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Right heart catheterization (RHC) is the diagnostic standard for establishing residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). A potential non-invasive alternative diagnostic test could be electrocardiography (ECG)-derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO). We studied 66 CTEPH patients who underwent PEA. A subgroup of 20 patients also had a cardiac MRI before and after PEA. The diagnostic performance of the VG-RVPO for the detection of residual PH as well as the potential to replace RHC were assessed. Different cut-off values to define a normal VG-RVPO were evaluated. Also, we evaluated the association between mean pulmonary artery pressure (mPAP) and CMR derived indexed right ventricular (RV) mass and the VG-RVPO. During follow-up, 28 patients had residual PH (42%). A decrease in VG-RVPO after PEA was associated with decrease in mPAP or indexed RV mass post PEA (r = 0.55, p < 0.05 and r = 0.64, p < 0.05, respectively). If a normal VG-RVPO would exclude residual PH, the need for RHC would be reduced with 15-48%, but up to 36% of the CTEPH patients with residual PH would have been missed as they had a normal VG-RVPO. Although there was an association between the change in VG-RPVO and changes in mPAP or indexed RV mass, our study demonstrated that VG-RPVO has limited value in excluding the presence of residual PH post-PEA as up to 36% of the CTEPH patients with residual PH would have been missed if residual PH would have been excluded based on a normal VG-RVPO.

Background and Objective High variability in tacrolimus pharmacokinetics directly after lung transplantation (LuTx) may increase the risk for acute kidney injury (AKI) and transplant rejection. The primary objective was to compare pharmacokinetic variability in patients receiving tacrolimus orally versus intravenously early after LuTx. Methods Pharmacokinetic and clinical data from 522 LuTx patients transplanted between 2010 and 2020 in two university hospitals were collected to compare orally administered tacrolimus to intravenous tacrolimus early post-transplantation. Tacrolimus blood concentration variability, measured as intrapatient variability (IPV%) and  percentage of time within the therapeutic range (TTR%), was analyzed within the first 14 days after LuTx. Secondary outcomes were AKI, acute rejection, length of stay in the intensive care unit (ICU), and mortality in the ICU and during hospital admission. Results We included 224 patients in the oral and 298 in the intravenous group. The mean adjusted IPV% was 10.8% (95% confidence interval [CI] 6.9–14.6; p < 0.001) higher in the oral group (27.2%) than the intravenous group (16.4%). The mean TTR% was 7.3% (95% CI − 11.3 to − 3.4; p < 0.001) lower in the oral group (39.6%) than in the intravenous group (46.9%). The incidence of AKI was 46.0% for oral and 42.6% for intravenous administration (adjusted odds ratio [OR] 1.2; 95% CI 0.8–1.8; p = 0.451). The frequencies of clinically diagnosed acute rejection in the oral and intravenous groups were nonsignificant (24.6% vs 17.8%; OR 1.5 [95% CI 1.0–2.3; p = 0.059]). ICU and hospital mortality rate and ICU length of stay were similar. Conclusions Administering tacrolimus orally directly after LuTx leads to a higher variability in blood concentrations compared to intravenous administration. There was no difference in the occurrence of AKI or transplant rejection.

According to computed tomography-pulmonary angiography, CTEPH was classified as either proximal (level I/II disease: lesions starting in the main or lobar arteries) or distal (level III-IV disease: lesions starting in the segmental and subsegmental) (3) for each side separately. [...]Zc may be a relevant additional component of afterload that was not accounted for in the current or any prior studies on load in CTEPH, which all focus on PVR and compliance. [...]RV function in CTEPH may be critically dependent on proximal vascular properties and wave propagations, which are not reflected in the three-component windkessel. [...]although patients with proximal and distal CTEPH present with similar resistance and compliance, we observed important differences in cardiac function.

