Guide
In order to further improve the diagnosis and treatment level and research ability of cerebrovascular diseases in mainland China, and actively promote the standardized prevention and treatment of cerebrovascular diseases in mainland China, the "24th China Cerebrovascular Disease Conference 2024" sponsored by the Chinese Medical Association and the Neurology Branch of the Chinese Medical Association was held in Wuhan on April 12~14. At the meeting, ischemic stroke and TK supplementation therapy became a hot topic and attracted widespread attention.
The scene of the 24th China Cerebrovascular Disease Conference (swipe right to see more)
Ischemic stroke is a kind of ischemic cerebrovascular disease, which seriously threatens people's health and life safety, although research and exploration have expanded the treatment options of patients, but the clinical benefit population is limited, and there is still an unmet treatment need for ischemic stroke. In recent years, tissue kallikrein (TK) supplementation therapy has been confirmed to have great potential in the treatment of ischemic stroke, and its R&D and clinical application have attracted much attention at home and abroad.
The conference provided a platform for experts and scholars in the field to communicate, and many speakers gave wonderful explanations on the mechanism of TK supplementation in the treatment of AIS, TK and collateral compensation, TK and distant ischemic adaptation (RIC), the relationship between TK medication duration and efficacy, and the application of TK in diabetes/glucose metabolism disorders combined with AIS. This article provides a brief summary of the main points of the conference for the benefit of readers.
TKIC Symposium (Swipe right to see more)
TKIC Symposium
When: April 13
Chairs: Prof. Pu Chuanqiang from the Chinese People's Liberation Army General Hospital, Prof. Cui Liying from Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Prof. Zeng Jinsheng from the First Affiliated Hospital of Sun Yat-sen University, and Prof. Peng Bin from Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Speakers: Professor Xu Yun from Drum Tower Hospital of Nanjing University, Professor Zhao Xingquan from Beijing Tiantan Hospital affiliated to Capital Medical University, Professor Chen Huisheng from the Northern Theater General Hospital of the Chinese People's Liberation Army, and Professor Ni Jun from Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Breakout sessions
When: April 13
Chairman: Professor Zhu Suiqiang, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Speaker: Professor Zhu Yicheng, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Latest developments
The research on the mechanism of TK supplementation therapy has been reported again
Special Report on "TK Complementary Therapy, Shaping a New Landscape of AIS Treatment" (Swipe right to see more)
Previous studies have found that TK plays a vital role in the regulation of microcirculation, blood pressure and blood flow, and is an important endogenous protective factor of cardiovascular and cerebrovascular diseases, which is related to the occurrence and recurrence of stroke, and its efficacy in the treatment of AIS has been confirmed by many studies at home and abroad. Regarding the mechanism of TK supplementation in the treatment of AIS, Professor Xu Yun elaborated on this topic. TK can promote the establishment of collateral circulation after the occurrence of AIS, thereby improving neurological function and achieving the therapeutic effect of AIS. Recently, further studies of its mechanism of action have found that TK is involved in comprehensive neuroprotection, and it can mediate neurovascular coupling through hypoxia-inducible factor-1α (HIF-1α) to protect neurovascular units. In addition, a study led by Professor Xu Yun showed that TK can also improve neurological function and reduce ischemic brain injury through B2 receptors.
Regarding the role of TK in the treatment of AIS, the chairman of the symposium believes that Professor Xu Yun introduced to us the role of TK in stroke recurrence and the role in the treatment of AIS, which has important clinical guiding significance.
Targeted and precise force
TK supplementation therapy solves the problem of "blood theft".
Special Report on "Lifting the Fog of "Stealing Blood": Perspective on the True Significance of Side Compensation in AIS" (Swipe right to see more)
The benefits of collateral circulation establishment and compensation for AIS patients have been emphasized, but the opening of collateral circulation may lead to blood theft. In this regard, Professor Zhao Xingquan gave a detailed explanation from the mechanism. AIS can lead to indiscriminate opening of secondary collateral in ischemic and normal areas, but only secondary collateral opening in ischemic areas can lead to effective perfusion, and secondary collateral opening in normal areas may be the cause of poor clinical outcomes and blood theft. Therefore, targeting the secondary collateral of the open ischemic penumbra is the key to the treatment of AIS. Studies have confirmed that TK supplementation therapy can quickly and actively target the secondary collateral of the ischemic region without causing blood theft. The mechanism lies in the fact that after the occurrence of AIS, TK can improve blood flow through the targeted dilation of blood vessels in the ischemic region by B2 receptors, and the compensatory increase of TK and B2 receptors in the ischemic penumbra is the mechanism of targeted regulation of the ischemic penumbra region in AIS.
