IntroductionRight ventricular (RV) function is of particular importance in systemic sclerosis (SSc), since common SSc complications, such as interstitial lung disease and pulmonary hypertension may... Show moreIntroductionRight ventricular (RV) function is of particular importance in systemic sclerosis (SSc), since common SSc complications, such as interstitial lung disease and pulmonary hypertension may affect RV afterload. Cardiovascular magnetic resonance (CMR) is the gold standard for measuring RV function. CMR-derived RV and right atrial (RA) strain is a promising tool to detect subtle changes in RV function, and might have incremental value, however, prognostic data is lacking. Therefore, the aim of this study was to evaluate the prognostic value of RA and RV strain in SSc. MethodsIn this retrospective study, performed at two Dutch hospitals, consecutive SSc patients who underwent CMR were included. RV longitudinal strain (LS) and RA strain were measured. Unadjusted cox proportional hazard regression analysis and likelihood ratio tests were used to evaluate the association and incremental value of strain parameters with all-cause mortality. ResultsA total of 100 patients (median age 54 [46-64] years, 42% male) were included. Twenty-four patients (24%) died during a follow-up of 3.1 [1.8-5.2] years. RA reservoir [Hazard Ratio (HR) = 0.95, 95% CI 0.91-0.99, p = 0.009] and conduit strain (HR = 0.93, 95% CI 0.88-0.98, p = 0.008) were univariable predictors of all-cause mortality, while RV LS and RA booster strain were not. RA conduit strain proved to be of incremental value to sex, atrial fibrillation, NYHA class, RA maximum volume indexed, and late gadolinium enhancement (p < 0.05 for all). ConclusionRA reservoir and conduit strain are predictors of all-cause mortality in SSc patients, whereas RV LS is not. In addition, RA conduit strain showed incremental prognostic value to all evaluated clinical and imaging parameters. Therefore, RA conduit strain may be a useful prognostic marker in SSc patients. Show less
Objective: To explore the course of vertigo attacks in patients with benign recurrent vertigo (BRV) as compared to patients with Meniere's disease (MD) and vestibular migraine (VM). Study design:... Show moreObjective: To explore the course of vertigo attacks in patients with benign recurrent vertigo (BRV) as compared to patients with Meniere's disease (MD) and vestibular migraine (VM). Study design: Prospective cohort study. Setting:Tertiary referral center. Patients: Adult patients who visited the Apeldoorn Dizziness Center between January 2015 and November 2016 and who were diagnosed with BRV, VM or MD. During 3 years participants were contacted every 6 months by telephone to complete a study-specific questionnaire. Main Outcome Measures: Vertigo attack frequency, use of medication, and Hospital Anxiety and Depression Scale (HADS). Results: The study population (n = 121) consisted of 44 patients with BRV, 34 with VM, and 43 with MD. For the total follow-up period no statistically significant differences between the three diagnosis groups were observed for being attack-free in the past 6 months: OR = 0.86 (95% CI 0.34-2.17; p = 0.745) for VM and OR = 1.06 (95% CI 0.44-2.51; p = 0.902) for MD, compared to BRV. Overall, 19 patients (43.2%) with BRV, 13 (38.2%) with VM, and 35 (81.0%) with MD used medication to prevent vertigo attacks at any point during their 3-year follow-up. Throughout the observation period patients with MD showed an average of 3.37 points (95% CI 0.68-6.07; p = 0.014) higher HADS scores relative to patients with BRV. Conclusion The course of vertigo attacks was rather favorable in the three groups, as 67-70% of the patients were free of vertigo attacks after 3 years of follow-up. The course of disease in patients with BRV was not distinctive from patients with MD and VM. We assume that BRV is a mild or incomplete variant of VM and MD, rather than a separate disease entity with distinct pathognomonic features. Show less
Stoppelenburg, A.; Arslan, M.; Owusuaa, C.; Gunnink, N.; Linden, Y.M. van der; Luelmo, S.A.C.; ... ; Heide, A. van der 2022
Objective This prospective study aimed to evaluate the performance of the 'Surprise Question' (SQ) 'Would I be surprised if this patient died in the next 12 months?' in predicting survival of 12, 6... Show moreObjective This prospective study aimed to evaluate the performance of the 'Surprise Question' (SQ) 'Would I be surprised if this patient died in the next 12 months?' in predicting survival of 12, 6, 3 and 1 month(s), respectively, in hospitalised patients with cancer. Methods In three hospitals, physicians were asked to answer SQs for 12/6/3/1 month(s) for inpatients with cancer. Sensitivity, specificity, positive and negative predictive values were calculated. Results A total of 783 patients were included, of whom 51% died in the 12-month period after inclusion. Sensitivity of the SQ predicting death within 12 months was 0.79, specificity was 0.66, the positive predictive value was 0.71 and the negative predictive value was 0.75. When the SQ concerned a shorter survival period, sensitivities and positive predictive values decreased, whereas specificities and negative predictive values increased. In multivariable logistic regression analysis, the SQ was significantly associated with mortality (OR 3.93, 95% CI 2.70-5.71, p < 0.01). Conclusions The 12-month SQ predicts death in patients with cancer admitted to the hospital reasonably well. Shortening the timeframe decreases sensitivities and increases specificities. The four surprise questions may help to identify patients for whom palliative care is indicated. Show less
