Trends in quality of care and dying perceived by family caregivers of nursing home residents with dementia 2005-2019.

BACKGROUND: Dementia palliative care is increasingly subject of research and practice improvement initiatives. AIM: To assess any changes over time in the evaluation of quality of care and quality of dying with dementia by family caregivers. DESIGN: Combined analysis of eight studies with bereaved family caregivers' evaluations 2005-2019. SETTING/PARTICIPANTS: Family caregivers of nursing home residents with dementia in the Netherlands (n = 1189) completed the End-of-Life in Dementia Satisfaction With Care (EOLD-SWC; quality of care) and Comfort Assessment in Dying (EOLD-CAD, four subscales; quality of dying) instruments. Changes in scores over time were analysed using mixed models with random effects for season and facility and adjustment for demographics, prospective design and urbanised region. RESULTS: The mean total EOLD-SWC score was 33.40 (SD 5.08) and increased by 0.148 points per year (95% CI, 0.052-0.244; adjusted 0.170 points 95% CI, 0.055-0.258). The mean total EOLD-CAD score was 30.80 (SD 5.76) and, unadjusted, there was a trend of decreasing quality of dying over time of -0.175 points (95% CI, -0.291 to -0.058) per year increment. With adjustment, the trend was not significant (-0.070 EOLD-CAD total score points, 95% CI, -0.205 to 0.065) and only the EOLD-CAD subscale 'Well being' decreased. CONCLUSION: We identified divergent trends over 14 years of increased quality of care, while quality of dying did not increase and well-being in dying decreased. Further research is needed on what well-being in dying means to family. Quality improvement requires continued efforts to treat symptoms in dying with dementia.

Prognostic Implications of Right Ventricular Remodeling and Function in Patients With Significant Secondary Tricuspid Regurgitation.

BACKGROUND: In patients with significant (moderate and severe) tricuspid regurgitation (TR), the decision to intervene is influenced by right ventricular (RV) size and function. RV remodeling in significant secondary TR has been underexplored. The aim of this study was to characterize RV remodeling in patients with significant secondary TR and to investigate its prognostic implications. METHODS: RV remodeling was characterized by transthoracic echocardiography in 1292 patients with significant secondary TR (median age 71 [62-78]; 50% male). Four patterns of RV remodeling were defined according to the presence of RV dilation (tricuspid annulus≥40 mm) and RV systolic dysfunction (tricuspid annulus systolic excursion plane<17 mm): pattern 1, normal RV size and systolic function; pattern 2, dilated RV with preserved systolic function; pattern 3, normal RV size with systolic dysfunction; and pattern 4, dilated RV systolic dysfunction. The primary end point was all-cause mortality and the event rates were compared across the 4 patterns of RV remodeling. RESULTS: A total of 183 (14%) patients showed pattern 1 RV remodeling; 256 (20%) showed pattern 2; 304 (24%) presented with pattern 3; and 549 (43%) had pattern 4 RV remodeling. Patients with pattern 4 RV remodeling were more frequently male; more often had coronary artery disease, worse renal function, and impaired left ventricular ejection fraction; and were more often symptomatic. Only 98 (8%) patients underwent tricuspid valve annuloplasty during follow-up. During a median follow-up of 34 (interquartile range, 0-60) months, 510 (40%) patients died. The 5-year survival rate was significantly worse in patients presenting with patterns 3 and 4 RV remodeling in comparison with pattern 1 (52% and 49% versus 70%; P=0.002 and P<0.001, respectively), and were independently associated with poor outcome on multivariable analysis. CONCLUSIONS: In patients with significant secondary TR, patients with RV systolic dysfunction have worse clinical outcome regardless of the presence of RV dilation.

Construction and assessment of prediction rules for binary outcome in the presence of missing predictor data using multiple imputation and cross-validation: Methodological approach and data-based evaluation.

