Impact on Hospital Resource Utilization of Endoluminal Bypass Using the Viabahn Endoprosthesis with Heparin Bioactive Surface Compared With Surgical Femoropopliteal Bypass.

OBJECTIVE: To assess the impact of heparin-bonded endoprosthesis compared with femoropopliteal bypass on key hospital resources and revenues up to 1-year follow-up. DESIGN: A 2-arm scenario resource consumption data analysis was modeled based on a multicentre prospective randomized controlled trial. SETTING: Six centers in the Netherlands. PARTICIPANTS: A total of 100 patients were assigned to 2 arms (50 each arm). The first arm evaluated endovascular treatment using the heparin-bonded Viabahn endoprosthesis and the second the femoropopliteal bypass. Resource consumption rates were compared between arms. PRIMARY AND SECONDARY OUTCOMES MEASURES: Resource consumption rates, including hospital stay for bypass procedure, operating room time, type of anesthesia, number of used (endo)grafts, use of different types of bed locations (vascular ward, medium or intensive care), readmission for wound infections, and reinterventions over a period of 12 months. RESULTS: Endovascular repair used fewer hospital resources, with an overall difference of €149.983. Hospital stay was 118 days less (261 vs 379), including 21 fewer days in medium/intensive care (5 vs 26) and 50 fewer operating room hours (100 vs 150). Fewer patients required general anesthesia (31 vs 39), and there were less surgical site infections (3 vs 12). In the surgical bypass group, there were 18 fewer days of hospital stay related to reinterventions (80 vs 62), and the cost of the devices was €309.996, cheaper. The total monetary difference was € 160.013, in favor of the femoropopliteal bypass (€3.200, per patient). CONCLUSIONS: Endovascular repair of the superficial femoral artery reduces the use of valuable hospital resources. Its major limitation is the cost of the devices, which should be balanced against the reduction in peri-procedural morbidity and faster recovery. In the context of shortage of hospital beds, it offers capacity benefits, allowing for the treatment of more patients overall. These benefits may outweigh the fewer reinterventions in the surgical bypass group. REGISTRATION: The SuperB Trial was registered in clinicaltrials.gov; NCT-ID: NCT01220245. CLINICAL IMPACT: Modeling is a useful technique to predict the impact of treatment modalities on hospital resources and revenue. This study uses real-world data from the SuperB Trial to compare two treatment strategies of superficial femoral artery disease, reflecting actual clinical practice and patient outcomes. The analysis focused on direct costs associated with hospital resources and device usage without considering indirect costs or long-term cost-effectiveness. The analysis showed that endovascular repair reduces the use of valuable hospital resources. Its major limitation is device costs, which should be balanced against the reduction in peri-procedural morbidity and faster recovery. In the context of shortage of hospital beds, it offers capacity benefits, allowing for the treatment of more patients overall.

Post hoc analysis of the SuperB and Zilverpass trials for treatment of long and complex superficial femoral artery lesions.

