Predictors of response to intra-arterial vasodilatory therapy of non-occlusive mesenteric ischemia in patients with severe shock: results from a prospective observational study

Background: Non-occlusive mesenteric ischemia (NOMI) is a life-threatening condition occurring in patients with shock and is characterized by vasoconstriction of the mesenteric arteries leading to intestinal ischemia and multi-organ failure. Although minimal invasive local intra-arterial infusion of vasodilators into the mesenteric circulation has been suggested as a therapeutic option in NOMI, current knowledge is based on retrospective case series and it remains unclear which patients might benefit. Here, we prospectively analyzed predictors of response to intra-arterial therapy in patients with NOMI. Methods: This is a prospective single-center observational study to analyze improvement of ischemia (indicated by reduction of blood lactate > 2 mmol/l from baseline after 24 h, primary endpoint) and 28-day mortality (key secondary endpoint) in patients with NOMI undergoing intra-arterial vasodilatory therapy. Predictors of response to therapy concerning primary and key secondary endpoint were identified using a) clinical parameters as well as b) data from 2D-perfusion angiography and c) experimental biomarkers of intestinal injury. Results: A total of 42 patients were included into this study. At inclusion patients had severe shock, indicated by high doses of norepinephrine (NE) (median (interquartile range (IQR)) 0.37 (0.21-0.60) μg/kg/min), elevated lactate concentrations (9.2 (5.2-13) mmol/l) and multi-organ failure. Patients showed a continuous reduction of lactate following intra-arterial prostaglandin infusion (baseline: (9.2 (5.2-13) mmol/l vs. 24 h: 4.4 (2.5-9.1) mmol/l, p 2 mmol/l at 24 h following intervention. Initial higher lactate concentrations and lower NE doses at baseline were independent predictors of an improvement of ischemia. 28-day mortality was 59% in patients with a reduction of lactate > 2 mmol/l 24 h after inclusion, while it was 85% in all other patients (hazard ratio 0.409; 95% CI, 0.14-0.631, p = 0.005). Conclusions: A reduction of lactate concentrations was observed following implementation of intra-arterial therapy, and lactate reduction was associated with better survival. Our findings concerning outcome predictors in NOMI patients undergoing intra-arterial prostaglandin therapy might help designing a randomized controlled trial to further investigate this therapeutic approach. Trial registration Retrospectively registered on January 22, 2020, at clinicaltrials.gov (REPERFUSE, NCT04235634), https://clinicaltrials.gov/ct2/show/NCT04235634?cond=NOMI&draw=2&rank=1 . Keywords: Intestinal failure; Non-occlusive mesenteric ischemia; Sepsis; Shoc

Fiskalische Kosten einer steuerlichen Förderung von Forschung und Entwicklung in Deutschland - Eine empirische Analyse verschiedener Gestaltungsoptionen

Der Beitrag berechnet die Aufkommensausfälle verschiedener Gestaltungsmodelle für eine steuerliche Forschungsförderung in Deutschland auf Basis eines Mikrosimulationsmodells. Die fiskalischen Kosten betragen zwischen 464 Mio. € und 5.701 Mio. €. Eine Erstattungsoption der Steuergutschrift über die Gewerbe- und Körperschaftsteuerschuld hinaus ist unerlässlich, da sonst etwa ein Drittel der Unternehmen nicht oder nur teilweise in den Genuss der Förderung kommen würde und sich dadurch starke Verzerrungen zwischen ertragsstarken und ertragsschwachen Unternehmen ergeben. Eine Differenzierung der Fördersätze für KMU und große Unternehmen kann die Aufkommensausfälle wirksam begrenzen. Eine Kappungsgrenze in Höhe eines absoluten Betrages ist wegen der Verzerrungen innerhalb der Gruppe großer Unternehmen ungünstig. Als besonders pragmatisch erscheint eine Verrechnung der Steuergutschrift mit der abzuführenden Lohnsteuer

Sensitivity of indocyanine green angiography compared to fluorescein angiography and enhanced depth imaging optical coherence tomography during tapering and fine-tuning of therapy in primary stromal choroiditis: A case series.

To investigate indocyanine green angiography (ICGA), fluorescein angiography (FA), and enhanced depth imaging optical coherence tomography measured choroidal thickness (EDI-OCT-CT) in the follow-up of inflammatory activity in stromal choroiditis [Vogt-Koyanagi-Harada disease (VKH) and birdshot retinochoroiditis (BRC)] under treatment in order to monitor tapering of therapy or readjustment of therapy in case of subclinical disease recurrence. Patients with initial onset disease and/or treatment-naive stromal choroiditis (VKH & BRC) at entry, quiet under therapy, and having had a follow-up of at least four years monitored with dual FA and ICGA and EDI-OCT-CT measurements were analyzed retrospectively. ICGA and FA scores and EDI-OCT-CT values were correlated with therapy, and significant changes of each modality were correlated with disease evolution. Of the 31 VKH and 29 BRC patients seen from 1995 to 2017 in our center, four patients (2 VKH and 2 BRC patients) fulfilled the inclusion criteria. During tapering, two patients (both VKH) showed no significant ICGA, FA, and EDI-OCT-CT changes (mean follow-up time 5.6 years) and allowed for safe tapering. In the other two (BRC) patients (mean follow-up time 6.25 years), a total of seven significant subclinical changes were demonstrated by ICGA alone after therapy modifications due to side-effects or during attempted tapering of therapy, while FA and EDI-OCT-CT remained unchanged. ICGA was the most sensitive monitoring modality of stromal choroiditis, able to identify subclinical recurrences following change of therapy and inversely treatment responses after readjusted therapy, events otherwise missed by FA and EDI-OCT. ICGA proved efficient for safe therapy tapering or for timely adjustment of therapy in stromal choroiditis when necessary