RESUMEN
Background: Hypertensive cerebral small vessel disease (HT-CSVD) is a cerebrovascular clinical, imaging and pathological syndrome caused by hypertension (HT). The condition manifests with lesions in various vessels including intracranial small/arterioles, capillaries, and small/venules. Hypertensive cerebral small vessel disease has complex and diverse clinical manifestations. For instance, it can present as an acute stroke which progresses to cause cognitive decline, affective disorder, unstable gait, dysphagia, or abnormal urination. Moreover, hypertensive cerebral small vessel disease causes 25-30% of all cases of ischemic strokes and more than 50% of all cases of single or mixed dementias. The 1-year recurrence rate of stroke in cerebral small vessel disease patients with hypertension is 14%. In the early stage of development, the symptoms of hypertensive cerebral small vessel disease are concealed and often ignored by patients and even clinicians. Patients with an advanced hypertensive cerebral small vessel disease manifest with severe physical and mental dysfunction. Therefore, this condition has a substantial economic burden on affected families and society. Naotaifang (NTF) is potentially effective in improving microcirculation and neurofunction in patients with ischemic stroke. In this regard, this multicenter randomized controlled trial (RCT) aims to furtherly evaluate the efficacy and safety of naotaifang capsules on hypertensive cerebral small vessel disease. Methods: This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 388 eligible subjects were recruited from the First Hospital of Hunan University of Chinese Medicine, Hunan Academy of Chinese Medicine Affiliated Hospital, the First Hospital of Shaoyang University, the First Traditional Chinese Medicine Hospital of Changde, and Jiangmen Wuyi Hospital of Traditional Chinese Medicine from July 2020 to April 2022. After a 4-week run-in period, all participants were divided into the intervention group (represented by Y-T, N-T) and control group (represented by Y-C, N-C); using a stratified block randomized method based on the presence or absence of brain damage symptoms in hypertensive cerebral small vessel disease (represented by Y and N). The Y-T and N-T groups were administered different doses of naotaifang capsules, whereas Y-C and N-C groups received placebo treatment. These four groups received the treatments for 6 months. The primary outcome included Fazekas scores and dilated Virchow-robin spaces (dVRS) grades on magnetic resonance imaging (MRI). The secondary outcomes included the number of lacunar infarctions (LI) and cerebral microbleeds (CMB) on magnetic resonance imaging, clinical blood pressure (BP) level, traditional Chinese medicine (TCM) syndrome scores, mini-mental state examination (MMSE) scale, and safety outcomes. Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds on magnetic resonance imaging were tested before enrollment and after 6 months of treatment. The clinical blood pressure level, traditional Chinese medicine syndrome scores, mini-mental state examination scale and safety outcomes were tested before enrollment, after 3-month, 6-month treatment and 12th-month follow-up respectively. Conclusion: The protocol will comfirm whether naotaifang capsules reduce Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds, clinical blood pressure, increase mini-mental state examination scores, traditional Chinese medicine syndrome scores of Qi deficiency and blood stasis (QDBS), and improve the quality of life of subjects. The consolidated evidence from this study will shed light on the benefits of Chinese herbs for hypertensive cerebral small vessel disease, such as nourishing qi, promoting blood circulation and removing blood stasis, and dredging collaterals. However, additional clinical trials with large samples and long intervention periods will be required for in-depth research. Clinical Trial registration: www.chictr.org.cn, identifier ChiCTR1900024524.
RESUMEN
Femur stiffness, for example axial and bending stiffness, integrates both geometric and material information of the bone, and thus can be an effective indicator of bone strength and hip fracture risk. Femur stiffness is ideally measured from quantitative computed tomography (QCT), but QCT is not recommended for routine clinical use due to the public concern about exposure to high-dosage radiation. Dual energy X-ray absorptiometry (DXA) is currently the primary imaging modality in clinic. However, DXA is two-dimensional and it is not clear whether DXA-estimated stiffness has adequate accuracy to replace its QCT counterpart for clinical application. This study investigated the accuracy of femur stiffness (axial and bending) estimated from CTXA (computed tomography X-ray absorptiometry) and DXA against those directly measured from QCT. Proximal-femur QCT and DXA from 67 subjects were acquired. For each femur, the QCT dataset was projected into CTXA using CTXA-Hip (Mindways Software, Inc., USA). Femur stiffness at the femoral neck and intertrochanter were then calculated from QCT, CTXA and DXA, respectively, and different elasticity-density relationships were considered in the calculation. Pearson correlations between QCT and CTXA/DXA measured stiffness were studied. The results showed that there were strong correlations between QCT and CTXA derived stiffness, although the correlations were affected by the adopted elasticity-density relationship. Correlations between QCT and DXA derived stiffness were much less strong, mainly caused by the inconsistence of femur orientation in QCT projection and in DXA positioning. Our preliminary clinical study showed that femur stiffness had slightly better performance than femur geometry in discrimination of hip fracture cases from controls.