OBJECTIVE: In two randomized controlled trials, the outcomes of endovascular treatment of complex femoropopliteal arterial lesions were compared with bypass surgery and considered a valid alternative treatment. The aim of this study was to compare both endovascular treatment options with the hypothesis that implantation of heparin-bonded self-expanding covered stents (Viabahn, SECS) or drug-eluting stents (ZilverPTX, DES) are related to similar clinical outcomes at one-year follow-up. METHODS: In a post-hoc analysis, the SuperB trial and Zilverpass databases were merged. Patients in the endovascular treatment arms were included and data was analyzed in an intention-to-treat (ITT) and a per-protocol (PP) fashion. Data included baseline and lesion characteristics, procedural details, and follow-up data. The primary endpoint of this study was primary patency at one-year follow-up. The secondary endpoints were secondary patency, target lesion revascularization (TLR), limb loss, and all-cause mortality. RESULTS: A total of 176 patients were included; 63 in the SECS arm and 113 in the DES arm. Through 1-year follow-up there were no significant differences in primary patency (ITT 63.4% vs 71.1%: p=0.183 and PP 60.8% vs 71.1%; p=0.100). Secondary patency rates were not significantly different in the ITT analysis (86.5% vs 95.1%; p=0.054), but in the PP analysis, there was a significant difference in favor of the DES group (SECS 85.6% versus DES 95.1%; p=0.038). There was no significant difference in freedom from TLR between groups (79.6% vs 77.0%, p=0.481). No major amputations were performed in the SECS group and two in the DES group (1.8%). Survival rate was 98.2% in the SECS group, and 91.3% in the DES group after one-year follow-up (p=0.106). Based on diagnosis (IC versus CLTI) no differences between IC and CLTI patients were observed in primary, secondary patency and freedom from TLR. CONCLUSIONS: Treatment of complex femoropopliteal arterial disease with the heparin-bonded Viabahn endoprosthesis and the Zilver PTX drug-eluting stent are related to similar primary and secondary patency, and TLR rates at one-year, except for secondary patency in the PP analysis. This study further supports the endovascular treatment of long complex lesions in the femoropopliteal artery.

Metabolic Dysfunction-Associated Fibrosis Score Predicts Liver Fibrosis Risk and Outcome in the General Population With Metabolic Dysfunction.

BACKGROUND & AIMS: There is an unmet need for noninvasive tests to improve case-finding and aid primary care professionals in referring patients at high risk of liver disease. METHODS: A metabolic dysfunction-associated fibrosis (MAF-5) score was developed and externally validated in a total of 21,797 individuals with metabolic dysfunction in population-based (National Health and Nutrition Examination Survey 2017-2020, National Health and Nutrition Examination Survey III, and Rotterdam Study) and hospital-based (from Antwerp and Bogota) cohorts. Fibrosis was defined as liver stiffness ≥8.0 kPa. Diagnostic accuracy was compared with FIB-4, nonalcoholic fatty liver disease fibrosis score, and steatosis-associated fibrosis estimator. MAF-5 was externally validated with liver stiffness measurement ≥8.0 kPa, with shear-wave elastography ≥7.5 kPa, and biopsy-proven steatotic liver disease according to Metavir and Nonalcoholic Steatohepatitis Clinical Research Network scores, and was tested for prognostic performance (all-cause mortality). RESULTS: The MAF-5 score comprised waist circumference, body mass index (calculated as kg / m2), diabetes, aspartate aminotransferase, and platelets. With this score, 60.9% was predicted at low, 14.1% at intermediate, and 24.9% at high risk of fibrosis. The observed prevalence was 3.3%, 7.9%, and 28.1%, respectively. The area under the receiver operator curve of MAF-5 (0.81) was significantly higher than FIB-4 (0.61), and outperformed the FIB-4 among young people (negative predictive value [NPV], 99%; area under the curve [AUC], 0.86 vs NPV, 94%; AUC, 0.51) and older adults (NPV, 94%; AUC, 0.75 vs NPV, 88%; AUC, 0.55). MAF-5 showed excellent performance to detect liver stiffness measurement ≥12 kPa (AUC, 0.86 training; AUC, 0.85 validation) and good performance in detecting liver stiffness and biopsy-proven liver fibrosis among the external validation cohorts. MAF-5 score >1 was associated with increased risk of all-cause mortality in (un)adjusted models (adjusted hazard ratio, 1.59; 95% CI, 1.47-1.73). CONCLUSIONS: The MAF-5 score is a validated, age-independent, inexpensive referral tool to identify individuals at high risk of liver fibrosis and all-cause mortality in primary care populations, using simple variables.

Artificial intelligence to advance acute and intensive care medicine.

