Efficacy, Safety, and Economic Feasibility of Dokhwalgisaeng-Tang for Degenerative Knee Osteoarthritis: Protocol for a Multicenter, Randomized, Assessor Blinded, Controlled Trial

Wonnam Kim,1,* Yeon-Cheol Park,2,3,* Bonhyuk Goo,2 Jung-Hyun Kim,2 Dongwoo Nam,3,4 Eunseok Kim,5,6 Hyun-Jong Lee,7 Dong-Hyun Pyun,8,9 Hae Sun Suh,8– 10 Yoonsung Lee,11 Man S Kim,11 Byung-Kwan Seo,2,3 Yong-Hyeon Baek2,3 1Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 2Department of Acupuncture & Moxibustion, Kyung Hee University College of Korean Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea; 3Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea; 4Department of Acupuncture & Moxibustion, Kyung Hee University College of Korean Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea; 5Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 6Department of Acupuncture and Moxibustion Medicine, Pusan National University Korean Medicine Hospital, Yangsan, Republic of Korea; 7Department of Acupuncture & Moxibustion, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 8Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea; 9Institute of Regulatory Innovation Through Science (IRIS), Kyung Hee University, Seoul, Republic of Korea; 10College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; 11Clinical Research Institute, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Yong-Hyeon Baek, Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea, Tel +82 2 440 6099, Fax +82 2 440 714, Email [email protected]: Knee osteoarthritis (KOA) is one of the most prevalent degenerative joint diseases worldwide. The herbal decoction, Dokhwalgisaeng-tang (DHGST), has been commonly used in East Asia to treat osteoarthritis. However, there is insufficient evidence to draw clear conclusions concerning its effectiveness and safety for patients with KOA. We aim to determine the efficacy, safety, and economic feasibility of DHGST compared with Celecoxib, an oral COX-2 inhibitor, for patients with degenerative KOA.Trial Design and Methods: This multicenter, randomized, noninferiority trial, involving 160 participants who will be randomized using block randomization with 1:1 allocation, will compare DHGST and Celecoxib. The total trial period is 24 weeks after random allocation, comprising 12 weeks of treatment and 12 weeks of follow-up. Participants with KOA will be administered 200 mg of DHGST (treatment group) or Celecoxib capsules (control group) for 12 weeks. Efficacy and safety evaluations will be conducted at weeks 0, 4, 8, and 12, and 24. The primary outcome measurement is the Korean Western Ontario McMaster score at week 12. Changes in pain intensity using a 100 mm visual analog scale, changes in quality of life using a EuroQol 5-dimension 5-level self-report survey, and patient satisfaction will also be measured to evaluate effectiveness between the two groups. A trial-based economic feasibility evaluation will be conducted to analyze treatment cost-effectiveness from societal and healthcare system perspectives. Drug safety will be assessed through adverse reactions and laboratory test findings.Discussion: This trial protocol has the following limitations. Applying a double-dummy design is not possible, as the tablet and granule forms can easily be distinguished visually, and achieving participant blinding is challenging. The trial findings are intended to inform participants, physicians, and other stakeholders in determining whether DHGST could be used as an alternative therapeutic option for KOA.Trial Registration Number: KCT0008424 (Clinical Research Information Service of the Republic of Korea), registered on 12 May 2023.Keywords: degenerative joint disease, Dokhwalgisaeng-tang, noninferiority trial, randomized controlled tria

Preliminary Evaluation of the Sural Nerve Using 22-MHz Ultrasound: A New Approach for Evaluation of Diabetic Cutaneous Neuropathy

Background: The application of 22-MHz high-frequency ultrasound allows for visualization of the inner part of the sural nerve. The aim of this study was to evaluate the morphological changes of sural nerves in patients with type 2 diabetes mellitus using ultrasound. Materials and Methods: The thickness/width (T/W) ratio, the cross-sectional area (CSA) of the sural nerves and the maximum thickness (MT) of the nerve fascicles were measured in 100 patients with type 2 diabetes mellitus and 50 healthy volunteers using 22-MHz ultrasound. Receiver operating characteristic (ROC) curves were plotted to determine the optimal cut-off values as well as the sensitivities and specificities. All parameters were significantly different between the subject and control groups. The ROC curves demonstrated that the MT was the most predictive of diabetic cutaneous neuropathy, with an optimal cut-off value of 0.365 mm that yielded a sensitivity of 90.3 % and a specificity of 87.7%. Conclusions: The results of this study suggest that 22-MHz ultrasound may be a valuable tool for evaluating diabeti

Antifungal and antioxidant activity of fatty acid methyl esters from vegetable oils

