Paragangliomas are neuroendocrine tumours that are often highly vascularized and, in most cases, benign. The gold-standard treatment is surgical resection for various reasons; however, this can be... Show moreParagangliomas are neuroendocrine tumours that are often highly vascularized and, in most cases, benign. The gold-standard treatment is surgical resection for various reasons; however, this can be challenging because of close proximity to coronary arteries. Paucity of data has resulted in different (hybrid) treatment strategies with unknown long -term outcomes, especially with respect to coronary reintervention after stenting. Here, we report a unique patient with multiple cardiac paragangliomas adjacent to both coronary arteries who underwent complete surgical resection. Cardioplegic arrest is recommended to facilitate resection and, if needed, to perform concomitant coronary artery bypass grafting or reconstruction of cardiovascular structures. Show less
Redeker, I.; Landewé, R.; Heijde, D. van der; Ramiro, S.; Boonen, A.; Dougados, M.; ... ; Kiltz, U. 2023
ObjectiveThe objective of this study is to build a structural model visualising and quantifying the interrelationships of different disease outcomes with the Assessment of SpondyloArthritis... Show moreObjectiveThe objective of this study is to build a structural model visualising and quantifying the interrelationships of different disease outcomes with the Assessment of SpondyloArthritis International Society Health Index (ASAS HI) in patients with axial spondyloarthritis (axSpA).MethodsCross-sectional data collected at month 72 of the Devenir des Spondylarthropathies Indifferenciees Recentes cohort was analysed. Combining prior knowledge and observed data, probabilistic Bayesian network modelling was used to study how the interplay of different disease outcomes affects the ASAS HI, which measures disease-specific overall functioning and health. Disease outcomes comprised, among others, the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS) and the Bath AS Functional Index (BASFI).ResultsData of 384 patients were analysed. The obtained structure suggests that ASAS HI is determined by both patient-reported physical function (BASFI) and disease activity (ASDAS). The parameters of the structural model show that an increase of ASDAS or BASFI by 1 unit corresponds to an increase of ASAS HI by 0.70 or 1.25 units, respectively. Moreover, the model suggests that disease activity has an indirect impact on ASAS HI via BASFI. No relationship between spinal mobility or structural damage and ASAS HI was found.ConclusionsThis is the first structural model developed to better understand the construct and the interplay between clinically relevant outcomes related to ASAS HI in axSpA patients. It shows that disease activity and physical function have a strong impact on ASAS HI, confirming it to be a valid construct of overall functioning and health in axSpA patients. Show less
Unal, S.; Feller, R.; Stadhouder, A.; Heineman, D.J.; Jiya, T.U.; Dorp, M. van; ... ; Dickhoff, C. 2023
Introduction: Curative-intent treatment of superior sulcus tumors (SSTs) of the lung invading the spine presents considerable challenges. We retrospectively studied outcomes in a single center,... Show moreIntroduction: Curative-intent treatment of superior sulcus tumors (SSTs) of the lung invading the spine presents considerable challenges. We retrospectively studied outcomes in a single center, uniformly staged patient cohort treated with induction concurrent chemoradiotherapy followed by surgical resection (trimodality therapy).Methods: An institutional surgical database from the period between 2002 and 2021 was accessed to identify SSTs in which the resection included removal of at least part of the vertebral body. All patients were staged using fluorodeox-yglucose positron emission tomography (/computed tomography), computed tomography scan of the chest/upper abdomen, and brain imaging. Surgical morbidity was assessed using the Clavien-Dindo classification. Overall and disease-free survival were calculated using the Kaplan Meier method.Results: A total of 18 patients were included: 8 complete and 10 partial vertebrectomies were performed, with six of the eight complete vertebrectomies involving two vertebral levels, resulting in Complete surgical