We investigate calibration and assessment of predictive rules when missing values are present in the predictors. Our paper has two key objectives. The first is to investigate how the calibration of the prediction rule can be combined with use of multiple imputation to account for missing predictor observations. The second objective is to propose such methods that can be implemented with current multiple imputation software, while allowing for unbiased predictive assessment through validation on new observations for which outcome is not yet available. We commence with a review of the methodological foundations of multiple imputation as a model estimation approach as opposed to a purely algorithmic description. We specifically contrast application of multiple imputation for parameter (effect) estimation with predictive calibration. Based on this review, two approaches are formulated, of which the second utilizes application of the classical Rubin's rules for parameter estimation, while the first approach averages probabilities from models fitted on single imputations to directly approximate the predictive density for future observations. We present implementations using current software that allow for validation and estimation of performance measures by cross-validation, as well as imputation of missing data in predictors on the future data where outcome is missing by definition. To simplify, we restrict discussion to binary outcome and logistic regression throughout. Method performance is verified through application on two real data sets. Accuracy (Brier score) and variance of predicted probabilities are investigated. Results show substantial reductions in variation of calibrated probabilities when using the first approach.

Inter-ethnic differences in valve morphology, valvular dysfunction, and aortopathy between Asian and European patients with bicuspid aortic valve.

Background: Transcatheter aortic valve replacement (TAVR) has been shown safe and feasible in patients with bicuspid aortic valve (BAV) morphology. Evaluation of inter-ethnic differences in valve morphology and function and aortic root dimensions in patients with BAV is important for the worldwide spread of this therapy in this subgroup of patients. Comparisons between large European and Asian cohorts of patients with BAV have not been performed, and potential differences between populations may have important implications for TAVR. Aim: The present study evaluated the differences in valve morphology and function and aortic root dimensions between two large cohorts of European and Asian patients with BAV. Methods and results: Aortic valve morphology was defined on transthoracic echocardiography according to the number of commissures and raphe: type 0 = no raphe and two commissures, type 1 = one raphe and two commissures, type 2 = two raphes and one commissure. Aortic stenosis and regurgitation were graded according to current recommendations. For this study, aortic root dimensions were manually measured on transthoracic echocardiograms at the level of the aortic annulus, sinus of Valsalva (SOV), sinotubular junction (STJ), and ascending aorta (AA). Of 1427 patients with BAV (45.2 ± 18.1 years, 71.9% men), 794 (55.6%) were Europeans and 633 (44.4%) were Asians. The groups were comparable in age and proportion of male sex. Asians had higher prevalence of type 1 BAV with raphe between right and non-coronary cusps than Europeans (19.7% vs. 13.6%, respectively; P < 0.001), whereas the Europeans had higher prevalence of type 0 BAV (two commissures, no raphe) than Asians (14.5% vs. 6.8%, respectively; P < 0.001). The prevalence of moderate and severe aortic regurgitation was higher in Europeans than Asians (44.2% vs. 26.8%, respectively; P < 0.001) whereas there were no differences in BAV with normal function or aortic stenosis. After adjusting for demographics, comorbidities, and valve function, the dimensions of the aortic annulus [mean difference 1.17 mm/m2, 95% confidence interval (CI) 0.96-1.39], SOV (mean difference 1.86 mm/m2, 95% CI 1.47-2.24), STJ (mean difference 0.52 mm/m2, 95% CI 0.14-0.90) and AA (mean difference 1.05 mm/m2, 95% CI 0.57-1.52) were significantly larger among Asians compared with Europeans. Conclusions: This large multicentre registry reports for the first time that Asians with BAV showed more frequently type 1 BAV (with fusion between right and non-coronary cusp) and have larger aortic dimensions than Europeans. These findings have important implications for prosthesis type and size selection for TAVR.

Impact of hepatic encephalopathy on liver transplant waiting list mortality in regions with different transplantation rates.

Overt hepatic encephalopathy (OHE) negatively impacts the prognosis of liver transplant candidates. However, it is not taken into account in most prioritizing organ allocation systems. We aimed to assess the impact of OHE on waitlist mortality in 3 cohorts of cirrhotic patients awaiting liver transplantation, with differences in the composition of patient population, transplantation policy, and transplantation rates. These cohorts were derived from two centers in the Netherlands (reference and validation cohort, n = 246 and n = 205, respectively) and one in Spain (validation cohort, n = 253). Competing-risk regression analysis was applied to assess the association of OHE with 1-year waitlist mortality. OHE was found to be associated with mortality, independently of MELD score, other cirrhosis-related complications and hepatocellular carcinoma (HCC; sHR = 4.19, 95% CI = 1.9-9.5, P = 0.001). The addition of extra MELD points for OHE counteracted its negative impact on survival. These findings were confirmed in the Dutch validation cohort, whereas in the Spanish cohort, containing a significantly greater proportion of HCC and with higher transplantation rates, OHE was not associated with mortality. In conclusion, OHE is an independent risk factor for 1-year waitlist mortality and might be a prioritization rule for organ allocation. However, its impact seems to be attenuated in settings with significantly higher transplantation rates.