ABSTRACT Fatty acid methyl esters (FAMEs) were obtained from vegetable oils of soybean, corn and sunflower. The current study was focused on evaluating the antifungal activity of FAMEs mainly against Paracoccidioides spp., as well as testing the interaction of these compounds with commercial antifungal drugs and also their antioxidant potential. FAMEs presented small IC50 values (1.86-9.42 μg/mL). All three FAMEs tested showed antifungal activity against isolates of Paracoccidioides spp. with MIC values ranging from 15.6-500 µg/mL. Sunflower FAMEs exhibited antifungal activity that extended also to other genera, with an MIC of 15.6 μg/mL against Candida glabrata and C. krusei and 31.2 μg/mL against C. parapsilosis. FAMEs exhibited a synergetic effect with itraconazole. The antifungal activity of the FAMEs against isolates of Paracoccidioides spp. is likely due to the presence of methyl linoleate, the major compound present in all three FAMEs. The results obtained indicate the potential of FAMEs as sources for antifungal and antioxidant activity

Modified deployment technique of off-the-shelf Gore thoracoabdominal multibranch endoprosthesis for post-dissection thoracoabdominal aortic aneurysm repair

The Thoracoabdominal Multibranch Endoprosthesis (TAMBE) is a commercially available off-the-shelf four-vessel inner branched endograft for complex abdominal and thoracoabdominal aortic aneurysms. As post-dissection thoracoabdominal aortic aneurysms (PD-TAAAs) were excluded from the pivotal trials, there is paucity of data on the use of TAMBE in PD-TAAAs. Here, we present a case demonstrating the feasibility of TAMBE in conjunction with iliac branch endoprosthesis to repair PD-TAAAs, with focus on the deployment technique specific to PD-TAAAs

Application of off-the-shelf thoracoabdominal multibranch endoprosthesis for urgent repair of pararenal and thoracoabdominal aortic aneurysms with occluded target vessels

The Thoracoabdominal Multibranch Endoprosthesis (TAMBE) is a commercially available off-the-shelf four-vessel inner branched endograft for thoracoabdominal aortic aneurysms (TAAA) and pararenal abdominal aortic aneurysms (AAA). However, there is paucity of data on the use of TAMBE in repair of pararenal AAA and TAAA with occluded target vessels. Here, we present two cases demonstrating the feasibility of TAMBE for repair of pararenal AAA and TAAA in patients with occluded target vessels

Technical strategies and pitfalls for total transfemoral implantation of off-the-shelf four vessel thoracoabdominal multibranch endoprosthesis with or without utilization of preloaded wires

The thoracoabdominal multibranch endoprosthesis is a commercially available off-the-shelf four-vessel inner branched endograft for complex abdominal and thoracoabdominal aortic aneurysms. Although the device is intended to be used with upper extremity access per its instructions for use, total transfemoral approach may be needed in patients with unfavorable arch anatomy and may decrease the risk of cerebrovascular events. This article describes technical strategies and pitfalls of total transfemoral thoracoabdominal multibranch endoprosthesis implantation techniques with conventional co-axial steerable sheath, as well as variations of techniques utilizing preloaded wires in “up-and-over” configuration

Endovascular rescue of failed physician-modified multibranched endografts with fabric tear, using Gore thoracoabdominal multibranched endoprosthesis

The thoracoabdominal multibranch endoprosthesis is a commercially available off-the-shelf four-vessel inner branched endograft for complex abdominal and thoracoabdominal aortic aneurysms. Type IIIb endoleak owing to fabric tear of fenestrated branched endovascular repair (FBEVAR) can be challenging, often requiring relining FBEVAR. Here, we present a case where thoracoabdominal multibranch endoprosthesis was used to reline the previous physician modified FBEVAR in a patient with a 10-cm extent IV thoracoabdominal aortic aneurysm distal to the previous open extent I thoracoabdominal aortic aneurysm repair

Double thoracic branch endoprosthesis to repair type IA endoleak after zone 2 thoracic branch endoprosthesis

Thoracic endovascular aortic repair has become the first-line treatment modality for descending thoracic aortic diseases. Coverage of the aortic arch branches is often required to extend the proximal seal zones during thoracic endovascular aortic repair. The thoracic branch endoprosthesis (TBE) is the first US Food and Drug Administration-approved branched device for thoracic endovascular repair allowing for incorporation of the left subclavian artery. Type IA endoleak after zone 2 TBE as well as its rescue options have not been well-described. In this report, we describe two cases of failed zone 2 TBE with a type IA endoleak, rescued with proximal extension zone 0 TBE to create a sandwiched double TBE configuration. Technical considerations as well as the limitations of this technique are discussed