resection (R0) in 94%. Nine patients had a 1-day procedure, and nine were staged over 2 days. The median follow-up was 30 months (inter quartile range 11-57). The 90-day postoperative morbidity was 44% (grade III/IV), with no 90-day surgery-related mortality. There were 83% who had a major pathologic response, associated with improved survival (p 1/4 0.044). The 5-year overall and disease-free survival were 55% and 40%, respectively. Disease progression occurred in 10 patients, comprising locoregional recurrences in two and distant metastases in eight patients.Conclusions: Multimodality treatment in selected patients with a superior sulcus tumor invading the spine is safe and results in good survival. Such patients should be referred to expert centers. Future research should focus on improving distant control (e.g. [neo]adjuvant immunotherapy).(c) 2023 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
OBJECTIVESAortic valve repair procedures are technically challenging, and current intraoperative evaluation methods often fail to predict the final echocardiographic result. We have developed a... Show moreOBJECTIVESAortic valve repair procedures are technically challenging, and current intraoperative evaluation methods often fail to predict the final echocardiographic result. We have developed a novel intraoperative aortic valve visualization and pressurization (AVP) device, enabling valve inspection under physiological conditions, and measuring aortic valve insufficiency (AI) during cardioplegic arrest.METHODSThe AVP device is attached to the (neo)aorta, after any type of aortic valve repair, while the heart is arrested. The root is pressurized (60–80 mmHg) using a saline solution and an endoscope is introduced. The valve is inspected, and the amount of valvular leakage is measured. Postoperative ‘gold standard’ transesophageal echocardiogram measurements of AI are performed and compared against regurgitation volume measured.RESULTSIn 24 patients undergoing valve-sparing root replacement, the AVP device was used. In 22 patients, postoperative echocardiographic AI was ≤ grade 1. The median leakage was 90 ml/min, IQR 60–120 ml/min. In 3 patients, additional adjustments after visual inspection was performed. In 2 patients, with complex anatomy, the valve was replaced. In one, after evaluation with the device, there was undesirable result visually and residual AI of 330 ml/min, and in another, 260 ml/min residual AI was measured and valve restriction on visual inspection.CONCLUSIONSThe novel AVP device enables intraoperative evaluation of the valve under physiological conditions, while still on arrested heart, and allows for targeted adjustments. The AVP device can be an important aid for intraoperative evaluation of the aortic valve, during valve repair and valve-sparing procedures, thereby making the operative result more predictable and the operation more efficient. Show less
PurposeMetastasectomy is a common treatment option for patients with colorectal lung metastases (CLM). Challenges exist with margin assessment and identification of small nodules, especially during... Show morePurposeMetastasectomy is a common treatment option for patients with colorectal lung metastases (CLM). Challenges exist with margin assessment and identification of small nodules, especially during minimally invasive surgery. Intraoperative fluorescence imaging has the potential to overcome these challenges. The aim of this study was to assess feasibility of targeting CLM with the carcinoembryonic antigen (CEA) specific fluorescent tracer SGM-101.MethodsThis was a prospective, open-label feasibility study. The primary outcome was the number of CLM that showed a true positive fluorescence signal with SGM-101. Fluorescence positive signal was defined as a signal-to-background ratio (SBR) ≥ 1.5. A secondary endpoint was the CEA expression in the colorectal lung metastases, assessed with the immunohistochemistry, and scored by the total immunostaining score.ResultsThirteen patients were included in this study. Positive fluorescence signal with in vivo, back table, and closed-field bread loaf imaging was observed in 31%, 45%, and 94% of the tumors respectively. Median SBRs for the three imaging modalities were 1.00 (IQR: 1.00–1.53), 1.45 (IQR: 1.00–1.89), and 4.81 (IQR: 2.70–7.41). All tumor lesions had a maximum total immunostaining score for CEA expression of 12/12.ConclusionThis study demonstrated the potential of fluorescence imaging of CLM with SGM-101. CEA expression was observed in all tumors, and closed-field imaging showed excellent CEA specific targeting of the tracer to the tumor nodules. The full potential of SGM-101 for in vivo detection of the tracer can be achieved with improved minimal invasive imaging systems and optimal patient selection. Show less