Aims The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the... Show moreAims The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the severity of anatomical CAD by coronary computed tomography angiography (CCTA) and (ii) to which extent CAD explains MACE in patients with dyspnoea. Methods and results: From the international COronary CT Angiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 4425 patients (750 with dyspnoea) with suspected but without known CAD were included and prospectively followed for >= 5 years. First, the association of dyspnoea with CAD severity was assessed using logistic regression analysis. Second, the prognostic value of dyspnoea for MACE (myocardial infarction and death), and specifically, the interaction between dyspnoea and CAD severity was investigated using Cox proportional-hazard analysis. Mean patient age was 60.3 +/- 11.9 years, 63% of patients were male and 592 MACE events occurred during a median follow-up duration of 5.4 (IQR 5.1-6.0) years. On uni- and multivariable analysis (adjusting for age, sex, body mass index, chest pain typicality, and risk factors), dyspnoea was associated with two- and three-vessel/left main (LM) obstructive CAD. The presence of dyspnoea increased the risk for MACE [hazard ratio (HR) 1.57, 95% confidence interval (CI): 1.29-1.90], which was modified after adjusting for clinical predictors and CAD severity (HR 1.26, 95% CI: 1.02-1.55). Conversely, when stratified by CAD severity, dyspnoea did not provide incremental prognostic value in one-, two-, or three-vessel/LM obstructive CAD, but dyspnoea did provide incremental prognostic value in non-obstructive CAD. Conclusion: In patients with suspected CAD, dyspnoea was independently associated with severe obstructive CAD on CCTA. The severity of obstructive CAD explained the elevated MACE rates in patients presenting with dyspnoea, but in patients with non-obstructive CAD, dyspnoea portended additional risk. Show less
Chimed, S.; Bijl, P. van der; Lustosa, R.; Fortuni, F.; Montero Cabezas, J.M.; Marsan, N.A.; ... ; Bax, J.J. 2022
Aims The current definition of post ST-segment elevation myocardial infarction (STEMI) left ventricular (LV) remodelling is purely structural (LV dilatation) and does not consider LV function ... Show moreAims The current definition of post ST-segment elevation myocardial infarction (STEMI) left ventricular (LV) remodelling is purely structural (LV dilatation) and does not consider LV function (ejection fraction, EF), even though it is known to be a predictor of long-term post-STEMI outcome. This study aimed to reclassify LV remodelling after STEMI by integrating LV dilatation and function (LVEF) and to investigate the prognostic implications.Methods and results Data from an ongoing registry of STEMI patients who were treated with primary percutaneous coronary intervention (PCI) were retrospectively evaluated. Four distinct remodelling subgroups were identified: (i) no LV dilatation, no LVEF impairment,(ii) no LV dilatation but LVEF impairment, (iii) LV dilatation but no LVEF impairment, and (iv) LV dilatation and LVEF impairment. The impact of functional LV remodelling on outcomes was analysed. A total of 2346 patients were studied (mean age 60 +/- 11 years, 76% men). During a median follow-up of 76 (interquartile range 52 to 107) months, 282 (12%) died, while the composite of death and heart failure hospitalization occurred in 305 (13%) patients. Those with LV remodelling and LVEF impairment had a significantly lower survival rate (P < 0.001) and event-free survival rate (P < 0.001) compared with other functional LV remodelling groups.Conclusions Employing a functional LV post-infarct remodelling classification has the potential to improve risk stratification beyond structural LV remodelling alone. Identification of patients with the worst prognosis by using a functional LV remodelling approach may allow institution of early preventative therapies. Show less
Kalisvaart, G.M.; Grootjans, W.; Bovee, J.V.M.G.; Gelderblom, H.; Hage, J.A. van der; Sande, M.A.J. van de; ... ; Geus-Oei, L.F. de 2021
