The predictive value of the modified early warning score for admission to the intensive care unit in patients with a hematologic malignancy – A multicenter observational study

Objectives: The modified early warning score (MEWS) is used to detect clinical deterioration of hospitalized patients. We aimed to investigate the predictive value of MEWS and derived quick Sequential Organ Failure Assessment (qSOFA) scores for intensive care unit admission in patients with a hematologic malignancy admitted to the ward. Design: Retrospective, observational study in two Dutch university hospitals. Setting: Data from adult patients with a hematologic malignancy, admitted to the ward over a 2-year period, were extracted from electronic patient files. Main outcome measures: Intensive care admission. Results: We included 395 patients with 736 hospital admissions; 2% (n = 15) of admissions resulted in admission to the intensive care unit. A higher MEWS (OR 1.5; 95 %CI 1.3–1.80) and qSOFA (OR 4.4; 95 %CI 2.1–9.3) were associated with admission. Using restricted cubic splines, a rise in the probability of admission for a MEWS ≥ 6 was observed. The AUC of MEWS for predicting admission was 0.830, the AUC of qSOFA was 0.752. MEWS was indicative for intensive care unit admission two days before admission. Conclusions: MEWS was a sensitive predictor of ICU admission in patients with a hematologic malignancy, superior to qSOFA. Future studies should confirm cut-off values and identify potential additional characteristics, to further enhance identification of critically ill hemato-oncology patients. Implications for Clinical Practice: The Modified Early Warning Score (MEWS) can be used as a tool for healthcare providers to monitor clinical deterioration and predict the need for intensive care unit admission in patients with a hematologic malignancy. Yet, consistent application and potential reevaluation of current thresholds is crucial. This will enable bedside nurses to more effectively identify patients needing adjunctive care, facilitating timely interventions and improved outcome.</p

Quantitative aortography for assessment of aortic regurgitation in the era of percutaneous aortic valve replacement

Paravalvular leak (PVL) is a shortcoming that can erode the clinical benefits of transcatheter valve replacement (TAVR) and therefore a readily applicable method (aortography) to quantitate PVL objectively and accurately in the interventional suite is appealing to all operators. The ratio between the areas of the time-density curves in the aorta and left ventricular outflow tract (LVOT-AR) defines the regurgitation fraction (RF). This technique has been validated in a mock circulation; a single injection in diastole was further tested in porcine and ovine models. In the clinical setting, LVOT-AR was compared with trans-thoracic and trans-oesophageal echocardiography and cardiac magnetic resonance imaging. LVOT-AR > 17% discriminates mild from moderate aortic regurgitation on echocardiography and confers a poor prognosis in multiple registries, and justifies balloon post-dilatation. The LVOT-AR differentiates the individual performances of many old and novel devices and is being used in ongoing randomized trials and registries

Quantitative aortography for assessment of aortic regurgitation in the era of percutaneous aortic valve replacement

Paravalvular leak (PVL) is a shortcoming that can erode the clinical benefits of transcatheter valve replacement (TAVR) and therefore a readily applicable method (aortography) to quantitate PVL objectively and accurately in the interventional suite is appealing to all operators. The ratio between the areas of the time-density curves in the aorta and left ventricular outflow tract (LVOT-AR) defines the regurgitation fraction (RF). This technique has been validated in a mock circulation; a single injection in diastole was further tested in porcine and ovine models. In the clinical setting, LVOT-AR was compared with trans-thoracic and trans-oesophageal echocardiography and cardiac magnetic resonance imaging. LVOT-AR &gt; 17% discriminates mild from moderate aortic regurgitation on echocardiography and confers a poor prognosis in multiple registries, and justifies balloon post-dilatation. The LVOT-AR differentiates the individual performances of many old and novel devices and is being used in ongoing randomized trials and registries

Comparative analysis of binding patterns of MADS-domain proteins in Arabidopsis thaliana

Background Correct flower formation requires highly specific temporal and spatial regulation of gene expression. In Arabidopsis thaliana the majority of the master regulators that determine flower organ identity belong to the MADS-domain transcription factor family. The canonical DNA binding motif for this transcription factor family is the CArG-box, which has the consensus CC(A/T)6GG. However, so far, a comprehensive analysis of MADS-domain binding patterns has not yet been performed. Results Eight publicly available ChIP-seq datasets of MADS-domain proteins that regulate the floral transition and flower formation were analyzed. Surprisingly, the preferred DNA binding motif of each protein was a CArG-box with an NAA extension. Furthermore, motifs of other transcription factors were found in the vicinity of binding sites of MADS-domain transcription factors, suggesting that interaction of MADS-domain proteins with other transcription factors is important for target gene regulation. Finally, conservation of CArG-boxes between Arabidopsis ecotypes was assessed to obtain information about their evolutionary importance. CArG-boxes that fully matched the consensus were more conserved than other CArG-boxes, suggesting that the perfect CArG-box is evolutionary more important than other CArG-box variants. Conclusion Our analysis provides detailed insight into MADS-domain protein binding patterns. The results underline the importance of an extended version of the CArG-box and provide a first view on evolutionary conservation of MADS-domain protein binding sites in Arabidopsis ecotypes

Comparative analysis of binding patterns of MADS-domain proteins in Arabidopsis thaliana

