ObjectivesEndobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has an important role in the diagnosis and staging of lung cancer. Evaluation of programmed death ligand 1 (PD... Show moreObjectivesEndobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has an important role in the diagnosis and staging of lung cancer. Evaluation of programmed death ligand 1 (PD-L1) expression and molecular profiling has become standard of care but cytological samples frequently contain insufficient tumor cells. The 22G Acquire needle with Franseen needle tip was developed to perform transbronchial needle biopsy (TBNB) with improved tissue specimens. This study evaluated if the 22G Acquire TBNB needle results in enhanced PD-L1 suitability rate compared to the regular Expect 22G TBNA needle.Methodsin this multi-center randomized clinical trial (Netherlands Trial Register NL7701), patients with suspected (N)SCLC and an indication for mediastinal/hilar staging or lung tumor diagnosis were recruited in five university and general hospitals in the Netherlands, Poland, Italy and Czech Republic. Patients were randomized (1:1) between the two needles. Two blinded reference pathologists evaluated the samples. The primary outcome was PD-L1 suitability rate in patients with a final diagnosis of lung cancer. In case no malignancy was diagnosed, the reference standard was surgical verification or 6 month follow-up.Results154 patients were randomized (n = 76 Acquire TBNB; n = 78 Expect TBNA) of which 92.9% (n = 143) had a final malignant diagnosis. Suitability for PD-L1 analysis was 80.0% (n = 56/70; 95 %CI 0.68–0.94) with the Acquire needle and 76.7% (n = 56/73; 95 %CI 0.65–0.85) with the Expect needle (p = 0.633). Acquire TBNB needle specimens provided more frequent superior quality (65.3% (95 %CI 0.57–0.73) vs 49.4% (95 %CI 0.41–0.57, p = 0.005) and contained more tissue cores (72.0% (95 %CI 0.60-0.81) vs 41.0% (95 %CI 0.31–0.54, p < 0.01). There were no statistically significant differences in tissue adequacy, suitability for molecular analysis and sensitivity for malignancy and N2/N3 disease.ConclusionThe 22G Acquire TBNB needle procured improved quality tissue specimens compared to the Expect TBNA needle but this did not result in an improved the suitability rate for PD-L1 analysis. Show less
Background There is a considerable diagnostic delay in the diagnosis 'benign acquired subglottic stenosis in adults' (SGS, diagnosed by the reference standard, i.e. laryngo- or bronchoscopy).... Show moreBackground There is a considerable diagnostic delay in the diagnosis 'benign acquired subglottic stenosis in adults' (SGS, diagnosed by the reference standard, i.e. laryngo- or bronchoscopy). Patients are frequently misdiagnosed since symptoms of this rare disease may mimic symptoms of 'asthma.' The 'Expiratory Disproportion Index' (EDI) obtained by spirometry, may be a simple instrument to detect an SGS-patient. The aim of this study was to evaluate the diagnostic accuracy of the EDI in differentiating SGS patients from asthma patients.Methods We calculated the EDI from spirometry results of all SGS-patients in the Leiden University Medical Center (LUMC), who had not received treatment 2 years before their spirometry examination. We compared these EDI results with the EDI results of all true asthma patients between 2011 and 2019, who underwent a bronchoscopy (exclusion of SGS by laryngo- or bronchoscopy).Results Fifty patients with SGS and 32 true asthma patients were included. Median and IQR ranges of the EDI for SGS and asthma patients were 67.10 (54.33-79.18) and 37.94 (32.41-44.63), respectively. Area under the curve (ROC) of the accuracy of the EDI at discriminating SGS and asthma patients was 0.92 (95% CI = 0.86-0.98). The best cut-off point for the EDI was > 48 (i.e. possible upper airway obstruction), with a sensitivity of 88.0%% (95%CI = 77.2-95.0%%) and specificity of 84.4% (95%CI = 69.4-94.1%).Conclusions The EDI has a good diagnostic accuracy discriminating subglottic stenosis patients from asthma patients, when compared to the reference standard. This measurement from spirometry may potentially shorten the diagnostic delay of SGS patients. Further studies are needed to evaluate clinical reproducibility. Show less
