Background Current risk stratification models for early invasive (T1) colorectal cancer are not able to discriminate accurately between prognostic favourable and unfavourable tumours, resulting in... Show moreBackground Current risk stratification models for early invasive (T1) colorectal cancer are not able to discriminate accurately between prognostic favourable and unfavourable tumours, resulting in over-treatment of a large (>80%) proportion of T1 colorectal cancer patients. The tumour-stroma ratio (TSR), which is a measure for the relative amount of desmoplastic tumour stroma, is reported to be a strong independent prognostic factor in advanced-stage colorectal cancer, with a high stromal content being associated with worse prognosis and survival. We aimed to investigate whether the TSR predicts clinical outcome in patients with non-pedunculated T1 colorectal cancer.Methods Haematoxylin and eosin (H&E)-stained tumour tissue slides from a retrospective multicentre case cohort of patients with nonpedunculated surgically treated T1 colorectal cancer were assessed for TSR by two independent observers who were blinded for clinical outcomes. The primary end point was adverse outcome, which was defined as the presence of lymph node metastasis in the resection specimen or colorectal cancer recurrence during follow-up.Results All 261 patients in the case cohort had H&E slides available for TSR scoring. Of these, 183 were scored as stroma-low, and 78 were scored as stroma-high. There was moderate inter-observer agreement kappa = 0.42). In total, 41 patients had lymph node metastasis, 17 patients had recurrent cancer and five had both. Stroma-high tumours were not associated with an increased risk for an adverse outcome (adjusted hazard ratio = 0.66, 95% confidence interval 0.37-1.18; p = 0.163).Conclusions Our study emphasises that existing prognosticators may not be simply extrapolated to T1 colorectal cancers, even though their prognostic value has been widely validated in more advanced-stage tumours. Show less
Acute pulmonary embolism (PE) is not only a serious and potentially life-threatening disease in the acute phase, in recent years it has become evident that it may also have a major impact on a... Show moreAcute pulmonary embolism (PE) is not only a serious and potentially life-threatening disease in the acute phase, in recent years it has become evident that it may also have a major impact on a patient's daily life in the long run. Persistent dyspnea and impaired functional status are common, occurring in up to 50% of PE survivors, and have been termed the post-PE syndrome (PPES). Chronic thromboembolic pulmonary hypertension is the most feared cause of post-PE dyspnea. When pulmonary hypertension is ruled out, cardiopulmonary exercise testing can play a central role in investigating the potential causes of persistent symptoms, including chronic thromboembolic pulmonary disease or other cardiopulmonary conditions. Alternatively, it is important to realize that post-PE cardiac impairment or post-PE functional limitations, including deconditioning, are present in a large proportion of patients. Health-related quality of life is strongly influenced by PPES, which emphasizes the importance of persistent limitations after an episode of acute PE. In this review, physiological determinants and the diagnostic management of persistent dyspnea after acute PE are elucidated. Show less
Evenhuis, R.E.; Acem, I.; Rueten-Budde, A.J.; Karis, D.S.A.; Fiocco, M.; Dorleijn, D.M.J.; ... ; Sande, M.A.J. van de 2021
Simple SummaryAge is one of many prognostic factors for overall survival in patients with skeletal osteosarcoma. This retrospective study provides an overview of survival in patients with high... Show moreSimple SummaryAge is one of many prognostic factors for overall survival in patients with skeletal osteosarcoma. This retrospective study provides an overview of survival in patients with high-grade osteosarcoma in different age groups. It shows prognostic variables for survival and local control among the overall cohort. In this study, in which 402 patients with skeletal high-grade osteosarcoma were included, poor survival was associated with increasing age. Age groups, tumor size, poor histopathological response, distant metastasis at presentation, and local recurrence were independent prognostic factors associated to overall survival and event-free survival. Differences in outcome among different age groups can be partially explained by patient characteristics and treatment characteristics.Age is a known prognostic factor for many sarcoma subtypes, however in the literature there are limited data on the different risk profiles of different age groups for osteosarcoma