Aims Lowering low-density lipoprotein (LDL-C) and blood pressure (BP) levels to guideline recommended values reduces the risk of major adverse cardiac events in patients who underwent coronary... Show moreAims Lowering low-density lipoprotein (LDL-C) and blood pressure (BP) levels to guideline recommended values reduces the risk of major adverse cardiac events in patients who underwent coronary artery bypass grafting (CABG). To improve cardiovascular risk management, this study evaluated the effects of mobile health (mHealth) on BP and cholesterol levels in patients after standalone CABG.Methods and results This study is a post hoc analysis of an observational cohort study among 228 adult patients who underwent standalone CABG surgery at a tertiary care hospital in The Netherlands. A total of 117 patients received standard care, and 111 patients underwent an mHealth intervention. This consisted of frequent BP and weight monitoring with regimen adjustment in case of high BP. Primary outcome was difference in systolic BP and LDL-C between baseline and value after three months of follow-up. Mean age in the intervention group was 62.7 years, 98 (88.3%) patients were male. A total of 26 449 mHealth measurements were recorded. At three months, systolic BP decreased by 7.0 mmHg [standard deviation (SD): 15.1] in the intervention group vs. -0.3 mmHg (SD: 17.6; P < 0.00001) in controls; body weight decreased by 1.76 kg (SD: 3.23) in the intervention group vs. -0.31 kg (SD: 2.55; P = 0.002) in controls. Serum LDL-C was significantly lower in the intervention group vs. controls (median: 1.8 vs. 2.0 mmol/L; P = 0.0002).Conclusion This study showed an association between home monitoring after CABG and a reduction in systolic BP, body weight, and serum LDL-C. The causality of the association between the observed weight loss and decreased LDL-C in intervention group patients remains to be investigated. Show less
Introduction: In patients with unresectable stage III non-small cell lung cancer, high-dose chemoradiotherapy (CRT) followed by consolidation durvalumab improves the 5-year overall survival... Show moreIntroduction: In patients with unresectable stage III non-small cell lung cancer, high-dose chemoradiotherapy (CRT) followed by consolidation durvalumab improves the 5-year overall survival compared to CRT alone. The feasibility and safety of salvage surgery for such patients who subsequently develop locoregional failure (LRF) is unclear. We evaluated our institutional experience with radical-intent salvage surgery in this patient population. Materials and methods: Details of patients undergoing salvage surgery for locoregional failure after CRT and durvalumab were identified from an institutional surgical database. Each patient's case underwent multidisciplinary discussion at initial disease presentation, and again at time of progression. Results: Ten patients underwent salvage surgery for LRF after prior concurrent (n = 9) or sequential (n = 1) platinum-based high-dose chemo-radiotherapy followed by durvalumab. Consolidation durvalumab was completed in 4 patients, and discontinued in 6, due to either toxicity or disease progression. Median time between end of radiotherapy to detection of LRF was 19 months (range 6-75). Seven patients underwent a lobectomy, 1 a bilobectomy and 2 patients a pneumonectomy. Postoperative morbidity (Clavien-Dindo grade III-V) and 90-day mortality were 10% and 0%, respectively. Median follow-up after surgery was 7 months (range 1-25) during which 2 patients died (both 9 months post-operatively), one due to distant progression, and one of sepsis/ bleeding. Eight patients are alive at 1-23 months post-surgery, with 6 showing no evidence of disease. Conclusions: Our results suggest that salvage pulmonary resection can be performed safely in selected patients with LRF following chemoradiotherapy and durvalumab. This radical-intent treatment option merits consideration by multidisciplinary lung tumor boards. Show less