The chairman of the symposium said that this report introduced the significance of effective collateral circulation in the pathogenesis and prognosis of ischemic stroke, and also introduced the clinical effect of TK in targeting the opening of collateral circulation.
Decrypting the RIC
or in conjunction with TK supplementation
Special report on "The Value of Tissue Kallikrein in Adaptation to Distant Ischemia" (Swipe right to see more)
In recent years, RIC has become a hot spot in the treatment of ischemic cerebrovascular disease, and Professor Chen Huisheng gave a wonderful explanation on the correlation between RIC and TK. Studies have shown that RAPostC can increase endogenous TK levels in ischemic regions, and RIPostC's effect of reducing cerebral infarct volume, improving neuronal cell survival, and increasing microvascular density in ischemic regions can be partially reversed with TK antagonists. The above results suggest that TK participates in the RIC process and plays an important role, and endogenous TK upregulation may be the mechanistic basis of the RIPostC effect. As the mechanism of action of RIC needs to be further studied, more robust evidence-based evidence is needed for its efficacy. The correlation between TK and RIC may mean that TK supplementation and RIC can bring more benefits to patients with AIS.
TK plays an important role in RIC, and the chair of the symposium said that the results of large-scale clinical studies in RIC have proved that RIC can improve neurological function, mainly through endogenous TK to exert neuroprotective effects.
Focus on the unmet clinical needs
Good benefits can be achieved with short-term administration of TK
Special Report on "RESK Study and Subgroup Analysis" (Swipe right to see more)
In 2021, the results of a large-scale, multicenter, phase IV study (RESK study) based on the Chinese patient population led by Professor Cui Liying and written by Professor Ni Jun confirmed the good efficacy and safety of TK in the treatment of AIS in a large population, but the hospital stay of AIS patients in mainland China is usually limited (7~13d), so it is very important to find drugs that can produce good efficacy within a limited time frame. At this conference, Professor Ni Jun focused on sharing the results of the subgroup analysis of the RESK study: after only 8 days of short-term treatment of TK, good short-term and long-term efficacy comparable to long-term treatment can be obtained, and appropriately prolonging the time of TK treatment can bring higher disability-free rate and quality of life to patients. In addition, patients who were given the drug earlier (<6 hours) may have a greater benefit, and TK beyond the window (> 48 hours of initiation) is still effective. The treatment of TK is in line with the current clinical practice in China and is worthy of clinical promotion.
The results of the RESK study and its subgroup analysis proved the advantages of TK in the treatment of AIS, and also provided a new evidence-based basis for the benefits of TK supplementation in the treatment of AIS.
Light up a new chapter
TK facilitates the additional benefit of diabetes/glucose dysmetabolism in combination with AIS
Special Report on the Value of TK in AIS Patients with Diabetes Mellitus/Glucose Metabolism Disorders (Swipe right to see more)
Diabetes/glucose dystrophy is closely related to AIS, and patients with AIS with diabetes/diabetes mellitus often face an increased risk of exacerbation and recurrence. Professor Zhu Yicheng said that TK not only affects many aspects of AIS, but also participates in the pathological process of diabetes. The decrease in TK levels in diabetes mellitus can damage the microvasculature, which is not conducive to post-ischemic perfusion, while TK can improve the vascular injury and target organ damage of diabetes/glucose metabolism. Elevated TK levels are beneficial not only for the treatment of AIS, but also for the recovery of diabetic patients. Studies have shown that TK has a tendency to reduce fasting blood glucose in patients with AIS and abnormal glucose metabolism, and has a significant effect on patients with diabetic target organ lesions. TK supplementation may provide additional benefit by improving neurological function in patients with diabetes/glucose dysbiscum AIS. In addition, it has been found that patients with a history of hypertension have a lower risk of blood pressure reduction with TK, suggesting that there may be more untapped potential for TK.
According to the chair of the symposium, diabetes mellitus is an independent risk factor for poor prognosis of ischemic stroke. Clinical studies have shown a reduction in TK levels in diabetes mellitus, and there is strong evidence for TK treatment for AIS (primarily by improving collateral circulation). For patients with diabetes/glucose dysmetabolism with AIS, TK supplementation can provide a double benefit.
summary
This conference provides an academic exchange platform for the majority of cerebrovascular disease medical workers, and demonstrates the latest research progress and diagnosis and treatment frontiers in the field of cerebrovascular diseases at home and abroad. At present, the global burden of diagnosis and treatment of ischemic stroke is still heavy, and there is a long way to go in the exploration of AIS treatment. TK supplementation therapy has good application value and is worthy of further research to promote more patients with AIS. Although the efficacy and safety of TK supplementation therapy have been widely validated in clinical practice, more research is still needed to fully explore the application potential of TK and help AIS therapy usher in a better future.