Purpose: Sepsis is one of the leading causes of morbidity and mortality worldwide with approximately 50 million annual cases. There is ongoing debate on the clinical benefit of hydrocortisone in... Show morePurpose: Sepsis is one of the leading causes of morbidity and mortality worldwide with approximately 50 million annual cases. There is ongoing debate on the clinical benefit of hydrocortisone in the prevention of death in septic patients. Here we evaluated the association between hydrocortisone treatment and mortality in patients diagnosed with sepsis in a large-scale clinical dataset.Methods: Data from patients between 2008 and 2019 were extracted from the retrospective Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients who received hydrocortisone after diagnosis were matched using propensity-score matching with patients who did not, to balance confounding (by indication and contraindication) factors between the groups. 90-day mortality and survivors' length of hospital stay was compared between patients who did or did not receive hydrocortisone.Results: A total of 31,749 septic patients were included in the study (mean age: 67, men: 57.3%, in-hospital mortality: 15.6%). 90-day mortality was higher among the 1802 patients receiving hydrocortisone when compared with the 6348 matched non-users (hazard ratio: 1.35, 95% CI: 1.24-1.47). Hydrocortisone treatment was also associated with increased in-hospital mortality (40.9% vs. 27.6%, p < 0.0001) and prolonged hospital stay in those who survived until discharge (median 12.6 days vs. 10.8 days, p < 0.0001). Stratification for age, gender, ethnicity, occurrence of septic shock, and the need for vasopressor drug administration such as (nor) epinephrine did not reveal sub-population(s) benefiting of hydrocortisone use.Conclusion: Hydrocortisone treatment is associated with increased risk of death as well as prolonged hospital stay in septic patients. Although residual confounding (by indication) cannot be ruled out completely due to the observational nature of the study, the present study suggests clinical implication of hydrocortisone use in patients with sepsis. Show less
This thesis has shed light on RPL practice and the management of RPL couples in need of counselling towards future pregnancies. Both clinical practice research and prediction research indicate that... Show moreThis thesis has shed light on RPL practice and the management of RPL couples in need of counselling towards future pregnancies. Both clinical practice research and prediction research indicate that there is room for improvements in RPL practice and RPL counselling. We studied quality of care by diving into clinical practice variation and quality of counselling by diving into prediction research.In the absence of effective treatment options that increase live birth rates in RPL couples, counselling towards future pregnancies plays a key role and enables couples to make an informed decision regarding further pregnancy attempts. This will still be present when future treatment options are investigated or discovered, as these models could then evaluate the effects of these treatments on performance of the model. It is therefore of utmost importance that prediction models are well developed and validated for use in clinical practice.In an era of technological advancement bringing societies, researchers and clinicians from all over the world more closely together, it is time to step up and work together, to unify RPL care and to create collaborations that hugely impact RPL research which can lead to high impact publications that can unravel the mysteries of RPL. Show less
Delgado, V.; Marsan, N.; Waha, S. de; Bonaros, N.; Brida, M.; Burri, H.; ... ; ESC Sci Document Grp 2023
PurposeHeavy pigmentation is known to be a prognostic risk factor in uveal melanoma (UM). We analyzed whether genetic tumor parameters were associated with tumor pigmentation and whether... Show morePurposeHeavy pigmentation is known to be a prognostic risk factor in uveal melanoma (UM). We analyzed whether genetic tumor parameters were associated with tumor pigmentation and whether pigmentation should be included in prognostic tests.DesignRetrospective comparison of clinical, histopathological, and genetic features and survival in UM with different pigmentation.ParticipantsA total of 1058 patients with UM from a White European population with diverse eye colors enucleated between 1972 and 2021.MethodsCox regression and log-rank tests were used for survival analysis; the chi-square test and Mann–Whitney U test were used for correlation analysis.Main Outcome MeasuresUveal melanoma–related survival based on tumor pigmentation and chromosome status, correlation of tumor pigmentation with prognostic factors.ResultsThe 5-year UM-related mortality