Significant incidents during X-ray exposures in humans - assessment and findings of the Federal Office for Radiation Protection. / Bedeutsame Vorkommnisse bei Röntgenanwendungen am Menschen ­ Auswertungen und Erkenntnisse des BfS.

In Germany, significant incidents must be reported to the competent authority since 12/31/2018 (section 108 Radiation Protection Ordinance (StrlSchV)). After assessment and evaluation of the reports, the competent authority submits the relevant information via a web-based reporting system (BeVoMed) to the Federal Office for Radiation Protection (BfS), which publishes the results derived therefrom. The present paper evaluates significant incidents related to X-ray exposures on humans.All reports on incidents in X-ray diagnostics and interventional radiology between 01/2019 and 10/2023, which were completed with detailed information until the reporting day (31/10/2023), were included. The following aspects were statistically evaluated: classification as an incident (section 1 subsection (22) StrlSchV), significance (section 108 StrSchV), classification to Annex 14 StrlSchV, assignment to the forms of care in the German healthcare system, and development of the reporting frequency over time. Furthermore, the content of the reports was systematically evaluated with regard to conspicuous clusters and typical problems.Until the reporting day, 383 reports (355 completed) were received. 252 reports (228 in X-ray diagnostics, 24 in interventional radiology) referred to significant incidents and were included in the detailed evaluation. Reporting frequency increased in X-ray diagnostics, whereas there was no trend in interventional radiology. Most of the significant incidents concerned examinations on an individual person (category I, criterion 2a or category II, criteria 2a and 3a) in the in-patient sector - especially in maximum care hospitals. Frequent errors concerned the inappropriate choice of parameters/protocols or were related to the administration of a contrast agent. Despite the overall positive trend, the establishment of awareness and error culture remains challenging. · In X-ray diagnostics, the reporting frequency of significant incidents increases.. · Most incidents concerned CT examinations in the in-patient sector.. · Main problems were selection of protocols/settings, contrast administration, and bolus-tracking.. · Uncertainties remain about the classification of an incident as significant and notifiable.. · Winter KS, Schweden M, Brix G et al. Significant incidents during X-ray exposures in humans - assessment and findings of the Federal Office for Radiation Protection. Fortschr Röntgenstr 2024; DOI 10.1055/a-2339-3684.

Compound-specific stable isotope analyses of fatty acids indicate feeding zones of zooplankton across the water column of a subalpine lake.

Spatial and temporal zooplankton feeding dynamics across the water column of lakes are key for understanding site-specific acquisition of diet sources. During this 6-week lake study, we examined stable carbon (δ13C) and nitrogen (δ15N) isotopes and conducted compound-specific fatty acid (FA) stable isotope analysis (CSIA) of edible seston in the epi-, meta-, and hypolimnion, and zooplankton of Lake Lunz, Austria. We predicted that CSIA of essential FA can discern the foraging grounds of zooplankton more accurately than the commonly used bulk stable isotopes. The δ13C and δ15N values of seston from different lake strata were similar, whereas a dual CSIA approach using stable carbon and hydrogen isotopes of FA (δ13CFA and δ2HFA) provided sufficient isotopic difference in essential FA to discern different lake strata-specific diet sources throughout the study period. We present a CSIA model that suggests strata-specific foraging grounds for different zooplankton groups, indicating higher preference of cladocerans for feeding on epilimnetic diet sources, while calanoid copepods retained more hypolimnetic resources. The CSIA approach thus yields strata-specific information on foraging strategies of different zooplankton taxa and provides more details on the spatial and temporal trophodynamics of planktonic food webs than commonly used bulk stable isotopes.

Response of stable isotopes (δ2H, δ13C, δ15N, δ18O) of lake water, dissolved organic matter, seston, and zooplankton to an extreme precipitation event.

