Assessing Diagnostic Accuracy of Four-dimensional CT for Instable Scapholunate Dissociation: The Prospective ACTION Trial.

Background Timely treatment of scapholunate instability depends on early identification, but current imaging methods are either intricate or fail to demonstrate the dynamic stages. Purpose To calculate the diagnostic accuracy of four-dimensional (4D) CT for diagnosing instable scapholunate ligament (SLL) tears. Materials and Methods This prospective study enrolled consecutive participants with clinically suspected SLL tears who underwent 4D CT from July 2020 to May 2022. A historical study sample diagnosed at cineradiography served as a comparison, and wrist arthroscopy was the reference standard. Scapholunate joints greater than 3 mm were interpreted as instable at index 4D CT and cineradiography. Diagnostic accuracy was expressed as sensitivity and specificity. Areas under the receiver operating characteristic curve and cutoff values for both index tests were calculated. Intraclass correlation coefficients (ICCs) were computed to compare interrater reliability. Effective radiation doses at 4D CT were measured with thermoluminescent dosimeters. Results The study included 40 participants (mean age, 43 years ± 14 [SD]; 24 male) evaluated at 4D CT and 78 patients (mean age, 45 years ± 11; 50 male) historically evaluated at cineradiography. Four-dimensional CT helped detect instable tears in 26 of 35 participants (sensitivity, 74.3% [95% CI: 56.7, 87.5]. Cineradiography revealed instable tears in 52 of 63 patients (sensitivity, 82.5% [95% CI: 70.9, 91]). Four of five participants with stable scapholunate joints were identified at 4D CT (specificity, 80.0% [95% CI: 28.4, 99.5]), and 12 of 15 patients with stable SLLs were identified at cineradiography (specificity, 80.0% [95% CI: 51.9, 95.7]). Interrater agreement of radiologic measurements on 4D CT scans was good to excellent (ICC range, 0.89-0.96). The effective radiation dose ranged from 67 to 72 mSv at the wrist and was less than 1 mSv at the head. Conclusion Four-dimensional CT results are highly reproducible. Instable scapholunate joints greater than 3 mm were detected with a sensitivity of 74.3% and a specificity of 80% in an exploratory trial. Further evidence from larger randomized trials is warranted. German Register for Clinical Trials no. DRKS00021110 (Universal Trial Number U1111-1249-7884) Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Demehri and Ibad in this issue.

Bone morphogenetic protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis.

BACKGROUND: Bone Morphogenetic Protein (BMP)-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described. METHODS: BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT)-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8) expression was quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-ß induced epithelial-to-mesenchymal transition (EMT), expression of TGF-ß receptor type I (TGF-ßRI) and phosphorylated Smad 2 (pSmad 2) as well as on TNF-α induced apoptosis of proximal tubular cells. RESULTS: BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml) were able to reverse TNF-α-induced apoptosis and TGF-ß-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-ßRI. In addition, BMP-7 was able to reverse TGF-ß-induced phosphorylation of Smad 2. CONCLUSIONS: The findings suggest a protective role for BMP-7 by counteracting the TGF-ß and TNF-α-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease.

The role of bone morphogenetic protein-5 (BMP-5) in human nephrosclerosis.

BACKGROUND: Bone morphogenetic protein-5 (BMP-5) has been shown to be essential for nephrogenesis. Its role in adult kidney and in patients with hypertensive nephrosclerosis is still unknown. METHODS: BMP-5 expression was evaluated by immunostaining and real-time PCR in tissue samples from normal and nephrosclerotic human kidneys. The impact of transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α) and angiotensin-II (AT-II) on expression of BMP-5 and its receptors was quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-5 were evaluated by testing its influence on TGF-ß-induced epithelial-to-mesenchymal transition (EMT), TNF-α-induced apoptosis of HK-2 cells and inflammatory cell infiltration. RESULTS: BMP-5 expression was localized in tubular epithelial cells and significantly decreased in nephrosclerotic kidneys. Stimulation of HK-2 cells with TGF-ß, TNF-α and AT-II resulted in a significant decreased expression of BMP-5 and its receptors. BMP-5 attenuated TGF-ß-induced EMT, TNF-α-induced apoptosis and migration of mononuclear cells. CONCLUSIONS: BMP-5 is expressed in the tubuli of adult kidneys. Its decreased expression in nephrosclerosis along with its regenerative capabilities in HK-2 cells may point to a protective role in hypertensive nephrosclerosis.