was 8% in patients with nonpigmented tumors (n = 54), 25% with lightly pigmented tumors (n = 489), 41% with moderately pigmented tumors (n = 333), and 33% with dark tumors (n = 178) (P < 0.001). The percentage of tumors with monosomy 3 (M3) or 8q gain increased with increasing pigmentation (31%, 46%, 62%, and 70% having M3 [P < 0.001], and 19%, 43%, 61%, and 63% having 8q gain [P < 0.001] in the 4 increasing pigment groups, respectively). BRCA-associated protein 1(BAP1) loss (known for 204 cases) was associated with increased tumor pigmentation (P = 0.001). Cox regression analysis on survival showed that when chromosome status and pigmentation were both included, pigmentation was not an independent prognostic indicator. Preferentially expressed antigen in melanoma (PRAME) expression was a significant prognostic marker in light tumors (P = 0.02) but not in dark tumors (P = 0.85).ConclusionsPatients with moderately and heavily pigmented tumors showed a significantly higher UM-related mortality than patients with unpigmented and light tumors (P < 0.001), supporting prior reports on the relation between increased tumor pigmentation and a worse prognosis. Although we previously showed that a dark eye color was associated with tumor pigmentation, we now show that the tumor’s genetic status (chromosome 3 and 8q/BAP1 status) is also related to tumor pigmentation. When pigmentation and chromosome 3 status are both included in a Cox regression analysis, pigmentation is not an independent prognostic factor. However, evidence from this and previous studies shows that chromosome changes and PRAME expression have a stronger association with survival when they occur in light tumors than in dark ones. Show less
Galloo, X.; Meucci, M.C.; Stassen, J.; Dietz, M.F.; Prihadi, E.A.; Bijl, P. van der; ... ; Delgado, V. 2023
Background: Changes in right ventricular (RV) dimensions and function after tricuspid valve (TV) surgery and their association with long-term outcomes remain largely unexplored. The current study... Show moreBackground: Changes in right ventricular (RV) dimensions and function after tricuspid valve (TV) surgery and their association with long-term outcomes remain largely unexplored. The current study evaluated RV reverse remodeling, based on changes in RV dimensions and function, after TV surgery for significant (moderate or severe) tricuspid regurgitation (TR) and their association with outcome. Methods: A total of 121 patients (mean age 63 +/- 12 years, 47% males) with significant TR treated with TV surgery were included in this analysis. The population was stratified by tertiles of percentage reduction of RV end-systolic area (RVESA) and absolute change of RV fractional area change (RVFAC). Five-year mortality rates were compared across the tertiles of RV remodeling and independent associates of mortality were investigated. Results: Tertile 3 consisted of patients presenting with a reduction in RVESA >= 17.2% and an improvement in RVFAC >= 2.3% after TV surgery. Cumulative survival rates were significantly better in patients within tertile 3 of RVESA reduction: 90% vs. 49% for tertile 1 and 69% for tertile 2 (log-rank p = 0.002) and within tertile 3 of RVFAC improvement: 87% vs. 57% for tertile 1 and 65% for tertile 2 (log-rank p = 0.02). Tertiles 3 of RVESA reduction and RVFAC improvement were both independently associated with better survival after TV surgery compared to tertiles 1 (hazard ratio: 0.221 [95% CI: 0.074-0.658] and 0.327 [95% CI: 0.118-0.907], respectively). Conclusions: The extent of RV reverse remodeling, based on reduction in RVESA and improvement in RVFAC, was associated with better survival at 5-year follow-up of TV surgery for significant TR. Show less
Background: Patients with osteosarcoma (OS) and Ewing sarcoma (ES) are considered to have a high venous thromboembolism (VTE) risk, although the exact incidence and prognostic impact are under... Show moreBackground: Patients with osteosarcoma (OS) and Ewing sarcoma (ES) are considered to have a high venous thromboembolism (VTE) risk, although the exact incidence and prognostic impact are under-researched in general as well as in relevant age groups. Aims: To study the impact of VTE and major bleeding (MB) in OS and ES patients, subdivided in children, Ad-olescents Young Adults (AYAs; aged 18-39) and older adults. Methods: Retrospective single-center chart review in 519 OS and 165 ES patients treated between 1980 and 2018. Patients were followed from sarcoma diagnosis until an outcome of interest (VTE, MB) or death occurred. Cu-mulative incidences were estimated with death as competing risk. Cox models were used to determine prognostic impact. Results: Five-year cumulative incidences of VTE were 12 % (95%CI 9.1-15) for OS and 6.7 % (95%CI 3.5-11) for ES patients, mostly happening in patients >= 18 years; the most frequent VTE presentation was catheter-related upper-extremity thrombosis (OS: 18/65, ES: 7/11). Five-year cumulative incidences for MB were 5.8 % (95% CI 4.0-8.1) in OS and 5.4 % (95%CI 2.5-9.8) in ES patients. 