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Liver diseases are common in China and the incidence and mortality of primary liver cancer are among the top in the world. As one of the therapeutic methods for hepatocellular carcinoma (HCC), liver transplantation has become an important technique in hepatic surgery. Most of patients with HCC have progressed to stage B or C of Barcelona Clinic Liver Cancer staging when diagnosed. How to reduce the dropout rate of HCC patients due to the progression of tumor when waiting for liver transplantation, develop individualized immunosuppressant plans for HCC patients after liver transplantation, and accurately manage patients with HCC recurrence after liver transplan-tation are the current hotspots of research. The authors review the relevant literature, summarize the treatment experience, and discuss the hot issues in liver transplantation for HCC, in order to provide reference for related treatment.
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ABSTRACT Introduction Chimeric antigen receptor T (CAR-T) cell therapy is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) that is a multi-step process involving various stakeholders. Appropriate education on the practical logistics is therefore paramount to ensure treatment success. Methods A group of key opinion leaders met to explore the key elements of setting up and running a CAR-T center in Brazil. For each step in the CAR-T cell therapy process, the experts agreed on basic requirements, gave their key recommendations from practical experience, and considered any remaining unanswered questions. Results This paper presents best-practice recommendations and advice on how to overcome common challenges for each step in the CAR-T cell therapy process, with a focus on the current situation in Brazil. Key themes throughout the process are collaboration within the multidisciplinary team and with the referring physician, along with communication and education for patients and their caregivers. Conclusion We believe that the expert insights presented in this paper, in particular on optimal patient selection and timing of CAR-T cell therapy, will deepen understanding of the CAR-T process and aid implementation of this novel therapy for patients with RRMM in Brazil.
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Immunotherapy, Adoptive , Multiple Myeloma , B-Cell Maturation Antigen , ImmunotherapyABSTRACT
Chimeric antigen receptor T (CAR-T) cell therapy is one of the most significant advances in cancer treatment in the last few decades, revolutionizing the treatment paradigm for patients with refractory / recurrent diffuse large B-cell lymphoma (R/R DLBCL) and effectively improving the survival rate of these patients. However, due to the high incidence of grade III-IV side effects of CAR-T cell therapy and the fact that some patients did not obtain remission after CAR-T cell therapy or developed rapid disease progression within a short period of time, researchers are attempting to explore combined therapies, such as chemotherapy, radiotherapy and immunotherapy, to reduce the incidence of side effects and prolong the duration of persistent remission in patients. Among these options, radiotherapy in combination with CAR-T cell therapy have been proven to improve clinical prognosis. In this article, the theoretical basis of synergistic treatment of radiotherapy and CAR-T cell therapy in patients with R/R DLBCL, the safety and efficacy of radiotherapy, the sequence of radiotherapy and CAR-T cell therapy, and the dose of the target area of radiotherapy were reviewed, aiming to provide more evidence for the application and optimization of radiotherapy combined with CAR-T cell therapy for R/R DLBCL.
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At present, heart transplantation is the most effective treatment for end-stage heart failure. Nevertheless, the shortage of donors is becoming an increasingly severe challenge. In recent years, rapid development of mechanical circulatory support technologies has provided multiple therapeutic options for patients with end-stage heart failure. As an important mechanical circulatory support device, ventricular assist device (VAD) are divided into durable VAD (dVAD) and temporary VAD (tVAD) according to the duration of assistance. dVAD shows application potential in bridging heart transplantation, destination therapy and bridge to decision. With technological progress and experience accumulation in clinical application, VAD is evolving towards the direction of more biocompatible, lighter, more bionic and intelligent. In this article, the development of VAD, application status at home and abroad and the overall application of VAD in our hospital were reviewed, aiming to provide reference for promoting the clinical application of VAD in China.
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Extracorporeal membrane oxygenation (ECMO) could pump the blood from human veins to the outside of the body, oxygenate the red blood cells in an artificial environment and then return them back into the body. ECMO could replace the heart and lungs to complete gas exchange and systemic blood perfusion in patients with severe cardiopulmonary insufficiency, which also plays an important role in the field of heart transplantation. Besides circulatory support treatment after heart transplantation, ECMO may also be used to prolong the waiting time for heart transplantation in patients with respiratory and circulatory failure before operation, as a bridging therapy for heart transplantation. However, at present, the application of ECMO in pediatric heart transplantation still exist challenges, such as high perioperative mortality and difficulty in determining the timing of treatment, etc. In this article, the development history of ECMO application in pediatric heart transplantation, use of ECMO before and after pediatric heart transplantation, ECMO-related complications in children, and application of ventricular assist device (VAD) in pediatric heart transplantation were briefly reviewed, aiming to provide reference for promoting the application of ECMO in pediatric heart transplantation.