PURPOSE OF REVIEW: This review explores recent key advancements in artificial intelligence for acute and intensive care medicine. As artificial intelligence rapidly evolves, this review aims to elucidate its current applications, future possibilities, and the vital challenges that are associated with its integration into emergency medical dispatch, triage, medical consultation and ICUs. RECENT FINDINGS: The integration of artificial intelligence in emergency medical dispatch (EMD) facilitates swift and accurate assessment. In the emergency department (ED), artificial intelligence driven triage models leverage diverse patient data for improved outcome predictions, surpassing human performance in retrospective studies. Artificial intelligence can streamline medical documentation in the ED and enhances medical imaging interpretation. The introduction of large multimodal generative models showcases the future potential to process varied biomedical data for comprehensive decision support. In the ICU, artificial intelligence applications range from early warning systems to treatment suggestions. SUMMARY: Despite promising academic strides, widespread artificial intelligence adoption in acute and critical care is hindered by ethical, legal, technical, organizational, and validation challenges. Despite these obstacles, artificial intelligence's potential to streamline clinical workflows is evident. When these barriers are overcome, future advancements in artificial intelligence have the potential to transform the landscape of patient care for acute and intensive care medicine.

Five-Year Outcomes of the SuperB Trial: A Multicenter Randomized Controlled Trial Comparing Heparin-Bonded Endograft to Surgical Femoropopliteal Bypass.

OBJECTIVE: This study aims to compare the 5-year outcomes of endoluminal bypass (EB) using heparin-bonded self-expanding covered stents versus bypass surgery for extensive femoropopliteal disease, including technical and clinical outcomes and health status. BACKGROUND: The surgical femoropopliteal bypass was the gold standard to treat peripheral arterial disease (PAD) for decades; however, endovascular treatment modalities are now recommended for most femoropopliteal lesions. One-year data of a randomized controlled trial comparing EB with surgical bypass (SB) have shown a faster recovery, less morbidity, and comparable patency rates between the two techniques. To date, long-term randomized controlled data regarding both techniques are lacking. METHODS: Five-year results of a multicenter randomized controlled trial comparing EB with SB in patients with femoropopliteal artery disease were evaluated based on intention-to-treat and per-protocol analyses. RESULTS: At 5-year follow-up, primary, primary-assisted, and secondary patency rates were 36.2%, 52.4%, and 68.1% for EB and 49.4%, 72.2%, and 77.8% for SB, respectively (p=0.608). Freedom from target lesion revascularization (fTLR) was 34.1% for EB and 57.6% for SB (p=0.365). In both groups, the ankle-brachial index, Rutherford classification, and walking distance significantly improved compared with baseline without differences between groups at follow-up. Freedom from major amputation rate was 92.6% in the EB group and 96.2% in the SB group (p=0.361). The 36-Item Short-Form Health Survey showed no significant differences between groups. CONCLUSION: Treatment of extensive femoropopliteal disease with self-expanding covered stents provides comparable clinical-related and health-related questionnaire outcomes when compared with SB through 5 years of follow-up. However, the EB is related to a higher number of reinterventions. CLINICAL IMPACT: This present study is the first to report five-year outcomes comparing an endoluminal (EB) using heparin-bonded self-expanding covered stents with surgical bypass (SB) for long and complex femoropopliteal disease. Although the advantages of treatment with EB are mostly seen in the early period after treatment, the outcomes support the use of EB for this indication and seems to be a valid and safe alternative for bypass surgery. Future trials comparing various endovascular strategies may provide further guidance for the development of an evidence-based treatment algorithm.

Corrigendum: Usability, feasibility, and effect of a biocueing intervention in addition to a moderated digital social therapy-platform in young people with emerging mental health problems: a mixed-method approach.

[This corrects the article DOI: 10.3389/fpsyt.2022.871813.].

Does Reinforcement Learning Improve Outcomes for Critically Ill Patients? A Systematic Review and Level-of-Readiness Assessment.