BackgroundPulmonary infarction (PI) is relatively common in pulmonary embolism (PE). The association between PI and persistent symptoms or adverse events is largely unknown.AimTo evaluate the... Show moreBackgroundPulmonary infarction (PI) is relatively common in pulmonary embolism (PE). The association between PI and persistent symptoms or adverse events is largely unknown.AimTo evaluate the predictive value of radiological PI signs at acute PE diagnosis on 3-month outcomes.MethodsWe studied a convenience cohort with computed tomographypulmonary angiography (CTPA)-confirmed PE for whom extensive 3-month follow-up data were available. The CTPAs were re-evaluated for signs of suspected PI. Associations with presenting symptoms, adverse events (recurrent thrombosis, PE-related readmission and mortality) and self-reported persistent symptoms (dyspnea, pain and post-PE functional impairment) at 3-month follow-up were investigated using univariate Cox regression analysis.ResultsAt re-evaluation of the CTPAs, 57 of 99 patients (58 %) had suspected PI, comprising a median of 1 % (IQR 1–3) of total lung parenchyma. Patients with suspected PI more often presented with hemoptysis (11 % vs. 0 %) and pleural pain (OR 2.7, 95%CI 1.2–6.2), and with more proximal PE on CTPA (OR 1.6, 95%CI 1.1–2.4) than patients without suspected PI. There was no association with adverse events, persistent dyspnea or pain at 3-month follow-up, but signs of PI predicted more functional impairment (OR 3.03, 95%CI 1.01–9.13). Sensitivity analysis with the largest infarctions (upper tertile of infarction volume) yielded similar results.ConclusionsPE patients radiologically suspected of PI had a different clinical presentation than patients without those signs and reported more functional limitations after 3 months of follow-up, a finding that could guide patient counselling. Show less
Liem, S.I.E.; Ciaffi, J.; Leeuwen, N.M. van; Boonstra, M.; Ahmed, S.; Voorde, L.J.J. van de; ... ; Vries-Bouwstra, J. de 2023
Background: Since 2009, Dutch patients with a confirmed diagnosis/suspicion of systemic sclerosis (SSc) can be referred to the Leiden Combined Care in Systemic Sclerosis (CCISS) cohort. This study... Show moreBackground: Since 2009, Dutch patients with a confirmed diagnosis/suspicion of systemic sclerosis (SSc) can be referred to the Leiden Combined Care in Systemic Sclerosis (CCISS) cohort. This study evaluated whether early recognition of SSc has improved over time and whether disease characteristics and survival has changed over time. Methods: 643 SSc patients fulfilling American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria were included and categorised into three groups based on cohort-entry year: (1) 2010-2013 (n=229 (36%)), (2) 2014-2017 (n=207 (32%)) and (3) 2018-2021 (n=207 (32%)). Variables including disease duration, interstitial lung disease (ILD), digital ulcers (DU), diffuse cutaneous SSc (dcSSc), antitopoisomerase (ATA) and anticentromere (ACA) antibodies, and survival from disease onset were compared between cohort-entry groups, including analyses stratified for sex and autoantibodies. Results: Over time, duration between onset of disease symptoms and cohort entry decreased in males and females, but was always longer in females than in males.The proportion of patients presenting with DU decreased, especially in ACA+SSc patients. Almost no ACA+ patients presented with ILD, while in ATA+ patients this proportion was 25% in 2010-2013 and decreased to 19% in 2018-2021. A reduction in patients presenting with clinically meaningful ILD and dcSSc was observed.Overall 8-year survival for males was 59% (95% CI 40% to 73%) and for females 89% (95% CI 82% to 93%). Eight-year survival showed a trend for improvement over time, and was always worse in males. Conclusion: We observed a decrease in disease duration in Leiden CCISS cohort at cohort entry, possibly indicating more timely diagnosis of SSc. This could provide opportunities for early interventions. While symptom duration at presentation is longer in females, mortality is consistently higher in males, underlining the urge for sex-specific treatment and follow-up. Show less