survival. This study aims to provide an overview of survival in patients with high-grade osteosarcoma in different age groups and prognostic variables for survival and local control among the entire cohort. In this single center retrospective cohort study, 402 patients with skeletal high-grade osteosarcoma were diagnosed and treated with curative intent between 1978 and 2017 at the Leiden University Medical Center (LUMC). Prognostic factors for survival were analyzed using a Cox proportional hazard model. In this study poor overall survival (OS) and event-free survival (EFS) were associated with increasing age. Age groups, tumor size, poor histopathological response, distant metastasis (DM) at presentation and local recurrence (LR) were important independent prognostic factors influencing OS and EFS. Differences in outcome among different age groups can be partially explained by patient and treatment characteristics. Show less
BackgroundMalignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with dismal prognosis. Pathological and genetic markers may predict more aggressive behavior in... Show moreBackgroundMalignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with dismal prognosis. Pathological and genetic markers may predict more aggressive behavior in MPNSTs but have uncommonly been investigated, and few are used in daily practice. This study reviews the prognostic value of immunohistochemical markers and genetic alterations in MPNST.MethodsA systematic search was performed in PubMed and Embase databases according to the PRISMA guidelines. Search terms related to 'MPNST' and 'prognostic' were used. Studies investigating the association of immunohistochemical markers or genetic alterations with prognosis were included. Qualitative synthesis was performed on all studies. A distinction was made between univariable and multivariable associations.ResultsForty-six studies were included after full-text screening. Sixty-seven different immunohistochemical markers were investigated. Absence of S100 and H3K27me3 and high Ki67 and p53 staining was most commonly independently associated with worse survival and disease-free survival. Several genetic alterations were investigated as well with varying association to survival. TP53, CDK4, RASSF1A alterations were independently associated with worse survival, as well as changes in chromosomal length in Xp, 10q, and 16p.ConclusionsMPNSTs harbor complex and heterogeneous biology. Immunohistochemical markers and genetic alterations have variable prognostic value. Absence of S100 and H3K27me3 and increased Ki67 can be of prognostic value. Alterations in TP53 or increase in p53 staining may distinguish MPNSTs with worse outcomes. Genetic alterations and staining of other cell cycle regulatory and Ras pathway proteins may also help stratifying patients with worse outcomes. A combination of markers can increase the prognostic value. Show less
Chronic thromboembolic pulmonary hypertension (CTEPH) is considered a long-term complication of acute pulmonary embolism (PE). Diagnosing CTEPH is challenging, as demonstrated by a considerable... Show moreChronic thromboembolic pulmonary hypertension (CTEPH) is considered a long-term complication of acute pulmonary embolism (PE). Diagnosing CTEPH is challenging, as demonstrated by a considerable diagnostic delay exceeding 1 year, which has a negative impact on the patient's prognosis. Dedicated screening CTEPH strategies in PE survivors could potentially help diagnosing CTEPH earlier, although the optimal strategy is unknown. Recently published updated principles for screening in medicine outline the conditions that must be considered before implementation of a population-based screening program. Following these extensive principles, we discuss the pros and cons of CTEPH screening, touching on the epidemiology of CTEPH, the prognosis of CTEPH in the perspective of emerging treatment possibilities, and potentially useful tests and test combinations for screening. This review provides a modern perspective on CTEPH screening including a novel approach using a simple noninvasive algorithm of sequential diagnostic tests applied to all PE survivors. Show less
Dijkland, S.A.; Helmrich, I.R.A.R.; Nieboer, D.; Jagt, M. van der; Dippel, D.W.J.; Menon, D.K.; ... ; CENTER-TBI Participants Investig 2020
