OBJECTIVES: This study evaluated the prognostic value of staging right heart failure in patients with significant tricuspid regurgitation (TR) undergoing tricuspid valve (TV) surgery.METHODS:... Show moreOBJECTIVES: This study evaluated the prognostic value of staging right heart failure in patients with significant tricuspid regurgitation (TR) undergoing tricuspid valve (TV) surgery.METHODS: Patients with significant TR who underwent TV surgery were divided into 4 right heart failure stages according to the presence of right ventricular (RV) dysfunction and clinical signs of right heart failure: stage 1 was defined as no RV dysfunction and no signs of right heart failure; stage 2 indicated RV dysfunction without signs of right heart failure; stage 3 included RV dysfunction and signs of right heart failure; and stage 4 was defined as RV dysfunction and refractory signs of right heart failure at rest.RESULTS: A total of 278 patients [mean age 64 (12), 49% males] were included, of whom 34 (12%) patients were classified as stages 1 and 2, 141 (51%) as stage 3 and 103 (37%) as stage 4 right heart failure. The majority of patients (91%) had TV surgery concomitant to left-sided valve surgery or coronary artery bypass grafting and 95% underwent TV annuloplasty. Cumulative survival rates were 89%, 78% and 61% at 1 month, 1 year and 5 years, respectively. Stages 1 and 2 and stage 3 were independently associated with better survival compared to stage 4 (hazard ratio: 0.391 [95% confidence interval: 0.186-0.823] and 0.548 [95% confidence interval: 0.369-0.813], respectively).CONCLUSIONS: Patients with significant TR undergoing TV surgery and diagnosed without advanced right heart failure have better survival as compared to patients with right heart failure. Show less
Boennelycke, M.; Peters, E.E.M.; Leon-Castillo, A.; Smit, V.T.H.B.M.; Bosse, T.; Christensen, I.J.; ... ; Hogdall, E. 2021
The aim of this study was to investigate the outcome of histological subtype review of high-grade endometrial carcinoma (EC) and its prognostic impact in a large well-documented Danish nationwide... Show moreThe aim of this study was to investigate the outcome of histological subtype review of high-grade endometrial carcinoma (EC) and its prognostic impact in a large well-documented Danish nationwide cohort. From the Danish Gynecological Cancer Database (DGCD) 2005-2012 cohort, we included 425 patients with an original diagnosis of high-grade EC, independent of histologic subtype. Of these, at least one hematoxylin and eosin (H&E)-stained slide from 396 cases (93.2%) was available for review. The histologic subtype was reviewed by specialized gynecopathologists blinded to the original diagnosis and clinical outcome. Interobserver variability between original and revised histologic subtypes was analyzed using simple Kappa statistics. Hazard ratios (HR), recurrence-free survival (RFS), and overall survival were calculated for original and revised subtypes, respectively. Overall histologic subtype agreement was moderate (kappa = 0.42) with the highest agreement for endometrioid-type EC (EEC; 75.5%) and serous-type EC (SEC; 63.8%). For clear cell carcinoma and un-/dedifferentiated EC, agreement was significantly lower: 30.1% and 33.3% respectively. Of the 396 reviewed cases, only two (0.5%) were re-classified as low-grade EEC upon revision. Interestingly, GR3 EEC had better RFS than SEC with stronger significance after revision (HR 2.36 (95% CI 1.43-3.89), p = 0.001), compared to original diagnosis (HR 1.74 (95% CI 1.07-2.81), p = 0.024). In conclusion, this study confirmed that pathology review results in substantial shift in histological subtype in high-grade EC. After review, a stronger prognostic benefit for GR3 EEC as compared to other histological subtypes was observed. This work supports maintaining a low threshold for pathology revision of high-grade EC in clinical practice. Show less
Shaw, L.J.; Blankstein, R.; Bax, J.J.; Ferencik, M.; Bittencourt, M.S.; Min, J.K.; ... ; Narula, J. 2021
