frequency into groups with frequencies >40%, 20%-40% and <20%. A total of 108 TP53 mutations were found in 98 patients (6.4%). Among these, 61 patients had variant allele frequencies >40%, 19 had variant allele frequencies between 20%-40% and 18 had frequencies <20%. Compared to specimens with clonal TP53 mutations, those with subclonal ones showed significantly fewer complex karyotypes and chromosomal losses. In either TP53 -mutated group, patients experienced significantly fewer complete responses ( P <0.001) and had worse overall and event-free survival rates ( P <0.0001). In Cox regression analyses adjusting for age, white blood cell count, cytogenetic risk and type of acute myeloid leukemia, the adverse prognostic effect of TP53 mutations remained significant for all TP53 -mutated subgroups. These data suggest that subclonal TP53 mutations are a novel prognostic parameter in acute myeloid leukemia and emphasize the usefulness of next-generation sequencing technologies for risk stratification in this disorder. The study was registered at ClinicalTrials.gov with number NCT00146120.

BackgroundA surgical safety checklist (SSC) was implemented and routinely evaluated within our hospital. The purpose of this study was to analyze compliance, knowledge of and satisfaction with the SSC to determine further improvements.MethodsThe implementation of the SSC was observed in a pilot unit. After roll-out into each operating theater, compliance with the SSC was routinely measured. To assess subjective and objective knowledge, as well as satisfaction with the SSC implementation, an online survey (N = 891) was performed.ResultsDuring two test runs in a piloting unit, 305 operations were observed, 175 in test run 1 and 130 in test run 2. The SSC was used in 77.1% of all operations in test run 1 and in 99.2% in test run 2. Within used SSCs, completion rates were 36.3% in test run 1 and 1.6% in test run 2. After roll-out, three unannounced audits took place and showed that the SSC was used in 95.3%, 91.9% and 89.9%. Within used SSCs, completion rates decreased from 81.7% to 60.6% and 53.2%. In 2014, 164 (18.4%) operating team members responded to the online survey, 160 of which were included in the analysis. 146 (91.3%) consultants and nursing staff reported to use the SSC regularly in daily routine.ConclusionThese data show that the implementation of new tools such as the adapted WHO SSC needs constant supervision and instruction until it becomes self-evident and accepted. Further efforts, consisting mainly of hands-on leadership and training are necessary.

Mutations of the TP53 gene occur in a subset of patients with acute myeloid leukemia (AML) and confer an exceedingly adverse prognosis. However, whether different types of TP53 mutations exert a uniformly poor outcome has not been investigated yet. Here, we addressed this issue by analyzing data of 1537 patients intensively treated within protocols of the German-Austrian AML study group. We classified TP53 mutations depending on their impact on protein structure and according to the evolutionary action (EAp53) score and the relative fitness score (RFS). In 98/1537 (6.4%) patients, 108 TP53 mutations were detected. While the discrimination depending on the protein structure and the EAp53 score did not show a survival difference, patients with low-risk and high-risk AML-specific RFS showed a different overall survival (OS; median, 12.9 versus 5.5 months, p = 0.017) and event-free survival (EFS; median, 7.3 versus 5.2 months, p = 0.054). In multivariable analyses adjusting for age, gender, white blood cell count, cytogenetic risk, type of AML, and TP53 variant allele frequency, these differences were statistically significant for both OS (HR, 2.14; 95% CI, 1.15–4.0; p = 0.017) and EFS (HR, 1.97; 95% CI, 1.06–3.69; p = 0.033). We conclude that the AML-specific RFS is of prognostic value in patients with TP53-mutated AML and a useful tool for therapeutic decision-making.