Lake ecosystems process and cycle organic substrates, thus serving as important bioreactors in the global carbon cycle. Climate change is predicted to increase extreme weather and precipitation events that can flush nutrients and organic matter from soils to streams and lakes. Here we report changes in stable isotopes (δ2H, δ13C, δ15N, or δ18O) of water, dissolved organic matter (DOM), seston, and zooplankton in a subalpine lake at short time resolution following an extreme precipitation event between early July to mid-August 2021. Water from excess precipitation and runoff remained in the lake epilimnion and coincided with increasing δ13C values of seston (-30 ‰ to -20 ‰), due to the input of carbonates and terrestrial organic matter. Particles settled into deeper lake layers after two days and contributed to the uncoupling of C and N cycling as the lake responded to this extreme precipitation event. Following the event, there was an increase in bulk δ13C values of zooplankton (from -35 ‰ to -32 ‰). Throughout this study, δ13C values of DOM remained stable throughout the water column (-29 ‰ to -28 ‰), while large isotopic fluctuations in DOM δ2H (-140 ‰ to -115 ‰) and δ18O (+9 ‰ to +15 ‰) values suggested DOM relocation and turnover. Integrating isotope hydrology, ecosystem ecology, and organic geochemistry offers an element-specific, detailed approach to investigating the impact of extreme precipitation events on freshwater ecosystems and particularly aquatic food webs.

Elevated temperature and browning increase dietary methylmercury, but decrease essential fatty acids at the base of lake food webs.

Climate change scenarios predict increases in temperature and organic matter supply from land to water, which affect trophic transfer of nutrients and contaminants in aquatic food webs. How essential nutrients, such as polyunsaturated fatty acids (PUFA), and potentially toxic contaminants, such as methylmercury (MeHg), at the base of aquatic food webs will be affected under climate change scenarios, remains unclear. The objective of this outdoor mesocosm study was to examine how increased water temperature and terrestrially-derived dissolved organic matter supply (tDOM; i.e., lake browning), and the interaction of both, will influence MeHg and PUFA in organisms at the base of food webs (i.e. seston; the most edible plankton size for zooplankton) in subalpine lake ecosystems. The interaction of higher temperature and tDOM increased the burden of MeHg in seston (< 40 µm) and larger sized plankton (microplankton; 40-200 µm), while the MeHg content per unit biomass remained stable. However, PUFA decreased in seston, but increased in microplankton, consisting mainly of filamentous algae, which are less readily bioavailable to zooplankton. We revealed elevated dietary exposure to MeHg, yet decreased supply of dietary PUFA to aquatic consumers with increasing temperature and tDOM supply. This experimental study provides evidence that the overall food quality at the base of aquatic food webs deteriorates during ongoing climate change scenarios by increasing the supply of toxic MeHg and lowering the dietary access to essential nutrients of consumers at higher trophic levels.

Compound-specific stable hydrogen isotope (δ2 H) analyses of fatty acids: A new method and perspectives for trophic and movement ecology.

RATIONALE: Compound-specific stable isotope analysis (CSIA) is a powerful tool for a better understanding of trophic transfer of dietary molecules in and across ecosystems. Hydrogen isotope values (δ2 H) in consumer tissues have potential to more clearly distinguish dietary sources than 13 C or 15 N values within and among habitats, but have not been used at the fatty acid level for ecological purposes. METHODS: Here we demonstrate a new online high-capacity gas chromatography-isotope ratio mass spectrometry technique (2 H-CSIA) that offers accurate and reproducible determination of δ2 H values for a range of fatty acids from organisms of aquatic food webs. RESULTS: We show that lipid extracts obtained from aquatic sources, such as biofilms, leaves, invertebrates, or fish muscle tissue, have distinctive δ2 H values that can be used to assess sources and trophic interactions, as well as dietary allocation and origin of fatty acids within consumer tissue. CONCLUSIONS: The new 2 H-CSIA method can be applied to evaluate sources and trophic dynamics of fatty acids in organisms ranging from food web ecology to migratory connectivity.

CT-Guided Drainage of Fluid Collections Following Liver Resection: Technical and Clinical Outcome of 143 Patients during a 14-Year Period.

PURPOSE: To retrospectively evaluate the technical and clinical outcome of patients with symptomatic postoperative fluid collections following liver resection treated with CT-guided drainage (CTD). METHODS: 143 suitable patients were examined between 2004 and 2017. Technical success was defined as (a) sufficient drainage of the fluid collection and (b) the non-occurrence of peri-interventional complications requiring surgical treatment with minor or prolonged hospitalization. Clinical success was defined as (a) decreasing or normalization of specific blood parameters within 30 days after intervention and (b) no surgical revision in addition to intervention required. C-reactive protein (CRP), leukocytes and Total Serum Bilirubin (TSB) were assessed. Dose length product (DLP) for the intervention parts was determined. RESULTS: Technical success was achieved in 99.5% of 189 performed interventions. Clinical success was reached in 74% for CRP, in 86.7% for Leukocytes and in 62.1% for TSB. The median of successful decrease was 6.0 days for CRP, 3.5 days for Leukocytes and 5.5 days for TSB. In 90.2%, no surgical revision was necessary. Total DLP was significantly lower in the second half of the observation period (median 536.0 mGy*cm between years 2011 and 2017 vs. median 745.5 mGy*cm between years 2004 and 2010). CONCLUSIONS: Technical success rate of CTD was very high, and clinical success rate was fair to good. Reduction of the radiation dose reflects developments of CT technology and increased experience of the interventional radiologists.