Coronary computed tomographic angiography (CCTA) provides a wealth of clinically meaningful information beyond anatomic stenosis alone, including the presence or absence of nonobstructive... Show moreCoronary computed tomographic angiography (CCTA) provides a wealth of clinically meaningful information beyond anatomic stenosis alone, including the presence or absence of nonobstructive atherosclerosis and high-risk plaque features as precursors for incident coronary events. There is, however, no uniform agreement on how to identify and quantify these features or their use in evidence-based clinical decision-making. This statement from the Society of Cardiovascular Computed Tomography and North American Society of Cardiovascular Imaging addresses this gap and provides a comprehensive review of the available evidence on imaging of coronary atherosclerosis. In this statement, we provide standardized definitions for high-risk plaque (HRP) features and distill the evidence on the effectiveness of risk stratification into usable practice points. This statement outlines how this information should be communicated to referring physicians and patients by identifying critical elements to include in a structured CCTA report - the presence and severity of atherosclerotic plaque (descriptive statements, CAD-RADS (TM) categories), the segment involvement score, HRP features (e.g., low attenuation plaque, positive remodeling), and the coronary artery calcium score (when performed). Rigorous documentation of atherosclerosis on CCTA provides a vital opportunity to make recommendations for preventive care and to initiate and guide an effective care strategy for at-risk patients. (C) 2020 Published by Elsevier Inc. on behalf of Society of Cardiovascular Computed Tomography. Show less
This thesis comprises immunophenotypic and molecular studies in several types of cutaneous lymphomas. These studies provide a better definition of the clinicopathologic entities and provide... Show moreThis thesis comprises immunophenotypic and molecular studies in several types of cutaneous lymphomas. These studies provide a better definition of the clinicopathologic entities and provide adjunctive diagnostic markers that may aid in diagnosis of these patients in routine diagnostics, including TOX expression in cutaneous T-cell lymphomas and MYC expression and MYC rearrangements in cutaneous B-cell lymphomas (CBCLs). Also, the results demonstrate that adverse prognostic factors in systemic lymphomas are not directly transferrable to cutaneous lymphoma patients, including TP63 rearrangements in primary cutaneous CD30+ lymphoproliferative disorders and double hit status in CBCL, underlining the importance of a separate classification system for cutaneous lymphomas. Finally, these studies may have consequences for the management and treatment of patients with cutaneous lymphomas, because of the identification of recurrent molecular alterations that could provide attractive targets for novel therapeutics, including MYD88 and CD79B mutations in patients with intravascular large B-cell lymphomas. Show less
Abou, R.; Goedemans, L.; Bijl, P. van der; Fortuni, F.; Prihadi, E.A.; Mertens, B.; ... ; Delgado, V. 2020
Background: Left ventricular (LV) mechanical dispersion (LVMD), measured with speckle-tracking echocardiography (STE) after ST-segment elevationmyocardial infarction (STEMI), has been proposed as a... Show moreBackground: Left ventricular (LV) mechanical dispersion (LVMD), measured with speckle-tracking echocardiography (STE) after ST-segment elevationmyocardial infarction (STEMI), has been proposed as a measurement of regional heterogeneity of myocardial contraction and may reflect changes in the myocardial structure (e.g., fibrosis or edema). Further insight into this parameter may aid in the risk stratification of STEMI patients.Methods: A total of 1,000 STEMI patients (77% male, 60 +/- 12 years) treated with primary percutaneous coronary intervention were retrospectively analyzed. The LVMD was assessed with two-dimensional STE within 48 hours following the index infarction. Patients were followed for the occurrence of all-cause mortality.Results: After a median follow-up of 117 months, 229 (23%) patients died. Nonsurvivors showed worse LV ejection fraction (43% +/- 10% vs 48% +/- 9%; P <.001) and global longitudinal strain (-12.0% +/- 3.5% vs -14.2% +/- 3.5%; P =.001) and prolonged LVMD (63 [interquartile range, 50-85] msec vs 52 [interquartile range, 42-63] msec; P <.001) compared with survivors. Increasing age, systolic blood pressure, and heart rate at discharge as well as diabetes mellitus, anterior STEMI, TIMI flow < 2, less usage of angiotensin converter enzyme inhibitors or angiotensin receptor blockers, and impaired LV global longitudinal strain were independently associated with more prolonged LVMD. On multivariable analysis, prolonged LVMD was independently associated with increased risk of all-cause mortality (hazard ratio = 1.012; 95% CI, 1.005-1.018; P =.001) and had incremental value for all-cause mortality over clinical and echocardiographic parameters.Conclusions: In contemporary STEMI patients, prolonged LVMD was associated with various clinical and echocardiographic parameters. Prolonged LVMD was associated with worse long-term outcome. Show less