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Worldwide, about 13% of the 200,000 annual recipients of prosthetic heart valves (PHV) present for various surgical procedures. Also, more and more females are opting for pregnancies after having PHV. All patients with PHV present unique challenges for the anesthesiologists, surgeons and obstetricians (in case of deliveries). They have to deal with the perioperative management of anticoagulation and a host of other issues involved. We reviewed the English language medical literature relevant to the different aspects of perioperative management of patients with PHV, particularly the guidelines of reputed societies that appeared in the last 20 years. Regression of cardiac pathophysiology following valve replacement is variable both in extent and timeline. The extent to which reverse remodeling occurs depends on the perioperative status of the heart. We discussed the perioperative assessment of patients with PHV, including focused history and relevant investigations with the inferences drawn. We examined the need for prophylaxis against infective endocarditis and management of anticoagulation in such patients in the perioperative period and the guidelines of reputed societies. We also reviewed the conduct of anesthesia, including general and regional anesthesia (neuraxial and peripheral nerve/plexus blocks) in such patients. Finally, we discussed the management of delivery in this group of high?risk patients. From the discussion of different aspects of perioperative management of patients with PHV, we hope to guide in formulating the comprehensive plan of management of safe anesthesia in such patients.
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Objective:To explore the effect of pre-transplant immunotherapy on the prognosis of transplant recipients with hepatocellular carcinoma(HCC).Methods:From June 2018 to September 2021, retrospective analysis was conducted for clinical data of 19 HCC-liver transplant recipients receiving pre-transplant immunotherapy in affiliated Huashan Hospital of Fudan University. Pre-transplant immunotherapy regimen, adverse reactions, post-transplant acute rejection, tumor recurrence and metastasis and other complications were recorded. According to the preoperative tumor imaging and the changes of alpha-fetoprotein level, tumor change during recipient waiting period was judged by the mRECIST standard. According to whether or not there was partial tumor remission, they were divided into two groups of non-remission( n=13)and remission( n=6). Postoperative conditions of two groups were compared. Kaplan-Meier method was used for calculating the survival rate of recipients after transplantation and survival curve and Log-rank test utilized for comparing the recurrence-free and overall survival rates of recipients at 1 and 2 years post-operation. Results:A total of 19 liver transplant recipients received immunotherapy plus targeted and transcatheter arterial chemoembolization(TACE) before transplant. In non-remission group, tumor was stable( n=9)and progressive( n=4); 6 cases in remission group had tumor partial remission. Two recipients in non-remission group were pathologically confirmed by liver biopsy to have acute rejection(2/19, 10.5%)and both recovered after glucocorticoid + rATG and glucocorticoid therapy. In non-remission group, 2 patients died from septic shock post-operation. Among 3 patients of tumor recurrence and metastasis post-operation, 2 cases survived with tumor and 1 died after tumor recurrence and metastasis. In remission group( n=6), none had postoperative tumor recurrence and metastasis. The recurrence-free survival rates of non-remission group recipients at 1 and 2 years post-operation were 76.9% and 76.9% and recurrence-free survival rates in remission group were 100% and 100% respectively and inter-group difference in RFS was not statistically significant( χ2=1.468, P=0.226). The overall survival rates of recipients in non-remission group at 1 and 2 years post-operation were 76.9% and 76.9% respectively. And recipients in remission group were 100% and 100% respectively and no statistically significant inter-group difference existed in OS( χ2=1.292, P=0.256). Conclusions:Without a significantly higher risk of acute rejection after transplant, immunotherapy may be an effective option for bridging treatment before liver transplantation for HCC. And it remains necessary to expand the sample size for verifications and supports.