192 OS and 77 ES AYAs were included, who faced similar VTE and MB incidences as older adults. In OS, VTE and MB were both associated with mortality (adjusted HRs 2.0 [95%CI 1.4-2.9] and 2.4 [95%CI 1.4-4.0], respectively), whereas in ES this association was only present for MB (aHR 3.4 [95%CI 1.2-9.6]). Conclusions: VTE is a frequent complication in adult OS and to a lesser extent in ES patients, while the rate of MB was comparably high in both sarcoma types. Show less
Background: In longitudinal research, switching between diagnoses should be considered when examining patients with depression and anxiety. We investigated course trajectories of affective... Show moreBackground: In longitudinal research, switching between diagnoses should be considered when examining patients with depression and anxiety. We investigated course trajectories of affective disorders over a nine-year period, comparing a categorical approach using diagnoses to a dimensional approach using symptom severity.Method: Patients with a current depressive and/or anxiety disorder at baseline (N = 1701) were selected from the Netherlands Study of Depression and Anxiety (NESDA). Using psychiatric diagnoses, we described 'consistently recovered,' 'intermittently recovered,' 'intermittently recurrent', and 'consistently chronic' at two-, four-, six-, and nine-year follow-up. Additionally, latent class growth analysis (LCGA) using depressive, anxiety, fear, and worry symptom severity scores was used to identify distinct classes.Results: Considering the categorical approach, 8.5% were chronic, 32.9% were intermittently recurrent, 37.6% were intermittently recovered, and 21.0% remained consistently recovered from any affective disorder at nine-year follow-up. In the dimensional approach, 66.6% were chronic, 25.9% showed partial recovery, and 7.6% had recovered.Limitations: 30.6% of patients were lost to follow-up. Diagnoses were rated by the interviewer and questionnaires were completed by the participant.Conclusions: Using diagnoses alone as discrete categories to describe clinical course fails to fully capture the persistence of affective symptoms that were observed when using a dimensional approach. The enduring, fluctuating presence of sub-threshold affective symptoms likely predisposes patients to frequent relapse. The commonness of subthreshold symptoms and their adverse impact on long-term prognoses deserve continuous clinical attention in mental health care as well further research. Show less
Introduction It is unknown how long-term prognosis after ST-elevation myocardial infarction (STEMI) in patients with a prior cancer diagnosis is impacted by cancer-related factors as diagnosis,... Show moreIntroduction It is unknown how long-term prognosis after ST-elevation myocardial infarction (STEMI) in patients with a prior cancer diagnosis is impacted by cancer-related factors as diagnosis, stage, and treatment. We aimed to assess long-term survival trends after STEMI in this population to evaluate both cardiovascular and cancer-related drivers of prognosis over a follow-up period of 5 years. Methods In this retrospective single-center cohort study, patients with a prior cancer diagnosis admitted with STEMI between 2004 and 2014 and treated with primary percutaneous coronary intervention (PCI) were recruited from the STEMI clinical registry of our institution. Results In the 211 included patients, the cumulative incidence of all-cause death after 5 years of follow-up was 38.1% (N = 60). The cause of death was predominantly malignancy-related (N = 29, 48.3% of deaths) and nine patients (15.0%) died of a cardiovascular cause. After correcting for age and sex, a recent cancer diagnosis (< 1 year relative to > 10 years, HRadj 2.98 [95% CI: 1.39-6.41], p = 0.005) and distant metastasis at presentation (HRadj 4.02 [1.70-9.53], p = 0.002) were significant predictors of long-term mortality. While maximum levels of cardiac troponin-T and creatinine kinase showed significant association with mortality (resp. HRadj 1.34 [1.08-1.66], p = 0.008; HRadj 1.36 [1.05-1.76], p = 0.019), other known determinants of prognosis after STEMI, e.g., hypertension and renal insufficiency, were not significantly associated with survival. Conclusions Patients with a prior cancer diagnosis admitted with STEMI have a poor survival rate. However, when the STEMI is optimally treated with primary PCI and medication, cardiac mortality is low, and prognosis is mainly determined by factors related to cancer stage. Show less
