EASIX und das sinusoidale Obstruktionssyndrom nach allogener Stammzelltransplantation

Das sinusoidale Obstruktionssyndrom/die venöse okklusive Leberkrankheit (SOS/VOD) zählt zu den frühen Komplikationen endothelialen Ursprungs nach hämatopoetischer Stammzelltransplantation (HSZT). Bei schwerem Verlauf von SOS/VOD ist die Mortalität hoch. Medikamente zur Prophylaxe sind verfügbar, weshalb die Identifizierung von Risikopatienten sinnvoll ist. Der ‚Endothelial Activation and Stress Index‘, kurz EASIX, ist ein aus den Parametern Laktatdehydrogenase, Kreatinin und Thrombozytenzahl bestehender Score, mit dem endotheliale Schädigungen erfasst werden. Wir untersuchten, ob in zwei unabhängigen Kohorten von Empfängern einer allogenen HSZT (alloHSZT) der EASIX-Score am Tag der Transplantation (EASIX-d0) signifikant mit der SOS/VOD-Inzidenz, dem Gesamtüberleben (OS) und der Nicht-Rezidiv-Mortalität (NRM) zusammenhängt. EASIX-d0 wurde mit den prädiktiven Fähigkeiten des kürzlich etablierten ‚VOD Risk Calculator‘ des CIBMTR verglichen. In einer dritten Kohorte untersuchten wir den Effekt von Pravastatin und Ursodesoxycholsäure (UDCA) auf die SOS/VOD-Inzidenz und das Überleben nach alloHSZT. Die kumulative Inzidenz von SOS/VOD innerhalb von 28 Tagen nach alloHSZT betrug 9,6% in der Trainingskohorte (Berlin, 2013-2015, n = 446) und 8,4% in der Validierungskohorte (Heidelberg, 2001-2009, n = 380). EASIX-d0 war in beiden Kohorten signifikant mit der SOS/VOD-Inzidenz, dem OS und der NRM assoziiert. Im Gegensatz dazu war in beiden Kohorten keine statistisch signifikante Assoziation des VOD Risk Scores des CIBMTR mit den Endpunkten SOS/VOD Inzidenz, OS oder NRM vorhanden. In der dritten Kohorte (Heidelberg, 2010-2015, n = 359) mit Pravastatin/UDCA-Gabe war die kumulative SOS/VOD Inzidenz mit 1,7% signifikant geringer im Vergleich zu der Trainings- und Validierungskohorte. Auch das OS und die NRM waren signifikant verbessert im Vergleich zu Patienten ohne Pravastatin/UDCA-Prophylaxe. Dieser protektive Effekt war besonders bei Patienten im höchsten EASIX-d0-Quartil ausgeprägt. EASIX-d0 stellt den ersten validierten Risikoscore dar, der Risikopatienten für SOS/VOD nach alloHSZT identifiziert. Die Gabe von Statin/UDCA scheint insbesondere bei Patienten mit erhöhtem Risiko für SOS/VOD eine präventive Wirkung zu haben.Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is an early complication of endothelial origin after hematopoietic stem cell transplantation (HSCT). Severe SOS/VOD is associated with high mortality. Preventive medications are available, therefore the identification of patients at high risk for SOS/VOD would be beneficial. The ‚Endothelial Activation and Stress Index‘ (EASIX) is a score based on the parameters lactate dehydrogenase, creatinine and thrombocyte count that captures endothelial damage. We studied if EASIX assessed on the day of HSCT (EASIX-d0) is significantly associated with SOS/VOD incidence, overall survival (OS) and non-relapse mortality (NRM) in two independent cohorts of patients receiving allogeneic HSCT (alloHSCT). EASIX-d0 was compared to the recently established ‚VOD Risk Calculator‘ by the CIBMTR. In a third cohort, we studied the effects of pravastatin and ursodeoxycholic acid (UDCA) on SOS/VOD incidence and survival after alloHSCT. The cumulative incidence of SOS/VOD within 28 days after alloHSCT was 9.6% in the training cohort (Berlin, 2013-2015, n = 446) and 8.4% in the validation cohort (Heidelberg, 2001-2009, n = 380). EASIX-d0 was significantly associated with SOS/VOD incidence, OS and NRM in both cohorts. In comparison, the VOD Risk Score by the CIBMTR was not significantly associated with the endpoints SOS/VOD incidence, OS or NRM in either cohorts. In the third cohort (Heidelberg, 2010-2015, n = 359), the cumulative SOS/VOD incidence was significantly lower at 1.7% compared to the training and validation cohort. Also, the OS and NRM was significantly improved compared to patients not receiving pravastatin/UDCA as prophylaxis. This protective effect was especially distinct in patients within the highest EASIX-d0 quartile. EASIX-d0 constitutes the first validated risk score for identifying patients at risk for SOS/VOD after alloHSCT. Statins/UDCA seem to have a prophylactic effect especially in patients at high risk for SOS/VOD