OBJECTIVE: Reinforcement learning (RL) is a machine learning technique uniquely effective at sequential decision-making, which makes it potentially relevant to ICU treatment challenges. We set out to systematically review, assess level-of-readiness and meta-analyze the effect of RL on outcomes for critically ill patients. DATA SOURCES: A systematic search was performed in PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection, Elsevier/SCOPUS and the Institute of Electrical and Electronics Engineers Xplore Digital Library from inception to March 25, 2022, with subsequent citation tracking. DATA EXTRACTION: Journal articles that used an RL technique in an ICU population and reported on patient health-related outcomes were included for full analysis. Conference papers were included for level-of-readiness assessment only. Descriptive statistics, characteristics of the models, outcome compared with clinician's policy and level-of-readiness were collected. RL-health risk of bias and applicability assessment was performed. DATA SYNTHESIS: A total of 1,033 articles were screened, of which 18 journal articles and 18 conference papers, were included. Thirty of those were prototyping or modeling articles and six were validation articles. All articles reported RL algorithms to outperform clinical decision-making by ICU professionals, but only in retrospective data. The modeling techniques for the state-space, action-space, reward function, RL model training, and evaluation varied widely. The risk of bias was high in all articles, mainly due to the evaluation procedure. CONCLUSION: In this first systematic review on the application of RL in intensive care medicine we found no studies that demonstrated improved patient outcomes from RL-based technologies. All studies reported that RL-agent policies outperformed clinician policies, but such assessments were all based on retrospective off-policy evaluation.

Longitudinal resting-state network connectivity changes in electroconvulsive therapy patients compared to healthy controls.

OBJECTIVE: Electroconvulsive therapy (ECT) is effective for major depressive episodes. Understanding of underlying mechanisms has been increased by examining changes of brain connectivity but studies often do not correct for test-retest variability in healthy controls (HC). In this study, we investigated changes in resting-state networks after ECT in a multicenter study. METHODS: Functional resting-state magnetic resonance imaging data, acquired before start and within one week after ECT, from 90 depressed patients were analyzed, as well as longitudinal data of 24 HC. Group-information guided independent component analysis (GIG-ICA) was used to spatially restrict decomposition to twelve canonical resting-state networks. Selected networks of interest were the default mode network (DMN), salience network (SN), and left and right frontoparietal network (LFPN, and RFPN). Whole-brain voxel-wise analyses were used to assess group differences at baseline, group by time interactions, and correlations with treatment effectiveness. In addition, between-network connectivity and within-network strengths were computed. RESULTS: Within-network strength of the DMN was lower at baseline in ECT patients which increased after ECT compared to HC, after which no differences were detected. At baseline, ECT patients showed lower whole-brain voxel-wise DMN connectivity in the precuneus. Increase of within-network strength of the LFPN was correlated with treatment effectiveness. We did not find whole-brain voxel-wise or between-network changes. CONCLUSION: DMN within-network connectivity normalized after ECT. Within-network increase of the LFPN in ECT patients was correlated with higher treatment effectiveness. In contrast to earlier studies, we found no whole-brain voxel-wise changes, which highlights the necessity to account for test-retest effects.

Fatty Liver Index and mortality after myocardial infarction: A prospective analysis in the Alpha Omega Cohort.

Accumulating evidence shows that NAFLD might play a role in the etiology and progression of CVD, but little is known on the association of NAFLD and CVD mortality in patients with a history of a myocardial infarction (MI). Therefore, we studied the relationship of Fatty Liver Index (FLI), as indicator for non-alcoholic fatty liver disease (NAFLD), with 12-year risk of cardiovascular disease (CVD) and all-cause mortality in post-MI patients. We included 4165 Dutch patients from the Alpha Omega Cohort aged 60-80 years who had an MI ≤10 years prior to study enrolment. NAFLD was defined as FLI ≥60. Patients were followed for cause-specific mortality from enrolment (2002-2006) through December 2018. Hazard ratios for CVD and all-cause mortality were obtained by multivariable Cox regression using FLI <30 (indicating absence of NAFLD) as the reference. Baseline FLI as a continuous measure was studied with mortality using restricted cubic splines analyses. The median (IQR) FLI was 68 (48-84). Sixty percent of the patients had FLI ≥60, who were more likely to be male and more often had diabetes, high blood pressure, and high serum cholesterol levels. During 12 years of follow-up, 2042 deaths occurred of which 846 from CVD. Patients with NAFLD were at increased risk of CVD mortality (HR: 1.55 [1.19, 2.03]) and all-cause mortality (HR: 1.21 [1.03; 1.41]) compared to patients without NAFLD. Results remained consistent after excluding patients with obesity and diabetes. To conclude, the adverse association of FLI with CVD mortality was stronger in female than in male patients with conventional cut-off points. FLI ≥60, indicating NAFLD, was a predictor for CVD and all-cause mortality in post-MI patients, independent of other cardiometabolic risk factors. However, cut-off points might differ between male and female patients for predicting CVD mortality.