Radiation dose and image quality of high-pitch emergency abdominal CT in obese patients using third-generation dual-source CT (DSCT).

In this third-generation dual-source CT (DSCT) study, we retrospectively investigated radiation dose and image quality of portal-venous high-pitch emergency CT in 60 patients (28 female, mean age 56 years) with a body mass index (BMI) ≥ 30 kg/m2. Patients were dichotomized in groups A (median BMI 31.5 kg/m2; n = 33) and B (36.8 kg/m2; n = 27). Volumetric CT dose index (CTDIvol), size-specific dose estimate (SSDE), dose length product (DLP) and effective dose (ED) were assessed. Contrast-to-noise ratio (CNR) and dose-independent figure-of-merit (FOM) CNR were calculated. Subjective image quality was assessed using a five-point scale. Mean values of CTDIvol, SSDE as well as normalized DLP and ED were 7.6 ± 1.8 mGy, 8.0 ± 1.8 mGy, 304 ± 74 mGy * cm and 5.2 ± 1.3 mSv for group A, and 12.6 ± 3.7 mGy, 11.0 ± 2.6 mGy, 521 ± 157 mGy * cm and 8.9 ± 2.7 mSv for group B (p < 0.001). CNR of the liver and spleen as well as each calculated FOM CNR were significantly higher in group A (p < 0.001). Subjective image quality was good in both groups. In conclusion, third-generation abdominal high-pitch emergency DSCT yields good image quality in obese patients. Radiation dose increases in patients with a BMI > 36.8 kg/m2.

Semi-automatic CT-angiography based evaluation of the aortic annulus in patients prior to TAVR: interchangeability with manual measurements.

To compare a semi-automatic software tool for the measurement of aortic annulus dimensions with manual measurements by expert readers and to analyze whether and to what extent interchangeability exists between semi-automatic and manual measurements. We retrospectively included 374 consecutive patients with high-grade aortic stenosis who had undergone CT-angiography of the heart prior to trans-catheter aortic valve replacement (TAVR). In independent analyses, two expert readers manually measured aortic annulus dimensions (long axis, short axis, circumference, area) as well as the distance of the coronary ostia from the annulus plane. A third independent reader performed annulus evaluation using a software tool for semi-automatic detection and measurement of the annulus plane. Intraclass correlation coefficients (ICC) and Bland-Altman analysis was used to compare both manual measurements as well as manual and semi-automatic measurements of annulus parameters. Using the respective measurements we simulated size selection for a Sapien XT transcatheter heart valve (THV). Interchangeability of methods was addressed by calculation of the estimated individual equivalence index γ. There was excellent agreement between both expert observers in manual measurements of the annulus with ICC's in the range 0.89-0.94 for all anatomic parameters. Similar high agreements were observed between semi-automatic and manual measurements, with ICC's in the range of 0.89-0.95. THV size recommendation based on manual versus semiautomatic measurements agreed in 80.7% of cases while agreement between both expert readers concerning THV size recommendation was 80.6%. Semi-automatic measurements of anatomic parameters of the aortic root show high agreement and interchangeability with manual measurements in CT-angiography prior to TAVR.

Towards volumetric thresholds in RECIST 1.1: Therapeutic response assessment in hepatic metastases.