Introduction: Optimized treatment of primary rectal cancer might have influenced treatment characteristics and outcome of locally recurrent rectal cancer (LRRC). Subgroup analysis of the Dutch TME... Show moreIntroduction: Optimized treatment of primary rectal cancer might have influenced treatment characteristics and outcome of locally recurrent rectal cancer (LRRC). Subgroup analysis of the Dutch TME trial showed that preoperative radiotherapy (PRT) for the primary tumour was an independent poor prognostic factor after diagnosis of LRRC. This cross-sectional population study aimed to evaluate treatment and overall survival (OS) of LRRC patients, stratified for prior preoperative radiotherapy (PRT) and intention of treatment of LRRC.Methods: All patients developing LRRC were selected from a collaborative Snapshot study on 2095 surgically treated rectal cancer patients from 71 Dutch hospitals in the year 2011. Cox proportional hazard analysis was performed to determine predictors for OS.Results: A total of 107 LRRC patients (5.1%) were included, of whom 88 (82%) underwent PRT for their primary tumour. LRRC was treated with initial curative intent in 31 patients (29%), with eventual resection in 20 patients (19%). Median OS was 22 and 8 months after curative and palliative intent treatment, respectively (p < 0.001). Initial CRM positivity and palliative intent treatment were associated with worse OS after LRRC, while prior PRT was not.Conclusions: This cross-sectional study revealed that rectal cancer patients, who underwent curative resection in the Netherlands in 2011 and subsequently developed local recurrence, were amenable for again curative intent treatment in 29%, with a corresponding median survival of 22 months. Prior PRT was not significantly associated with survival after diagnosis of LRRC. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Wynants, L.; Smeden, M. van; McLernon, D.J.; Timmerman, D.; Steyerberg, E.W.; Calster, B. van; Topic Grp Evaluating Diagnosti 2019
Background: Right ventricular (RV) systolic function in patients admitted with ST-segment elevation myocardial infarction (STEMI) with chronic obstructive pulmonary disease (COPD) and its impact on... Show moreBackground: Right ventricular (RV) systolic function in patients admitted with ST-segment elevation myocardial infarction (STEMI) with chronic obstructive pulmonary disease (COPD) and its impact on prognosis have not been characterized. The present study aims to compare the prevalence of RV systolic dysfunction in COPD versus non-COPD patients with STEMI and evaluate the prognostic implications.Methods: One hundred seventeen STEMI patients with COPD with transthoracic echocardiography performed within 48 hours of admission were retrospectively selected. Matched on age, gender, and infarct size (determined by cardiac biomarkers and left ventricular ejection fraction [LVEF]), 207 non-COPD patients were selected. RV dysfunction was defined based on tricuspid annular plane systolic excursion <17 mm (TAPSE), tricuspid annular systolic velocity <6 cm/s (S'), RV fractional area change <35% (FAC), and RV longitudinal free wall strain (FWSL) measured with speckle-tracking echocardiography >-20%. Patients were followed for the occurrence of all-cause mortality.Results: RV assessment was feasible in 112 COPD and 199 non-COPD patients (mean age, 69 +/- 10; 74% male; mean, LVEF 47% +/- 8%). Patients with COPD had significantly lower RV FAC (38% +/- 11% vs 40% +/- 9%; P = .04), equal TAPSE and S' (17.9 +/- 3.7 vs 18.1 +/- 3.8 mm, P = .72; and 8.4 +/- 2.2 vs 8.5 +/- 2.2 cm/sec, P = .605, respectively) and more impaired RV FWSL (-21.1% +/- 6.6% vs -23.4% +/- 6.5%, P = .005), compared with patients without COPD. RV dysfunction was more prevalent in patients with COPD, particularly when assessed with RV FWSL (46% vs 32%; P = .021). During a median followup of 30 (interquartile range 1.5-44) months, 49 patients died (16%). Multivariate models stratified for COPD status showed that RV FWS >-20% was independently associated with 5-year all-cause mortality (hazard ratio, 2.05; 95% CI, 1.12-3.76; P = .020), after adjusting for age, diabetes, peak troponin level, and LVEF. Interestingly, RV FAC < 35%, S'< 6 cm/sec, and TAPSE < 17 mm were not independently associated with survival.Conclusion: In a STEMI population with relatively preserved LVEF, COPD patients had significantly worse RV FWSL compared with patients without COPD. Moreover, RV FWSL > -20% was independently associated with worse survival. In contrast, conventional parameters were not associated with survival. Show less