Zhai, Z.W.; Boon, G.J.A.M.; Staring, M.; Dam, L.F. van; Kroft, L.J.M.; Girón, I.H.; ... ; Stoel, B.C. 2023
The shape and distribution of vascular lesions in pulmonary embolism (PE) and chronic thromboembolic pulmonary hypertension (CTEPH) are different. We investigated whether automated quantification... Show moreThe shape and distribution of vascular lesions in pulmonary embolism (PE) and chronic thromboembolic pulmonary hypertension (CTEPH) are different. We investigated whether automated quantification of pulmonary vascular morphology and densitometry in arteries and veins imaged by computed tomographic pulmonary angiography (CTPA) could distinguish PE from CTEPH. We analyzed CTPA images from a cohort of 16 PE patients, 6 CTEPH patients, and 15 controls. Pulmonary vessels were extracted with a graph-cut method, and separated into arteries and veins using deep-learning classification. Vascular morphology was quantified by the slope (α) and intercept (β) of the vessel radii distribution. To quantify lung perfusion defects, the median pulmonary vascular density was calculated. By combining these measurements with densities measured in parenchymal areas, pulmonary trunk, and descending aorta, a static perfusion curve was constructed. All separate quantifications were compared between the three groups. No vascular morphology differences were detected in contrast to vascular density values. The median vascular density (interquartile range) was −567 (113), −452 (95), and −470 (323) HU, for the control, PE, and CTEPH group. The static perfusion curves showed different patterns between groups, with a statistically significant difference in aorta-pulmonary trunk gradient between the PE and CTEPH groups (p = 0.008). In this proof of concept study, not vasculature morphology but densities differentiated between patients of three groups. Further technical improvements are needed to allow for accurate differentiation between PE and CTEPH, which in this study was only possible statistically by measuring the density gradient between aorta and pulmonary trunk. Show less
Liem, S.I.E.; Ciaffi, J.; Leeuwen, N.M. van; Boonstra, M.; Ahmed, S.; Voorde, L.J.J. van de; ... ; Vries-Bouwstra, J. de 2023
Background Since 2009, Dutch patients with a confirmed diagnosis/suspicion of systemic sclerosis (SSc) can be referred to the Leiden Combined Care in Systemic Sclerosis (CCISS) cohort. This study... Show moreBackground Since 2009, Dutch patients with a confirmed diagnosis/suspicion of systemic sclerosis (SSc) can be referred to the Leiden Combined Care in Systemic Sclerosis (CCISS) cohort. This study evaluated whether early recognition of SSc has improved over time and whether disease characteristics and survival has changed over time.Methods 643 SSc patients fulfilling American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria were included and categorised into three groups based on cohort-entry year: (1) 2010–2013 (n=229 (36%)), (2) 2014–2017 (n=207 (32%)) and (3) 2018–2021 (n=207 (32%)). Variables including disease duration, interstitial lung disease (ILD), digital ulcers (DU), diffuse cutaneous SSc (dcSSc), antitopoisomerase (ATA) and anticentromere (ACA) antibodies, and survival from disease onset were compared between cohort-entry groups, including analyses stratified for sex and autoantibodies.Results Over time, duration between onset of disease symptoms and cohort entry decreased in males and females, but was always longer in females than in males.The proportion of patients presenting with DU decreased, especially in ACA+SSc patients. Almost no ACA+ patients presented with ILD, while in ATA+ patients this proportion was 25% in 2010–2013 and decreased to 19% in 2018–2021. A reduction in patients presenting with clinically meaningful ILD and dcSSc was observed.Overall 8-year survival for males was 59% (95% CI 40% to 73%) and for females 89% (95% CI 82% to 93%). Eight-year survival showed a trend for improvement over time, and was always worse in males.Conclusion We observed a decrease in disease duration in Leiden CCISS cohort at cohort entry, possibly indicating more timely diagnosis of SSc. This could provide opportunities for early interventions. While symptom duration at presentation is longer in females, mortality is consistently higher in males, underlining the urge for sex-specific treatment and follow-up. Show less
