Pulmonary Vessel Obstruction Does Not Correlate with Severity of Pulmonary Embolism

The aim of the present study was to analyze possible relationships between pulmonary vessel obstruction and clinically relevant parameters and scores in patients with pulmonary embolism (PE). Overall, 246 patients (48.8% women and 51.2% men) with a mean age of 64.0 17.1 years were involved in the retrospective study. The following clinical scores were calculated in the patients: Wells score, Geneva score, and pulmonary embolism severity index (PESI) score. Levels of D-dimer (g/mL), lactate, pH, troponin, and N-terminal natriuretic peptide (BNP, pg/mL) were acquired. Thrombotic obstruction of the pulmonary arteries was quantified according to Mastora score. The data collected were evaluated by means of descriptive statistics. Spearman’s correlation coeffcient was used to analyze associations between the investigated parameters. P values < 0.05 were taken to indicate statistical significance. Mastora score correlated weakly with lactate level and tended to correlate with D-dimer and BNP levels. No other clinical or serological parameters correlated significantly with clot burden. Thrombotic obstruction of pulmonary vessels did not correlate with clinical severity of PE

The antimicrobial lysine-peptoid hybrid LP5 inhibits DNA replication and induces the SOS response in Staphylococcus aureus

BACKGROUND: The increase in antibiotic resistant bacteria has led to renewed interest in development of alternative antimicrobial compounds such as antimicrobial peptides (AMPs), either naturally-occurring or synthetically-derived. Knowledge of the mode of action (MOA) of synthetic compounds mimicking the function of AMPs is highly valuable both when developing new types of antimicrobials and when predicting resistance development. Despite many functional studies of AMPs, only a few of the synthetic peptides have been studied in detail. RESULTS: We investigated the MOA of the lysine-peptoid hybrid, LP5, which previously has been shown to display antimicrobial activity against Staphylococcus aureus. At concentrations of LP5 above the minimal inhibitory concentration (MIC), the peptoid caused ATP leakage from bacterial cells. However, at concentrations close to the MIC, LP5 inhibited the growth of S. aureus without ATP leakage. Instead, LP5 bound DNA and inhibited macromolecular synthesis. The binding to DNA also led to inhibition of DNA gyrase and topoisomerase IV and caused induction of the SOS response. CONCLUSIONS: Our data demonstrate that LP5 may have a dual mode of action against S. aureus. At MIC concentrations, LP5 binds DNA and inhibits macromolecular synthesis and growth, whereas at concentrations above the MIC, LP5 targets the bacterial membrane leading to disruption of the membrane. These results add new information about the MOA of a new synthetic AMP and aid in the future design of synthetic peptides with increased therapeutic potential

Risikostratifizierung durch Korrelation der pulmonal- arteriellen Gefäßobstruktion mit klinischen Parametern bei Patient*innen mit akuter Lungenarterienembolie

Die Lungenarterienembolie zählt nach dem Myokardinfarkt und dem Apoplex zur dritthäufigsten kardiovaskulären Todesursache weltweit. Sowohl die Diagnose als auch die Behandlung erfordern eine enge interdisziplinäre Zusammenarbeit von radiologisch und klinisch tätigen Ärztinnen und Ärzten. Dem Anliegen der Interdisziplinarität soll in dieser Arbeit Rechnung getragen werden. Grundanliegen ist es klinisch und bildgebend relevante Parameter im Hinblick auf die Prognose nach akuter Lungenarterienembolie zu erheben und in Bezug zueinander zu setzen. Dafür wurden in einer retrospektiven Auswertung Daten von 246 Patient*innen erhoben, die zwischen 2013 und 2017 mit der Diagnose einer LAE am Universitätsklinikum Leipzig behandelt wurden. Ein erstes Ergebnis dieser Untersuchung fand Ausdruck in der am 28.04.2019 im Journal of Clinical Medicine erschienenen Publikation „Pulmonary Vessel Obstruction Does Not Correlate with Severity of Pulmonary Embolism“. Die sich anschließende Dissertationsschrift ergänzt die Publikation durch Ausführungen zur Ableitung der Rationale: dafür wird zunächst die gesamtgesellschaftliche Bedeutung betrachtet, gefolgt von Ausführungen zu Definitionen, Pathophysiologie und Ätiologie mit dem Ziel für diese Arbeit relevante Parameter einzuführen. Die Arbeit schließt mit einer Zusammenfassung und der Formulierung möglicher zukünftiger Forschungsfragen. Das Supplement beinhaltet eine Auflistung aller erhobenen Parameter dieser Untersuchung, sowie eine detaillierte Aufschlüsselung relevanter prädiktiver und prognostischer Scores.:ABBILDUNGSVERZEICHNIS EINFÜHRUNG ÜBERBLICK BEDEUTUNG DER LUNGENARTERIENEMBOLIE DEFINITION UND PATHOPHYSIOLOGIE THROMBUSLAST UND PULMONAL- ARTERIELLE OBSTRUKTION KLINISCHE SYMPTOMATIK UND KLASSIFIKATION NACH AMERICAN HEART ASSOCIATION ÄTIOLOGIE PRÄDIKTIVE UND PROGNOSTISCHE SCORES ABLEITUNG DER RATIONALE METHODIK PUBLIKATIONSMANUSKRIPT ZUSAMMENFASSUNG DER ARBEIT ABSCHLIEßENDE BEWERTUNG LIMITATIONEN SCHLUSSFOLGERUNG UND AUSBLICK REFERENZEN SUPPLEMENT ERHOBENE KLINISCHE, PARAKLINISCHE UND BILDGEBENDE PARAMETER DARSTELLUNG DES EIGENEN BEITRAGS ERKLÄRUNG ÜBER DIE EIGENSTÄNDIGE ABFASSUNG DER ARBEIT LEBENSLAUF VERZEICHNIS DER WISSENSCHAFTLICHEN VERÖFFENTLICHUNGE