Predicting sinusoidal obstruction syndrome after allogeneic stem cell transplantation with the EASIX biomarker panel

No biomarker panel is established for prediction of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), a major complication of allogeneic stem cell transplantation (alloSCT). We compared the potential of the Endothelial Activation and Stress Index (EASIX), based on lactate dehydrogenase, creatinine, and thrombocytes, with that of the SOS/VOD CIBMTR clinical risk score to predict SOS/VOD in two independent cohorts. In a third cohort, we studied the impact of endothelium-active prophylaxis with pravastatin and ursodeoxycholic acid (UDA) on SOS/VOD risk. The cumulative incidence of SOS/VOD within 28 days after alloSCT in the training cohort (Berlin, 2013-2015, n=446) and in the validation cohort (Heidelberg, 2002-2009, n=380) was 9.6% and 8.4%, respectively. In both cohorts, EASIX assessed at the day of alloSCT (EASIX-d0) was significantly associated with SOS/VOD incidence (p<0.0001), overall survival (OS) and non-relapse mortality (NRM). In contrast, the CIBMTR score showed no statistically significant association with SOS/VOD incidence, and did not predict OS and NRM. In patients receiving pravastatin/UDA, the cumulative incidence of SOS/VOD was significantly lower at 1.7% (p<0.0001, Heidelberg, 2010-2015, n=359) than in the two cohorts not receiving pravastatin/UDA. The protective effect was most pronounced in patients with high EASIX-d0. The cumulative SOS/VOD incidence in the highest EASIX-d0 quartiles were 18.1% and 16.8% in both cohorts without endothelial prophylaxis as compared to 2.2% in patients with pravastatin/UDA prophylaxis (p<0.0001). EASIX-d0 is the first validated biomarker for defining a subpopulation of alloSCT recipients at high risk for SOS/VOD. Statin/UDA endothelial prophylaxis could constitute a prophylactic measure for patients at increased SOS/VOD risk

Research on Surface Water Quality Assessment and Its Driving Factors: A Case Study in Taizhou City, China

It is necessary to assess and analyze the factors that influence surface water since they are crucial to human activities such as agriculture, raising livestock, and industry. Previous research has mostly focused on how land use and landscape patterns affect the quality of surface waters; it has seldom addressed the industrial and agricultural production activities that are directly connected to human society. Therefore, the research area’s surface water quality was assessed by single factor index (SFI) and composite water quality index (WQI), divided into flood and non-flood periods, and water quality indicators with severe pollution and significant seasonal variations were selected; A total of 28 indicators were selected from three main factors-topography, socio-economic, and land use type-and analyzed using the Spearman correlation coefficient model. (1) SFI data reveal substantial seasonal changes in pH, DO, NH3-N, TN, and TP water quality indicators. The well-developed agricultural and aquaculture in the studied region is the primary cause of the excess TN and NH3-N concentrations; (2) The sample points’ water quality index (WQI) scores range from 50 to 80, with 62% of them having “medium” water quality; (3) The study area’s seasonal variation in water quality is primarily caused by human socio-economic activities (GDP, industrial effluent discharge, COD discharge, aquatic product quality, and the proportion of primary, secondary, and tertiary industries), as well as land use type (forest, shrubland, and cropland). Topography has little effect on the study area’s surface water quality. This study offers a fresh viewpoint on surface water quality management and driver analysis, and a new framework for managing and safeguarding aquatic ecosystems