Background: Prognostic biomarkers are pivotal for adequate treatment decision making. The objective of this study was to determine the added prognostic value of quantitative [F-18]FDG-PET features... Show moreBackground: Prognostic biomarkers are pivotal for adequate treatment decision making. The objective of this study was to determine the added prognostic value of quantitative [F-18]FDG-PET features in patients with metastases from soft tissue sarcoma (STS). Methods: Patients with metastases from STS, detected by (re)staging [F-18]FDG-PET/CT at Leiden University Medical Centre, were retrospectively included. Clinical and histopathological patient characteristics and [F-18]FDG-PET features (SUVmax, SUVpeak, SUVmean, total lesion glycolysis, and metabolic tumor volume) were analyzed as prognostic factors for overall survival using a Cox proportional hazards model and Kaplan-Meier methods. Results: A total of 31 patients were included. SUVmax and SUVpeak were significantly predictive for overall survival (OS) in a univariate analysis (p = 0.004 and p = 0.006, respectively). Hazard ratios (HRs) were 1.16 per unit increase for SUVmax and 1.20 per unit for SUVpeak. SUVmax and SUVpeak remained significant predictors for overall survival after correction for the two strongest predictive clinical characteristics (number of lesions and performance status) in a multivariate analysis (p = 0.02 for both). Median SUVmax and SUVpeak were 5.7 and 4.9 g/mL, respectively. The estimated mean overall survival in patients with SUVmax > 5.7 g/mL was 14 months; otherwise, it was 39 months (p < 0.001). For patients with SUVpeak > 4.9 g/mL, the estimated mean overall survival was 18 months; otherwise, it was 33 months (p = 0.04). Conclusions: In this study, SUVmax and SUVpeak were independent prognostic factors for overall survival in patients with metastases from STS. These results warrant further investigation of metabolic imaging with [F-18]FDG-PET/CT in patients with metastatic STS. Show less
Pierre, M.; Mainguy, A.; Chatziralli, I.; Pakzad-Vaezi, K.; Ruiz-Medrano, J.; Bodaghi, B.; ... ; Touhami, S. 2021
Objective: The study aimed to determine the outcomes and prognostic factors of vitrectomy, subretinal injection of tissue-plasminogen activator and gas tamponade in macular hemorrhage (MaH) due to... Show moreObjective: The study aimed to determine the outcomes and prognostic factors of vitrectomy, subretinal injection of tissue-plasminogen activator and gas tamponade in macular hemorrhage (MaH) due to age-related macular degeneration (AMD) or retinal arterial macroaneurysm (RAM). Methods: The study design utilized a multicentric retrospective case series design of consecutive patients undergoing surgery between 2014 and 2019. Results: A total of 65 eyes from 65 patients were included in the study. Surgery was performed after a mean period of 7.1 days. Displacement of MaH was achieved in 82% of the eyes. Mean best-corrected visual acuity (BCVA) improved from 20/500 to 20/125 at month(M)1 and M6 (p < 0.05). At M6, BCVA worsening was associated with an older age at diagnosis (p = 0.0002) and higher subretinal OCT elevation of MaH (p = 0.03). The use of treat and extend (TE) (OR = 16.7, p = 0.001) and small MaH fundus size (OR = 0.64 and 0.74 for horizontal and vertical fundus size, p < 0.05) were predictive of a higher likelihood of obtaining a countable BCVA at M1. Baseline BCVA was predictive of postoperative BCVA (p < 0.05). Retinal detachment and MaH recurrence occurred in 3% and 9.3% of cases at M6. Conclusion: MaH surgery stabilizes or improves BCVA in 85% of cases. Younger age at diagnosis, better baseline BCVA figures, smaller subretinal MaH height and use of TE regime were predictive of the best postoperative outcomes. Show less
Baart, S.J.; Palen, R.L.F. van der; Putter, H.; Tsonaka, R.; Blom, N.A.; Rizopoulos, D.; Geloven, N. van 2021
BACKGROUND: Most patients with congenital heart disease survive into adulthood; however, residual abnormalities remain and management of the patients is life-long and personalized. Patients with... Show moreBACKGROUND: Most patients with congenital heart disease survive into adulthood; however, residual abnormalities remain and management of the patients is life-long and personalized. Patients with surgical repair of transposition of the great arteries, for example, face the risk to develop neoaortic valve regurgitation. Cardiologists update the prognosis of the patient intuitively with updated information of the cardiovascular status of the patient, for instance from echocardiographic imaging.METHODS: Usually a time-dependent version of the Cox model is used to analyze repeated measurements with a time-to-event outcome. New statistical methods have been developed with multiple advantages, of which the most prominent one being the joint model for longitudinal and time-to-event outcome. In this tutorial, the joint modeling framework is introduced and applied to patients with transposition of the great arteries after surgery with a long-term follow-up, where repeated echocardiographic values of the neoaortic root are evaluated against the risk of neoaortic valve regurgitation.RESULTS: The data are analyzed with the time-dependent Cox model as benchmark method, and the results are compared with a joint model, leading to different conclusions. The flexibility of the joint model is shown by adding the growth rate of the neoaortic root to the model and adding repeated values of body surface area to obtain a multimarker model. Lastly, it is demonstrated how the joint model can be used to obtain personalized dynamic predictions of the event.CONCLUSIONS: The joint model for longitudinal and time-to-event data is an attractive method to analyze data in follow-up studies with repeated measurements. Benefits of the method include using the estimated natural trajectory of the longitudinal outcome, great flexibility through multiple extensions, and dynamic individualized predictions. Show less
Intermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at... Show moreIntermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of hemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International THrOmbolysis (PEITHO)-3 study (ClinicalTrials.gov Identifier: NCT04430569) is a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up. We will compare the efficacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate-high-risk PE will also fulfill at least one clinical criterion of severity: systolic blood pressure <= 110mm Hg, respiratory rate >20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, hemodynamic decompensation, or PE recurrence within 30 days of randomization. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical benefit (primary efficacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, hemodynamic decompensation, or stroke within 30 days; dyspnea, functional limitation, or RV dysfunction at 6 months and 2 years; and utilization of health care resources within 30 days and 2 years. The study is planned to enroll 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations. Show less
OBJECTIVES This study aimed to evaluate the prevalence and prognostic value of the extent of extra-aortic valvular cardiac abnormalities in a large multicenter registry of patients with moderate AS... Show moreOBJECTIVES This study aimed to evaluate the prevalence and prognostic value of the extent of extra-aortic valvular cardiac abnormalities in a large multicenter registry of patients with moderate AS.BACKGROUND The prognostic significance of a new classification system that incorporates the extent of cardiac injury (beyond the aortic valve) has been proposed in patients with severe aortic stenosis (AS). Whether this can be applied to patients with moderate AS is unclear.METHODS Based on the echocardiographic findings at the time of diagnosis of moderate AS (aortic valve area between 1.0 and 1.5 cm(2) and dimensionless velocity index ratio of >= 0.25), a total of 1,245 patients were included and analyzed retrospectively. They were recategorized into 5 groups according to the extent of extra-aortic valvular cardiac abnormalities: none (Group 0), involving the left ventricle (Group 1), the left atrial or mitral valve (Group 2), the pulmonary artery vasculature or tricuspid valve (Group 3), or the right ventricle (Group 4). Patients were followed for all-cause mortality and combined endpoint (all-cause mortality, stroke, heart failure, or myocardial infarction).RESULTS The distribution of patients according to the proposed classification was 13.1%, 26.8%, 42.6%, 10.6%, and 6.9% in Groups 0, 1, 2, 3, and 4, respectively. During a median follow-up of 4.3 (2.4 to 6.9) years, 564 (45.3%) patients died. There was a significant higher mortality rates with increasing extent of extra-aortic valvular cardiac abnormalities (log-rank p < 0.001). On multivariable analysis, the presence of extra-aortic valvular cardiac abnormalities remained independently associated with all-cause mortality and combined outcome, adjusted for aortic valve replacement as a time-dependent covariable. In particular, Group 2 and above were independently associated with all-cause mortality.CONCLUSIONS In patients with moderate AS, the presence of extra-aortic valvular cardiac abnormalities is associated with poor outcome. (C) 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation. Show less
Yedidya, I.; Lustosa, R.P.; Fortuni, F.; Bijl, P. van der; Namazi, F.; Vo, N.M.; ... ; Delgado, V. 2021
Background: Assessment of left ventricular (LV) function in patients with secondary mitral regurgitation (SMR) remains challenging but is an important parameter for risk stratification. The... Show moreBackground: Assessment of left ventricular (LV) function in patients with secondary mitral regurgitation (SMR) remains challenging but is an important parameter for risk stratification. The association of LV myocardial work components (work index [GWI], constructive [GCW] and wasted [GWW] work, and work efficiency) derived from pressure-strain loops obtained with speckle tracking echocardiography, and all-cause mortality in patients with SMR was investigated. Methods: LV myocardial GWI, GCW, GWW, and global work efficiency were measured with speckle