Background Correct flower formation requires highly specific temporal and spatial regulation of gene expression. In Arabidopsis thaliana the majority of the master regulators that determine flower organ identity belong to the MADS-domain transcription factor family. The canonical DNA binding motif for this transcription factor family is the CArG-box, which has the consensus CC(A/T)6GG. However, so far, a comprehensive analysis of MADS-domain binding patterns has not yet been performed. Results Eight publicly available ChIP-seq datasets of MADS-domain proteins that regulate the floral transition and flower formation were analyzed. Surprisingly, the preferred DNA binding motif of each protein was a CArG-box with an NAA extension. Furthermore, motifs of other transcription factors were found in the vicinity of binding sites of MADS-domain transcription factors, suggesting that interaction of MADS-domain proteins with other transcription factors is important for target gene regulation. Finally, conservation of CArG-boxes between Arabidopsis ecotypes was assessed to obtain information about their evolutionary importance. CArG-boxes that fully matched the consensus were more conserved than other CArG-boxes, suggesting that the perfect CArG-box is evolutionary more important than other CArG-box variants. Conclusion Our analysis provides detailed insight into MADS-domain protein binding patterns. The results underline the importance of an extended version of the CArG-box and provide a first view on evolutionary conservation of MADS-domain protein binding sites in Arabidopsis ecotypes

Comparative analysis of binding patterns of MADS-domain proteins in Arabidopsis thaliana

BACKGROUND: Correct flower formation requires highly specific temporal and spatial regulation of gene expression. In Arabidopsis thaliana the majority of the master regulators that determine flower organ identity belong to the MADS-domain transcription factor family. The canonical DNA binding motif for this transcription factor family is the CArG-box, which has the consensus CC(A/T)6GG. However, so far, a comprehensive analysis of MADS-domain binding patterns has not yet been performed. RESULTS: Eight publicly available ChIP-seq datasets of MADS-domain proteins that regulate the floral transition and flower formation were analyzed. Surprisingly, the preferred DNA binding motif of each protein was a CArG-box with an NAA extension. Furthermore, motifs of other transcription factors were found in the vicinity of binding sites of MADS-domain transcription factors, suggesting that interaction of MADS-domain proteins with other transcription factors is important for target gene regulation. Finally, conservation of CArG-boxes between Arabidopsis ecotypes was assessed to obtain information about their evolutionary importance. CArG-boxes that fully matched the consensus were more conserved than other CArG-boxes, suggesting that the perfect CArG-box is evolutionary more important than other CArG-box variants. CONCLUSION: Our analysis provides detailed insight into MADS-domain protein binding patterns. The results underline the importance of an extended version of the CArG-box and provide a first view on evolutionary conservation of MADS-domain protein binding sites in Arabidopsis ecotypes

Comparative analysis of binding patterns of MADS-domain proteins in Arabidopsis thaliana

BACKGROUND: Correct flower formation requires highly specific temporal and spatial regulation of gene expression. In Arabidopsis thaliana the majority of the master regulators that determine flower organ identity belong to the MADS-domain transcription factor family. The canonical DNA binding motif for this transcription factor family is the CArG-box, which has the consensus CC(A/T)6GG. However, so far, a comprehensive analysis of MADS-domain binding patterns has not yet been performed. RESULTS: Eight publicly available ChIP-seq datasets of MADS-domain proteins that regulate the floral transition and flower formation were analyzed. Surprisingly, the preferred DNA binding motif of each protein was a CArG-box with an NAA extension. Furthermore, motifs of other transcription factors were found in the vicinity of binding sites of MADS-domain transcription factors, suggesting that interaction of MADS-domain proteins with other transcription factors is important for target gene regulation. Finally, conservation of CArG-boxes between Arabidopsis ecotypes was assessed to obtain information about their evolutionary importance. CArG-boxes that fully matched the consensus were more conserved than other CArG-boxes, suggesting that the perfect CArG-box is evolutionary more important than other CArG-box variants. CONCLUSION: Our analysis provides detailed insight into MADS-domain protein binding patterns. The results underline the importance of an extended version of the CArG-box and provide a first view on evolutionary conservation of MADS-domain protein binding sites in Arabidopsis ecotypes

Comparative analysis of binding patterns of MADS-domain proteins in Arabidopsis thaliana

Background: Correct flower formation requires highly specific temporal and spatial regulation of gene expression. In Arabidopsis thaliana the majority of the master regulators that determine flower organ identity belong to the MADS-domain transcription factor family. The canonical DNA binding motif for this transcription factor family is the CArG-box, which has the consensus CC(A/T)6GG. However, so far, a comprehensive analysis of MADS-domain binding patterns has not yet been performed. Results: Eight publicly available ChIP-seq datasets of MADS-domain proteins that regulate the floral transition and flower formation were analyzed. Surprisingly, the preferred DNA binding motif of each protein was a CArG-box with an NAA extension. Furthermore, motifs of other transcription factors were found in the vicinity of binding sites of MADS-domain transcription factors, suggesting that interaction of MADS-domain proteins with other transcription factors is important for target gene regulation. Finally, conservation of CArG-boxes between Arabidopsis ecotypes was assessed to obtain information about their evolutionary importance. CArG-boxes that fully matched the consensus were more conserved than other CArG-boxes, suggesting that the perfect CArG-box is evolutionary more important than other CArG-box variants. Conclusion: Our analysis provides detailed insight into MADS-domain protein binding patterns. The results underline the importance of an extended version of the CArG-box and provide a first view on evolutionary conservation of MADS-domain protein binding sites in Arabidopsis ecotypes.</p

Additional file 16: of Comparative analysis of binding patterns of MADS-domain proteins in Arabidopsis thaliana

Table S8. Number of CArG-boxes with and without mutations. Note that the CArG-boxes in this table all match to the motif of AG because these CArG-boxes were used for all mutation analyses. The total number of CArG-boxes therefore differs from that in Additional file 5: Table S4. (PDF 47 kb