Stal, R.; Ramiro, S.; Heijde, D. van der; Gaalen, F.A. van; Baraliakos, X.; Machado, P.M.; ... ; Sepriano, A. 2023
Objectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. Methods Patients with radiographic... Show moreObjectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. Methods Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine lowdose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by ≥2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition. Results Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition. Conclusion In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition. Show less
Stal, R.; Ramiro, S.; Heijde, D. van der; Gaalen, F.A. van; Baraliakos, X.; Machado, P.M.; ... ; Sepriano, A. 2023
Objectives: To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. Methods: Patients with... Show moreObjectives: To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. Methods: Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine low-dose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by & GE;2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition. Results: Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition. Conclusion: In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition. Show less
Stal, R.; Ramiro, S.; Heijde, D. van der; Gaalen, F.A. van; Baraliakos, X.; Machado, P.M.; ... ; Sepriano, A. 2023
Objectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition.Methods Patients with radiographic... Show moreObjectives To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition.Methods Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine low-dose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by ≥2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition.Results Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition.Conclusion In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition. Show less
Braun, J.; Blanco, R.; Marzo-Ortega, H.; Gensler, L.S.; Bosch, F. van den; Hall, S.; ... ; Deodhar, A. 2023
Background: Radiographic progression and course of inflammation over 2 years in patients with non-radiographic axial spondyloarthritis (nr-axSpA) from the phase 3, randomized, PREVENT study are... Show moreBackground: Radiographic progression and course of inflammation over 2 years in patients with non-radiographic axial spondyloarthritis (nr-axSpA) from the phase 3, randomized, PREVENT study are reported here. Methods: In the PREVENT study, adult patients fulfilling the Assessment of SpondyloArthritis International Society classification criteria for nr-axSpA with elevated CRP and/or MRI inflammation received secukinumab 150 mg or placebo. All patients received open-label secukinumab from week 52 onward. Sacroiliac (SI) joint and spinal radiographs were scored using the modified New York (mNY) grading (total sacroiliitis score; range, 0-8) and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS; range, 0-72), respectively. SI joint bone marrow edema (BME) was assessed using the Berlin Active Inflammatory Lesions Scoring (0-24) and spinal MRI using the Berlin modification of the AS spine MRI (ASspiMRI) scoring (0-69). Results: Overall, 78.9% (438/555) of patients completed week 104 of the study. Over 2 years, minimal changes were observed in total radiographic SI joint scores (mean [SD] change, - 0.04 [0.49] and 0.04 [0.36]) and mSASSS scores (0.04 [0.47] and 0.07 [0.36]) in the secukinumab and placebo-secukinumab groups. Most of the patients showed no structural progression (increase <= smallest detectable change) in SI joint score (87.7% and 85.6%) and mSASSS score (97.5% and 97.1%) in the secukinumab and placebo-secukinumab groups. Only 3.3% (n = 7) and 2.9% (n = 3) of patients in the secukinumab and placebo-secukinumab groups, respectively, who were mNY-negative at baseline were scored as mNY-positive at week 104. Overall, 1.7% and 3.4% of patients with no syndesmophytes at baseline in the secukinumab and placebo-secukinumab group, respectively, developed >= 1 new syndesmophyte over 2 years. Reduction in SI joint BME observed at week 16 with secukinumab (mean [SD], - 1.23 [2.81] vs - 0.37 [1.90] with placebo) was sustained through week 104 (- 1.73 [3.49]). Spinal inflammation on MRI was low at baseline (mean score, 0.82 and 1.07 in the secukinumab and placebo groups, respectively) and remained low (mean score, 0.56 at week 104). Conclusion: Structural damage was low at baseline and most patients showed no radiographic progression in SI joints and spine over 2 years in the secukinumab and placebo-secukinumab groups. Secukinumab reduced SI joint inflammation, which was sustained over 2 years. Show less