The additive value of CA19.9 monitoring in a pancreatic cyst surveillance program.

BACKGROUND: Surveillance of pancreatic cysts focuses on the detection of (mostly morphologic) features warranting surgery. European guidelines consider elevated CA19.9 as a relative indication for surgery. We aimed to evaluate the role of CA19.9 monitoring for early detection and management in a cyst surveillance population. METHODS: The PACYFIC-registry is a prospective collaboration that investigates the yield of pancreatic cyst surveillance performed at the discretion of the treating physician. We included participants for whom at least one serum CA19.9 value was determined by a minimum follow-up of 12 months. RESULTS: Of 1865 PACYFIC participants, 685 met the inclusion criteria for this study (mean age 67 years, SD 10; 61% female). During a median follow-up of 25 months (IQR 24, 1966 visits), 29 participants developed high-grade dysplasia (HGD) or pancreatic cancer. At baseline, CA19.9 ranged from 1 to 591 kU/L (median 10 kU/L [IQR 14]), and was elevated (≥37 kU/L) in 64 participants (9%). During 191 of 1966 visits (10%), an elevated CA19.9 was detected, and these visits more often led to an intensified follow-up (42%) than those without an elevated CA19.9 (27%; p < 0.001). An elevated CA19.9 was the sole reason for surgery in five participants with benign disease (10%). The baseline CA19.9 value was (as continuous or dichotomous variable at the 37 kU/L threshold) not independently associated with HGD or pancreatic cancer development, whilst a CA19.9 of ≥ 133 kU/L was (HR 3.8, 95% CI 1.1-13, p = 0.03). CONCLUSIONS: In this pancreatic cyst surveillance cohort, CA19.9 monitoring caused substantial harm by shortening surveillance intervals (and performance of unnecessary surgery). The current CA19.9 cutoff was not predictive of HGD and pancreatic cancer, whereas a higher cutoff may decrease false-positive values. The role of CA19.9 monitoring should be critically appraised prior to implementation in surveillance programs and guidelines.

The Role of the Retinal Nerve Fiber Layer Thickness on OCT in the Evaluation of Papillitis in Childhood Uveitis.

PURPOSE: To investigate the diagnostic value of using retinal nerve fiber layer thickness measured on optical coherence tomography (OCT-RNFL) to diagnose papillitis in pediatric uveitis. DESIGN: Retrospective cohort study. METHODS: Demographic and clinical data were collected retrospectively for 257 children with uveitis (with 455 affected eyes). Receiver operating characteristic (ROC) analysis was performed to compare fluorescein angiography (FA, the diagnostic gold standard for papillitis) to OCT-RNFL in a subgroup of 93 patients. An ideal cut-off value for OCT-RNFL was then determined by calculating the highest Youden index. Finally, a multivariate analysis was applied to the clinical ophthalmological data. RESULTS: Based on a subset of 93 patients who underwent both OCT-RNFL and FA, the ideal cut-off OCT-RNFL for diagnosing papillitis was >130 µm, with 79% sensitivity and 85% specificity. Among the entire cohort, the prevalence of OCT-RNFL >130 µm was 19% (27/141), 72% (26/36), and 45% (36/80) in patients with anterior uveitis, intermediate uveitis, and panuveitis, respectively. Our multivariate analysis of the clinical data revealed that OCT-RNFL >130 µm was associated with a higher prevalence of cystoid macular edema, active uveitis, and optic disc swelling on fundoscopy, with odds ratios of 5.3, 4.3, and 13.7, respectively (all P < .001). CONCLUSIONS: OCT-RNFL can be a useful noninvasive additional imaging tool for diagnosing papillitis in pediatric uveitis with relatively high sensitivity and specificity. OCT-RNFL was >130 µm in approximately one-third of all children with uveitis and was particularly prevalent in cases of intermediate uveitis and panuveitis.