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Objective:To investigate the safety and efficacy of low molecular weight heparin (LMWH) bridging program in the perioperative period of mini-percutaneous nephrolithotomy (mPCNL) for long-term antithrombotic patients.Methods:The clinical data of 50 patients who received long-term antithrombotic therapy with mPCNL in Sun Yat-sen Memorial Hospital from January 2013 to December 2017 were retrospectively analyzed. Perioperative anticoagulation plans were drawn up after discussion with an internist. Patients with high thrombosis risk were bridged with LMWH during the perioperative period. Resumed LMWH anticoagulation within 48 hours after surgery. Patients with low or medium thrombosis risk directly discontinued anticoagulation one week before surgery. Preoperative anticoagulation was resumed within 48 hours after removing the nephrostomy tube in all patients. We analyzed the general information before surgery, data during surgery, postoperative hemoglobin changes and stone-free rate (SRF) of all cases. 21 patients were treated with LMWH bridging (bridging group), and 29 patients were directly discontinued with anticoagulant drugs (non-bridging group). There was no statistical difference between the two groups in age [(59.7±7.1) vs. (52.4±10.4)years] , gender [(male/female), 14/7 vs. 19/10], BMI [ (24.3±3.9) kg/m 2 vs. (24.7±5.1) kg/m 2], S. T.O.N.E. score (7.4±1.1 vs. 6.9±1.0), stone surface area [ 314.0(31.4-1 130.4) mm 2 vs. 282.5(64.7-866.0) mm 2], the number of calculi involved in calyces (6/15 vs. 13/16) and stone-related surgical history [ 34% (7/21) vs. 24% (7/29) ]. Results:In the bridging group, 18 patients (86%) performed single-channel mPCNL, 3 patients (14%) underwent dual-channel mPCNL, and the operation time was 80 (35-180) min. In the non-bridging group, 27 patients (93%) underwent single-channel mPCNL, 2 patients (7%) performed dual-channel mPCNL, and the operation time was 80 (30-60) min. The mean changes in hemoglobin in the bridging group and the non-bridging group was 18 (-2 -66) g/L and 14 (-25-64) g/L, respectively ( P = 0.073). The average postoperative hospital stay in the bridging group was (8.6 ± 3.5) days, and the non-bridging group was (7.1 ± 2.3) days ( P= 0.057). Two patients in each group received blood transfusion, and no patients received interventional embolization. The SRF of bridging group and non-bridging group was 81.0% (17/21) vs. 75.9% (22/29) ( P = 0.67) 1 month after the operation. During the perioperative period, no patients had thrombotic complications. Conclusions:When mPCNL was required for long-term antithrombotic treatment patients, the use of LWMH alternatives during the perioperative period did not increase bleeding related complications.
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Currently, several major challenges still exist in liver transplantation for hepatocellular carcinoma (HCC), including the opportunity of liver transplantation for HCC patients beyond selection criteria, drop-out from the waiting list for HCC patients within selection criteria due to tumor progression and the tumor recurrence after liver transplantation. In recent years, revolutionary efficacy has been achieved in treating advanced HCC by employing systemic drugs, such as lenvatinib and systemic drug-based comprehensive treatment, which also sheds light on the down-staging therapy and bridging therapy for HCC patients listed for liver transplantation, and prevention and treatment of tumor recurrence after liver transplantation for HCC individuals. Systemic drug-based comprehensive treatment probably has the potential to improve the clinical efficacy of liver transplantation for HCC, which deserves in-depth investigation. In this review, we summarize the progress on down-staging therapy, bridging therapy as well as prevention and treatment of tumor recurrence after liver transplantation for HCC individuals, aiming to provide reference for clinical managementof HCC.
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Lung transplantation is the ultimate treatment for many kinds of end-stage lung diseases. However, the perioperative management of lung transplantation is complicated with high fatality of patients. Extracorporeal membrane oxygenation (ECMO) is an effective method of extracorporeal respiration and circulation support. ECMO plays an important role in the perioperative support treatment of lung transplantation, which breaks the limitation of contraindications and promotes the development of lung transplantation. In this article, the indications, catheter placement strategies and application of ECMO in the perioperative period of lung transplantation were reviewed.
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The 25th Annual Congress of International Liver Transplantation Society (ILTS) was held from May 15 to 18, 2019 in Toronto, Canada. Focusing on the special topic of liver transplantation for liver cancer, down-staging liver cancer and bridging therapy before liver transplantation, prediction of liver cancer recurrence after liver transplantation, individualized immunosuppressive scheme, prevention and treatment of liver cancer recurrence after liver transplantation were summarized in this article. In addition, the literatures published in recent two years related to the research progress were reviewed.