Objective: To assess whether the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and a shorter version of this tool can identify clinical prediction models (CPMs) that perform poorly at... Show moreObjective: To assess whether the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and a shorter version of this tool can identify clinical prediction models (CPMs) that perform poorly at external validation. Study Design and Setting: We evaluated risk of bias (ROB) on 102 CPMs from the Tufts CPM Registry, comparing PROBAST to a short form consisting of six PROBAST items anticipated to best identify high ROB. We then applied the short form to all CPMs in the Registry with at least 1 validation (n = 556) and assessed the change in discrimination (dAUC) in external validation cohorts (n = 1,147). Results: PROBAST classified 98/102 CPMS as high ROB. The short form identified 96 of these 98 as high ROB (98% sensitivity), with perfect specificity. In the full CPM registry, 527 of 556 CPMs (95%) were classified as high ROB, 20 (3.6%) low ROB, and 9 (1.6%) unclear ROB. Only one model with unclear ROB was reclassified to high ROB after full PROBAST assessment of all low and unclear ROB models. Median change in discrimination was significantly smaller in low ROB models (dAUC -0.9%, IQR -6.2-4.2%) compared to high ROB models (dAUC -11.7%, IQR -33.3-2.6%; P < 0.001). Conclusion: High ROB is pervasive among published CPMs. It is associated with poor discriminative performance at validation, supporting the application of PROBAST or a shorter version in CPM reviews. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http:// creativecommons.org/ licenses/ by- nc- nd/ 4.0/ ) Show less
The studies in this thesis contribute to more accurate risk assessment and prognosis prediction for DCIS and to better response evaluation of IBC treatment.For the Ductal Carcinoma In Situ (DCIS)... Show moreThe studies in this thesis contribute to more accurate risk assessment and prognosis prediction for DCIS and to better response evaluation of IBC treatment.For the Ductal Carcinoma In Situ (DCIS) studies, unbiased cohorts were used within the international Grand Challenge PRECISION consortium, funded by Cancer Research UK and KWF Dutch Cancer Society. DCIS is graded as low-, intermediate-, or high-grade depending on how abnormal the DCIS-cells look like. However, we showed that pathologists often disagree on grade. To overcome this limitation, we found that almost all DCIS scored as non-high-grade by the majority of pathologists express the estrogen receptor (ER) and are negative for the growth factor receptor HER2, whereas high-grade DCIS is mixed in expression for ER and HER2. We also provided insights in the recurrence risks of DCIS after treatment. See also https://cancergrandchallenges.org/teams/precision.The studies on Invasive Breast Cancer (IBC) were performed on a hospital-based cohort. We found for example substantial variation in tumour response evaluation for HER2-positive IBC after pre-operative chemotherapy due to different guidelines used. For accurate outcome analysis, reducing such variation is mandatory. Therefore, we are working on reaching international consensus of response evaluation. Show less
Fortuni, F.; Dietz, M.F.; Prihadi, E.A.; Bijl, P. van der; Ferrari, G.M. de; Bax, J.J.; ... ; Marsan, N.A. 2021
Background: Conventional approaches for the assessment of secondary tricuspid regurgitation (STR) severity do not correct for right heart dimensions. The authors hypothesized that STR severity can... Show moreBackground: Conventional approaches for the assessment of secondary tricuspid regurgitation (STR) severity do not correct for right heart dimensions. The authors hypothesized that STR severity can be proportional or disproportional to the dilation of the tricuspid annulus (TA) and investigated the prognostic impact of this novel definition. Methods: A total of 334 patients with moderate to severe STR and preserved left ventricular systolic function were included. The ratio between vena contracta (VC) width and tricuspid annular diameter was calculated. The cutoff value for VC/TA ratio associated with increased risk for all-cause death was identified using spline-curve analysis. Results: The cutoff value of VC/TA ratio associated with a mortality excess was 0.24, and 165 patients (49%) had VC/TA ratios >_ 0.24. Compared with those with VC/TA ratios < 0.24, patients with VC/TA ratios >_ 0.24 had a higher prevalence of moderate to severe mitral regurgitation, had higher pulmonary pressures, and were more frequently treated with diuretics. During a median follow-up period of 62 months (interquartile range, 28-101 months), 128 patients (38%) died. The cumulative 5-year survival rate was significantly worse in patients with VC/TA ratios >_ 0.24 (55% vs 71%, P = .001). VC/TA ratio >_ 0.24 was independently associated with poor outcomes on multivariate analysis (hazard ratio, 1.567; 95% CI, 1.044-2.352; P = .030) together with coronary artery disease, renal impairment, right ventricular systolic function (evaluated using either tricuspid annular plane systolic excursion or right ventricular free wall strain), and pulmonary pressures. Conclusions: VC/TA ratio >_ 0.24 is independently associated with poor prognosis in patients with STR. This parameter may be considered as a marker of disproportionate STR and could improve risk stratification and clinical decision-making. (J Am Soc Echocardiogr 2021;34:944-54.) Show less