Shahin, G.M.M.; Vos, P.P.W.K.; Hutteman, M.; Stigt, J.A.; Braun, J. 2023
Robot-assisted thoracic surgery (RATS) for higher stages non-small cell lung carcinoma (NSCLC) remains controversial. This study reports the feasibility of RATS in patients with stages IIB-IVA... Show moreRobot-assisted thoracic surgery (RATS) for higher stages non-small cell lung carcinoma (NSCLC) remains controversial. This study reports the feasibility of RATS in patients with stages IIB-IVA NSCLC. A single-institute, retrospective study was conducted with patients undergoing RATS for stages IIB-IVA NSCLC, from January 2015 until January 2020. Unforeseen N2 disease was excluded. Data were collected from the Dutch Lung Cancer Audit database. Conversion rate, radical (R0) resection rate, local recurrence rate and complications were analyzed, as were risk factors for conversion. RATS was performed in 95 patients with NSCLC clinical or pathological stages IIB (N = 51), IIIA (N = 39), IIIB (N = 2) and IVA (N = 3). 10.5% had received neoadjuvant chemoradiotherapy. Pathological staging was T3 in 33.7% and T4 in 34.7%. RATS was completed in 77.9% with a radical resection rate of 94.8%. Lobectomy was performed in 67.4% of the total resections. Conversion was for strategic (18.9%) and emergency (3.2%) reasons. Pneumonectomy (p = 0.001), squamous cell carcinoma (p < 0.001), additional resection of adjacent structures (p = 0.025) and neoadjuvant chemoradiation (p = 0.017) were independent risk factors for conversion. Major post-operative complications occurred in ten patients (10.5%) including an in-hospital mortality of 2.1% (n = 2). Median recurrence-free survival was estimated at 39.4 months (CI 16.4-62.5). Two- and 5-year recurrence-free survival rates were 53.8% and 36.7%, respectively. This study concludes that RATS is safe and feasible in higher staged NSCLC tumors after exclusion of unforeseen N2 disease. It brings new perspective on the potential of RATS in higher stages, dealing with larger and more invasive tumors. Show less
Stal, R.; Ramiro, S.; Baraliakos, X.; Braun, J.; Reijnierse, M.; Berg, R. van den; ... ; Gaalen, F.A. van 2023
Objectives: To assess construct validity of the CT Syndesmophyte Score (CTSS) for the measurement of structural spinal damage in patients with radiographic axial spondyloarthritis. Methods: Low... Show moreObjectives: To assess construct validity of the CT Syndesmophyte Score (CTSS) for the measurement of structural spinal damage in patients with radiographic axial spondyloarthritis. Methods: Low-dose CT and conventional radiography (CR) were performed at baseline and 2 years. CT was assessed with CTSS by two readers and CR with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by three readers. Two hypotheses were tested: (1) syndesmophytes scored with CTSS are also detected with mSASSS at baseline or 2 years later; (2) CTSS is non-inferior to mSASSS in correlations with spinal mobility measures. Presence of a syndesmophyte was determined per reader per corner for all anterior cervical and lumbar corners on CT at baseline and CR at baseline and 2 years. Correlations of CTSS and mSASSS with six spinal/hip mobility measurements plus Bath Ankylosing Spondylitis Metrology Index (BASMI) were tested. Results: Data from 48 patients (85% male, 85% HLA-B27+, mean age 48 years) were available for hypothesis 1 and 41/48 were available for hypothesis 2. At baseline, syndesmophytes were scored with CTSS in 348 (reader 1, 38%) and 327 (reader 2, 36%) corners out of 917. Of these, depending on reader pairs, 62%-79% were also seen on CR at baseline or after 2 years. CTSS correlated well (r(s)0.46-0.73), and with higher correlation coefficients than mSASSS (r(s)0.34-0.64), with all spinal mobility measures and BASMI. Conclusions:The good agreement between syndesmophytes detected by CTSS and mSASSS and the strong correlation of CTSS with spinal mobility support the construct validity of the CTSS. Show less