Spleen Stiffness Measurement Across the Spectrum of Liver Disease Patients in Real-World Practice.

Objectives: Spleen stiffness measurement (SSM) provides a non-invasive surrogate marker for clinical significant portal hypertension (CSPH). Results obtained in highly selected populations were promising but require validation across the spectrum of liver disease. We aimed to investigate the clinical applicability of SSM in a real-world setting. Methods: We prospectively enrolled patients referred for liver ultrasound (January-May 2021). Patients with a portosystemic shunt, liver transplant, or extrahepatic etiology of portal hypertension were excluded. We performed liver ultrasound, liver stiffness measurement (LSM) and SSM (dedicated software, 100 Hz-probe). Probable CSPH was established if ≥1 of the following items occurred: ascites, varices, encephalopathy, splenomegaly, recanalized umbilical vein, collaterals, dilated portal veins, hypertensive gastropathy, or LSM ≥25 kPa. Results: We enrolled 185 patients (53% male; age 53years [37-64], 33% viral hepatitis, 21% fatty liver disease). Of them, 31% of patients had cirrhosis (68% Child-Pugh A) and 38% of patients had signs of portal hypertension. SSM (23.8 kPa [16.2-42.3]) and LSM (6.7 kPa [4.6-12.0]) were successful and met reliability criteria in 70% and 95%, respectively. Spleen size was inversely associated with SSM failure (odds ratio: 0.66 increment/cm, 95% confidence interval: 0.52-0.82). Optimal spleen stiffness cut-off to detect probable CSPH was >26.5 kPa (likelihood ratio: 4.5, sensitivity: 83%; specificity: 82%). Spleen stiffness did not outperform liver stiffness in detecting probable CSPH (P = 1.0). Conclusions: In real-world practice, reliable SSM were obtained in 70% and could potentially stratify patients between high- and low-risk of probable CSPH. However, cut-offs for CSPH might be substantially lower than previously reported. Future studies validating these results are required. Clinical trial number: Netherlands Trial Register (Registration number: NL9369).

The Steatosis-associated fibrosis estimator (SAFE) score: validation in the general US population.

BACKGROUND: Noninvasive tests are important in the initial risk stratification of people at risk of fibrosis. The recently developed steatosis-associated fibrosis estimator (SAFE) score may have such potential but awaits external validation. METHODS: We analyzed 6973 participants aged 18-80 in the National Health and Nutrition Examination Survey 2017-2020 cycle with data on liver stiffness and SAFE score without prevalent heart failure. Fibrosis was defined as liver stiffness ≥8.0 kPa. Accuracy was evaluated by AUC and assessment of test characteristics at the prespecified cutoffs for ruling out/ruling in fibrosis. RESULTS: The SAFE score categorized 14.7% of the population as high risk, 30.4% as intermediate risk, and 54.9% as low risk for fibrosis. The actual fibrosis prevalence in these groups was 28.0%, 10.9%, and 4.0%, respectively, translating into a positive predictive value of 0.28 at the high-risk cutoff and a negative predictive value of 0.96 at the low-risk cutoff. The AUC of the SAFE score (0.748) was significantly higher than the fibrosis-4 index (0.619) or NAFLD fibrosis score (0.718). However, test performance strongly depended on age categories: 90% of participants aged 18-40 years were considered at low risk for fibrosis, including 89/134 (66%) of clinically significant fibrosis cases. In the oldest group (60-80 y), fibrosis could only be safely ruled out among 17%, corresponding to a high referral rate of up to 83%. The best SAFE score performance was found in the middle-aged group (40-60 y). The results were consistent in target populations with metabolic dysfunction or steatosis. CONCLUSIONS: The SAFE score has overall good diagnostic accuracy in detecting fibrosis but was highly dependent on age. The SAFE score lacked sensitivity in younger populations and the ability to rule out fibrosis in older populations.