Pulmonary function tests (PFTs) play an important role in screening and following-up pulmonary involvement in systemic sclerosis (SSc). However, some patients are not able to perform PFTs due to... Show morePulmonary function tests (PFTs) play an important role in screening and following-up pulmonary involvement in systemic sclerosis (SSc). However, some patients are not able to perform PFTs due to contraindications. In addition, it is unclear how lung function is affected by changes in lung structure in SSc. Therefore, this study aims to explore the potential of automatically estimating PFT results from chest CT scans of SSc patients and how different regions influence the estimation of PFTs. Deep regression networks were developed with transfer learning to estimate PFTs from 316 SSc patients. Segmented lungs and vessels were used to mask the CT images to train the network with different inputs: from entire CT scan, lungs-only to vessels-only. The network trained on entire CT scans with transfer learning achieved an ICC of 0.71, 0.76, 0.80, and 0.81 for the estimation of DLCO, FEV1, FVC and TLC, respectively. The performance of the networks gradually decreased when trained on data from lungs-only and vessels-only. Regression attention maps showed that regions close to large vessels were highlighted more than other regions, and occasionally regions outside the lungs were highlighted. These experiments show that apart from the lungs and large vessels, other regions contribute to PFT estimation. In addition, adding manually designed biomarkers increased the correlation (R) from 0.75, 0.74, 0.82, and 0.83 to 0.81, 0.83, 0.88, and 0.90, respectively. This suggests that that manually designed imaging biomarkers can still contribute to explaining the relation between lung function and structure. Show less
Khidir, S.J.H.; Boonstra, M.; Bergstra, S.A.; Boerrigter, G.W.M.; Voog-van der Harst, E.M.; Ninaber, M.K.; ... ; Vries-Bouwstra, J.K. de 2022
Objective: Decreased maximal mouth opening is a common and disabling manifestation in systemic sclerosis patients. We aimed to study the course of maximal mouth opening, determinants of smaller... Show moreObjective: Decreased maximal mouth opening is a common and disabling manifestation in systemic sclerosis patients. We aimed to study the course of maximal mouth opening, determinants of smaller maximal mouth opening over time and the burden of smaller maximal mouth opening on mouth handicap. Methods: Consecutive systemic sclerosis patients participating in the prospective Leiden Combined Care in systemic sclerosis cohort were included. Annual clinical assessment included maximal mouth opening measurement and mouth handicap evaluation (Mouth Handicap in Systemic Sclerosis scale). Presence of microstomia (maximal mouth opening < 30 mm) was studied. Maximal mouth opening over time was assessed on group level and for all patients individually. Baseline characteristics were analysed for their association with smaller maximal mouth opening over time (linear mixed-effects models). Furthermore, cross-sectional association between maximal mouth opening with Mouth Handicap in Systemic Sclerosis scale was assessed (linear regression analysis). Results: A total of 382 systemic sclerosis patients were studied with median follow-up time of 2.0 years (interquartile range = 0.0-3.0). At baseline, mean maximal mouth opening was 42.2 +/- 8.0 mm and 7% suffered from microstomia. Annual decrease of > 5.0 mm in maximal mouth opening during follow-up occurred in 63 patients and was accompanied by increase in disease severity. Disease characteristics at baseline independently predictive for smaller maximal mouth opening over time were: more extended skin subtype; peripheral vasculopathy; pulmonary, renal and gastrointestinal involvement. Smaller maximal mouth opening was significantly associated with more reported mouth handicap. Conclusion: The course of maximal mouth opening is stable in a majority of systemic sclerosis patients. Still, maximal mouth opening over time was smaller in patients with more severe organ involvement. Although microstomia was infrequent, a smaller maximal mouth opening was significantly associated with more mouth handicap, indicating the importance to address maximal mouth opening in routine care of systemic sclerosis patients. Show less