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While hospital admissions for myocardial infarction (MI) and pulmonary embolism (PE) are decreased during the COVID-19 pandemic, controversy remains about respective complication and mortality rates. This study evaluated admission rates, complications, and intrahospital mortality for selected life-threatening cardiovascular emergencies (MI, PE, and acute aortic dissection (AAD)) during COVID-19-associated restrictive social measures (RM) in Styria, Austria. By screening a patient information system for International Statistical Classification of Diseases and Related Health Problems (ICD) diagnosis codes covering more than 85% of acute hospital admissions in the state of Styria (~1.24 million inhabitants), we retrospectively identified patients with admission diagnoses for MI (I21, I22), PE (I26), and AAD (I71). Rates of complications such as cardiogenic shock and cardiopulmonary resuscitation, treatment escalations (thrombolysis for PE), and mortality were analyzed by patient chart review during 6 weeks following onset of COVID-19 associated RM, and during respective time frames in the years 2016 to 2019. 1,668 patients were included. Cumulative admissions for MI, PE and AAD decreased (RR 0.77; p<0.001) during RM compared to previous years. In contrast, intrahospital mortality increased by 65% (RR 1.65; p = 0.041), mainly driven by mortality following MI (RR 1.80; p = 0.042). PE patients received more frequently thrombolysis treatment (RR 3.63; p = 0.006), while rates of cardiogenic shock and cardiopulmonary resuscitation remained unchanged. Of 226 patients hospitalized during RM, 81 patients with suspected COVID-19 disease were screened for SARS-CoV-2 infection with only 5 testing positive. Thus, cumulative hospital admissions for cardiovascular emergencies decreased during COVID-19 associated RM while intrahospital mortality increased.

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Background“The Surgical Safety Checklist (SSC) is important, but we don’t use it adequately” is a well-suited statement that reflects the SSC's application in hospitals. Our aim was to follow up on our initial study on compliance (2014) by analysing differences between individual perception and compliance with the SSC.MethodsWe conducted a follow-up online survey to assess healthcare professionals’ individual perception of, as well as satisfaction and compliance with the SSC three years following its thorough implementation.Results171 (19.5%) of 875 operating team members completed the online survey. 99.4% confirmed using the SSC. Self-estimated subjective knowledge about the intention of the checklist was high, whereas objective knowledge was moderate, but improved as compared to 2014. According to an independent audit the SSC was used in 93.1% of all operations and among the SSCs used the completion rate was 57.2%. The use of the SSC was rated as rather easy [median (IQR): 7 (6–7)], familiar [7 (6–7)], generally important [7 (7–7)], and good for patients [7 (6–7)] as well as for employees [7 (7–7)]. Only comfort of use was rated lower [6 (5–7)].ConclusionThere is a gap between individual perception and actual application of the SSC. Despite healthcare professionals confirming the importance of the SSC, compliance was moderate. The introduction of SSCs in the health care sector remains a constant challenge and requires continuous re-evaluation as well as a sensible integration into existing workflows in hospitals.

Clinical studies have shown that assessing circulating concentrations of high-density lipoprotein (HDL) particles by nuclear magnetic resonance (NMR) spectroscopy is superior to HDL-cholesterol in predicting cardiovascular risk. We tested the hypothesis that circulating concentrations of HDL particles predict 3-month mortality of patients with acute heart failure (AHF). Out of 152 included patients, 52% were female, additionally the mean patient age was 75.2 ± 10.3 years, and three-month mortality was 27%. Serum lipoprotein profile at admission was determined by NMR spectroscopy. Univariate logistic regression analyses revealed a significant inverse association of total (odds ratio (OR) 0.38 per 1-SD increase, 95% confidence interval (CI) 0.23–0.60, p < 0.001) and small HDL particle concentrations (OR 0.35 per 1-SD increase, 95% CI 0.19–0.60, p < 0.001) with 3-month mortality, whereas concentrations of large HDL particles (p = 0.353) or HDL-cholesterol (p = 0.107) showed no significant association. After adjustment for age, sex, mean arterial pressure, low-density lipoprotein cholesterol, glomerular filtration rate, urea, and N-terminal pro-brain natriuretic peptide, both the total and small HDL particle concentrations remained significantly associated with 3-month mortality. Based on our results, we conclude that total and small HDL particle concentrations strongly and independently predict 3-month mortality in AHF patients.