Soluble Receptor for Advanced Glycation End Products (sRAGE) Is a Sensitive Biomarker in Human Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive condition with an unmet need for early diagnosis, better monitoring, and risk stratification. The receptor for advanced glycation end products (RAGE) is activated in response to hypoxia and vascular injury, and is associated with inflammation, cell proliferation and migration in PAH. For the adult cohort, we recruited 120 patients with PAH, 83 with idiopathic PAH (IPAH) and 37 with connective tissue disease-associated PAH (CTD-PAH), and 48 controls, and determined potential plasma biomarkers by enzyme-linked immunoassay. The established heart failure marker NTproBNP and IL-6 plasma levels were several-fold higher in both adult IPAH and CTD-PAH patients versus controls. Plasma soluble RAGE (sRAGE) was elevated in IPAH patients (3044 ± 215.2 pg/mL) and was even higher in CTD-PAH patients (3332 ± 321.6 pg/mL) versus controls (1766 ± 121.9 pg/mL; p < 0.01). All three markers were increased in WHO functional class II+III PAH versus controls (p < 0.001). Receiver-operating characteristic analysis revealed that sRAGE has diagnostic accuracy comparable to prognostic NTproBNP, and even outperforms NTproBNP in the distinction of PAH FC I from controls. Lung tissue RAGE expression was increased in IPAH versus controls (mRNA) and was located predominantly in the PA intima, media, and inflammatory cells in the perivascular space (immunohistochemistry). In the pediatric cohort, plasma sRAGE concentrations were higher than in adults, but were similar in PH (n = 10) and non-PH controls (n = 10). Taken together, in the largest adult sRAGE PAH study to date, we identify plasma sRAGE as a sensitive and accurate PAH biomarker with better performance than NTproBNP in the distinction of mild PAH from controls.

Functional, Spiroergometric, and Subjective Comparisons Between Forearm Crutches and Hands-Free Single Crutches in a Crossover Study.

Background: Following below-knee surgery, the optimal medical mobility device remains controversial as adequate nonweightbearing of the operated extremity is critical to ensure successful healing. The use of forearm crutches (FACs) is well established but requires using both upper extremities. The hands-free single orthosis (HFSO) is an alternative that spares the upper extremities. This pilot study compared functional, spiroergometric, and subjective parameters between HFSO and FAC. Methods: Ten healthy (5 females, 5 males) participants were asked to use HFSOs and FACs in a randomized order. Five functional tests were performed: climbing stairs (CS), an L-shaped indoor course (IC), an outdoor course (OC), a 10-meter walk test (10MWT), and a 6-minute walk test (6MWT). Tripping events were counted while performing IC, OC, and 6MWT. Spiroergometric measurements consisted of a 2-step treadmill test with speeds of 1.5 and 2 km/h, each for 3 minutes. Lastly, a VAS questionnaire was completed to collect data regarding comfort, safety, pain, and recommendations. Results: Significant differences between both aids were observed in CS and IC (HFSO: 29.3 seconds; FAC: 26.1 seconds, P < .03; and HFSO: 33.2 seconds, FAC: 18 seconds, P < .001, respectively). The other functional tests showed no significant differences. The trip events were not significantly different between the use of the 2 aids. Spiroergometric tests showed significant differences regarding heart rate (HFSO: 131.1 bpm at 1.5 km/h and 131 bpm at 2 km/h; FAC: 148.1 bpm at 1.5 km/h and 161.8 bpm at 2 km/h) and oxygen consumption (HFSO: 15.4 mL/min/kg at 1.5 km/h and 16 mL/min/kg at 2 km/h; FAC: 18.3 mL/min/kg at 1.5 km/h and 21.9 mL/min/kg at 2 km/h) at both speeds (all P < .01). In addition, significantly different ratings regarding the items comfort, pain, and recommendation were recorded. Both aids were equally rated for safety. Conclusion: HFSOs may be an alternative to FACs, especially in activities that require physical stamina. Further prospective studies in patients with below-knee surgical intervention concerning everyday clinical use would be interesting. Level of Evidence: Level IV pilot-study.