Khidir, S.J.H.; Boonstra, M.; Bergstra, S.A.; Boerrigter, G.W.M.; Voog-van der Harst, E.M.; Ninaber, M.K.; ... ; Vries-Bouwstra, J.K. de 2022
Objective:Decreased maximal mouth opening is a common and disabling manifestation in systemic sclerosis patients. We aimed to study the course of maximal mouth opening, determinants of smaller... Show moreObjective:Decreased maximal mouth opening is a common and disabling manifestation in systemic sclerosis patients. We aimed to study the course of maximal mouth opening, determinants of smaller maximal mouth opening over time and the burden of smaller maximal mouth opening on mouth handicap.Methods:Consecutive systemic sclerosis patients participating in the prospective Leiden Combined Care in systemic sclerosis cohort were included. Annual clinical assessment included maximal mouth opening measurement and mouth handicap evaluation (Mouth Handicap in Systemic Sclerosis scale). Presence of microstomia (maximal mouth opening < 30 mm) was studied. Maximal mouth opening over time was assessed on group level and for all patients individually. Baseline characteristics were analysed for their association with smaller maximal mouth opening over time (linear mixed-effects models). Furthermore, cross-sectional association between maximal mouth opening with Mouth Handicap in Systemic Sclerosis scale was assessed (linear regression analysis).Results:A total of 382 systemic sclerosis patients were studied with median follow-up time of 2.0 years (interquartile range = 0.0–3.0). At baseline, mean maximal mouth opening was 42.2 ± 8.0 mm and 7% suffered from microstomia. Annual decrease of > 5.0 mm in maximal mouth opening during follow-up occurred in 63 patients and was accompanied by increase in disease severity. Disease characteristics at baseline independently predictive for smaller maximal mouth opening over time were: more extended skin subtype; peripheral vasculopathy; pulmonary, renal and gastrointestinal involvement. Smaller maximal mouth opening was significantly associated with more reported mouth handicap.Conclusion:The course of maximal mouth opening is stable in a majority of systemic sclerosis patients. Still, maximal mouth opening over time was smaller in patients with more severe organ involvement. Although microstomia was infrequent, a smaller maximal mouth opening was significantly associated with more mouth handicap, indicating the importance to address maximal mouth opening in routine care of systemic sclerosis patients. Show less
Survivors of acute pulmonary embolism (PE) are at risk of developing persistent, sometimes disabling symptoms of dyspnea and/or functional limitations despite adequate anticoagulant treatment,... Show moreSurvivors of acute pulmonary embolism (PE) are at risk of developing persistent, sometimes disabling symptoms of dyspnea and/or functional limitations despite adequate anticoagulant treatment, fulfilling the criteria of the post-PE syndrome (PPES). PPES includes chronic thromboembolic pulmonary hypertension (CTEPH), chronic thromboembolic pulmonary disease, post-PE cardiac impairment (characterized as persistent right ventricle impairment after PE), and post-PE functional impairment. To improve the overall health outcomes of patients with acute PE, adequate measures to diagnose PPES and strategies to prevent and treat PPES are essential. Patient-reported outcome measures are very helpful to identify patients with persistent symptoms and functional impairment. The primary concern is to identify and adequately treat patients with CTEPH as early as possible. After CTEPH is ruled out, additional diagnostic tests including cardiopulmonary exercise tests, echocardiography, and imaging of the pulmonary vasculature may be helpful to rule out non-PE-related comorbidities and confirm the ultimate diagnosis. Most PPES patients will show signs of physical deconditioning as main explanation for their clinical presentation. Therefore, cardiopulmonary rehabilitation provides a good potential treatment option for this patient category, which warrants testing in adequately designed and executed randomized trials. In this review, we describe the definition and characteristics of PPES and its diagnosis and management. Show less