Association Between the Presence of Metabolic Comorbidities and Liver-Related Events in Patients With Chronic Hepatitis B.

BACKGROUND & AIMS: Patients with chronic hepatitis B (CHB) are at increased risk of hepatocellular carcinoma and (liver-related) mortality. In addition to hepatitis B-related factors, metabolic comorbidities may contribute to the progression of fibrosis. Therefore, we studied the association between metabolic comorbidities and adverse clinical outcomes in patients with CHB. METHODS: We conducted a retrospective cohort study of CHB patients attending the Erasmus MC University Medical Center (Rotterdam, The Netherlands) and CHB patients who underwent liver biopsy at the Toronto General Hospital (Toronto, Canada). The presence of metabolic comorbidities (ie, overweight, diabetes mellitus, hypertension, and dyslipidemia) was assessed based on chart review. The primary end point was liver-related events, defined as the first composite of hepatocellular carcinoma, liver transplantation, or liver-related mortality. RESULTS: We analyzed 1850 patients, of whom 926 (50.1%) were overweight, 161 (8.7%) had hypertension, 116 (6.3%) had dyslipidemia, and 82 (4.4%) had diabetes. During a median follow-up period of 7.3 years (interquartile range, 2.9-11.5 y), a total of 111 first events were recorded. Hypertension (hazard ratio [HR], 8.3; 95% CI, 5.5-12.7), diabetes (HR, 5.4; 95% CI, 3.2-9.1), dyslipidemia (HR, 2.8; 95% CI, 1.6-4.8), and overweight (HR, 1.7; 95% CI, 1.1-2.5) were associated with an increased risk for liver-related events. The presence of multiple comorbidities further increased the risk. Findings were consistent for patients with and without cirrhosis, among noncirrhotic hepatitis B e antigen-negative patients with hepatitis B virus DNA less than 2000 IU/mL and in multivariable analysis adjusting for age, sex, ethnicity, hepatitis B e antigen status, hepatitis B virus DNA, use of antiviral therapy, and the presence of cirrhosis. CONCLUSIONS: Metabolic comorbidities in CHB patients are associated with an increased risk for liver-related events, with the highest risk observed in patients with multiple comorbidities. Findings were consistent in various clinically relevant subgroups, underscoring the need for thorough metabolic assessment in patients with CHB.

Real world impact of added FFR-CT to coronary CT angiography on clinical decision-making and patient prognosis - IMPACT FFR study.

OBJECTIVES: The addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of coronary CT angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD). METHODS: This retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACEs) during the 1-year follow-up using chi-square tests for independence. Kaplan-Meier curves were used to visualize the occurrence of safety outcomes over time. RESULTS: A total of 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group, and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA group, and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA), and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA, and three (2.2%) SPECT (p < 0.001 for all three options). The revascularization rate after ICA was similar between groups (p = 0.15). However, patients in the CCTA group more often underwent revascularization (p = 0.007). CONCLUSION: Addition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after 1 year. KEY POINTS: • Previous studies have shown that computed tomography-derived fractional flow reserve improves the accuracy of coronary computed tomography angiography without changes in acquisition protocols. • This study shows that use of computed tomography-derived fractional flow reserve as gatekeeper to invasive coronary angiography in patients suspected of stable coronary artery disease leads to less invasive testing and revascularization without observed difference in outcomes after 1 year. • This could lead to a significant reduction in costs, complications and (retrospectively unnecessary) usage of diagnostic testing capacity, and a significant increase in patient satisfaction.

