Limited access to liver transplantation and TIPS despite high mortality, healthcare resource use and costs of cirrhosis in Germany

Background and Aims Data on number of patients with cirrhosis in Germany are limited. We therefore aimed to estimate prevalence, comorbidities, mortality, utilization of healthcare resources and costs of patients with cirrhosis and incidence of decompensation of cirrhosis in Germany. Methods This longitudinal observational study was based on an anonymized representative claims database including 4.9 million persons insured by a statutory health insurance (SHI) between 2015–2020. Patients with decompensated and compensated cirrhosis were selected via diagnostic ICD codes and followed for 2 years. Results Prevalence of cirrhosis in 2015 was 250/100 000, resulting in 201 747 (95% CI: 197 540–206 040) patients extrapolated to the German population. Out of all patients with compensated cirrhosis in 2015 who did not deceased, 16.0% developed a decompensation within 3 years. Overall, 978 patients (Ø-age: 68 years; 60% male) were included in the decompensated, and 5135 patients (Ø-age: 66 years; 59% male) in the compensated cirrhosis cohort. Patients with decompensated cirrhosis had a higher burden of comorbidities (Charlson Comorbidity Index 7.3 vs. 4.4) and 3 times higher costs per quarter (7172 € vs. 2213 €) than patients with compensated cirrhosis. 1-year mortality after decompensation was 51% compared to 8% in compensated cirrhosis. Of note, only few patients with decompensated cirrhosis received a liver transplantation or transjugular intrahepatic portosystemic shunts (TIPS) (1% and 5%). Conclusion Patients with cirrhosis have a high healthcare burden in especially decompensated stage. Accordingly, 1-year mortality of decompensated cirrhosis in Germany is high. Despite high health resource utilization, only few patients have access to liver transplantation or TIPS

Characterizing Subsiding Shells in Shallow Cumulus Using Doppler Lidar and Large-Eddy Simulation

The existence of subsiding shells on the periphery of shallow cumulus clouds has major implications concerning the parameterization of shallow convection, with the mass exchange between the shell and cloudy air representing a significant deviation from the commonly used bulk-plume parameterization. We examine the structure and frequency of subsiding shells in shallow cumulus convection using Doppler lidars at the Atmospheric Radiation Measurement Southern Great Plains facility in the central United States and at the Julich ObservatorY for Cloud Evolution in western Germany. Doppler lidar indicates that the vertical subsiding shell extent is asymmetric, while shell width is typically similar to 100 m. Large-eddy simulation can reasonably simulate the observed shell structure using a grid spacing of 10 m and suggests that much of the observed asymmetry is not a result of transient cloud evolution

Table1_Fractional flow reserve measurements and long-term mortality—results from the FLORIDA study.docx

BackgroundRandomized evidence suggested improved outcomes in fractional flow reserve (FFR) guidance of coronary revascularization compared to medical therapy in well-defined patient cohorts. However, the impact of FFR-guided revascularization on long-term outcomes of unselected patients with chronic or acute coronary syndromes (ACS) is unknown.AimsThe FLORIDA (Fractional FLOw Reserve In cardiovascular DiseAses) study sought to investigate outcomes of FFR-guided vs. angiography-guided treatment strategies in a large, real-world cohort.MethodsThis study included patients enrolled into the German InGef Research Database. Patients undergoing coronary angiography between January 2014 and December 2015 were included in the analysis. Eligible patients had at least one inpatient coronary angiogram for suspected coronary artery disease between January 2014 and December 2015. Patients were stratified into FFR arm if a coronary angiography with adjunctive FFR measurement was performed, otherwise into the angiography-only arm. Matching was applied to ensure a balanced distribution of baseline characteristics in the study cohort. Patients were followed for 3 years after index date and primary endpoint was all-cause mortality.ResultsIn the matched population, mortality at 3 years was 9.6% in the FFR-assessed group and 12.6% in the angiography-only group (p = 0.002), corresponding to a 24% relative risk reduction with use of FFR. This effect was most pronounced in patients in whom revascularization was deferred based on FFR (8.7% vs. 12.3%, p = 0.04) and in high-risk subgroups including patients aged ≥75 years (14.9% vs. 20.1%, p ConclusionsFFR-based revascularization strategy was associated with reduced mortality at 3 years. These findings further support the use of FFR in everyday clinical practice.</p

Table2_Fractional flow reserve measurements and long-term mortality—results from the FLORIDA study.docx