Survivors of acute pulmonary embolism (PE) are at risk of developing persistent, sometimes disabling symptoms of dyspnea and/or functional limitations despite adequate anticoagulant treatment,... Show moreSurvivors of acute pulmonary embolism (PE) are at risk of developing persistent, sometimes disabling symptoms of dyspnea and/or functional limitations despite adequate anticoagulant treatment, fulfilling the criteria of the post-PE syndrome (PPES). PPES includes chronic thromboembolic pulmonary hypertension (CTEPH), chronic thromboembolic pulmonary disease, post-PE cardiac impairment (characterized as persistent right ventricle impairment after PE), and post-PE functional impairment. To improve the overall health outcomes of patients with acute PE, adequate measures to diagnose PPES and strategies to prevent and treat PPES are essential. Patient-reported outcome measures are very helpful to identify patients with persistent symptoms and functional impairment. The primary concern is to identify and adequately treat patients with CTEPH as early as possible. After CTEPH is ruled out, additional diagnostic tests including cardiopulmonary exercise tests, echocardiography, and imaging of the pulmonary vasculature may be helpful to rule out non-PE-related comorbidities and confirm the ultimate diagnosis. Most PPES patients will show signs of physical deconditioning as main explanation for their clinical presentation. Therefore, cardiopulmonary rehabilitation provides a good potential treatment option for this patient category, which warrants testing in adequately designed and executed randomized trials. In this review, we describe the definition and characteristics of PPES and its diagnosis and management. Show less
Background At the most severe end of the spectrum of congenital heart disease are patients with an univentricular physiology. They comprise a heterogeneous group of congenital heart malformations... Show moreBackground At the most severe end of the spectrum of congenital heart disease are patients with an univentricular physiology. They comprise a heterogeneous group of congenital heart malformations that have the common characteristic that the cardiac morphology is not equipped for sustaining a biventricular circulation. Case summary Here, we present a case of an adult patient after Fontan palliation, illustrative of the complex clinical course and the broad spectrum of complications that can be encountered during follow-up, highlighting the need for a multidisciplinary approach in the clinical care for these patients. Discussion During the surgical Fontan procedure, the inferior vena cava is connected to the pulmonary circulation, after prior connection of the superior vena cava to the pulmonary arterial circulation. The resulting cavopulmonary connection, thus lacking a subpulmonic ventricle, provides non-pulsatile passive flow of oxygen-poor blood from the systemic venous circulation into the lungs, and the functional monoventricle pumps the oxygen-rich pulmonary venous return blood into the aorta. With an operative mortality of <5% and current 30-year survival rates up to 85%, the adult population of patients with a Fontan circulation is growing. This increase in survival is, however, inevitably accompanied by long-term complications affecting multiple organ systems, resulting in decline in cardiovascular performance. Conclusion For optimal treatment, the evaluation in a multidisciplinary team is mandatory, using the specific expertise of the team members to timely detect and address late complications and to support quality of life. Show less
Ciaffi, J.; Leeuwen, N.M. van; Boonstra, M.; Kroft, L.J.M.; Schouffoer, A.A.; Ninaber, M.K.; ... ; Vries-Bouwstra, J.K. de 2022