tracking strain echocardiography in 373 patients (72% men, median age 68 years) with various grades of SMR. All-cause mortality was the primary end point. Results: Mild SMR was observed in 143 patients, 128 had moderate SMR, and 102 had severe SMR. Patients with severe SMR had the largest LV volumes and the worst LV ejection fraction and LV global longitudinal strain. In patients with severe SMR, LV GWI and GCW were more impaired (500 mm Hg% versus 680 mm Hg% P=0.024 and 678 mm Hg% versus 851 mm Hg% P=0.006, respectively), while GWW was lower (130 mm Hg% versus 260 mm Hg% P<0.001, respectively) and global work efficiency was significantly higher (82% versus 76%, P=0.001) compared with patients with mild SMR. After a median follow-up of 56 months, 161 patients died. LV GWI <= 500 mm Hg%, LV GCW <= 750 mm Hg%, and LV GWW Conclusions: Patients with severe SMR had the worst LV GWI and LV GCW but better LV GWW and global work efficiency reflecting the unloading of the LV in the low-pressure left atrial chamber. These parameters were independently associated with worse long-term survival in patients with SMR. Show less
Aims: Major adverse event (MAE) rates during left ventricular assist device (LVAD) therapy in advanced heart failure (HF) patients are high, and impair quality of life and survival. Prediction and... Show moreAims: Major adverse event (MAE) rates during left ventricular assist device (LVAD) therapy in advanced heart failure (HF) patients are high, and impair quality of life and survival. Prediction and risk stratification of MAEs in order to improve patient selection and thereby outcome during LVAD therapy is therefore warranted. Circulating natriuretic peptides (NPs) are strong predictors of MAEs and mortality in chronic HF patients. However, whether NPs can identify patients who are at risk of MAEs and mortality or tend toward myocardial recovery after LVAD implantation is unclear. The aim of this systematic review is to analyze the prognostic value of circulating NP levels before LVAD implantation for all-cause mortality, MAEs and myocardial recovery after LVAD implantation.Methods and Results: Electronic databases were searched for studies analyzing circulating NP in adults with advanced HF before LVAD implantation in relation to mortality, MAEs, or myocardial recovery after LVAD implantation. Twenty-four studies published between 2008 and 2021 were included. Follow-up duration ranged from 48 hours to 5 years. Study sample size ranged from 14 to 15,138 patients. Natriuretic peptide levels were not predictive of all-cause mortality. However, NPs were predictive of right ventricular failure (RVF) and MAEs such as ventricular arrhythmias, moderate or severe aortic regurgitation, and all-cause rehospitalization. No relation between NPs and myocardial recovery was found.Conclusion: This systematic review found that NP levels before LVAD implantation are not predictive of all-cause mortality after LVAD implantation. Thus, NP levels may be of limited value in patient selection for LVAD therapy. However, NPs help in risk stratification of MAEs and may be used to identify patients who are at risk for RVF, ventricular arrhythmias, moderate or severe aortic regurgitation, and all-cause rehospitalization after LVAD implantation. Show less
Terhuerne, J.; Diepen, M. van; Kramann, R.; Erpenbeck, J.; Dekker, F.; Marx, N.; ... ; Schlieper, G. 2021
Background. Cardiovascular disease is the major cause of death in end-stage renal disease (ESRD). To develop better means to assess cardiovascular risk in these patients, we compared conventional... Show moreBackground. Cardiovascular disease is the major cause of death in end-stage renal disease (ESRD). To develop better means to assess cardiovascular risk in these patients, we compared conventional echocardiography-derived left ventricular ejection fraction (EF) with the novel method of 2D speckle-tracking echocardiography to determine cardiac strain.Methods. Predictive performances of conventional EF and speckle-tracking echocardiography-derived global longitudinal strain (GLS) were compared using receiver-operator curve (ROC) analyses and calibration by calibration plots. We also took into account other known cardiovascular risk factors through multivariable logistic regression analysis.Results. The study comprised 171 ESRD patients (mean age 64 years, 64% male) on maintenance dialysis therapy (93% haemodialysis, 7% peritoneal dialysis) for an average period of 39 months. During 2.1 years of follow-up, 42 patients (25%) died from cardiovascular disease. ROC analysis of GLS resulted in an area under the curve of 0.700 [95% confidence interval (CI) 0.603-0.797] compared with an area under the curve of EF of 0.615 (95% CI 0.514-0.716) (P = 0.059 for difference). The total absolute deviation between predicted and observed outcome frequencies obtained by calibration plots were 13.8% for EF compared with only 6.4% for GLS. Best results of ROC analysis (area under the curve = 0.759; P = 0.06), calibration and goodness-of-fit (chi(2) = 28.34, P <= 0.0001, R-2 = 0.25) were achieved for GLS added to a baseline model consisting of known cardiovascular risk factors in a multivariate regression analysis.Conclusions. In summary, in chronic dialysis patients, GLS is a more precise predictor of cardiovascular mortality than conventional echocardiography-derived EF. Show less