The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict... Show moreThe International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict functional outcome after moderate and severe traumatic brain injury (TBI). We aimed to assess their performance in a contemporary cohort of patients across Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective, observational cohort study in patients presenting with TBI and an indication for brain computed tomography. The CENTER-TBI core cohort consists of 4509 TBI patients available for analyses from 59 centers in 18 countries across Europe and Israel. The IMPACT validation cohort included 1173 patients with GCS <= 12, age >= 14, and 6-month Glasgow Outcome Scale-Extended (GOSE) available. The CRASH validation cohort contained 1742 patients with GCS <= 14, age >= 16, and 14-day mortality or 6-month GOSE available. Performance of the three IMPACT and two CRASH model variants was assessed with discrimination (area under the receiver operating characteristic curve; AUC) and calibration (comparison of observed vs. predicted outcome rates). For IMPACT, model discrimination was good, with AUCs ranging between 0.77 and 0.85 in 1173 patients and between 0.80 and 0.88 in the broader CRASH selection (n = 1742). For CRASH, AUCs ranged between 0.82 and 0.88 in 1742 patients and between 0.66 and 0.80 in the stricter IMPACT selection (n = 1173). Calibration of the IMPACT and CRASH models was generally moderate, with calibration-in-the-large and calibration slopes ranging between -2.02 and 0.61 and between 0.48 and 1.39, respectively. The IMPACT and CRASH models adequately identify patients at high risk for mortality or unfavorable outcome, which supports their use in research settings and for benchmarking in the context of quality-of-care assessment. Show less
Schmidt, D.E.; Edslev, P.W.; Heitink-Polle, K.M.J.; Mertens, B.; Bruin, M.C.A.; Kapur, R.; ... ; Haas, M. de 2020
Background Childhood immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The prognosis (transient, persistent, or chronic ITP) remains difficult to predict. The morbidity is most... Show moreBackground Childhood immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The prognosis (transient, persistent, or chronic ITP) remains difficult to predict. The morbidity is most pronounced in children with persistent and chronic ITP. Clinical characteristics are associated with ITP outcomes, but there are no validated multivariate prediction models.Objective Development and external validatation of the Childhood ITP Recovery Score to predict transient versus persistent ITP in children with newly diagnosed ITP.Methods Patients with a diagnosis platelet count <= 20 x 10(9)/L and age below 16 years were included from two prospective multicenter studies (NOPHO ITP study, N = 377 [development cohort]; TIKI trial, N = 194 [external validation]). The primary outcome was transient ITP (complete recovery with platelets >= 100 x 10(9)/L 3 months after diagnosis) versus persistent ITP. Age, sex, mucosal bleeding, preceding infection/vaccination, insidious onset, and diagnosis platelet count were used as predictors.Results In external validation, the score predicted transient versus persistent ITP at 3 months follow-up with an area under the receiver operating characteristic curve of 0.71. In patients predicted to have a high chance of recovery, we observed 85%, 90%, and 95% recovered 3, 6, and 12 months after the diagnosis. For patients predicted to have a low chance of recovery, this was 32%, 46%, and 71%. The score also predicted cessation of bleeding symptoms and the response to intravenous immunoglobulins (IVIg).Conclusion The Childhood ITP Recovery Score predicts prognosis and may be useful to individualize clinical management. In future research, the additional predictive value of biomarkers can be compared to this score. A risk calculator is available (). Show less
Abou, R.; Prihadi, E.A.; Goedemans, L.; Geest, R. van der; Mahdiui, M. el; Schalij, M.J.; ... ; Delgado, V. 2020
Aims Left ventricular (LV) mechanical dispersion (MD) may result from heterogeneous electrical conduction and is associated with adverse events. The present study investigated (i) the association... Show moreAims Left ventricular (LV) mechanical dispersion (MD) may result from heterogeneous electrical conduction and is associated with adverse events. The present study investigated (i) the association between LV MD and the extent of LV scar as assessed with contrast-enhanced cardiac magnetic resonance (CMR) and (ii) the prognostic implications of LV MD in patients after ST-segment elevation myocardial infarction.Methods and results LV MD was calculated by echocardiography and myocardial scar was analysed on CMR data retrospectively. Infarct core and border zone were defined as >50% and 35-50% of maximal signal intensity, respectively. Patients were followed for the occurrence of the combined endpoint (all-cause mortality and appropriate implantable cardioverter-defibrillator therapy). In total, 96 patients (87% male, 57 +/- 10 years) were included. Median LV MD was 53.5 ms [interquartile