Namazi, F.; Bijl, P. van der; Vo, N.M.; Wijngaarden, S.E. van; Marsan, N.A.; Delgado, V.; Bax, J.J. 2021
Aims Secondary mitral regurgitation (MR) is more frequent in men than in women. However, little is known about differences in prognosis between men and women with secondary MR. The objective of... Show moreAims Secondary mitral regurgitation (MR) is more frequent in men than in women. However, little is known about differences in prognosis between men and women with secondary MR. The objective of this study is to investigate the sex distribution of secondary MR and the prognostic differences between sexes.Methods Patients with significant secondary MR, of both ischaemic and non-ischaemic aetiologies, were identified through the departmental electronic patient files and retrospectively analysed. The primary endpoint was all-cause mortality.Results A total of 698 patients (mean age 66 +/- 11 years) with significant secondary MR were included: 471 (67%) men and 227 (33%) women. Ischaemic heart failure was significantly more common in men (61%), whereas non-ischaemic heart failure was more prevalent in women (63%). Women had significantly smaller left ventricular (LV) volumes when compared with men and more preserved LV systolic function when assessed with LV global longitudinal strain (GLS; 8.5 +/- 4.1% vs. 7.5 +/- 3.6%; P = 0.004). Women more often underwent surgical mitral valve repair (34%) when compared with men (26%), although no differences were observed for transcatheter mitral valve repair. During a median follow-up of 57 [interquartile range 29-110] months, 373 (53%) patients died. Women showed significantly lower mortality rates at 1-, 2- and 5-year follow-up (9%, 16% and 33% vs. 10%, 20% and 42%) when compared with men (P = 0.001).Conclusions Significant secondary MR is more frequently observed in men as compared with women and is associated with worse prognosis. Show less
Hond, A. de; Raven, W.; Schinkelshoek, L.; Gaakeer, M.; Avest, E. ter; Sir, O.; ... ; Groot, B. de 2021
Objective: Early identification of emergency department (ED) patients who need hospitalization is essential for quality of care and patient safety. We aimed to compare machine learning (ML) models... Show moreObjective: Early identification of emergency department (ED) patients who need hospitalization is essential for quality of care and patient safety. We aimed to compare machine learning (ML) models predicting the hospitalization of ED patients and conventional regression techniques at three points in time after ED registration.Methods: We analyzed consecutive ED patients of three hospitals using the Netherlands Emergency Department Evaluation Database (NEED). We developed prediction models for hospitalization using an increasing number of data available at triage, similar to 30 min (including vital signs) and similar to 2 h (including laboratory tests) after ED registration, using ML (random forest, gradient boosted decision trees, deep neural networks) and multivariable logistic regression analysis (including spline transformations for continuous predictors). Demographics, urgency, presenting complaints, disease severity and proxies for comorbidity, and complexity were used as covariates. We compared the performance using the area under the ROC curve in independent validation sets from each hospital.Results: We included 172,104 ED patients of whom 66,782 (39 %) were hospitalized. The AUC of the multi-variable logistic regression model was 0.82 (0.78-0.86) at triage, 0.84 (0.81-0.86) at similar to 30 min and 0.83 (0.75-0.92) after similar to 2 h. The best performing ML model over time was the gradient boosted decision trees model with an AUC of 0.84 (0.77-0.88) at triage, 0.86 (0.82-0.89) at similar to 30 min and 0.86 (0.74-0.93) after similar to 2 h.Conclusions: Our study showed that machine learning models had an excellent but similar predictive performance as the logistic regression model for predicting hospital admission. In comparison to the 30-min model, the 2-h model did not show a performance improvement. After further validation, these prediction models could support management decisions by real-time feedback to medical personal. 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
