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BackgroundRisk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). The current European guidelines propose a 3-strata model to categorise risk as low, intermediate, or high, based on the expected 1-year mortality. However, with this model, most patients are categorised as intermediate risk. We investigated a modified approach based on 4 risk categories with intermediate risk subdivided into intermediate-low and intermediate-high risk.MethodsWe analysed data from COMPERA, a European pulmonary hypertension registry, and calculated risk at diagnosis and first follow-up based on functional class (FC), 6 min walking distance (6 MWD) and serum levels of brain natriuretic peptide (BNP) or N-terminal fragment of pro-BNP (NT-proBNP), using refined cut-off values. Survival was assessed with Kaplan-Meier analyses, log-rank testing, and Cox proportional hazards models.ResultsData from 1,655 patients with PAH were analysed. Using the 3-strata model, most patients were classified as intermediate risk (76.0% at baseline and 63.9% at first follow-up). The refined 4-strata risk model yielded a more nuanced separation and predicted long-term survival, especially at follow-up assessment. Changes in risk from baseline to follow-up were observed in 31.1% of the patients with the 3-strata model and in 49.2% with the 4-strata model. These changes, including those between the intermediate-low and intermediate-high strata, were associated with changes in long-term mortality risk.ConclusionsModified risk stratification using a 4-strata model based on refined cut-off levels for FC, 6MWD and BNP/NT-proBNP was more sensitive to prognostically relevant changes in risk than the original 3-strata model.

Introduction Aneurysmal bone cysts (ABCs) are expansive and destructive lesions positive for osteoclast markers, resembling benign giant cell tumors (GCTs). Treatment options include surgical resection, curettage and cavity filling, embolization, injection of fibrosing agents, or radiotherapy. Particularly in children and adolescents with spinal ABCs, these options may be unsatisfactory, and innovative forms of treatment are needed. Denosumab is a human monoclonal antibody that inhibits osteoclast function by blocking the cytokine receptor activator of the nuclear factor-kappa B ligand. Satisfactory results with denosumab in treating GCTs and immunohistochemical similarities suggest that it may also have positive effects on ABCs. Methods and ResultsThis report is the first description of the therapeutic use of denosumab in two patients with spinal ABCs. Two boys (aged 8 and 11) had recurrent ABCs at C5 after surgery with intralesional tumor resection. Treatment options were discussed by the interdisciplinary tumor board. Arterial embolization was attempted, but failed due to an absence of appropriate afferent arteries. After the families had received extensive information and provided written consent, denosumab therapy was initiated as an individualized treatment, despite the absence as yet of scientific evidence. After the start of denosumab therapy, both patients recovered from pain and neurologic symptoms significantly and are now in a healthy condition with no severe side effects. Magnetic resonance imaging check-ups after 2 or 4 months of denosumab treatment, respectively, showed tumor regression in both patients. Discussion Longer follow-up and clinical studies are warranted to establish the value of denosumab in the treatment of ABCs.

Pulmonary arterial hypertension (PAH) results in chronic right heart failure, which is associated with an increase in sympathetic tone. This may adversely affect cardiac autonomic control. We investigated the changes in cardiac autonomic nervous activity in relation to disease severity in patients with PAH.In 48 ) and 41 controls, cardiac autonomic nervous activity was evaluated by measurement of heart rate variability (HRV) and baroreflex sensitivity. All patients underwent cardiopulmonary exercise testing (peak oxygen uptake 13.2¡5.1 mL?kg, minute ventilation/carbon dioxide production slope 47¡16).In patients with PAH, spectral power of HRV was reduced in the high-frequency (239¡64 versus 563¡167 ms 2 ), low-frequency (245¡58 versus 599¡219 ms 2 ) and very low-frequency bands (510¡149 versus 1106¡598 ms 2 ; all p,0.05). Baroreflex sensitivity was also blunted (5.8¡0.6versus 13.9¡1.2 ms?mmHg; p,0.01). The reduction in high-frequency (r50.3, p50.04) and lowfrequency (r50.33, p50.02) spectral power and baroreflex sensitivity (r50.46, p,0.01) was related to the reduction in peak oxygen uptake.Patients with PAH have a marked alteration in cardiac autonomic control that is related to exercise capacity and may, therefore, serve as an additional marker of disease severity.

AimsPulmonary hypertension is a clinical syndrome characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are key subgroups of this disorder with comparable clinical and pathological findings. Resting pulmonary haemodynamics correlate only moderately with functional parameters and do not predict prognosis in these patients sufficiently accurately. We therefore correlated exercise haemodynamics with peak oxygen uptake (peakVO 2 ) and determined their prognostic significance. Methods and resultsThirty-six consecutive patients (21 female, 54 + 15 years) with PAH (n ¼ 21) or inoperable CTEPH were studied. The mean follow-up period was 1709 + 837 days. All patients underwent right heart catheterization at rest and during exercise, and cardiopulmonary exercise testing. Patients had severe pulmonary hypertension at rest (mean pulmonary artery pressure 46 + 11 mmHg, cardiac index 2.2 + 0.6 L/min/m 2 , pulmonary vascular resistance 861 + 330 dynes/s/cm 5 ). Exercise cardiac index correlated with peakVO 2 (r ¼ 0.59, P , 0.001) and was the only independent predictor of peakVO 2 on multivariate stepwise linear regression analyses (P , 0.001). PeakVO 2 was the strongest predictor of survival (x 2 ¼ 14.5, P ¼ 0.003). Among haemodynamic variables, only exercise cardiac index (x 2 ¼ 5.6, P ¼ 0.018) and the slope of the pressure/flow relationship (x 2 ¼ 4.1, P ¼ 0.04) were significant prognostic indicators. ConclusionThe ability of the right ventricle to increase the cardiac index during exercise is an important determinant of exercise capacity in patients with pulmonary hypertension. It also predicts prognosis and might therefore be useful in the clinical assessment of these patients.--