Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening

Severe combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment options. The objective of the study was to assess the morbidity, mortality, and diagnostic and therapeutic delay in children with SCID in the Netherlands in the last 15 years. These data may help to judge whether SCID should be considered to be included in our national neonatal screening program. In the period 1998–2013, 43 SCID patients were diagnosed in the Netherlands, 11 of whom were atypical SCID (presentation beyond the first year). The median interval between the first symptom and diagnosis was 2 months (range 0–1173 months). The total mortality was 42 %. In total, 32 patients were treated with HSCT of whom 8 were deceased. Nine patients died due to severe infectious complications before curative treatment could be initiated. Conclusion: Because of a high mortality of patients with SCID before HSCT could be initiated, only a national newborn screening program and pre-emptive HSCT or GT will be able to improve survival of these patients

Endobronchial blocker use for massive, focal pulmonary hemorrhage during pulmonary endarterectomy for CTEPH

Chronic thromboembolic pulmonary hypertension (CTEPH) has a poor prognosis if left untreated but can be cured by pulmonary endarterectomy (PEA). Massive endobronchial pulmonary hemorrhage is a potentially fatal complication of PEA, occurring in 0.5%of patients. We describe the use of an endobronchial blocker (EBB) as an additional method to successfully treat massive, focal pulmonary hemorrhage during PEA

Patients with CTEPH and mild hemodynamic severity of disease improve to a similar level of exercise capacity after pulmonary endarterectomy compared to patients with severe hemodynamic disease

Abstract The correlation between hemodynamics and degree of pulmonary vascular obstruction (PVO) is known to be poor in chronic thromboembolic pulmonary hypertension (CTEPH), which makes the selection of patients eligible for pulmonary endarterectomy (PEA) challenging. It can be postulated that patients with similar PVO but different hemodynamic severity have different postoperative hemodynamics and exercise capacity. Therefore, we aimed to assess the effects of PEA on hemodynamics and exercise physiology in mild and severe CTEPH patients. We retrospectively studied 18 CTEPH patients with a mild hemodynamic profile (mean pulmonary arterial pressure [mPAP] between 25 and 30 mmHg at rest) and CTEPH patients with a more severe hemodynamic profile (mPAP > 30 mmHg), matched by age, gender, and PVO. Cardiopulmonary exercise testing parameters were evaluated at baseline and 18 months following PEA. At baseline, exercise capacity, defined as oxygen uptake, was less severely impaired in the mild CTEPH group compared to the severe CTEPH group. After PEA, in the mild CTEPH group, ventilatory efficiency and oxygen pulse improved significantly (p < 0.05), however, the change in ventilatory efficiency and oxygen pulse was smaller compared to the severe CTEPH group. Only in the severe CTEPH group exercise capacity improved significantly (p < 0.001). Hence, in the present study, postoperative hemodynamic outcome and the CPET‐determined recovery of exercise capacity in mild CTEPH patients did not differ from a matched group of severe CTEPH patients

Application of [18F]FLT-PET in pulmonary arterial hypertension: a clinical study in pulmonary arterial hypertension patients and unaffected bone morphogenetic protein receptor type 2 mutation carriers

Pulmonary arterial hypertension is a heterogeneous group of diseases characterized by vascular cell proliferation leading to pulmonary vascular remodelling and ultimately right heart failure. Previous data indicated that 3′-deoxy-3′-[18F]-fluorothymidine (18FLT) positron emission tomography (PET) scanning was increased in pulmonary arterial hypertension patients, hence providing a possible biomarker for pulmonary arterial hypertension as it reflects vascular cell hyperproliferation in the lung. This study sought to validate 18FLT-PET in an expanded cohort of pulmonary arterial hypertension patients in comparison to matched healthy controls and unaffected bone morphogenetic protein receptor type 2 mutation carriers. 18FLT-PET scanning was performed in 21 pulmonary arterial hypertension patients (15 hereditary pulmonary arterial hypertension and 6 idiopathic pulmonary arterial hypertension), 11 unaffected mutation carriers and 9 healthy control subjects. In-depth kinetic analysis indicated that there were no differences in lung 18FLT k3 phosphorylation among pulmonary arterial hypertension patients, unaffected bone morphogenetic protein receptor type 2 mutation carriers and healthy controls. Lung 18FLT uptake did not correlate with haemodynamic or clinical parameters in pulmonary arterial hypertension patients. Sequential 18FLT-PET scanning in three patients demonstrated uneven regional distribution in 18FLT uptake by 3D parametric mapping of the lung, although this did not follow the clinical course of the patient. We did not detect significantly increased lung 18FLT uptake in pulmonary arterial hypertension patients, nor in the unaffected bone morphogenetic protein receptor type 2 mutation carriers, as compared to healthy subjects. The conflicting results with our preliminary human 18FLT report may be explained by a small sample size previously and we observed large variation of lung 18FLT signals between patients, challenging the application of 18FLT-PET as a biomarker in the pulmonary arterial hypertension clinic