range (IQR) 43.4-62.8]. On CMR, total scar burden was 11.4% (IQR 3.8-17.1%), infarct core tissue 6.2% (IQR 2.0-12.7%), and border zone was 3.5% (IQR 1.5-5.7%). Correlations were observed between LV MD and infarct core (r= 0.517, P < 0.001), total scar burden (r= 0.497, P < 0.001), and border zone (r=0.298, P=0.003). In total, 14 patients (15%) reached the combined endpoint. Patients with LV MD >53.5 ms showed higher event rates as compared to their counterparts. Finally, LV MD showed the highest area under the curve for the prediction of the combined endpoint.Conclusion LV MD is correlated with LV scar burden. In addition, patients with prolonged LV MD showed higher event rates. Finally, LV MD provided the highest predictive value for the combined endpoint when compared with other parameters. Show less
Vollema, E.M.; Amanullah, M.R.; Prihadi, E.A.; Ng, A.C.T.; Bijl, P. van der; Sin, Y.K.; ... ; Bax, J.J. 2020
Aims Cardiac damage in severe aortic stenosis (AS) can be classified according to a recently proposed staging classification. The present study investigated the incremental prognostic value of left... Show moreAims Cardiac damage in severe aortic stenosis (AS) can be classified according to a recently proposed staging classification. The present study investigated the incremental prognostic value of left ventricular (LV) global longitudinal strain (GLS) over stages of cardiac damage in patients with severe AS.Method and results From an ongoing registry, a total of 616 severe symptomatic AS patients with available LV GLS by speckle tracking echocardiography were selected and retrospectively analysed. Patients were categorized according to cardiac damage on echocardiography: Stage 0 (no damage), Stage 1 (LV damage), Stage 2 (mitral valve or left atrial damage), Stage 3 (tricuspid valve or pulmonary artery vasculature damage), or Stage 4 (right ventricular damage). LV GLS was divided by quintiles and assigned to the different stages. The endpoint was all-cause mortality. Over a median follow-up of 44 [24-89] months, 234 (38%) patients died. LV GLS was associated with all-cause mortality independent of stage of cardiac damage. After incorporation of LV GLS by quintiles into the staging classification, Stages 2-4 were independently associated with outcome. LV GLS showed incremental prognostic value over clinical characteristics and stages of cardiac damage.Conclusion In this large single-centre cohort of severe AS patients, incorporation of LV GLS by quintiles in a novel proposed staging classification resulted in refinement of risk stratification by identifying patients with more advanced cardiac damage. LV GLS was shown to provide incremental prognostic value over the originally proposed staging classification. Show less
Cardelli, M.; Doorn, R. van; Larcher, L.; Donato, M. di; Piacenza, F.; Pierpaoli, E.; ... ; Kumar, R. 2020
Aim: To evaluate CpG methylation of long interspersed nuclear elements 1 (LINE-1) and human endogenous retrovirus K (HERV-K) retroelements as potential prognostic biomarkers in cutaneous melanoma.... Show moreAim: To evaluate CpG methylation of long interspersed nuclear elements 1 (LINE-1) and human endogenous retrovirus K (HERV-K) retroelements as potential prognostic biomarkers in cutaneous melanoma. Materials & methods: Methylation of HERV-K and LINE-1 retroelements was assessed in resected melanoma tissues from 82 patients ranging in age from 14 to 88 years. In addition, nevi from eight patients were included for comparison with nonmalignant melanocytic lesions. Results: Methylation levels were lower in melanomas than in nevi. HERV-K and LINE-1 methylation were decreased in melanoma patients with clinical parameters associated with adverse prognosis, while they were independent of age and gender. Hypomethylation of HERV-K (but not LINE-1) was an independent predictor of reduced disease-free survival. Conclusion: HERV-K hypomethylation can be a potential independent biomarker of melanoma recurrence. Show less
Background Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare disease, which is commonly classified with the modified Pittsburgh classification. Our aim was to evaluate... Show moreBackground Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare disease, which is commonly classified with the modified Pittsburgh classification. Our aim was to evaluate the predictive performance of this classification in relation to disease-free survival (DFS). Methods We examined retrospective data from a nationwide Dutch cohort study including patients with primary EAC SCC. These data were combined with individual patient data from the literature. Using the combined data, the predictive performances were calculated using the c-index. Results A total of 381 patients were included, 294 for clinical and 281 for the pathological classification analyses. The c-indices of the clinical and the pathological modified Pittsburgh classification predicting DFS were 0.725 (0.668-0.782) and 0.729 (0.672-0.786), respectively. Conclusion The predictive performance of the modified Pittsburgh classification system as such appears to be acceptable to predict the DFS of EAC SCC. Other factors need to be added to a future model to improve the predicted performance. Show less