Marques, M.L.; Silva, N.P. da; Heijde, D. van der; Stal, R.; Baraliakos, X.; Braun, J.; ... ; Gaalen, F.A. van 2023
Objective: To investigate whether in radiographic axial spondyloarthritis (r-axSpA) inflammation is associated with lower trabecular bone density (TBD), and subsequently, if a lower TBD increases... Show moreObjective: To investigate whether in radiographic axial spondyloarthritis (r-axSpA) inflammation is associated with lower trabecular bone density (TBD), and subsequently, if a lower TBD increases the likelihood of 2-year bone formation at the same vertebra. Methods: Whole spine (C3-L5) data from patients included in the multicentre 2-year Sensitive Imaging in Ankylosing Spondylitis cohort was used. Two readers measured baseline TBD by Hounsfield units (HU) on low-dose CT (ldCT). Baseline MRI bone marrow oedema (BME) status scores and ldCT syndesmophyte formation and/or growth change-from-baseline scores were assessed by three and two readers, respectively. Average of readers' continuous measurements or readers' agreement in binary scores generated within the same vertebra (1-present in >= 1 quadrant/0-absent in all quadrants) were used. Multilevel generalised estimating equations models were used, the unit of analysis being the vertebra. Results: In 50 patients with r-axSpA, TBD HU decreased from cranial to caudal vertebrae. Baseline MRI-BME was present in 300/985 (30%) and syndesmophytes in 588/910 (65%) vertebrae, both most prevalent at thoracolumbar region. Syndesmophyte formation or growth was observed in 18% of at-risk vertebrae (124/691). A significant confounder-adjusted association was found between inflammation and lower TBD (regression coefficient=-51; 95% CI-63 to -39). TBD was not associated with 2-year syndesmophyte formation or growth (adjusted OR 1.00; 95% CI 0.99 to 1.00). Conclusion: In r-axSpA, while vertebral inflammation was associated with lower vertebral TBD, lower vertebral TBD itself did not increase the risk for new bone formation at the same vertebra. In preventing syndesmophyte progression, targeting local inflammation seems more important than targeting vertebral trabecular bone loss. Show less
Marques, M.L.; Silva, N.P. da; Heijde, D. van der; Stal, R.; Baraliakos, X.; Braun, J.; ... ; Gaalen, F.A. van 2023
Objective To investigate whether in radiographic axial spondyloarthritis (r-axSpA) inflammation is associated with lower trabecular bone density (TBD), and subsequently, if a lower TBD increases... Show moreObjective To investigate whether in radiographic axial spondyloarthritis (r-axSpA) inflammation is associated with lower trabecular bone density (TBD), and subsequently, if a lower TBD increases the likelihood of 2-year bone formation at the same vertebra.Methods Whole spine (C3–L5) data from patients included in the multicentre 2-year Sensitive Imaging in Ankylosing Spondylitis cohort was used. Two readers measured baseline TBD by Hounsfield units (HU) on low-dose CT (ldCT). Baseline MRI bone marrow oedema (BME) status scores and ldCT syndesmophyte formation and/or growth change-from-baseline scores were assessed by three and two readers, respectively. Average of readers’ continuous measurements or readers’ agreement in binary scores generated within the same vertebra (1—present in ≥1 quadrant/0—absent in all quadrants) were used. Multilevel generalised estimating equations models were used, the unit of analysis being the vertebra.Results In 50 patients with r-axSpA, TBD HU decreased from cranial to caudal vertebrae. Baseline MRI-BME was present in 300/985 (30%) and syndesmophytes in 588/910 (65%) vertebrae, both most prevalent at thoracolumbar region. Syndesmophyte formation or growth was observed in 18% of at-risk vertebrae (124/691). A significant confounder-adjusted association was found between inflammation and lower TBD (regression coefficient=−51; 95% CI−63 to −39). TBD was not associated with 2-year syndesmophyte formation or growth (adjusted OR 1.00; 95% CI 0.99 to 1.00).Conclusion In r-axSpA, while vertebral inflammation was associated with lower vertebral TBD, lower vertebral TBD itself did not increase the risk for new bone formation at the same vertebra. In preventing syndesmophyte progression, targeting local inflammation seems more important than targeting vertebral trabecular bone loss. 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