To what extent do autoantibodies help to identify high-risk patients in systemic sclerosis?

OBJECTIVES: To evaluate the additive value of autoantibodies in identifying systemic sclerosis (SSc) patients with high complication risk. METHODS: Patients entering the Combined Care In SSc cohort, Leiden University Medical Centre between April 2009 and May 2016 were included. Subgroups of patients were determined using hierarchical clustering, performed on Principal Component Analysis scores, 1) using baseline data of demographic and clinical variables only and 2) with additional use of antibody status. Disease-risk within subgroups was assessed by evaluating 5-year mortality rates. Clinical and autoantibody characteristics of obtained subgroups were compared. RESULTS: In total 407 SSc patients were included, of which 91% (n=371) fulfilled ACR/EULAR 2013 criteria for SSc. Prevalences of autoantibodies were: anti-centromere 37%, anti-topoisomerase (ATA) 24%, anti-RNA polymerase III 5%, anti-fibrillarin 4% and anti-Pm/Scl 5%. Clinical cluster analysis identified 4 subgroups, with two subgroups showing higher than average mortality (resp. 17% and 7% vs. total group mortality of 4%). ATA-positivity ranged from 10 to 21% in low-risk groups and from 30 to 49% among high-risk groups. Adding autoantibody status to the cluster process resulted in 5 subgroups with 3 showing higher than average mortality. Still, 22% of ATA- positive patients were clustered into a low-risk subgroup, while the total number of patients stratified to a high-risk subgroup increased. CONCLUSIONS: Autoantibodies only partially contribute to risk-stratification and clinical subsetting in SSc. The current findings confirm that not all ATA-positive patients have worse prognosis and as such, additional biomarkers are needed to guide clinical follow-up in SSc.

Bayesian variable selection logistic regression with paired proteomic measurements.

We explore the problem of variable selection in a case-control setting with mass spectrometry proteomic data consisting of paired measurements. Each pair corresponds to a distinct isotope cluster and each component within pair represents a summary of isotopic expression based on either the intensity or the shape of the cluster. Our objective is to identify a collection of isotope clusters associated with the disease outcome and at the same time assess the predictive added-value of shape beyond intensity while maintaining predictive performance. We propose a Bayesian model that exploits the paired structure of our data and utilizes prior information on the relative predictive power of each source by introducing multiple layers of selection. This allows us to make simultaneous inference on which are the most informative pairs and for which-and to what extent-shape has a complementary value in separating the two groups. We evaluate the Bayesian model on pancreatic cancer data. Results from the fitted model show that most predictive potential is achieved with a subset of just six (out of 1289) pairs while the contribution of the intensity components is much higher than the shape components. To demonstrate how the method behaves under a controlled setting we consider a simulation study. Results from this study indicate that the proposed approach can successfully select the truly predictive pairs and accurately estimate the effects of both components although, in some cases, the model tends to overestimate the inclusion probability of the second component.

Relationship Between Coronary Contrast-Flow Quantitative Flow Ratio and Myocardial Ischemia Assessed by SPECT MPI.

PURPOSE: A new method has been developed to calculate fractional flow reserve (FFR) from invasive coronary angiography, the so-called "contrast-flow quantitative flow ratio (cQFR)". Recently, cQFR was compared to invasive FFR in intermediate coronary lesions showing an overall diagnostic accuracy of 85%. The purpose of this study was to investigate the relationship between cQFR and myocardial ischemia assessed by single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI). METHODS: Patients who underwent SPECT MPI and coronary angiography within 3 months were included. The cQFR computation was performed offline, using dedicated software. The cQFR computation was based on 3-dimensional quantitative coronary angiography (QCA) and computational fluid dynamics. The standard 17-segment model was used to determine the vascular territories. Myocardial ischemia was defined as a summed difference score ≥2 in a vascular territory. A cQFR of ≤0.80 was considered abnormal. RESULTS: Two hundred and twenty-four coronary arteries were analysed in 85 patients. Overall accuracy of cQFR to detect ischemia on SPECT MPI was 90%. In multivariable analysis, cQFR was independently associated with ischemia on SPECT MPI (OR per 0.01 decrease of cQFR: 1.10; 95% CI 1.04-1.18, p = 0.002), whereas clinical and QCA parameters were not. Furthermore, cQFR showed incremental value for the detection of ischemia compared to clinical and QCA parameters (global chi square 48.7 to 62.6; p <0.001). CONCLUSIONS: A good relationship between cQFR and SPECT MPI was found. cQFR was independently associated with ischemia on SPECT MPI and showed incremental value to detect ischemia compared to clinical and QCA parameters.