Care for patients with acute pulmonary embolism (PE) involves more than determination of the duration of anticoagulant therapy. After choosing the optimal initial management strategy based on... Show moreCare for patients with acute pulmonary embolism (PE) involves more than determination of the duration of anticoagulant therapy. After choosing the optimal initial management strategy based on modern risk stratification schemes, patients require focused attention aimed at prevention of major bleeding, identification of underlying (malignant) disease, prevention of cardiovascular disease, and monitoring for long-term complications. The most frequent complication of PE is the so-called "post-PE syndrome," a phenomenon of permanent functional limitations after PE occurring in up to 50% of patients. The post-PE syndrome is caused by persistent deconditioning, anxiety, and/or ventilatory or circulatory impairment as a result of acute PE. The most severe and most feared presentation of the post-PE syndrome is chronic thromboembolic pulmonary hypertension (CTEPH), a deadly disease if it remains untreated. While CTEPH may be successfully treated with pulmonary endarterectomy, balloon pulmonary angioplasty, and/or pulmonary hypertension drugs, the major challenge is to diagnose CTEPH at an early stage. Poor awareness for the post-PE syndrome and in particular for CTEPH, high prevalence of persistent symptoms after PE and inefficient application of diagnostic tests in clinical practice all contribute to an unacceptable diagnostic delay and underdiagnosis. Its consequences are dire: increased mortality in patients with CTEPH, and excess health care costs, higher prevalence of depression, more unemployment and poorer quality of life in patients with post-PE syndrome in general. In this review, we provide an overview of the incidence and impact of the post-PE syndrome, and illustrate the clinical presentation, optimal diagnostic strategy as well as therapeutic options. Show less
Dietz, M.F.; Prihadi, E.A.; Bijl, P. van der; Marsan, N.A.; Delgado, V.; Bax, J.J. 2020
OBJECTIVES The purpose of this study was to evaluate the prognostic value of staging right heart failure (RHF) in patients with significant secondary tricuspid regurgitation (TR).BACKGROUND Right... Show moreOBJECTIVES The purpose of this study was to evaluate the prognostic value of staging right heart failure (RHF) in patients with significant secondary tricuspid regurgitation (TR).BACKGROUND Right ventricular dysfunction (RVD), defined as tricuspid annular plane systolic excursion <17 mm and clinical signs of RHF, defined as New York Heart Association functional class peripheral edema, or use of diuretics, do not always coincide in patients with significant secondary TR and may have different prognostic implications.METHODS A total of 1,311 patients with significant secondary TR (median age: 71 [interquartile range: 62 to 78] years; 50% mate) were divided into 4 RHF Stages according to the presence or absence of RVD and clinical signs of RHF: Stage 1 was defined as no RVD and no signs of RHF; Stage 2 indicated RVD but no signs of RHF; Stage 3 included RVD and signs of RHF; Stage 4 was defined as RVD and refractory signs of RHF at rest. Five-year mortality rates were compared across the 4 Stages of RHF, and the independent associates of mortality were identified by using multivariate Cox proportional hazards models.RESULTS A total of 101 patients (8%) were classified as Stage 1, 124 (10%) as Stage 2, 683 (52%) as Stage 3, and 403 (31%) as Stage 4. Patients in higher Stages of RHF had more comorbidities and worse renal and left ventricular systolic function. Cumulative 5-year survival was 54%. RHF Stages 3 and 4 were independently associated with increased mortality compared to Stage 1 (hazard ratio: 2.110 [95% confidence interval (CI): 1.163 to 3.828] and 3.318 [95% CI: 1.795 to 6.133], respectively).CONCLUSIONS In patients with significant secondary TR, higher Stages of RHF are independently associated with allcause mortality at long-term follow-up. (C) 2020 by the American College of Cardiology Foundation. Show less