Background: Lung cancer is one kind of malignant tumor with a high risk for morbidity and mortality compared to other solid organ malignancies. Brain metastases occur in 30-55% of non-small cell... Show moreBackground: Lung cancer is one kind of malignant tumor with a high risk for morbidity and mortality compared to other solid organ malignancies. Brain metastases occur in 30-55% of non-small cell lung cancer (NSCLC) patients. Prognosis of NSCLC patients with brain metastases is very poor. Our previous study showed that cell adhesion molecule 2 (CADM2) could regulate the development of brain metastasis in NSCLC cells. Therefore, the objective of the study is to evaluate the effect of CADM2 on the prognosis of NSCLC patients with brain metastases.Methods: The expression of CADM2 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in the tissue of the primary tumor. Patients were followed up and overall survival (OS) was calculated. The relationships between CADM2 and clinicopathological features were analyzed using the chi-square test. Kaplan-Meier analysis was carried out to demonstrate the influence of CADM2 on the OS of patients. Univariate and multivariate Cox analyses were used to determine the prognosis of NSCLC patients with brain metastases.Results: A total of 139 NSCLC patients with brain metastases from the Affiliated Cancer Hospital & Institute of Guangzhou Medical University, treated between January 2015 and December 2017 were evaluated retrospectively. The expression level of CADM2 in patients ranged from 1 to 17.2677, with a median of 6.0772. Chi-square analysis showed that CADM2 gene expression level was not significantly associated with gender, age, tumor location, histological subtype, tumor T stage, extracranial metastasis, or smoking status. However, CADM2 expression was notably associated with risk for lymph node metastasis. The results of the Kaplan-Meier analysis showed that high expression [CADM2 messenger RNA (mRNA) >= 6.0772] of CADM2 was markedly associated with poor prognosis. Univariate and multivariate Cox analyses demonstrated that CADM2 was an independent risk factor for survival in NSCLC patients with brain metastases (P<0.05).Conclusions: CADM2 expression is up-regulated and closely associated with disease progression and poor prognosis in NSCLC patients with brain metastases. CADM2 expression warrants special consideration given its potential prognostic significance that might help inform clinical decision making. Show less
Schmidt, D.E.; Heitink-Polle, K.M.J.; Mertens, B.; Porcelijn, L.; Kapur, R.; Schoot, C.E. van der; ... ; Haas, M. de 2021
Background In childhood immune thrombocytopenia (ITP), an autoimmune bleeding disorder, there is a need for better prediction of individual disease courses and treatment outcomes.Objective To... Show moreBackground In childhood immune thrombocytopenia (ITP), an autoimmune bleeding disorder, there is a need for better prediction of individual disease courses and treatment outcomes.Objective To predict the response to intravenous immunoglobulins (IVIg) and ITP disease course using genetic and immune markers.Methods Children aged younger than 7 years with newly diagnosed ITP (N = 147) from the Treatment With or Without IVIG for Kids with ITP study were included, which randomized children to an IVIg or observation group. A total of 46 variables were available: clinical characteristics, targeted genotyping, lymphocyte immune phenotyping, and platelet autoantibodies.Results In the treatment arm, 48/80 children (60%) showed a complete response (platelets >= 100 x 10(9)/L) that lasted for at least 1 month (complete sustained response [CSR]) and 32 exhibited no or a temporary response (absence of a sustained response [ASR]). For a biological risk score, five variables were selected by regularized logistic regression that predicted ASR vs CSR: (1) hemoglobin; (2) platelet count; (3) genetic polymorphisms of Fc-receptor (Fc gamma R) IIc; (4) the presence of immunoglobulin G (IgG) anti-platelet antibodies; and (5) preceding vaccination. The ASR sensitivity was 0.91 (95% confidence interval, 0.80-1.00) and specificity was 0.67 (95% confidence interval, 0.53-0.80). In the 67 patients of the observation arm, this biological score was also associated with recovery during 1 year of follow-up. The addition of the biological score to a predefined clinical score further improved the discrimination of favorable ITP disease courses.Conclusions The prediction of disease courses and IVIg treatment responses in ITP is improved by using both clinical and biological stratification. Show less