Accounting for isotopic clustering in Fourier transform mass spectrometry data analysis for clinical diagnostic studies.

Mass spectrometry based clinical proteomics has emerged as a powerful tool for high-throughput protein profiling and biomarker discovery. Recent improvements in mass spectrometry technology have boosted the potential of proteomic studies in biomedical research. However, the complexity of the proteomic expression introduces new statistical challenges in summarizing and analyzing the acquired data. Statistical methods for optimally processing proteomic data are currently a growing field of research. In this paper we present simple, yet appropriate methods to preprocess, summarize and analyze high-throughput MALDI-FTICR mass spectrometry data, collected in a case-control fashion, while dealing with the statistical challenges that accompany such data. The known statistical properties of the isotopic distribution of the peptide molecules are used to preprocess the spectra and translate the proteomic expression into a condensed data set. Information on either the intensity level or the shape of the identified isotopic clusters is used to derive summary measures on which diagnostic rules for disease status allocation will be based. Results indicate that both the shape of the identified isotopic clusters and the overall intensity level carry information on the class outcome and can be used to predict the presence or absence of the disease.

The use of intrarenal Doppler ultrasonography as predictor for positive outcome after renal artery revascularization.

Whether patients with renal artery stenosis should undergo therapeutic revascularization is controversial. In this retrospective study, we evaluated prognostic intrarenal Doppler ultrasound parameters that might have a predictive value for a beneficial response after renal revascularization. From January 2003 until December 2012, all renovascular interventions for renal artery stenosis were analyzed. The resistive index and the maximal systolic acceleration were determined by Doppler ultrasonography prior to intervention. Thirty-two patients who underwent a renal revascularization procedure were included: 13 combined positive responders and 19 combined non-responders. The combined positive responders had a significant lower resistive index than the combined non-responders (0.5 vs. 0.6, P = 0.001) and a significant lower maximal systolic acceleration (1.0 vs. 3.8, P = 0.001) before revascularization. A prediction model (RI ≤ 0.5 and ACCmax ≤ 1.3 m/s2) was formulated to identify a subgroup that benefits from renal revascularization. This model has an expected sensitivity of 69% and specificity of 89% for improvement in renal function and/or blood pressure after revascularization. The non-invasive intrarenal Doppler ultrasound parameters resistive index and maximal systolic acceleration can be used as tools to predict improvement in renal function and/or blood pressure after revascularization of renal artery stenosis. The clinical value of this prediction model should be evaluated in a prospective trial.

Inclusion of emergency department patients in early stages of sepsis in a quality improvement programme has the potential to improve survival: a prospective dual-centre study.

STUDY OBJECTIVE: Sepsis quality improvement programmes typically focus on severe sepsis (ie, with acute organ failure). However, quality of ED care might be improved if these programmes included patients whose progression to severe sepsis could still be prevented (ie, infection without acute organ failure). We compared the impact on mortality of implementing a quality improvement programme among ED patients with a suspected infection with or without acute organ failure. METHODS: This prospective observational study among ED patients hospitalised with suspected infection was conducted in two hospitals in the Netherlands. After stratification by sepsis category (with or without organ failure), in-hospital mortality was compared between a full compliance (all quality performance measures achieved) and an incomplete compliance group. Multivariable logistic regression analysis was used to quantify the impact of full compliance on in-hospital mortality, adjusting for disease severity, disposition and hospital. RESULTS: There were 1732 ED patients and 130 deaths. Full compliance was independently associated with approximately two-thirds reduction in the odds of hospital mortality (adjusted OR of 0.30 (95% CI 0.19 to 0.47), which was similar in patients with and without organ failure. Among the 1379 patients with suspected infection without acute organ failure, there were 64 deaths, 15 (1.1%) in the full compliance group and 49 (3.6%) in the incomplete compliance group (mortality difference 2.5% (95% CI 1.6% to 3.3%)). Among 353 patients with organ failure, there were 66 deaths, 12 (3.4%) in the full compliance compared with 54 (15.3%) in the incomplete compliance group (mortality difference 11.9% (95% CI 8.5% to 15.3%)). Thus, there was a difference of 76 deaths between full and incomplete compliance groups, and 34 (45%) who benefited were those without acute organ failure. CONCLUSIONS: Sepsis quality improvement programmes should incorporate ED patients in earlier stages of sepsis given the potential to reduce in-hospital mortality among this population.