Purpose: Intraoperative identification of lung tumors can be challenging. Tumor-targeted fluorescence-guided surgery can provide surgeons with a tool for real-time intraoperative tumor detection.... Show morePurpose: Intraoperative identification of lung tumors can be challenging. Tumor-targeted fluorescence-guided surgery can provide surgeons with a tool for real-time intraoperative tumor detection. This study evaluated cell surface biomarkers, partially selected via data-driven selection software, as potential targets for fluorescence-guided surgery in non-small cell lung cancers: adenocarcinomas (ADC), adenocarcinomas in situ (AIS), and squamous cell carcinomas (SCC). Procedures: Formalin-fixed paraffin-embedded tissue slides of resection specimens from 15 patients with ADC and 15 patients with SCC were used and compared to healthy tissue. Molecular targets were selected based on two strategies: (1) a data-driven selection using > 275 multi-omics databases, literature, and experimental evidence; and (2) the availability of a fluorescent targeting ligand in advanced stages of clinical development. The selected targets were carbonic anhydrase 9 (CAIX), collagen type XVII alpha 1 chain (collagen XVII), glucose transporter 1 (GLUT1), G protein-coupled receptor 87 (GPR87), transmembrane protease serine 4 (TMPRSS4), carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), folate receptor alpha (FR alpha), integrin alpha v beta 6 (alpha v beta 6), and urokinase-type plasminogen activator receptor (uPAR). Tumor expression of these targets was assessed by immunohistochemical staining. A total immunostaining score (TIS, range 0-12), combining the percentage and intensity of stained cells, was calculated. The most promising targets in ADC were explored in six AIS tissue slides to explore its potential in non-palpable lesions. Results: Statistically significant differences in TIS between healthy lung and tumor tissue for ADC samples were found for CEA, EpCAM, FR alpha, alpha v beta 6, CAIX, collagen XVII, GLUT-1, and TMPRSS4, and of these, CEA, CAIX, and collagen XVII were also found in AIS. For SCC, EpCAM, uPAR, CAIX, collagen XVII, and GLUT-1 were found to be overexpressed. Conclusions: EpCAM, CAIX, and Collagen XVII were identified using concomitant use of data-driven selection software and clinical evidence as promising targets for intraoperative fluorescence imaging for both major subtypes of non-small cell lung carcinomas. Show less
Marques, M.L.; Silva, N.P. da; Heijde, D. van der; Reijnierse, M.; Baraliakos, X.; Braun, J.; ... ; Ramiro, S. 2022
Objectives: To describe low dose Computed Tomography (ldCT) Hounsfield Units (HU) two-year change-from -baseline values (expressing trabecular bone density changes) and analyse their inter-reader... Show moreObjectives: To describe low dose Computed Tomography (ldCT) Hounsfield Units (HU) two-year change-from -baseline values (expressing trabecular bone density changes) and analyse their inter-reader reliability per vertebra in radiographic axial spondyloarthritis (r-axSpA). Methods: We used 49 patients with r-axSpA from the multicentre two-year Sensitive Imaging in Ankylosing Spondylitis (SIAS) study. LdCT HU were independently measured by two trained readers at baseline and two years. Mean (standard deviation, SD) for the change-from-baseline HU values were provided per vertebra by reader. Intraclass correlation coefficients (ICC; absolute agreement, two-way random effect), Bland-Altman plots and smallest detectable change (SDC) were obtained. Percentages of vertebrae in which readers agreed on the direction of change and on change >|SDC| were computed. Results: Overall, 1,053 (98% of all possible) vertebrae were assessed by each reader both at baseline and two years. Over two years, HU mean change values varied from-23 to 28 and 29 for reader 1 and 2, respectively. Inter-reader reliability of the two-year change-from-baseline values per vertebra was excellent: ICC:0.91-0.99; SDC:6-10; Bland-Altman plots were homoscedastic, with negligible systematic error between readers. Readers agreed on the direction of change in 88-96% and on change >|SDC| in 58-94% of vertebrae, per vertebral level, from C3 to L5. Overall, similar results were obtained across all vertebrae. Conclusion: LdCT measurement of HU is a reliable method to assess two-year changes in trabecular bone density at each vertebra from C3-L5. Being reliable across all vertebrae, this methodology can aid the study of trabecular bone density changes over time in r-axSpA, a disease affecting the whole spine. Show less