Background:Patients with peripheral arterial disease (PAD) are at increased risk of cardiovascular morbidity and mortality. Medical prevention with antithrombotic and statin therapies is a mainstay... Show moreBackground:Patients with peripheral arterial disease (PAD) are at increased risk of cardiovascular morbidity and mortality. Medical prevention with antithrombotic and statin therapies is a mainstay of treatment to prevent adverse outcomes; nevertheless, patients with PAD are often undertreated. This study describes the temporal changes in medical prevention and adverse outcomes in a national cohort of patients with symptomatic PAD after revascularization.Methods:We identified all patients with a first open surgical or endovascular revascularization procedure in the lower extremities or abdomen in Denmark, from 2000 to 2016. We examined temporal changes in the use of aspirin, clopidogrel, and statins and 1-year cause-specific hazard ratios for adverse clinical outcomes, after adjusting for procedure type, treatment indication, age, sex, and cardiovascular risk factors. The analyses were performed overall and within strata of index procedure (endovascular versus surgical), treatment indication, age, sex, and high-risk comorbidities.Results:Between 2000 and 2016, we identified 32 911 patients who underwent revascularization for symptomatic PAD. The mean age was 69 years and increased over time, as did the burden of comorbidity. The cumulative incidence of medication use increased between 2000 to 2004 and 2013 to 2016, respectively, from 57.3% to 64.3% for aspirin, 3.6% to 24.8% for clopidogrel, and 36.2% to 77.1% for statins. Concurrently, the 1-year outcome rates declined. Compared with 2000 to 2004, the adjusted hazard ratios in 2013 to 2016 were 0.73 (95% CI, 0.62-0.84) for major adverse cardiovascular events, 0.92 (95% CI, 0.85-1.00) for major adverse limb events, 0.60 (95% CI, 0.48-0.74) for myocardial infarction, 0.94 (95% CI, 0.75-1.18) for ischemic stroke, 0.92 (95% CI, 0.75-1.12) for major bleeding, 0.54 (95% CI, 0.39-0.76) for cardiovascular death, and 0.80 (95% CI, 0.72-0.88) for all-cause death. These improvements in prognosis were most prominent from 2000 to 2004 to 2005 to 2008 and occurred in all strata of index procedure, treatment indication, sex, age, and comorbidity. In contrast, the adjusted hazard ratio for major amputations was 1.00 (95% CI, 0.90-1.11) when comparing 2013 to 2016 to 2000 to 2004.Conclusions:Medical prevention of adverse events has increased considerably over time in patients who underwent revascularization for symptomatic PAD. This increase was accompanied by reductions in all adverse outcomes, except major amputations. Show less
Deseive, S.; Kupke, M.; Straub, R.; Stocker, T.J.; Broersen, A.; Kitslaar, P.; ... ; Hausleiter, J. 2021
Aims Automated coronary total plaque volume (TPV) quantification derived from coronary computed tomographic angiography (CTA) datasets provide exact and reliable assessment of calcified and non... Show moreAims Automated coronary total plaque volume (TPV) quantification derived from coronary computed tomographic angiography (CTA) datasets provide exact and reliable assessment of calcified and non-calcified coronary atheroscler- osis burden. The aim of this analysis was to investigate the long-term predictive value of TPV.Methods and results TPV was quantified in 1577 patients undergoing coronary CTA and cardiovascular events were collected during 10.5 years (interquartile range 6.0-11.4) of follow-up. The study endpoint comprised cardiac death and acute cor- onary syndrome and occurred in 59 (3.7%) patients. Coronary TPV provided additive prognostic value over clinical risk assessed with the Morise Score and coronary artery disease severity (rise in C-index from 0.744 to 0.769, P=0.03). A category-based reclassification approach combining the Morise Score and TPV revealed superior risk stratification (categorical net reclassification improvement: 0.48 with 95% CI 0.13-0.68, P< 0.001) and resulted in reclassification of 800 (51%) patients compared with the Morise Score alone. The 10-year risk for the study endpoint was 0.6% (95% CI 0-1.3) for patients classified as low risk (n = 807), 4.8% (95% CI 2.4-7.2) for patients at intermediate risk (n = 400), and 10.3% (95% CI 6.6-13.9) for patients at high risk (n = 370) using the combined reclassification approach.Conclusion Quantification of TPV from coronary CTA permits an improved 10-year cardiovascular risk stratification. Show less
Hanna Sawires, R.G.; Schiphuis, J.H.; Wuhrer, M.; Vasen, H.F.A.; Leerdam, M.E. van; Bonsing, B.A.; ... ; Tollenaar, R.A.E.M. 2021
Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo... Show morePancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival. It is furthermore foreseen that precision medicine will provide improved prognostic stratification and prediction of therapeutic response. In this review, omics-based discovery efforts are presented that aim for novel diagnostic and prognostic biomarkers of PDAC. For this purpose, we systematically evaluated the literature published between 1999 and 2020 with a focus on protein- and protein-glycosylation biomarkers in pancreatic cancer patients. Besides genomic and transcriptomic approaches, mass spectrometry (MS)-based proteomics and glycomics of blood- and tissue-derived samples from PDAC patients have yielded new candidates with biomarker potential. However, for reasons discussed in this review, the validation and clinical translation of these candidate markers has not been successful. Consequently, there has been a change of mindset from initial efforts to identify new unimarkers into the current hypothesis that a combination of biomarkers better suits a diagnostic or prognostic panel. With continuing development of current research methods and available techniques combined with careful study designs, new biomarkers could contribute to improved detection, prognosis, and prediction of pancreatic cancer. Show less
Background: The impact of precision psychiatry for clinical practice has not been systematically appraised. This study aims to provide a comprehensive review of validated prediction models to... Show moreBackground: The impact of precision psychiatry for clinical practice has not been systematically appraised. This study aims to provide a comprehensive review of validated prediction models to estimate the individual risk of being affected with a condition (diagnostic), developing outcomes (prognostic), or responding to treatments (predictive) in mental disorders. Methods: PRISMA/RIGHT/ CHARMS-compliant systematic review of the Web of Science, Cochrane Central Register of Reviews, and Ovid/PsycINFO databases from inception until July 21, 2019 (PROSPERO CRD42019155713) to identify diagnostic/prognostic/predictive prediction studies that reported individualized estimates in psychiatry and that were internally or externally validated or implemented. Random effect meta-regression analyses addressed the impact of several factors on the accuracy of prediction models. Findings: Literature search identified 584 prediction modeling studies, of which 89 were included. 10.4% of the total studies included prediction models internally validated (n = 61), 4.6% models externally validated (n = 27), and 0.2% (n = 1) models considered for implementation. Across validated prediction modeling studies (n = 88), 18.2% were diagnostic, 68.2% prognostic, and 13.6% predictive. The most frequently investigated condition was psychosis (36.4%), and the most frequently employed predictors clinical (69.5%). Unimodal compared to multimodal models (beta = .29, P = .03) and diagnostic compared to prognostic (beta = .84, p < .0001) and predictive (beta = .87, P = .002) models were associated with increased accuracy. Interpretation: To date, several validated prediction models arc available to support the diagnosis and prognosis of psychiatric conditions, in particular, psychosis, or to predict treatment response. Advancements of knowledge are limited by the lack of implementation research in real-world clinical practice. A new generation of implementation research is required to address this translational gap. Show less
Strijker, M.; Veldhuisen, E. van; Geest, L.G. van der; Busch, O.R.; Bijlsma, M.F.; Mohammad, N.H.; ... ; Dutch Pancreatic Canc Grp 2021
BackgroundIdentification of metastatic pancreatic cancer (mPC) patients with the worst prognosis could help to tailor therapy. We evaluated readily available biomarkers for the prediction of 90-day... Show moreBackgroundIdentification of metastatic pancreatic cancer (mPC) patients with the worst prognosis could help to tailor therapy. We evaluated readily available biomarkers for the prediction of 90-day mortality in a nationwide cohort of mPC patients.MethodsPatients with synchronous mPC were included from the Netherlands Cancer Registry (2015-2017). Baseline CA19-9, albumin, CRP, LDH, CRP/albumin ratio, and (modified) Glasgow Prognostic Score ((m)GPS composed of albumin and CRP) were evaluated. Multivariable logistic regression analyses were performed to identify predictors of 90-day mortality. Prognostic value per predictor was quantified by Nagelkerke's partial R-2.ResultsOverall, 4248 patients were included. Median overall survival was 2.2 months and 90-day mortality was 59.4% (n = 1629). All biomarkers predicted 90-day mortality in univariable analysis, and remained statistically significant after adjustment for clinically relevant factors and all other biomarkers (all p < 0.001). The prognostic value of the biomarkers combined was similar to WHO performance status. Patients who received chemotherapy had better outcomes than those who did not, regardless of biomarker levels.ConclusionsIn mPC patients, albumin, CA19-9, CRP, LDH, CRP/albumin ratio, and (m)GPS are prognostic for poor survival. Biomarkers did not predict response to chemotherapy. These readily available biomarkers can be used to better inform patients and to stratify in clinical trials. Show less