PIPKs are essential for rhizoid elongation and caulonemal cell development in the moss Physcomitrella patens

PtdIns-4,5-bisphosphate is a lipid messenger of eukaryotic cells playing critical roles in processes such as cytoskeleton organization, intracellular vesicular trafficking, secretion, cell motility, regulation of ion channels and nuclear signalling pathways. The enzymes responsible for the synthesis of PtdIns(4,5)P2 are phosphatidylinositol phosphate kinases (PIPKs). The moss Physcomitrella patens contains two PIPKs, PpPIPK1 and PpPIPK2. To study their physiological role, both genes were disrupted by targeted homologous recombination and as a result mutant plants with lower PtdIns(4,5)P2 levels were obtained. A strong phenotype for pipk1, but not for pipk2 single knockout lines, was obtained. The pipk1 knockout lines were impaired in rhizoid and caulonemal cell elongation, whereas pipk1-2 double knockout lines showed dramatic defects in protonemal and gametophore morphology manifested by the absence of rapidly elongating caulonemal cells in the protonemal tissue, leafy gametophores with very short rhizoids, and loss of sporophyte production. pipk1 complemented by overexpression of PpPIPK1 fully restored the wild type phenotype whereas overexpression of the inactive PpPIPK1E885A did not. Overexpression of PpPIPK2 in the pipk1-2 double knockout did not restore the wild type phenotype demonstrating that PpPIPK1 and PpPIPK2 are not functionally redundant. In vivo imaging of the cytoskeleton network revealed that the shortened caulonemal cells in the pipk1 mutants was the result of the absence of the apicobasal gradient of cortical F-actin cables normally observed in wild type caulonemal cells. Our data indicate that both PpPIPKs play a crucial role in the development of the moss P. patens, and particularly in the regulation of tip growth

Contrast reflux into the inferior vena cava on computer tomographic pulmonary angiography is a predictor of 24-hour and 30-day mortality in patients with acute pulmonary embolism

Background: Acute pulmonary embolism (PE) is a common disease with a high mortality. Computed tomographic pulmonary angiography (CTPA) represents the current gold standard for the evaluation of patients with suspected PE. Purpose: To search possible CTPA predictors of 24-h and 30-day mortality in PE. Material and Methods: Overall, 224 patients with PE (46.4% women, mean age 64.716.7 years) were acquired. CTPA was performed on a multi-slice CT scanner. The following radiological parameters were estimated: thrombotic obstruction index; diameter of the pulmonary trunk (mm); short axis ratio of right ventricle/left ventricle; diameter of the azygos vein (mm); diameter of the superior and inferior vena cava (mm); and reflux of contrast medium into the inferior vena cava (IVC). Results: Patients who died within the first 24 h after admission (n¼32, 14.3%) showed a reflux grade 3 into IVC more often than survivors (odds ratio [OR] 7.6, 95% confidence interval [CI] 3.3–17.7; P<0.001). Other relevant CTPA parameters were diameter of IVC (OR 1.1, 95% CI 1.01–1.21; P¼0.034) and diameter of the pulmonary trunk (OR 0.91, 95% CI 0.82–1.01, P¼0.074), whereas the Mastora score showed nearly no influence (OR 1.01, 95% CI 0.99–1.02, P¼0.406). Furthermore, 61 (27.2%) patients died within the first 30 days after admission. These patients showed a reflux grade 3 into IVC more often than survivors (OR 3.4, 95% CI 1.7–7.0; P¼0.001). Other CTPA parameters, such as diameter of IVC (OR 1.04, 95% CI 0.97–1.12; P¼0.277) and diameter of the pulmonary trunk (OR 0.96, 95% CI 0.89– 1.04; P¼0.291), seem to have no relevant influence, whereas Mastora score did (OR 0.99, 95% CI 0.976–0.999, P¼0.045). Conclusion: Subhepatic contrast reflux into IVC is a strong predictor of 24-h and 30-day mortality in patients with acute PE

