MOESM1 of High sensitivity troponin T and I reflect mitral annular plane systolic excursion being assessed by cardiac magnetic resonance imaging

Additional file 1: Table S1. Distribution of cardiac MRI indices according to MAPSE subgroups

MOESM2 of High sensitivity troponin T and I reflect mitral annular plane systolic excursion being assessed by cardiac magnetic resonance imaging

Additional file 2: Table S2. Univariate correlations between hsTn and cardiac MRI parameters in all patients (n = 84)

Diagnostic and prognostic role of platelets in patients with sepsis and septic shock

Studies investigating the prognostic role of platelets commonly include critically ill patients, whereas data regarding the prognostic impact of platelet count in patients admitted with sepsis and septic shock is limited. Therefore, the study investigates the prognostic role of platelet count in patients with sepsis and septic shock. Consecutive patients with sepsis and septic shock from 2019 to 2021 were included monocentrically. Blood samples were retrieved from the day of disease onset (day 1), days 2, 3, 5, 7 and 10. Firstly, the diagnostic value of platelet count was tested for septic shock compared to sepsis. Secondly, the prognostic value of platelet count was tested for 30-day all-cause mortality. Statistical analyses included univariable t-test, Spearman’s correlation, C-statistics, Kaplan–Meier analyses, as well as multivariable mixed analysis of variance (ANOVA), Cox proportional regression analyses and propensity score matching. A total of 358 patients with sepsis and septic shock were included with a median platelet count of 176 × 106/ml. The presence of thrombocytopenia (i.e. 6/ml) was associated with increased risk of 30-day mortality (HR = 1.409; 95% CI 1.057–1.878; p = .019), which was still demonstrated after propensity score matching. During the course of sepsis, a nadir was observed on sepsis day 5 with a decrease in the mean platelet count by 21.5%. Especially serum lactate, mean arterial pressure and the presence of malignancies were found to predict platelet decline during the course of sepsis/septic shock. The presence of platelet decline >25% was associated with an increased risk of 30-day all-cause mortality (HR = 1.484; 95% CI 1.045–2.109; p = .028). Following platelet decline, recovery was observed from day 5 to day 10 (mean increase 7.5%). However, platelet recovery was not found to be associated with 30-day all-cause mortality (HR = 1.072; 95% CI 0.567–2.026; p = .832). In conclusion, both thrombocytopenia and platelet decline during the course of sepsis were associated with an increased risk of 30-day all-mortality in patients admitted with sepsis or septic shock. What is the context?Despite improved treatment strategies in intensive care medicine, sepsis and septic shock represent one of the major causes of death at intensive care units worldwide.Although it is known that platelets are associated with prognosis, most studies included “critically illness” patients and were not restricted to patients admitted with sepsis or septic shock. Furthermore, studies focusing on patients with sepsis were predominantly published prior to the sepsis-3 criteria. Specifically, the course of the platelet count during ICU hospitalization needs further investigation. Despite improved treatment strategies in intensive care medicine, sepsis and septic shock represent one of the major causes of death at intensive care units worldwide. Although it is known that platelets are associated with prognosis, most studies included “critically illness” patients and were not restricted to patients admitted with sepsis or septic shock. Furthermore, studies focusing on patients with sepsis were predominantly published prior to the sepsis-3 criteria. Specifically, the course of the platelet count during ICU hospitalization needs further investigation. What is new?The present study suggests that the platelet count reflects a reliable tool for the diagnosis of septic shock during the first week of ICU hospitalization.Furthermore, platelet count and the platelet-to-white-blood-cell-ratio are predictive for 30-day all-cause mortality in the presence of sepsis or septic shock.Especially, a decrease in platelet count during the first 5 days of ICU hospitalizations was associated with an increased risk of 30-day all-cause mortality in patients with sepsis and septic shock, whereas the platelet recovery was not found to be associated with a worse prognosis. The present study suggests that the platelet count reflects a reliable tool for the diagnosis of septic shock during the first week of ICU hospitalization. Furthermore, platelet count and the platelet-to-white-blood-cell-ratio are predictive for 30-day all-cause mortality in the presence of sepsis or septic shock. Especially, a decrease in platelet count during the first 5 days of ICU hospitalizations was associated with an increased risk of 30-day all-cause mortality in patients with sepsis and septic shock, whereas the platelet recovery was not found to be associated with a worse prognosis. What is the impact?This study provides further evidence that the platelet count represents a reliable tool for the diagnosis of septic shock and furthermore predicts short-term prognosis in patients admitted with sepsis or septic shock during the first 10 days of ICU hospitalization. This study provides further evidence that the platelet count represents a reliable tool for the diagnosis of septic shock and furthermore predicts short-term prognosis in patients admitted with sepsis or septic shock during the first 10 days of ICU hospitalization.</p

A Practical, Protecting-Group-Free Synthesis of a PI3K/mTOR Inhibitor

We report a practical and protecting-group-free synthesis amenable to produce multikilogram amounts of PI3K/mTOR inhibitor <b>GDC-0980</b>. The route employed metalation/formylation and reductive amination followed by a metal catalyzed Suzuki–Miyaura cross-coupling. The metalation was performed via triarylmagnesiate intermediates allowing formylation under noncryogenic conditions. 2-Picoline·BH₃ was employed to replace Na­(OAc)₃BH in the reductive amination and to eliminate the use of molecular sieves. A concise one-step synthesis was developed for the selective monoamidation of piperazine with (<i>S</i>)-lactate to produce the piperazine lactamide starting material. The boronic acid was produced from 2-amino-5-bromopyrimidine in a one-step and protecting-group-free approach. The final crystallization in 1-propanol and water afforded the API in 59% overall yield in four steps and >99% purity by HPLC