Background Patients with a primary spontaneous pneumothorax (PSP) who are treated with chest tube drainage are traditionally connected to an analogue chest drainage system, containing a water seal and using a visual method of monitoring air leakage. Electronic systems with continuous digital monitoring of air leakage provide better insight into actual air leakage and changes in leakage over time, which may lead to a shorter length of hospital stay. Methods We performed a randomized controlled trial comparing the digital with analogue system, with the aim of demonstrating that use of a digital drainage system in PSP leads to a shorter hospital stay. Results In 102 patients enrolled with PSP we found no differences in total duration of chest tube drainage and hospital stay between the groups. However, in a post-hoc analysis, excluding 19 patients needing surgery due to prolonged air leakage, hospital stay was significantly shorter in the digital group (median 1 days, IQR 1–5 days) compared to the analogue group (median 3 days, IQR 2–5 days) (p 0.014). Treatment failure occurred in 3 patients in both groups; the rate of recurrence within 12 weeks was not significantly different between groups (16% in the digital group versus 8% in the analogue group, p 0.339). Conclusion Length of hospital stay was not shorter in patients with PSP when applying a digital drainage system compared to an analogue drainage system. However, in the large subgroup of uncomplicated PSP, a significant reduction in duration of drainage and hospital stay was demonstrated with digital drainage. These findings suggest that digital drainage may be a practical alternative to manual aspiration in the management of PSP. Trial registration Registered 22 September 2013 - Retrospectively registered, Trial NL4022 (NTR4195)

Background. Cancer has become an important cause of death in solid organ transplant patients. The cause of malignancies in patients with solid organ transplants is multifactorial, but the use of intensive immunosuppression is regarded as an important factor. We describe the spontaneous, complete regression of colon cancer liver metastases, without initiation of antitumor therapy, in a solid organ transplant patient after modulation of immunosuppressants. Case Presentation. A 59-year-old female was admitted with fever, general discomfort, and elevated liver enzymes. She had received a single lung transplant, five years prior, for end-stage chronic obstructive pulmonary disease. Abdominal ultrasound and a computed tomography scan showed extensive liver lesions, and liver biopsy determined that the lesions were liver metastases originating from a colonic adenocarcinoma. Histopathologic analysis revealed that the primary tumor and liver metastases were mismatch repair-deficient (BRAFV600E mutant and MLH1/PMS2-deficient), also known as a microsatellite instable tumor. The patient’s clinical condition deteriorated rapidly, and she was discharged home with palliative care. No antitumor treatment was initiated. Additionally, there was a short period without any immunosuppressants. Unexpectedly, her clinical condition improved, and complete regression of liver metastases was observed on imaging two months later. Unfortunately, the patient developed rejection of her lung transplant and succumbed to pulmonary disease six months following her cancer diagnosis. The autopsy confirmed the primary colon tumor location and complete regression of >40 liver metastases. Conclusions. Disinhibition and reset of the host immune response could have led to immune destruction of the liver metastases of this patient’s immunogenic dMMR colon carcinoma. This case underscores the huge impact that temporary relief from immunosuppressive therapy could have on tumor homeostasis. Balanced management of care for organ transplant recipients with malignancies requires a multidisciplinary approach involving medical oncologists and transplant physicians to reach the best quality of care in these complex cases.

Residual pulmonary hypertension is an important sequela after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Recurrent thrombosis or embolism could be a contributor to this residual pulmonary hypertension but the potential extent of its role is unknown in part because data on incidence are lacking. We aimed to analyze the incidence of new intravascular abnormalities after pulmonary endarterectomy and determine hemodynamic and functional implications. A total of 33 chronic thromboembolic pulmonary hypertension patients underwent routine CT pulmonary angiography before and six months after pulmonary endarterectomy, together with right heart catheterization and exercise testing. New vascular lesions were defined as (1) a normal pulmonary artery before pulmonary endarterectomy and containing a thrombus, web, or early tapering six months after pulmonary endarterectomy or (2) a pulmonary artery already containing thrombus, web, or early tapering at baseline, but increasing six months after pulmonary endarterectomy. Nine of 33 (27%) chronic thromboembolic pulmonary hypertension patients showed new vascular lesions on CT pulmonary angiography six months after pulmonary endarterectomy. In a subgroup of patients undergoing CT pulmonary angiography 18 months after pulmonary endarterectomy, no further changes in lesions were noted. Hemodynamic and functional outcomes were not different between patients with and without new vascular lesions. New vascular lesions are common after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension; currently their origin, dynamics, and long-term consequences remain unknown.