Objective Hematopoietic stem cell transplantation (HSCT) and cyclophosphamide (CYC) are treatment options for progressive systemic sclerosis associated with interstitial lung disease (SSc-ILD). The... Show moreObjective Hematopoietic stem cell transplantation (HSCT) and cyclophosphamide (CYC) are treatment options for progressive systemic sclerosis associated with interstitial lung disease (SSc-ILD). The aims of our retrospective observational study were to evaluate: 1) the evolution of SSc-ILD in SSc patients treated with HSCT (assessed by high-resolution computed tomography [HRCT]; a group of patients treated with CYC was included as frame of reference); 2) how results of pulmonary function tests (PFTs) are associated with HRCT findings; and 3) which factors predict ILD reduction. Methods We semiquantitatively scored total ILD extent, reticulations, and ground-glass opacities (GGO) scores at baseline and at the 1-year HRCTs of SSc patients treated with HSCT or CYC. Linear association between changes in HRCT scores and PFT results and predictors of ILD improvement were studied. Results We included 51 patients (those treated with HSCT [n = 20] and those treated with CYC [n = 31]). The mean change in total ILD score was -5.1% (95% confidence interval [95% CI] -10.2, 0.0) in the HSCT treatment group (P = 0.050), and -1.0% (95% CI -4.3, 2.3) in the CYC treatment group (P = 0.535). For all patients, the evolution of HRCT scores was weakly associated with relative changes in PFT results. In univariate logistic regression, higher ground-glass opacities, higher total ILD, and lower single-breath diffusing capacity for carbon monoxide scores at baseline predicted improvement of ILD extent after treatment, but a multivariable model could not be built to assess independency of predictors. Conclusion One year after treatment with HSCT, a nonsignificant but clear reduction of SSc-ILD extent was observed. Changes in PFT results were associated with changes in HRCT scores but the correlation was weak and cannot be considered conclusive. Show less
Ciaffi, J.; Gegenava, M.; Ninaber, M.K.; Huizinga, T.W.J. 2021
Background and objective: Endosonography with intrathoracic nodal sampling is proposed as the single test with the highest granuloma detection rate in suspected sarcoidosis stage I/II. However,... Show moreBackground and objective: Endosonography with intrathoracic nodal sampling is proposed as the single test with the highest granuloma detection rate in suspected sarcoidosis stage I/II. However, most studies have been performed in limited geographical regions. Studies suggest that oesophageal endosonographic nodal sampling has higher diagnostic yield than endobronchial endosonographic nodal sampling, but a head-to-head comparison of both routes has never been performed.Methods: Global (14 hospitals, nine countries, four continents) randomized clinical trial was conducted in consecutive patients with suspected sarcoidosis stage I/II presenting between May 2015 and August 2017. Using an endobronchial ultrasound (EBUS) scope, patients were randomized to EBUS or endoscopic ultrasound (EUS)-B-guided nodal sampling, and to 22- or 25-G ProCore needle aspiration (2 x 2 factorial design). Granuloma detection rate was the primary study endpoint. Final diagnosis was based on cytology/pathology outcomes and clinical/radiological follow-up at 6 months.Results: A total of 358 patients were randomized: 185 patients to EBUS-transbronchial needle aspiration (EBUS-TBNA) and 173 to EUS-B-fine-needle aspiration (FNA). Final diagnosis was sarcoidosis in 306 patients (86%). Granuloma detection rate was 70% (130/185; 95% CI, 63-76) for EBUS-TBNA and 68% (118/173; 95% CI, 61-75) for EUS-B-FNA (p = 0.67). Sensitivity for diagnosing sarcoidosis was 78% (129/165; 95% CI, 71-84) for EBUS-TBNA and 82% (115/141; 95% CI, 74-87) for EUS-B-FNA (p = 0.46). There was no significant difference between the two needle types in granuloma detection rate or sensitivity.Conclusion: Granuloma detection rate of mediastinal/hilar nodes by endosonography in patients with suspected sarcoidosis stage I/II is high and similar for EBUS and EUS-B. These findings imply that both diagnostic tests can be safely and universally used in suspected sarcoidosis patients. Show less