Typing Pseudomonas aeruginosa Isolates with Ultrahigh Resolution MALDI-FTICR Mass Spectrometry.

The introduction of standardized matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) platforms in the medical microbiological practice has revolutionized the way microbial species identification is performed on a daily basis. To a large extent, this is due to the ease of operation. Acquired spectra are compared to profiles obtained from cultured colonies present in a reference spectra database. It is fast and reliable, and costs are low compared to previous diagnostic approaches. However, the low resolution and dynamic range of the MALDI-TOF profiles have shown limited applicability for the discrimination of different bacterial strains, as achieved with typing based on genetic markers. This is pivotal in cases where certain strains are associated with, e.g., virulence or antibiotic resistance. Ultrahigh resolution MALDI-FTICR MS allows the measurement of small proteins at isotopic resolution and can be used to analyze complex mixtures with increased dynamic range and higher precision than MALDI-TOF MS, while still generating results in a similar time frame. Here, we propose to use ultrahigh resolution 15T MALDI-Fourier transform ion cyclotron resonance (FTICR) MS to discriminate clinically relevant bacterial strains after species identification performed by MALDI-TOF MS. We used a collection of well characterized Pseudomonas aeruginosa strains, featuring distinct antibiotic resistance profiles, and isolates obtained during hospital outbreaks. Following cluster analysis based on amplification fragment length polymorphism (AFLP), these strains were grouped into three different clusters. The same clusters were obtained using protein profiles generated by MALDI-FTICR MS. Subsequent intact protein analysis by electrospray ionization (ESI)-collision-induced dissociation (CID)-FTICR MS was applied to identify protein isoforms that contribute to the separation of the different clusters, illustrating the additional advantage of this analytical platform.

Validation of a prediction model for early reconnection after cryoballoon ablation.

BACKGROUND: We previously developed an early reconnection/dormant conduction (ERC) prediction model for cryoballoon ablation to avoid a 30-min waiting period with adenosine infusion. We now aimed to validate this model based on time to isolation, number of unsuccessful cryo-applications, and nadir balloon temperature. METHODS: Consecutive atrial fibrillation patients who underwent their first cryoballoon ablation in 2018-2019 at the Leiden University Medical Center were included. Model performance at the previous and at a new optimal cutoff value was determined. RESULTS: A total of 201 patients were included (85.57% paroxysmal AF, 139 male, median age 61 years (IQR 53-69)). ERC was found in 35 of 201 included patients (17.41%) and in 41 of 774 veins (5.30%). In the present study population, the previous cutoff value of - 6.7 provided a sensitivity of 37.84% (previously 70%) and a specificity of 89.07% (previously 86%). Shifting the cutoff value to - 7.2 in both study populations resulted in a sensitivity of 72.50% and 72.97% and a specificity of 78.22% and 78.63% in data from the previous and present study respectively. Negative predictive values were 96.55% and 98.11%. Applying the model on the 101 patients of the present study with all necessary data for all veins resulted in 43 out of 101 patients (43%) not requiring a 30-min waiting period with adenosine testing. Two patients (2%) with ERC would have been missed when applying the model. CONCLUSIONS: The previously established ERC prediction model performs well, recommending its use for centers routinely using adenosine testing following PVI.

How effective is topical miconazole or amorolfine for mild to moderately severe onychomycosis in primary care: the Onycho Trial - a randomised double-blind placebo-controlled trial.