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Stroke is the first cause of death in China, and ischemic stroke is the most common stroke and accounts for 70% of all new stroke cases. The treatment efficiency of acute ischemic stroke is closely related to the health of people in China. Bridging therapy has been proven safe and effective for acute ischemic stroke with anterior circulation large vessel occlusion. The incidence of symptomatic intracerebral hemorrhage is similar in the patients with bridging therapy and intravenous thrombolysis, suggesting that the complication is not due to intra-artery thrombectomy, but rather to intravenous thrombolysis. Thus it has become a research focus whether direct intra-artery thrombectomy is feasible for acute ischemic stroke, skipping intravenous thrombolysis. This paper discusses the related issues.
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Objective To explore the efficacy and safety of intravenous thrombolysis or bridging therapy for acute minor ischemic stroke (MIS) with large artery occlusion. Methods Seventy-three acute MIS patients with large artery occlusion, who admitted to our hospital via stroke green channel within 4.5 h after onset from Sep. 2013 to Jun. 2018, were enrolled in this study, including 55 cases in intravenous thrombolysis group and 18 cases in bridging therapy group. The patients in the intravenous thrombolysis group underwent intravenous thrombolysis treatment with recombinant tissue plasminogen activator (rt-PA), and the patients in the bridging therapy group underwent thrombectomy within time window after intravenous thrombolysis. National Institutes of Health stroke scale (NIHSS) score at admission and modified Rankin scale (mRS) score at 90 days after treatment were evaluated in all patients. The mRS scoring 0-2 was good prognosis, and 3-6 was poor prognosis. Results There were no significant differences in the gender, age, medical history, smoking history, ratio of asymptomatic cerebral infarction, NIHSS score at admission, Glasgow coma scale score, Alberta stroke program early conputed tomography score, door-to-needle time or onset-to-needle time between the two groups (all P>0.05). The rates of good prognosis at 7 d and 90 d after treatment, incidence of symptomatic intracranial hemorrhage and mortality were not significantly different between the two groups (all P>0.05), while the incidence of systemic complications was significantly lower in the intravenous thrombolysis group than that in the bridging therapy group (23.6% [13/55] vs 44.4% [8/18]; χ2=2.434, P=0.019). Conclusion Intravenous thrombolysis and bridging therapy have similar clinical efficacy and safety in treatment of acute MIS with large artery occlusion; although the incidence of systemic complications in patients with bridging therapy is higher than that in patients treated with intravenous thrombolysis, the long-term effects are both good.
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OBJECTIVE: The perioperative management of antithrombotic therapy is often challenging and it requires a fine balance between the risk of hemorrhage and thrombosis. We aimed to evaluate the antithrombotic management for moderate to high risk patients in real world setting. METHODS: Among the patients who were consulted to the neurologist for the evaluation of perioperative risk from 2010 to 2012, patients undergoing moderate to high risk surgery and taking antithrombotics within 30 days were identified. We analyzed the timing of discontinuation and reinitiation of antithrombotic drugs before or after surgery as well as the status of bridging therapy. In addition, the conformity with the guideline suggested by American College of Chest Physicians was assessed. The rate of thromboembolic event and major hemorrhage were also investigated. RESULTS: A total of 329 patients were included. The concordance rate of warfarin stop and restart time with guideline was 23.4% and 10.3%, respectively. Continuing aspirin in patients undergoing coronary artery bypass surgery or non-cardiac surgery in patients with high risk for cardiovascular events were 59.2% and 2.6%, respectively. Bridging therapy was adopted in 92.9% and 81.2% in patients who had received anticoagulant before surgery and who were at high and low risk thromboembolism, respectively. In entire cohorts, 30-day incidence of major bleeding and thromboembolic event were 31.9% and 3.0%. Co-morbid renal disease were shown as independent predictor for major bleeding (adjusted OR 2.65. 95% CI 1.33-5.28). CONCLUSION: The concordance rate with guideline regarding perioperative antithrombotic use was low and bridging therapy was prevalent in patients undergoing moderate to high risk surgery.
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Humans , Anticoagulants , Aspirin , Cohort Studies , Coronary Artery Bypass , Hemorrhage , Incidence , Thorax , Thromboembolism , Thrombosis , WarfarinABSTRACT
The periprocedural management of patients on long-term antithrombotic therapy (antiplatelet agents or vitamin K antagonists) who may require temporary disruption, given that an invasive procedure is always a dilemma for clinicians. Discontinuation of antithrombotic therapy can place patients at an increased risk of thromboembolic complications while the continuation of antithrombotic therapy can increase the procedure-related bleeding risk. Therefore, it is imperative for clinicians to be proficient in making thoughtful and individualized decisions on the appropriate management of periprocedural anticoagulants, drawing from recent evidence-based guidelines.