Pulmonary infarction results from occlusion of the distal pulmonary arteries leading to ischemia, hemorrhage and ultimately necrosis of the lung parenchyma. It is most commonly caused by acute... Show morePulmonary infarction results from occlusion of the distal pulmonary arteries leading to ischemia, hemorrhage and ultimately necrosis of the lung parenchyma. It is most commonly caused by acute pulmonary embolism (PE), with a reported incidence of around 30%. Following an occlusion of the pulmonary artery, the bronchial arteries are recruited as primary source of perfusion of the pulmonary capillaries. The relatively higher blood pressure in the bronchial circulation causes an increase in the capillary blood flow, leading to extravasation of erythrocytes (i.e. alveolar hemorrhage). If this hemorrhage cannot be resorbed, it results in tissue necrosis and infarction. Different definitions of pulmonary infarction are used in literature (clinical, radiological and histological), although the diagnosis is nowadays mostly based on radiological characteristics. Notably, the infarcted area is only replaced by a fibrotic scar over a period of months. Hence and formally, the diagnosis of pulmonary infarction cannot be confirmed upon diagnosis of acute PE. Little is known of the impact and relevance of pulmonary infarction in acute PE, and whether specific management strategies should be applied to prevent and/ or treat complications such as pain, pneumonia or post-PE syndrome. In this review we will summarize current knowledge on the pathophysiology, epidemiology, diagnosis and prognosis of pulmonary infarction in the setting of acute PE. We highlight the need for dedicated studies to overcome the current knowledge gaps. Show less
There is a pending need for prognostic and predictive biomarkers in the treatment of patients with colorectal cancer.This thesis describes the prognostic and predictive application of the tumor... Show moreThere is a pending need for prognostic and predictive biomarkers in the treatment of patients with colorectal cancer.This thesis describes the prognostic and predictive application of the tumor-stroma ratio (TSR) in colorectal cancer, focusing on expanding current clinical-pathological standards and combining TSR with other diagnostic parameters. The TSR is a microscopy scoring method performed on hematoxylin-eosin stained tissue slides used for routine pathology assessment, and has proven to be a robust prognostic maker. Here, we investigate whether the TSR also exhibits predictive value with regard to adjuvant targeted therapy in stage II and III colon cancer. Moreover, exploring the value of collagen fiber organization in the intratumoral stroma, as well as combining this parameter with the TSR. Finally, expanding the application of the TSR with radiological diagnostics in rectal cancer. Assessing is there is a correlation between TSR and apparent diffusion coefficient values obtained from diagnostically performed MRI-DWI scans, in order to determine if there is potential with regards to neoadjuvant treatment choices or patient follow-up. 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
Gonzalez-Gonzalez, A.I.; Dinh, T.S.; Meid, A.D.; Blom, J.W.; Akker, M. van den; Elders, P.J.M.; ... ; Muth, C. 2021
The prevalence of multimorbidity and polypharmacy increases significantly with age and are associated with negative health consequences. However, most current interventions to optimize medication... Show moreThe prevalence of multimorbidity and polypharmacy increases significantly with age and are associated with negative health consequences. However, most current interventions to optimize medication have failed to show significant effects on patient-relevant outcomes. This may be due to ineffectiveness of interventions themselves but may also reflect other factors: insufficient sample sizes, heterogeneity of population. To address this issue, the international PROPERmed collaboration was set up to obtain/synthesize individual participant data (IPD) from five cluster-randomized trials. The trials took place in Germany and The Netherlands and aimed to optimize medication in older general practice patients with chronic illness. PROPERmed is the first database of IPD to be drawn from multiple trials in this patient population and setting. It offers the opportunity to derive prognostic models with increased statistical power for prediction of patient-relevant outcomes resulting from the interplay of multimorbidity and polypharmacy. This may help patients from this heterogeneous group to be stratified according to risk and enable clinicians to identify patients that are likely to benefit most from resource/timeintensive interventions. The aim of this manuscript is to describe the rationale behind PROPERmed collaboration, characteristics of the included studies/participants, development of the harmonized IPD database and challenges faced during this process. Show less