BackgroundThe current diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is unacceptably long, causing loss of quality-adjusted life years and excess mortality. Validated screening strategies for early CTEPH diagnosis are lacking. Echocardiographic screening among all PE survivors is associated with overdiagnosis and cost-ineffectiveness. We aimed to validate a simple screening strategy for excluding CTEPH early after acute PE, limiting the number of performed echocardiograms.MethodsIn this prospective, international, multicentre management study, consecutive patients were managed according to a screening algorithm starting 3 months after acute PE to determine whether echocardiographic evaluation of pulmonary hypertension (PH) was indicated. If the ‘CTEPH prediction score’ indicated high pretest probability or matching symptoms were present, the ‘CTEPH rule-out criteria’ were applied, consisting of ECG reading and N-terminalpro-brain natriuretic peptide. Only if these results could not rule out possible PH, the patients were referred for echocardiography.Results424 patients were included. Based on the algorithm, CTEPH was considered absent in 343 (81%) patients, leaving 81 patients (19%) referred for echocardiography. During 2-year follow-up, one patient in whom echocardiography was deemed unnecessary by the algorithm was diagnosed with CTEPH, reflecting an algorithm failure rate of 0.29% (95% CI 0% to 1.6%). Overall CTEPH incidence was 3.1% (13/424), of whom 10 patients were diagnosed within 4 months after the PE presentation.ConclusionsThe InShape II algorithm accurately excluded CTEPH, without the need for echocardiography in the overall majority of patients. CTEPH was identified early after acute PE, resulting in a substantially shorter diagnostic delay than in current practice.

Background Pulmonary embolism is an important cause of preventable mortality. Treatment strategies depend on risk stratification. High-risk patients, and some intermediate-high-risk patients, require urgent reperfusion therapy. Systemic thrombolysis (ST) is the effective first-choice treatment in these patients; however, the high risk of bleeding complications is a major drawback. In this single-centre retrospective cohort study, we report our experience with the FlowTriever thrombosuction system as an alternative or adjunct to ST in intermediate-high and high-risk pulmonary embolism. Methods Demographic and clinical data of all patients treated with the FlowTriever system from December 2021 until March 2024 were retrieved from the electronic medical records. Primary outcomes were technical success rate, 30-day all-cause mortality and major bleeding. Results Twenty-one patients were treated with the FlowTriever system, 14 of whom were considered high risk. The technical success rate was 100%. Thirty-day all-cause mortality was 29% and major bleeding was recorded in 5 patients (24%), of which one bleeding event was related to the FlowTriever procedure. A significant reduction was seen in mean pulmonary arterial pressure and right ventricular end-diastolic dimension. Conclusion In intermediate-high and high-risk pulmonary embolism patients with ST treatment failure or a contraindication for ST, the FlowTriever thrombosuction system seems to be a minimally invasive alternative treatment modality with low complication rates.

The circle of Willis (CoW) is a circular arrangement of arteries in the human brain, exhibiting significant anatomical variability. The CoW is extensively studied in relation to neurovascular pathologies, with certain anatomical variants previously linked to ischemic stroke and intracranial aneurysms. In an individual CoW, arteries might be absent (aplasia) or underdeveloped (hypoplasia, diameter < 1 mm). As the assessment of such variations is time-consuming and susceptible to subjectivity, robust automatic extraction of personalized CoW topology from time-of-flight magnetic resonance angiography (TOF-MRA) images would highly benefit large-scale clinical investigations. Previous work has sought to extract CoW topology from voxel-based semantic segmentation masks. However, hypoplastic arteries are challenging to recover in voxel-based segmentation. Instead, we propose using a complete CoW as an anatomical prior for extracting all possible CoW arteries as shortest paths between automatically identified anatomical landmarks, guided by automatically determined artery orientation vector fields. These fields are obtained using a scale-invariant and rotation-equivariant mesh-CNN-based model (SIRE). For a 3D TOF-MRA volume, a potentially overcomplete graph of the CoW is thus extracted in which each edge represents an artery. Subsequently, a binary Random Forest classifier labels each artery as normal or hypo-/aplastic. The model was optimized and validated using a data set of 351 3D TOF-MRA scans in a cross-validation setup. We showed that using a shortest path algorithm with a cost function based on local artery orientations results in continuous artery paths, even in hypoplastic cases. We tracked the correct path in the posterior communicating arteries in 70–74% of the cases, an artery that is known to pose challenges in voxel-based segmentation models. Our downstream artery path classifier obtained an average F1 score of 0.91, demonstrating the potential of our proposed framework to extract personalized CoW topology automatically.