Aims In patients with bicuspid aortic valve (BAV) and preserved left ventricular (LV) ejection fraction (EF), the frequency of impaired LV global longitudinal strain (GLS) and its prognostic... Show moreAims In patients with bicuspid aortic valve (BAV) and preserved left ventricular (LV) ejection fraction (EF), the frequency of impaired LV global longitudinal strain (GLS) and its prognostic implications are unknown. The present study evaluated the proportion and prognostic value of impaired LV GLS in patients with BAV and preserved LVEF.Methods and results Five hundred and thirteen patients (68% men; mean age 44 +/- 18 years) with BAV and preserved LVEF (>50%) were divided into five groups according to the type of BAV dysfunction: (i) normal function BAV, (ii) mild aortic stenosis (AS) or aortic regurgitation (AR), (iii) >= moderate isolated AS, (iv) >= moderate isolated AR, and (v) >= moderate mixed AS and AR. LV systolic dysfunction based on 2D speckle-tracking echocardiography was defined as a cut-off value of LVGLS (-13.6%). The primary outcome was aortic valve intervention or all-cause mortality. The proportion of patients with LVGLS <=-13.6% was the highest in the normal BAV group (97%) and the lowest in the group with moderate and severe mixed AS and AR (79%). During a median follow-up of 10 years, 210 (41%) patients underwent aortic valve replacement and 17 (3%) died. Patients with preserved LV systolic function (LVGLS <= -13.6%) had significantly better event-free survival compared to those with impaired LV systolic function (LVGLS > -13.6%). LVGLS was independently associated with increased risk of events (mainly aortic valve replacement): hazard ratio 1.09; P < 0.001.Conclusion Impaired LVGLS in BAV with preserved LVEF is not infrequent and was independently associated with increased risk of events (mainly aortic valve replacement events). Show less
Melchers, R.C.; Willemze, R.; Loo, M. van de; Doorn, R. van; Jansen, P.M.; Cleven, A.H.G.; ... ; Quint, K.D. 2020
Unlike systemic anaplastic large cell lymphoma, the vast majority of primary cutaneous anaplastic large cell lymphomas (C-ALCL) do not carry translocations involving the ALK gene and do not express... Show moreUnlike systemic anaplastic large cell lymphoma, the vast majority of primary cutaneous anaplastic large cell lymphomas (C-ALCL) do not carry translocations involving the ALK gene and do not express ALK. Expression of ALK protein therefore strongly suggests secondary cutaneous involvement of a systemic anaplastic large cell lymphoma. Recent studies described a small subgroup of ALK-positive C-ALCL, but information on frequency, prognosis, and translocation partners is virtually lacking. A total of 6/309 (2%) C-ALCL patients included in the Dutch registry for cutaneous lymphomas between 1993 and 2019 showed immunohistochemical ALK expression. Clinical and histopathologic characteristics, immunophenotype and disease course were evaluated. Underlying ALK translocations were analyzed with anchored multiplex polymerase chain reaction-based targeted next-generation sequencing. Median age at diagnosis was 39 years (range: 16 to 53 y). All patients presented with a solitary lesion. Treatment with radiotherapy (n=5) or anthracycline-based chemotherapy (n=1) resulted in complete responses in all 6 patients. Three patients developed a relapse, of whom 2 extracutaneous. After a median follow-up of 41 months, 5 patients were alive without disease and 1 patient died of lymphoma. Immunohistochemically, 3 cases (50%) showed combined nuclear and cytoplasmic ALK expression with underlying NPM1-ALK fusions, while 3 cases (50%) showed solely cytoplasmic ALK expression with variant ALK fusion partners (TRAF1, ATIC, TPM3). ALK-positive C-ALCL is extremely uncommon, has a comparable favorable prognosis to ALK-negative C-ALCL, and should be treated in the same way with radiotherapy as first-line treatment. Show less
Background: Mitotic rate is a strong predictor of outcome in adult patients with primary cutaneous melanoma, but for children and adolescent patients this is unknown.Objective: We sought to assess... Show moreBackground: Mitotic rate is a strong predictor of outcome in adult patients with primary cutaneous melanoma, but for children and adolescent patients this is unknown.Objective: We sought to assess the prognostic value of primary tumor mitotic rate in children and adolescents with primary melanoma.Methods: This was a cohort study of 156 patients who were <20 years of age and who had clinically localized cutaneous melanoma. Patients <12 years of age were classified as children and those 12 to 19 years of age as adolescents. Clinicopathologic and outcome data were collected. Recurrence-free and melanoma-specific survival were calculated. Univariable and multivariable