Meulen, M. van der; Dirven, L.; Bakunina, K.; Bent, M.J. van den; Issa, S.; Doorduijn, J.K.; Bromberg, J.E.C. 2021
Introduction To assess the value of the Mini-Mental State Examination (MMSE)-score at baseline in predicting survival in adult primary central nervous system lymphoma (PCNSL) patients. Methods In... Show moreIntroduction To assess the value of the Mini-Mental State Examination (MMSE)-score at baseline in predicting survival in adult primary central nervous system lymphoma (PCNSL) patients. Methods In the HOVON 105/ ALLG NHL 24 phase III study patients with newly-diagnosed PCNSL were randomized between high-dose methotrexate-based chemotherapy with or without rituximab. Data on potential (MMSE-score), and known baseline prognostic factors (age, performance status, serum LDH, cerebrospinal fluid total protein, involvement of deep brain structures, multiple cerebral lesions, and the IELSG-score) were collected prospectively. Multivariable stepwise Cox regression analyses were used to assess the prognostic value of all factors on progression-free survival (PFS) and overall survival (OS) among patients with available MMSE score at baseline. Age was analyzed as continuous variable, the MMSE-score both as a continuous and as a categorical variable. Results In univariable analysis, age, MMSE-score and whether the patient received rituximab were statistically significantly prognostic factors for PFS. Age and MMSE-score were statistically significantly associated with OS. In a multivariable analysis of the univariately significant factors only MMSE-score was independently associated with the survival endpoints, as a continuous variable (HR for PFS 1.04, 95% CI 1.01-1.08; OS 1.06 (95% CI 1.02-1.10) and as categorical variable HR (< 27 versus >= 27 for PFS 1.55 (1.02-2.35); OS 1.68 (1.05-2.70). In our population, performance status, serum LDH, and CSF protein level were not of prognostic value. Conclusion Neurocognitive disturbances, measured with the MMSE at baseline, are an unfavorable prognostic factor for both PFS and OS in adult PCNSL patients up to 70 years-old. Show less
Dietz, M.F.; Prihadi, E.A.; Bijl, P. van der; Marsan, N.A.; Bax, J.J.; Delgado, V. 2021
Background: Obesity may cause right ventricular (RV) remodeling due to volume overload. However, obesity is also associated with better prognosis compared with normal weight in patients with... Show moreBackground: Obesity may cause right ventricular (RV) remodeling due to volume overload. However, obesity is also associated with better prognosis compared with normal weight in patients with various cardiac diseases. The aim of this study was to assess the impact of obesity on RV remodeling and long-term prognosis in patients with significant (moderate and severe) tricuspid regurgitation (TR).Methods: A total of 951 patients with significant TR (median age, 70 years; interquartile range, 61-77 years; 50% men) were divided into three groups according to body mass index (BMI): normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI >= 30 kg/m(2)). Patients with congenital heart disease, peripheral edema, active endocarditis, and BMI < 18.5 kg/m(2) were excluded. RV size and function for each group were measured using transthoracic echocardiography and compared with reference values of healthy study populations. The primary end point was all-cause mortality. Event rates were compared across the three BMI categories.Results: Four hundred seventy-six patients (50%) with significant TR had normal weight, 356 (37%) were over-weight, and 119 (13%) were obese. RV end-diastolic and end-systolic areas were larger in overweight and obese patients compared with normal-weight patients. However, no differences in RV systolic function were observed. During a median follow-up period of 5 years, 358 patients (38%) died. Five-year survival rates were significantly better in overweight and obese patients compared with patients with normal weight (65% and 67% vs 58%, respectively, P < .001 and P = .005). In multivariate analysis, overweight and obesity were independently associated with lower rates of all-cause mortality compared with normal weight (hazard ratios, 0.628 [95% CI, 0.493-0.800] and 0.573 [95% CI, 0.387-0.848], respectively).Conclusions: In patients with significant TR, overweight and obese patients demonstrated more RV remodeling compared with patients with normal weight. Nevertheless, a higher BMI was independently associated with better long-term survival, confirming the obesity paradox in this context. Show less