OBJECTIVES: To evaluate the efficacy of topical miconazole or amorolfine compared to placebo for mild to moderately severe onychomycosis. DESIGN: Randomised, double-blind, placebo-controlled trial, with computer-generated treatment allocation at a 1:1:1 ratio. SETTING: Primary care, recruitment from February 2020 to August 2022. PARTICIPANTS: 193 patients with suspected mild to moderately severe onychomycosis were recruited via general practices and from the general public, 111 of whom met the study criteria. The mean age of participants was 51 (SD 13.1), 51% were female and onychomycosis was moderately severe (mean OSI 12.1 (SD 8.0)). INTERVENTIONS: Once-daily miconazole 20 mg/g or once-weekly amorolfine 5% nail lacquer solution was compared with placebo (denatonium benzoate solution). MAIN OUTCOME MEASURES: Complete, clinical and mycological cure at 6 months. Secondary outcomes were clinical improvement, symptom burden, quality of life, adverse effects, compliance, patient-perceived improvement and treatment acceptability. RESULTS: Based on intention-to-treat analysis, none of the participants receiving miconazole or amorolfine reached complete cure compared with two in the placebo group (OR not estimable (n.e.), p=0.493 and OR n.e., p=0.240, respectively). There was no evidence of a significant difference between groups regarding clinical cure (OR n.e., p=0.493 and OR 0.47, 95% CI 0.04 to 5.45, p=0.615) while miconazole and amorolfine were less effective than placebo at reaching both mycological cure (OR 0.25, 95% CI 0.06 to 0.98, p=0.037 and OR 0.23, 95% CI 0.06 to 0.92, p=0.029, respectively) and clinical improvement (OR 0.26, 95% CI 0.08 to 0.91, p=0.028 and OR 0.25, 95% CI 0.07 to 0.85, p=0.021, respectively). There was no evidence of a significant difference in disease burden, quality of life, adverse reactions, compliance, patient-perceived improvement or treatment acceptability. CONCLUSIONS: Topical miconazole and amorolfine were not effective in achieving a complete, clinical or mycological cure of mild to moderately severe onychomycosis, nor did they significantly alleviate the severity or symptom burden. These treatments should, therefore, not be advised as monotherapy to treat onychomycosis. TRIAL REGISTRATION NUMBER: WHO ICTRP NL8193.

Plasma Lipidomics and Coronary Plaque Changes: A Substudy of the SMARTool Clinical Trial.

AIMS: To date, no studies have investigated the association between lipid species and coronary plaque changes over time, quantitatively assessed by serial imaging. We aimed to prospectively determine the association between lipid species quantified by plasma lipidomic analysis, with coronary plaque changes according to composition assessed by quantitative serial analysis of coronary computed tomography angiography (CTA). METHODS AND RESULTS: Patients with suspected coronary artery disease (CAD) undergoing baseline coronary CTA were prospectively enrolled by 7 EU Centers in the SMARTool study and submitted to clinical, molecular and coronary CTA re-evaluation at follow-up (interscan period 6.39 ± 1.17 years). From the 202 patients that were analysed in the SMARTool main clinical study, lipidomic analysis was performed in 154 patients before the baseline coronary CTA, and this group was included in the present study. Quantitative CTA analysis was performed by a separate core laboratory blinded from clinical data. In univariable analysis, no lipid species were significantly associated with annual total and calcified plaque changes. After adjusting for clinical variables at baseline and statin use, 3 lipid species were significantly associated with non-calcified plaque progression. In detail, cholesteryl ester (CE)(20:3), sphingomyelin (SM)(40:3) and SM(41:1) were found positively related to non-calcified plaque progression (Bonferroni adjusted P-value = 0.005, 0.016 and 0.004, respectively). CONCLUSION: The current study showed an independent relationship between specific lipid species determined by plasma lipidomic analysis, and non-calcified coronary plaque progression assessed by serial, quantitative coronary CTA analysis.

Effect of Sodium-Glucose Cotransporter 2 Inhibitors in Adults With Congenital Heart Disease.