OBJECTIVES: To empirically determine thresholds for volumetric assessment of response and progress of liver metastases in line with the unidimensional RECIST thresholds. METHODS: Patients with metastatic colorectal cancer initially enrolled in a multicentre clinical phase-III trial were included. In all CT scans, the longest axial diameters and volumes of hepatic lesions were determined semi-automatically. The sum of diameters and volumes of 1, ≤2 and ≤5 metastases were compared to all previous examinations. Volumetric thresholds corresponding to RECIST 1.1 thresholds were predicted with loess-regression. In sensitivity analysis, the concordances of proposed thresholds, weight-maximizing thresholds and thresholds from loess-regression were compared. Classification concordance for measurements of ≤2 metastases was further analyzed. RESULTS: For measurements of ≤2 metastases, 348 patients with 629 metastases were included, resulting in 4,773 value pairs. Regression analysis yielded volumetric thresholds of -65.3% for a diameter change of -30%, and +64.6% for a diameter change of +20%. When comparing measurements of unidimensional RECIST assessment with volumetric measurements, there was a concordance of significant progress (≥+20% and ≥+65%) in 88.3% and of significant response (≤-30% and ≤-65%) in 85.0%. CONCLUSIONS: In patients with hepatic metastases, volumetric thresholds of +65% and -65% were yielded corresponding to RECIST thresholds of +20% and -30%. KEY POINTS: • Volumes and diameters of liver metastases from colorectal cancer were determined. • Volumetric thresholds of +65%/-65% corresponding to RECIST 1.1 are proposed. • Comparing both measurements, concordance was 88.3% (significant progress) and 85.0% (significant response).

Temperature increase and fluctuation induce phytoplankton biodiversity loss - Evidence from a multi-seasonal mesocosm experiment.

Global climate change scenarios predict lake water temperatures to increase up to 4°C and extreme weather events, including heat waves and large temperature fluctuations, to occur more frequently. Such changes may result in a reorganization of the plankton community structure, causing shifts in diversity and structure toward a community dominated by fewer species that are more adapted to endure warmer and irregular temperature conditions. We designed a long-term (8 months) mesocosm experiment to explore how ambient water temperature (C: control), induced increased temperature (T: +4°C), and temperature fluctuations (F: ±4°C relative to T) change phytoplankton phenology, taxonomical diversity, and community structure, and how such changes affected zooplankton abundance and composition. Synthesis. Our results show that T and F relative to C significantly decreased phytoplankton diversity. Moreover, there was a clear effect of the temperature treatments (T and F) on phytoplankton size structure that resulted in a significantly lower growth of large species (i.e., large Chlorophyta) compared to C. Decreased diversity and evenness in the T and F treatments pushed the community toward the dominance of only a few phytoplankton taxa (mainly Cyanobacteria and Chlorophyta) that are better adapted to endure warmer and more irregular temperature conditions. The observed shift toward Cyanobacteria dominance may affect trophic energy transfer along the aquatic food web.

Postpartum Blood Loss in Women Treated for Intrahepatic Cholestasis of Pregnancy.

OBJECTIVE: To evaluate postpartum blood loss in women with treated intrahepatic cholestasis of pregnancy. METHODS: In a retrospective case-control study, 15,083 deliveries including 348 women with intrahepatic cholestasis of pregnancy (2.3%) were analyzed from 2004 to 2014. To adjust for differences in baseline characteristics, a propensity analysis was performed and women in the control group were matched to the women in the intrahepatic cholestasis of pregnancy group in a 5:1 ratio. Blood loss was analyzed by estimated blood loss and Δ hemoglobin (Hb, difference between prepartum and postpartum Hb). A subgroup analysis regarding severity of intrahepatic cholestasis of pregnancy based on maximum bile acid level (mild [less than 40 micromoles/L], moderate [40-99 micromoles/L], and severe intrahepatic cholestasis of pregnancy [100 micromoles/L or greater]) was performed. Differences in estimated blood loss, ΔHb, and meconium staining between subgroups were analyzed. A Spearman rank correlation was performed to evaluate the association of bile acid levels and blood loss within subgroups. RESULTS: Estimated blood loss (median 400 [300-600] mL compared with 400 [300-600] mL, P=.22), ΔHb (14.0 [5.0-22.0] compared with 12.0 [4.0-21.0] g/L, P=.09), meconium staining (14.5% compared with 11.4%, P=.12), and number of stillbirths after 26 weeks of gestation (0.6% compared with 1.8%, P=.10) were not significantly different in the study compared with the control group. In moderate and severe intrahepatic cholestasis of pregnancy, meconium staining was observed significantly more often compared with that in a control group (23.0% and 32.3% compared with 11.4%, P<.01). There was no correlation between estimated blood loss or ΔHb and severity of intrahepatic cholestasis of pregnancy. CONCLUSIONS: In our cohort of women with intrahepatic cholestasis of pregnancy who are treated with ursodeoxycholic acid and have planned delivery (induction of labor or planned cesarean delivery) at 38 weeks of gestation, no differences in postpartum blood loss were seen.

Intravoxel Incoherent Motion Magnetic Resonance Imaging in Partially Nephrectomized Kidneys.