Background: The Post-Pulmonary Embolism Syndrome (PPES) comprises heterogeneous entities, including chronic thromboembolic disease with/without pulmonary hypertension (CTEPH/CTEPD), and... Show moreBackground: The Post-Pulmonary Embolism Syndrome (PPES) comprises heterogeneous entities, including chronic thromboembolic disease with/without pulmonary hypertension (CTEPH/CTEPD), and deconditioning. Objectives: To assess underlying physiological determinants of PPES, and efficacy and safety of rehabilitation training in these patients.Methods: 56 consecutive PE patients with persistent dyspnea and/or functional limitations despite >3 months of anticoagulation underwent standardized diagnostic work-up including exercise testing as part of routine practice. All diagnostic (imaging and cardiopulmonary function) tests were interpreted by a core group of experienced clinicians. A subgroup of patients without CTEPH or other treatable conditions was referred for a 12-week personalized rehabilitation program, studying changes in physical condition and patient-reported outcome measures.Results: Persistent vascular occlusions were observed in 21/56 patients (38%) and CTEPH was confirmed in ten (18%). Regarding those without CTEPH, impaired cardiopulmonary responses were evident in 18/39 patients with available CPET data (46%), unrelated to chronic thrombi. Rehabilitation was completed by 27 patients after excluding 29 (patients with CTEPH or treatable comorbidities, refusal, ineligibility, or training elsewhere). Training intensity, PE-specific quality of life (PEmb-QoL) and fatigue (CIS) improved with a median difference of 20 W (p = 0.001), 3.9 points (p < 0.001) and 16 points (p = 0.003), respectively. Functional status (Post-VTE Functional Status Scale) improved >1 grade in 18 (67%) patients, and declined in one (3.7%).Conclusions: Our findings suggest that abnormal cardiopulmonary responses to exercise are common in patients with PPES and are not limited to those with chronic thrombi. Offering pulmonary rehabilitation to patients not treated otherwise seems safe and promising. Show less
Ouwerkerk, L. van; Meulen-de Jong, A.E. van de; Ninaber, M.K.; Teng, Y.K.O.; Huizinga, T.W.; Allaart, C.F. 2021
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
Objectives SLE and/or antiphospholipid syndrome (SLE/APS) are complex and rare systemic autoimmune diseases that predominantly affect women of childbearing age. Women with SLE/APS are at high risk... Show moreObjectives SLE and/or antiphospholipid syndrome (SLE/APS) are complex and rare systemic autoimmune diseases that predominantly affect women of childbearing age. Women with SLE/APS are at high risk of developing complications during pregnancy. Therefore, clinical practice guidelines recommend that patients with SLE/APS should receive multidisciplinary counselling before getting pregnant. We investigated the clinical effectiveness of implementing a multidisciplinary clinical pathway including prepregnancy counselling of patients with SLE/APS. Methods A clinical pathway with specific evaluation and prepregnancy counselling for patients with SLE/APS was developed and implemented in a tertiary, academic hospital setting. Patients were prospectively managed within the clinical pathway from 2014 onwards and compared with a retrospective cohort of patients that was not managed in a clinical pathway. Primary outcome was a combined outcome of disease flares for SLE and thromboembolic events for APS. Secondary outcomes were maternal and fetal pregnancy complications. Results Seventy-eight patients with 112 pregnancies were included in this study. The primary combined outcome was significantly lower in the pathway cohort (adjusted OR (aOR) 0.20 (95% CI 0.06 to 0.75)) which was predominantly determined by a fivefold risk reduction of SLE flares (aOR 0.22 (95% CI 0.04 to 1.09)). Maternal and fetal pregnancy complications were not different between the cohorts (respectively, aOR 0.91 (95% CI 0.38 to 2.17) and aOR 1.26 (95% CI 0.55 to 2.88)). Conclusions The outcomes of this study suggest that patients with SLE/APS with a pregnancy wish benefit from a multidisciplinary clinical pathway including prepregnancy counselling. Show less