Pulmonary Vessel Obstruction Does Not Correlate with Severity of Pulmonary Embolism

The aim of the present study was to analyze possible relationships between pulmonary vessel obstruction and clinically relevant parameters and scores in patients with pulmonary embolism (PE). Overall, 246 patients (48.8% women and 51.2% men) with a mean age of 64.0 17.1 years were involved in the retrospective study. The following clinical scores were calculated in the patients: Wells score, Geneva score, and pulmonary embolism severity index (PESI) score. Levels of D-dimer (g/mL), lactate, pH, troponin, and N-terminal natriuretic peptide (BNP, pg/mL) were acquired. Thrombotic obstruction of the pulmonary arteries was quantified according to Mastora score. The data collected were evaluated by means of descriptive statistics. Spearman’s correlation coeffcient was used to analyze associations between the investigated parameters. P values < 0.05 were taken to indicate statistical significance. Mastora score correlated weakly with lactate level and tended to correlate with D-dimer and BNP levels. No other clinical or serological parameters correlated significantly with clot burden. Thrombotic obstruction of pulmonary vessels did not correlate with clinical severity of PE

Pulmonary Vessel Obstruction Does Not Correlate with Severity of Pulmonary Embolism

The aim of the present study was to analyze possible relationships between pulmonary vessel obstruction and clinically relevant parameters and scores in patients with pulmonary embolism (PE). Overall, 246 patients (48.8% women and 51.2% men) with a mean age of 64.0 &#177; 17.1 years were involved in the retrospective study. The following clinical scores were calculated in the patients: Wells score, Geneva score, and pulmonary embolism severity index (PESI) score. Levels of D-dimer (&#181;g/mL), lactate, pH, troponin, and N-terminal natriuretic peptide (BNP, pg/mL) were acquired. Thrombotic obstruction of the pulmonary arteries was quantified according to Mastora score. The data collected were evaluated by means of descriptive statistics. Spearman&#8217;s correlation coefficient was used to analyze associations between the investigated parameters. P values &lt; 0.05 were taken to indicate statistical significance. Mastora score correlated weakly with lactate level and tended to correlate with D-dimer and BNP levels. No other clinical or serological parameters correlated significantly with clot burden. Thrombotic obstruction of pulmonary vessels did not correlate with clinical severity of PE

Pulmonary Vessel Obstruction Does Not Correlate with Severity of Pulmonary Embolism

The aim of the present study was to analyze possible relationships between pulmonary vessel obstruction and clinically relevant parameters and scores in patients with pulmonary embolism (PE). Overall, 246 patients (48.8% women and 51.2% men) with a mean age of 64.0 17.1 years were involved in the retrospective study. The following clinical scores were calculated in the patients: Wells score, Geneva score, and pulmonary embolism severity index (PESI) score. Levels of D-dimer (g/mL), lactate, pH, troponin, and N-terminal natriuretic peptide (BNP, pg/mL) were acquired. Thrombotic obstruction of the pulmonary arteries was quantified according to Mastora score. The data collected were evaluated by means of descriptive statistics. Spearman’s correlation coeffcient was used to analyze associations between the investigated parameters. P values < 0.05 were taken to indicate statistical significance. Mastora score correlated weakly with lactate level and tended to correlate with D-dimer and BNP levels. No other clinical or serological parameters correlated significantly with clot burden. Thrombotic obstruction of pulmonary vessels did not correlate with clinical severity of PE

A New Index for the Prediction of 30-Day Mortality in Patients With Pulmonary Embolism: The Pulmonary Embolism Mortality Score (PEMS)

Our aim was to analyze possibility of combination of basic clinical and radiological signs to predict 30-day mortality after acute pulmonary embolism (PE). We included 486 patients. Age, gender, simplified pulmonary embolism index (sPESI), pH, troponin, N-terminal natriuretic peptide, minimal systolic and diastolic blood pressure, O2 saturation, syncope, need for vasopressors, thrombotic obstruction, vessel diameter, short axis ratio right ventricle/left ventricle, and contrast medium reflux into the inferior vena cava (IVC) were analyzed. A backward algorithm in a logistic regression model was used to identify relevant risk factors. Multiple logistic regression analysis identified that sPESI, pH, minimal diastolic blood pressure, IVC reflux, and need for vasopressors influenced 30-day mortality. A score for mortality prediction was constructed (the Pulmonary Embolism Mortality Score): sPESI >2 points (1 point), pH <7.35 (1 point), minimal diastolic blood pressure <45 mm Hg (1 point), IVC reflux (1 point), and need for vasopressors (2 points). Patients with >3 points showed higher 30-day mortality (sensitivity: 84.9%, specificity: 83.0%, positive predictive value: 51.8%, negative predictive value: 96.2%). The net reclassification improvement compared with the sPESI was 0.94 (95% CI ¼ 0.73-1.15). In conclusion, a new score can predict 30-day mortality in patients with PE and is more sensitive than sPES