BackgroundRandomized evidence suggested improved outcomes in fractional flow reserve (FFR) guidance of coronary revascularization compared to medical therapy in well-defined patient cohorts. However, the impact of FFR-guided revascularization on long-term outcomes of unselected patients with chronic or acute coronary syndromes (ACS) is unknown.AimsThe FLORIDA (Fractional FLOw Reserve In cardiovascular DiseAses) study sought to investigate outcomes of FFR-guided vs. angiography-guided treatment strategies in a large, real-world cohort.MethodsThis study included patients enrolled into the German InGef Research Database. Patients undergoing coronary angiography between January 2014 and December 2015 were included in the analysis. Eligible patients had at least one inpatient coronary angiogram for suspected coronary artery disease between January 2014 and December 2015. Patients were stratified into FFR arm if a coronary angiography with adjunctive FFR measurement was performed, otherwise into the angiography-only arm. Matching was applied to ensure a balanced distribution of baseline characteristics in the study cohort. Patients were followed for 3 years after index date and primary endpoint was all-cause mortality.ResultsIn the matched population, mortality at 3 years was 9.6% in the FFR-assessed group and 12.6% in the angiography-only group (p = 0.002), corresponding to a 24% relative risk reduction with use of FFR. This effect was most pronounced in patients in whom revascularization was deferred based on FFR (8.7% vs. 12.3%, p = 0.04) and in high-risk subgroups including patients aged ≥75 years (14.9% vs. 20.1%, p ConclusionsFFR-based revascularization strategy was associated with reduced mortality at 3 years. These findings further support the use of FFR in everyday clinical practice.</p

Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice

Injury and loss of podocytes are leading factors of glomerular disease and renal failure. The postmitotic podocyte is the primary glomerular target for toxic, immune, metabolic, and oxidant stress, but little is known about how this cell type copes with stress. Recently, autophagy has been identified as a major pathway that delivers damaged proteins and organelles to lysosomes in order to maintain cellular homeostasis. Here we report that podocytes exhibit an unusually high level of constitutive autophagy. Podocyte-specific deletion of autophagy-related 5 (Atg5) led to a glomerulopathy in aging mice that was accompanied by an accumulation of oxidized and ubiquitinated proteins, ER stress, and proteinuria. These changes resulted ultimately in podocyte loss and late-onset glomerulosclerosis. Analysis of pathophysiological conditions indicated that autophagy was substantially increased in glomeruli from mice with induced proteinuria and in glomeruli from patients with acquired proteinuric diseases. Further, mice lacking Atg5 in podocytes exhibited strongly increased susceptibility to models of glomerular disease. These findings highlight the importance of induced autophagy as a key homeostatic mechanism to maintain podocyte integrity. We postulate that constitutive and induced autophagy is a major protective mechanism against podocyte aging and glomerular injury, representing a putative target to ameliorate human glomerular disease and aging-related loss of renal function

FESSTVaL: the Field Experiment on Submesoscale Spatio-Temporal Variability in Lindenberg

Numerical weather prediction models operate on grid spacings of a few kilometers, where deep convection begins to become resolvable. Around this scale, the emergence of coherent structures in the planetary boundary layer, often hypothesized to be caused by cold pools, forces the transition from shallow to deep convection. Yet, the kilometer-scale range is typically not resolved by standard surface operational measurement networks. The measurement campaign FESSTVaL aimed at addressing this gap by observing atmospheric variability at the hectometer to kilometer scale, with a particular emphasis on cold pools, wind gusts and coherent patterns in the planetary boundary layer during summer. A unique feature was the distribution of 150 self-developed and low-cost instruments. More specifically, FESSTVaL included dense networks of 80 autonomous cold pool loggers, 19 weather stations and 83 soil sensor systems, all installed in a rural region of 15-km radius in eastern Germany, as well as self-developed weather stations handed out to citizens. Boundary layer and upper air observations were provided by 8 Doppler lidars and 4 microwave radiometers distributed at 3 supersites; water vapor and temperature were also measured by advanced lidar systems and an infrared spectrometer; and rain was observed by a X-band radar. An uncrewed aircraft, multicopters and a small radiometer network carried out additional measurements during a four-week period. In this paper, we present FESSTVaL’s measurement strategy and show first observational results including unprecedented highly-resolved spatio-temporal cold-pool structures, both in the horizontal as well as in the vertical dimension, associated with overpassing convective systems

FESSTVaL: The Field Experiment on Submesoscale Spatio-Temporal Variability in Lindenberg

Numerical weather prediction models operate on grid spacings of a few kilometers, where deep convection begins to become resolvable. Around this scale, the emergence of coherent structures in the planetary boundary layer, often hypothesized to be caused by cold pools, forces the transition from shallow to deep convection. Yet, the kilometer-scale range is typically not resolved by standard surface operational measurement networks. The measurement campaign Field Experiment on Submesoscale Spatio-Temporal Variability in Lindenberg (FESSTVaL) aimed at addressing this gap by observing atmospheric variability at the hectometer-to-kilometer scale, with a particular emphasis on cold pools, wind gusts, and coherent patterns in the planetary boundary layer during summer. A unique feature was the distribution of 150 self-developed and low-cost instruments. More specifically, FESSTVaL included dense networks of 80 autonomous cold pool loggers, 19 weather stations, and 83 soil sensor systems, all installed in a rural region of 15-km radius in eastern Germany, as well as self-developed weather stations handed out to citizens. Boundary layer and upper-air observations were provided by eight Doppler lidars and four microwave radiometers distributed at three supersites; water vapor and temperature were also measured by advanced lidar systems and an infrared spectrometer; and rain was observed by a X-band radar. An uncrewed aircraft, multicopters, and a small radiometer network carried out additional measurements during a 4-week period. In this paper, we present FESSTVaL’s measurement strategy and show first observational results including unprecedented highly resolved spatiotemporal cold-pool structures, both in the horizontal as well as in the vertical dimension, associated with overpassing convective systems