OBJECTIVE: The aim of this study was to investigate the effects of partial nephrectomy (PN) in kidneys with solid renal masses on the apparent diffusion coefficient (ADC) and on intravoxel incoherent motion (IVIM)-based parameters using diffusion-weighted magnetic resonance imaging (DWI). METHODS: Fifteen patients with renal masses underwent DWI before and 1 week after PN on a clinical 3 T scanner using a single-shot echo planar imaging sequence with 10 diffusion weightings. Motion-corrected images were quantified using a monoexponential model fit to calculate ADCs and a segmented biexponential fit to calculate IVIM parameters f (perfusion fraction), Dslow and Dfast ("slow" and "fast" diffusion coefficients), as well as the pseudoflow (PF) Dfast × f. The median values derived from multislice (minimum of 3 slices) regions of interest encompassing the kidney cortex were used for statistical analysis. Estimated glomerular filtration rate values were calculated based on serum creatinine levels on each examination day using the Modification of Diet in Renal Disease formula. RESULTS: The follow-up measurement yielded significantly lower values in the partially nephrectomized kidneys compared with contralateral kidneys for the parameters ADC (P = 0.002), Dfast (P = 0.43), f (P = 0.001), and PF (P = 0.0008). Comparing baseline and follow-up, partially nephrectomized kidneys showed a significant decrease for ADC (P = 0.01), Dfast (P = 0.43), f (P = 0.002), and PF (P = 0.002). Nonnephrectomized kidneys expressed a significant increase for ADC (P = 0.01) and PF (P = 0.01). Follow-up Modification of Diet in Renal Disease showed positive correlations with all DWI parameters in the partially nephrectomized kidneys (ADC: r(2) = 0.63, P = 0.0004; Dfast: r(2) = 0.59, P = 0.0009; f: r(2) = 0.36, P = 0.018; PF: r(2) = 0.60, P = 0.00075) except for Dslow. CONCLUSIONS: Our study suggests that quantitative parameters derived from DWI are highly indicative of renal function. Apparent diffusion coefficients showed substantial differences in the renal cortex after PN, whereas an IVIM analysis delivered additional insight into kidney physiology. Quantitative DWI, particularly perfusion-related IVIM parameters, therefore demonstrated great potential as truly noninvasive biomarker to obtain information about single kidney function.

Increasing Water Temperature Triggers Dominance of Small Freshwater Plankton.

Climate change scenarios predict that lake water temperatures will increase up to 4°C and rainfall events will become more intense and frequent by the end of this century. Concurrently, supply of humic substances from terrestrial runoff is expected to increase, resulting in darker watercolor ("brownification") of aquatic ecosystems. Using a multi-seasonal, low trophic state mesocosm experiment, we investigated how higher water temperature and brownification affect plankton community composition, phenology, and functioning. We tested the hypothesis that higher water temperature (+3°C) and brownification will, a) cause plankton community composition to shift toward small sized phytoplankton and cyanobacteria, and, b) extend the length of the growing season entailing higher phytoplankton production later in the season. We demonstrate that the 3°C increase of water temperature favored the growth of heterotrophic bacteria and small sized autotrophic picophytoplankton cells with significantly higher primary production during warmer fall periods. However, 3X darker water (effect of brownification) caused no significant changes in the plankton community composition or functioning relative to control conditions. Our findings reveal that increased temperature change plankton community structure by favoring smaller sized species proliferation (autotrophic phytoplankton and small size cladocerans), and increase primary productivity and community turnover. Finally, results of this multi-seasonal experiment suggest that warming by 3°C in aquatic ecosystems of low trophic state may cause planktonic food web functioning to become more dominated by fast growing, r-trait species (i.e., small sizes and rapid development).

Dynamic contrast-enhanced magnetic resonance imaging assessment of kidney function and renal masses: single slice versus whole organ/tumor.