analyses were performed using Cox proportional hazard models.Results: Thirteen of 156 patients (8%) were children. The mitotic rate was >= 1/mm(2) in 104 patients (67%) and correlated with increasing Breslow thickness. A positive sentinel node was found in 23 of 61 patients (38%) in whom a sentinel lymph node biopsy specimen was obtained. The median follow-up was 61 months. Five-year melanoma-specific and recurrence-free survival rates were 91% and 84%, respectively. Mitotic rate was a stronger predictor of outcome than tumor thickness and was the only factor independently associated with recurrence-free survival.Limitations: This research was conducted at a single institution and the sample size was small.Conclusion: Mitotic rate is an independent predictor of recurrence-free survival in children and adolescents with clinically localized melanoma. Show less
PURPOSE. A subgroup of uveal melanoma (UM) gives rise to metastases at a late stage. Our objective was to identify patient and tumor characteristics that are associated with UM-related death in... Show morePURPOSE. A subgroup of uveal melanoma (UM) gives rise to metastases at a late stage. Our objective was to identify patient and tumor characteristics that are associated with UM-related death in patients who survived 5 years following enucleation.METHODS. A retrospective analysis was performed in 583 primary UM cases, enucleated at the Leiden University Medical Center between 1983 and 2013. Univariable and multivariable Cox regression analyses were performed in the total cohort and separately in those surviving more than 5 years (n = 297).RESULTS. In the total cohort, the median age was 62.6 years, and the median tumor diameter was 12.0 mm. Monosomy 3 was detected in 53% of cases and gain of 8q in 47%. In the cohort surviving 5 years, the median age was 59.5 years, and the median tumor diameter was 11.0 mm. Monosomy 3 and gain of 8q were detected in 33% and 31% of cases, respectively. In the total cohort, male gender (P = 0.03), tumor diameter (P < 0.001), mitotic count (P < 0.001), extravascular matrix loops (P = 0.03), extraocular growth (P < 0.001), and gain of 8q (P < 0.001) were independently associated with UM-related death. In patients surviving 5 years after enucleation, univariable analysis revealed that age (P = 0.03), tumor diameter (P < 0.001), monosomy 3 (P = 0.04), and 8q gain (P = 0.003) were associated with subsequent UM-related death. Using a multivariable analysis, only male gender (P = 0.03) and gain of 8q (P = 0.01) remained significant.CONCLUSIONS. Predictors of UM-related death change over time. Among UM patients who survived the initial 5 years following enucleation, male gender and chromosome 8q status were the remaining factors related to UM-related death later on. Show less
Namazi, F.; Bijl, P. van der; Hirasawa, K.; Kamperidis, V.; Wijngaarden, S.E. van; Mertens, B.; ... ; Bax, J.J. 2020
BACKGROUND Left ventricular (LV) systolic function may be overestimated in patients with secondary mitral regurgitation (MR) when using LV ejection fraction (EF). LV global longitudinal strain (GLS... Show moreBACKGROUND Left ventricular (LV) systolic function may be overestimated in patients with secondary mitral regurgitation (MR) when using LV ejection fraction (EF). LV global longitudinal strain (GLS) is a less load-dependent measure of LV function. However, the prognostic value of LV GLS in secondary MR has not been evaluated. OBJECTIVES This study sought to demonstrate the prognostic value of LV GLS over LVEF in patients with secondary MR. METHODS A total of 650 patients (mean 66 +/- 11 years of age, 68% men) with significant secondary MR were included. The study population was subdivided based on the LV GLS value at which the hazard ratio (HR) for all-cause mortality was >1 using a spline curve analysis (LV GLS <7.0%, impaired LV systolic function vs. LV GLS $7.0%, preserved LV systolic function). The primary endpoint was all-cause mortality. RESULTS During a median follow-up of 56 (interquartile range: 28 to 106 months) months, 334 (51%) patients died. Patients with a more impaired LV GLS showed significantly higher mortality rates at 1-, 2-, and 5-year follow-up (13%, 23%, and 44%, respectively) when compared with patients with more preserved LV systolic function (5%, 14%, and 31%, respectively). On multivariable analysis, LV GLS <7.0% was associated with increased mortality (HR: 1.337; 95% confidence interval: 1.038 to 1.722; p = 0.024), whereas LVEF #30% was not (HR: 1.055; 95% confidence interval: 0.794 to 1.403; p = 0.711). CONCLUSIONS In patients with secondary MR, impaired LV GLS was independently associated with an increased risk for all-cause mortality, whereas LVEF was not. LV GLS may therefore be useful in the risk stratification of patients with secondary MR. (c) 2020 by the American College of Cardiology Foundation. Show less