Neo(adjuvant) systemic treatment regimens containing anthracyclines such as doxorubicin cause a significant risk of heart failure. These regimens are one of the corner stones of osteosarcoma... Show moreNeo(adjuvant) systemic treatment regimens containing anthracyclines such as doxorubicin cause a significant risk of heart failure. These regimens are one of the corner stones of osteosarcoma treatment, and therefore several guidelines are in place to steer cardiotoxicity monitoring through baseline risk stratification and cardiac surveillance during and after completion of cancer therapy. Importantly, baseline risk stratification modules are dependent on age, prior cardiovascular disease and cardiovascular risk factors. Because the majority of osteosarcoma patients are below 30 years of age these criteria rarely apply and most patients are assigned to low or medium risk categories, whereas cardiovascular complications have profound impact on morbidity and mortality in this young population. Therefore, cardiac surveillance is very important in this group for timely detection of cardiotoxicity. Moreover, when severe cardiotoxicity that requires advanced heart failure treatment occurs, a cancer diagnosis has significant implications on treatment options, i.e. mechanical circulatory support and heart transplantation. These challenges are presented in this case of a patient without clinical risk factors admitted with cardiogenic shock requiring advanced heart failure treatment within 1 month after completion of doxorubicin containing chemotherapy for the treatment of high grade osteosarcoma. Show less
Webers, C.; Kiltz, U.; Braun, J.; Heijde, D. van der; Boonen, A. 2022
Objective To investigate the effect of pharmacological treatment of SpA on depressive symptoms and explore whether this effect differs between drug classes. Methods Data from the observational... Show moreObjective To investigate the effect of pharmacological treatment of SpA on depressive symptoms and explore whether this effect differs between drug classes. Methods Data from the observational Assessment of SpondyloArthritis international Society Health Index Validation Study were used. Patients were assessed at baseline and after initiation of NSAIDs/conventional synthetic DMARDs (csDMARDs)/TNF inhibitors (TNFis). Depressive symptoms were assessed with the Hospital Anxiety and Depression Scale depression subscale [HADS-D; 0-21 (best-worst)]. Covariables included demographics and disease characteristics, including disease activity [Ankylosing Spondylitis Disease Activity Score (ASDAS)/BASDAI]. The change in HADS-D from baseline was compared between treatments (NSAIDs/csDMARDs/TNFis) with analysis of variance and multivariable regression analysis. Results A total of 304 patients were included; 102/45/157 initiated NSAIDs/csDMARDs/TNFis and 260 (85%) / 44 (15%) had axial/peripheral SpA. At baseline, the mean HADS-D was 6.9 (s.d. 4.2); 126 (42%) were possibly depressed (HADS-D >= 8) and 66 (22%) were probably depressed (HADS-D >= 11). At follow-up, depressive symptoms significantly improved in all treatment groups. In multivariable regression without disease activity measures, initiating TNFis compared with NSAIDs was associated with greater improvement in depressive symptoms [beta = -1.27 (95% CI -2.23, -0.32)] and lower odds of possible depression at follow-up [odds ratio 0.47 (95% CI 0.23, 0.94)]. This association was attenuated after additional adjustment for disease activity (ASDAS/BASDAI) but not CRP. csDMARDs did not differ from NSAIDs regarding their effect on HADS-D. Between-drug class results were confirmed in axial SpA (axSpA), although less clear in peripheral SpA. Conclusion Treatment of active SpA also improves depressive symptoms. Especially in axSpA, TNFis have a greater effect than NSAIDs, which is mainly explained by a stronger effect on disease activity. We found no evidence for a direct link between CRP-mediated inflammation and depressive symptoms in SpA. Show less