OBJECTIVES: The aim of this study was to compare single-slice and 3-dimensional (3D) analysis for magnetic resonance renography (plasma flow [FP], plasma volume [VP], and glomerular filtration rate [GFR]) and for dynamic contrast-enhanced magnetic resonance imaging (MRI) of renal tumors (FP, VP, permeability-surface area product), respectively. MATERIAL AND METHODS: We prospectively included 22 patients (43 kidneys with 22 suspicious renal lesions) and performed preoperative and postoperative imaging before and after partial nephrectomy, respectively. Of the 22 renal lesions, 15 turned out to be renal cell carcinoma and were included in the tumor analysis, altogether leading to 86 renal and 15 tumor MRI scans, respectively. Dynamic contrast-enhanced MRI was performed with a time-resolved angiography with stochastic trajectories sequence (spatial resolution, 2.6 × 2.6 × 2.6 mm3; temporal resolution, 2.5 seconds) at 3 T (Magnetom Verio; Siemens Healthcare Sector) after injection of 0.05 mmol/kg body weight Gadobutrol (Bayer Healthcare Pharmaceuticals). Analysis was performed using regions of interest encompassing a single central slice and the whole kidney/tumor, respectively. A 2-compartment model yielding FP, VP, GFR, or tumor permeability-surface area product was used for kinetic modelling. Modelling was performed based on relative contrast enhancement to account for coil-related inhomogeneity. Significance in difference, agreement, and goodness of fit of the data to the curve was assessed with paired t tests, Bland-Altman plots, and χ2 test, respectively. RESULTS: Bland-Altman analysis revealed a good agreement between both types of measurement for kidneys and tumors, respectively. Results between single-slice and whole-kidney regions of interest showed significant differences for Fp (single slice, 256.1 ± 104.1 mL/100 mL/min; whole kidney, 217.2 ± 92.5 mL/100 mL/min; P < 0.01). Regarding VP and GFR, no significant differences were observed. The χ2 test showed a significantly better goodness of fit of the data to the curve for whole kidneys (0.30% ± 0.18%) than for single slices (0.43% ± 0.26%) (P < 0.01). In contrast to renal assessment, tumor analysis showed no significant differences regarding functional parameters and χ test, respectively. CONCLUSION: In dynamic contrast-enhanced MRI of the kidney, both 3D whole-organ/tumor and single-slice analyses provide roughly comparable values in functional analysis. However, 3D assessment is considerably more precise and should be preferred if available.

Inhibition of mTOR down-regulates scavenger receptor, class B, type I (SR-BI) expression, reduces endothelial cell migration and impairs nitric oxide production.

The mammalian target of rapamycin (mTOR) inhibiting drug rapamycin (Sirolimus) has severe side effects in patients including hyperlipidemia, an established risk factor for atherosclerosis. Recently, it was shown that rapamycin decreases hepatic LDL receptor (LDL-R) expression, which likely contributes to hypercholesterolemia. Scavenger receptor, class B, type I (SR-BI) is the major HDL receptor and consequently regulating HDL-cholesterol levels and the athero-protective effects of HDL. By using the mTOR inhibitor rapamycin, we show that SR-BI is down-regulated in human umbilical vein endothelial cells (HUVECs). This reduction of SR-BI protein as well as mRNA levels by about 50% did not alter HDL particle uptake or HDL-derived lipid transfer. However, rapamycin reduced HDL-induced activation of eNOS and stimulation of endothelial cell migration. The effects on cell migration could be counteracted by SR-BI overexpression, indicating that decreased SR-BI expression is in part responsible for the rapamycin-induced effects. We demonstrate that inhibition of mTOR leads to endothelial cell dysfunction and decreased SR-BI expression, which may contribute to atherogenesis during rapamycin treatment.

Endoplasmic reticulum stress impairs cholesterol efflux and synthesis in hepatic cells.

Metabolic disorders such as type 2 diabetes cause hepatic endoplasmic reticulum (ER) stress, which affects neutral lipid metabolism. However, the role of ER stress in cholesterol metabolism is incompletely understood. Here, we show that induction of acute ER stress in human hepatic HepG2 cells reduced ABCA1 expression and caused ABCA1 redistribution to tubular perinuclear compartments. Consequently, cholesterol efflux to apoA-I, a key step in nascent HDL formation, was diminished by 80%. Besides ABCA1, endogenous apoA-I expression was reduced upon ER stress induction, which contributed to reduced cholesterol efflux. Liver X receptor, a key regulator of ABCA1 in peripheral cells, was not involved in this process. Despite reduced cholesterol efflux, cellular cholesterol levels remained unchanged during ER stress. This was due to impaired de novo cholesterol synthesis by reduction of HMG-CoA reductase activity by 70%, although sterol response element-binding protein-2 activity was induced. In mice, ER stress induction led to a marked reduction of hepatic ABCA1 expression. However, HDL cholesterol levels were unaltered, presumably because of scavenger receptor class B, type I downregulation under ER stress. Taken together, our data suggest that ER stress in metabolic disorders reduces HDL biogenesis due to impaired hepatic ABCA1 function.