OBJECTIVES This study sought to investigate whether left ventricular (LV) global longitudinal strain (GLS) is associated with long-term outcome after mitral valve (MV) surgery for primary mitral... Show moreOBJECTIVES This study sought to investigate whether left ventricular (LV) global longitudinal strain (GLS) is associated with long-term outcome after mitral valve (MV) surgery for primary mitral regurgitation (MR) and assess the differences in outcome according to MR etiology: Barlow's disease (BD), fibroelastic deficiency (FED), and forme fruste (FF).BACKGROUND Appropriate timing of MV surgery for primary MR is still challenging and may differ according to the etiology. In these patients, LV-GLS has been proposed as more sensitive measure to detect subtle LV dysfunction as compared with LV ejection fraction.METHODS Echocardiography was performed in 593 patients (64% men, age 65 +/- 12 years) with severe primary MR who underwent MV surgery, including assessment of LV-GLS. The etiology (BD, FED, or FF) was defined based on surgical observation. During follow-up, primary endpoint was all-cause mortality and a secondary endpoint included cardiovascular death, heart failure hospitalizations, and cerebrovascutar accidents.RESULTS During a median follow-up of 6.4 (interquartile range: 3.6 to 10.4) years, 146 patients died (16 within 30 days after surgery), 46 patients were hospitalized for heart failure, and 13 patients had a cerebrovascutar accident. Age (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.05 to 1.11; p < 0.001) and LV-GLS (HR: 1.13; 95% CI: 1.06 to 1.21; p < 0.001) were independently associated with all-cause mortality. Patients with LV-GLS >-20.6% (more impaired) showed significant worse survival than did patients with LV-GLS <=-20.6%; of interest, patients with BD showed similar prognosis compared with FED and FF. In addition, previous atrial fibrillation (HR: 1.70; 95% CI: 1.01 to 2.86; p = 0.045) and LV-GLS (HR: 1.01; 95% CI: 1.01 to 1.15; p = 0.019) were independently associated with the secondary endpoint.CONCLUSIONS LV-GLS is independently associated with all-cause mortality and cardiovascular events after MV surgery for primary MR and might be helpful to guide surgical timing. Importantly, patients with BD showed similar prognosis when corrected for age, compared with patients with FED or FF. (C) 2020 by the American College of Cardiology Foundation. Show less
Bijl, P. van der; Abou, R.; Goedemans, L.; Gersh, B.J.; Holmes, D.R.; Marsan, N.A.; ... ; Bax, J.J. 2020
OBJECTIVES This study sought to investigate the impact of post-infarct left ventricular (LV) remodeling on outcomes in the contemporary era.BACKGROUND LV remodeling after ST-segment elevation... Show moreOBJECTIVES This study sought to investigate the impact of post-infarct left ventricular (LV) remodeling on outcomes in the contemporary era.BACKGROUND LV remodeling after ST-segment elevation myocardial infarction (STEMI) is associated with heart failure and increased mortality. Pivotal studies have mostly been performed in the era of thrombotysis, whereas the tong-term prognostic impact of LV remodeling has not been reinvestigated in the current era of primary percutaneous coronary intervention (PCI) and optimal pharmacotherapy.METHODS Data were obtained from an ongoing registry of patients with STEMI (all treated with primary PCI). Baseline, 3-month, 6-month, and 12-month echocardiograms were analyzed. LV remodeling was defined as a >= 20% increase in LV end-diastolic volume at 3, 6, or 12 months post-infarct. The impact of LV remodeling on outcomes was analyzed.RESULTS A total of 1,995 patients with STEMI were studied (mean age 60 +/- 12 years, 77% men), 953 (48%) of whom demonstrated remodeling in the first 12 months of follow-up. After a median follow-up of 94 (interquartite range: 69 to 119) months, 225 (11%) patients had died. There was no difference in survival between remodelers and nonremodelers (p = 0.144). However, LV remodelers were more likely to be admitted to hospital for heart failure than were nonremodelers (p < 0.001).CONCLUSIONS In the contemporary era, in which STEMS is treated with primary PCI and optimal pharmacotherapy, almost one-half of patients demonstrate LV post-infarct remodeling. However, there is no difference in tong-term survival between LV remodelers and nonremodelers, and LV remodelers experience a higher rate of heart failure hospitalization, which indicates the need to intensify preventative strategies in these patients. (C) 2020 by the American College of Cardiology Foundation. Show less