BACKGROUND: Heart failure (HF) is the principal cause of morbidity and mortality in adults with congenital heart disease (ACHD). Robust evidence-based treatment options are lacking. OBJECTIVES: This study aims to evaluate the safety, tolerability, and short-term HF-related effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in a real-world ACHD population. METHODS: All patients with ACHD treated with SGLT2i in 4 European ACHD centers were included in this retrospective study. Data were collected from 1 year before starting SGLT2i to the most recent follow-up. Data on side effects, discontinuation, mortality, and hospitalizations were collected. RESULTS: In total, 174 patients with ACHD were treated with SGLT2i from April 2016 to July 2023. The mean age was 48.7 ± 15.3 years, 72 (41.4%) were female, and 29 (16.7%) had type 2 diabetes mellitus. Ten (5.7%) patients had mild, 75 (43.1%) moderate, and 89 (51.1%) severe congenital heart disease. HF was the most frequent starting indication (n = 162, 93.1%), followed by type 2 diabetes (n = 11, 6.3%) and chronic kidney disease (n = 1, 0.6%). At median follow-up of 7.7 months (Q1-Q3: 3.9-13.2 months), 18 patients (10.3%) reported side effects, 12 (6.9%) permanently discontinued SGLT2i, and 4 (2.3%) died of SGLT2i-unrelated causes. A significant reduction in the HF hospitalization rate was observed from 6 months before to 6 months after starting SGLT2i (relative rate = 0.30; 95% CI: 0.14-0.62; P = 0.001). CONCLUSIONS: SGLT2i generally seem safe, well-tolerated, and potentially beneficial in patients with ACHD. SGLT2i was associated with a 3-fold reduction in the 6-month HF hospitalization rate. These results warrant prospective randomized investigation of the potential benefits of SGLT2i for patients with ACHD.

External validation of the lung-molGPA to predict survival in patients treated with stereotactic radiotherapy for brain metastases of non-small cell lung cancer.

BACKGROUND: In the era of personalized medicine, individualized prognostic models with tumor characteristics are needed to inform patients about survival. Before clinical use, external validation of such models by an independent group is needed. An updated version of the graded prognostic assessment (GPA) estimates survival in patients with brain metastases (BMs) of non-small cell lung cancer (NSCLC). This is the first external validation of the updated Lung-molGPA in patients treated with stereotactic radiotherapy (SRT) for one or more BMs. MATERIALS AND METHODS: Patients treated with SRT for BMs from NSCLC adenocarcinoma were retrospectively included. GPA score was calculated for each patient based on six prognostic factors including age, Karnofsky Performance Status, number of BMs, extracranial metastases, EGFR/ALK status and PD-L1 expression. Kaplan-Meier analysis evaluated survival probability. Impact of individual prognostic factors on survival was assessed by univariate and multivariate analyses using the Cox proportional hazard model. Predictive performance was evaluated using discrimination (C-statistic) and calibration (Brier test). RESULTS: The cohort (n = 241) was divided into four prognostic groups. Overall median survival was 15 months. Predicted and observed median survival were similar between the original and validation cohorts, apart from the most favorable prognostic group. With adequate C-statistics and Brier scores, the Lung-molGPA provided accurate survival predictions. CONCLUSION: The Lung-molGPA accurately predicted survival in our European population, except for an overestimation of survival in the small most favorable prognostic group. This prognostic model was externally validated and is therefore useful for counseling of patients with BMs of NSCLC adenocarcinoma.

Detection of pancreatic cancer using serum protein profiling.

BACKGROUND: Currently, no suitable biomarkers for the early detection of pancreatic cancer (PC) are available. Proteins present in the serum could reflect a state of the disease. In this study, these profiles as a diagnostic marker for PC were evaluated. METHODS: Serum samples were obtained from PC patients (n = 50 calibration set, n = 39 validation set) and healthy volunteers (n = 110 and n = 75 respectively) according to a uniform standardized collection and processing protocol. For peptide and protein isolation, automated solid-phase extraction (SPE) with Weak Cation Exchange (WCX) magnetic beads (MB) was performed using a 96-channel liquid handling platform. Protein profiles were obtained by mass spectrometry (MS) and evaluated by linear discriminant analysis with double cross-validation. RESULTS: A discriminating profile for PC has been identified, with a sensitivity of 78% and a specificity of 89% in the calibration set with an area under the curve (AUC) of 90%. These results were validated with a sensitivity of 74% and a specificity of 91% (AUC 90%). CONCLUSION: Serum profiles of healthy controls and PC can be discrimated between. Further research is warranted to evaluate specificity and whether this biosignature can be used for early detection in a high risk population.