Liver stiffness is associated with excess mortality in the general population driven by heart failure: The Rotterdam Study.

BACKGROUND: Elevated liver stiffness reflects hepatic fibrosis but can also be secondary to venous congestion. We aimed to study the association between liver stiffness and mortality in the general population, stratified for heart failure and/or coronary heart disease (CHD). METHODS: We analysed individuals enrolled in the ongoing prospective population-based Rotterdam Study who attended a visit between 2009-2014 that included liver stiffness measurement. Exclusion criteria for the primary analysis were incomplete data on heart failure, unreliable liver stiffness, alcohol abuse and viral hepatitis, leaving 4.153 participants (aged 67.5 ± 8.4 years, 44.2% male) for analysis with a median follow-up of 6.0 (interquartile range: 5.1-7.0) years. Secondary analysis included participants with viral hepatitis, alcohol abuse and/or unreliable measurement. The association between liver stiffness and mortality was assessed using Cox regression. Associations between heart failure, CHD, and echocardiographic characteristics and liver stiffness were quantified with linear regression. RESULTS: Liver stiffness ≥8.0 kPa was associated with mortality (aHR: 1.37, 95%CI: 1.00-1.89). However, this was driven by participants with heart failure (aHR: 2.48, 95%CI: 1.15-5.35), since high liver stiffness was not associated with mortality in participants without heart failure and/or CHD (aHR: 1.07, 95%CI: 0.70-1.64). Results were consistent when individuals with viral hepatitis, alcohol abuse or unreliable liver stiffness measurement were not excluded. Several cardiovascular characteristics were significantly associated with higher liver stiffness, e.g. heart failure, moderate/poor diastolic dysfunction, and right atrium diameter > 4.5 cm. CONCLUSION: In our cohort of community-dwelling elderly, high liver stiffness was associated with excess mortality, primarily explained by participants with heart failure. Moreover, heart failure and its indicators were associated with increased liver stiffness.

Plasma proteomic signature of fatty liver disease: The Rotterdam Study.

BACKGROUND AND AIMS: Fatty liver disease (FLD) is caused by excess fat in the liver, and its global prevalence exceeds 33%. The role of protein expression on the pathogenesis of FLD and accompanied fibrosis and its potential as a disease biomarker is currently not clear. Hence, we aimed to identify plasma proteomics associated with FLD and fibrosis using population-based data. APPROACH AND RESULTS: Blood samples were collected from 2578 participants from the population-based Rotterdam Study cohort. The proximity extension assay reliably measured plasma levels of 171 cardiometabolic and inflammatory-related proteins (Olink Proteomics). FLD was assessed by ultrasound, and fibrosis by transient elastography. Logistic regression models quantified the association of plasma proteomics with FLD and fibrosis. In addition, we aimed to validate our results in liver organoids. The cross-sectional analysis identified 27 proteins significantly associated with FLD surpassing the Bonferroni-corrected p <2.92×10 -4 . The strongest association was observed for FGF-21 (ß=0.45, p =1.07×10 -18 ) and carboxylesterase 1 (CES1) protein (ß=0.66, p =4.91×10 -40 ). Importantly, 15 of the 27 proteins significantly associated with FLD were also associated with liver fibrosis. Finally, consistent with plasma proteomic profiling, we found the expression levels of IL-18 receptor 1 (IL-18R1) and CES1 to be upregulated in an FLD model of 3-dimensional culture human liver organoids. CONCLUSIONS: Among the general population, several inflammatory and cardiometabolic plasma proteins were associated with FLD and fibrosis. Particularly, plasma levels of FGF-21, IL-18R1, and CES1 were largely dependent on the presence of FLD and fibrosis and may therefore be important in their pathogenesis.