Objective. There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS)... Show moreObjective. There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT.Methods. We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3-4 NACT cycles and >6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS).Results. 877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5-65) and 28 months (IQR 7-92) respectively. CRS3 was seen in 249 patients (28%). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0.55 (95% CI, 0.45-0.66; P < 0.001) and 0.65 (95% CI 0.50-0.85, P = 0.002) respectively; no heterogeneity was identified (PFS: Q = 6.42, P = 0.698, I2 = 0.0%; OS: Q = 6.89, P = 0 648, I2 = 0.0%). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0.027).Conclusions. CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design. (C) 2019 The Authors. Published by Elsevier Inc. Show less
Ventricular-arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent... Show moreVentricular-arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent diagnostic and prognostic value and may be used to refine riskstratification and monitor therapeutic interventions. Traditionally, VAC is assessed by the non-invasive measurement of the ratio of arterial (Ea) to ventricular end-systolic elastance (Ees). With disease progression, both Ea and Ees may become abnormal and the Ea/Ees ratio may approximate its normal values. Therefore, the measurement of each component of this ratio or of novel more sensitive markers of myocardial (e.g. global longitudinal strain) and arterial function (e.g. pulse wave velocity) may better characterize VAC. In valvular heart disease, systemic arterial compliance and valvulo-arterial impedance have an established diagnostic and prognostic value and may monitor the effects of valve replacement on vascular and cardiac function. Treatment guided to improve VAC through improvement of both or each one of its components may delay incidence of heart failure and possibly improve prognosis in heart failure. In this consensus document, we describe the pathophysiology, the methods of assessment as well as the clinical implications of VAC in cardiac diseases and heart failure. Finally, we focus on interventions that may improve VAC and thus modify prognosis. Show less
Background: To investigate the incremental prognostic value of low-attenuation plaque volume (LAPV) from coronary CT angiography datasets.Methods: Quantification of LAPV was performed using... Show moreBackground: To investigate the incremental prognostic value of low-attenuation plaque volume (LAPV) from coronary CT angiography datasets.Methods: Quantification of LAPV was performed using dedicated software equipped with an adaptive plaque tissue algorithm in 1577 patients with suspected CAD. A combination of death and acute coronary syndrome was defined as primary endpoint. To assess the incremental prognostic value of LAPV, parameters were added to a baseline model including clinical risk and obstructive coronary artery disease (CAD), a baseline model including clinical risk and calcium scoring (CACS) and a baseline model including clinical risk and segment involvement score (SIS).Results: Patients were followed for 5.5 years either by telephone contact, mail or clinical visits. The primary endpoint occurred in 30 patients. Quantified LAPV provided incremental prognostic information beyond clinical risk and obstructive CAD (c-index 0.701 vs. 0.767, p<.001), clinical risk and CACS (c-index 0.722 vs. 0.771, p<.01) and clinical risk and SIS (c-index 0.735 vs. 0.771, p<.01. A combined approach using quantified LAPV and clinical risk significantly improved the stratification of patients into different risk categories compared to clinical risk alone (categorical net reclassification index 0.69 with 95% CI 0.27 and 0.96, p<.001). The combined approach classified 846 (53.6%) patients as low risk (annual event rate 0.04%), 439 (27.8%) patients as intermediate risk (annual event rate 0.5%) and 292 (18.5%) patients as high risk (annual event rate 0.99%).Conclusion: Quantification of LAPV provides incremental prognostic information beyond established CT risk patterns and permits improved stratification of patients into different risk categories. Show less
