Hypertriglyceridemic pancreatitis(HTGP) accounts for up to 10% of acute pancreatitis presentations in nonpregnant individuals and is the third most common cause of acute pancreatitis after alcohol and gallstones. Ther...Hypertriglyceridemic pancreatitis(HTGP) accounts for up to 10% of acute pancreatitis presentations in nonpregnant individuals and is the third most common cause of acute pancreatitis after alcohol and gallstones. There are a number of retrospective studies and case reports that have suggested a role for apheresis and insulin infusion in the acute inpatient setting. We report a case of HTGP in a male with hyperlipoproteinemia type Ⅲ who was treated successfully with insulin and apheresis on the initial inpatient presentation followed by bi-monthly outpatient maintenance apheresis sessions for the prevention of recurrent HTGP. We also reviewed the literature for the different inpatient and outpatient management modalities of HTGP. Given that there are no guidelines or randomized clinical trials that evaluate the outpatient management of HTGP, this case report may provide insight into a possible role for outpatient apheresis maintenance therapy.展开更多
Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, i...Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients’ disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much展开更多
Active ulcerative colitis （UC） is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential ...Active ulcerative colitis （UC） is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes/macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis （GMCAP） for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session （session time, 60 min） per week for five consecutive weeks （a total of five apheresis sessions） has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, doubleblind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs ￥145 000 （$1 300）. However, if this treatment p展开更多
AIM: To investigate if the clinical efficacy of granulocytes and monocytes by adsorption (GMA) is associated with an increased frequency of peripheral regulatory T cells (Tregs), as these cells have proven to be succe...AIM: To investigate if the clinical efficacy of granulocytes and monocytes by adsorption (GMA) is associated with an increased frequency of peripheral regulatory T cells (Tregs), as these cells have proven to be successful in suppressing inflammatory bowel disease (IBD) in animal models. METHODS: We report four cases of corticosteroid- dependent ulcerative colitis (UC) and two Crohn’s disease (CD) cases with severe cutaneous lesions who received GMA therapy. The frequency of CD4+ CD25high (Tregs) in peripheral blood was analyzed by flow cytometry and the expression of FoxP3 and TGF beta in purified CD4+ T cells was determined by real time PCR prior to and one month after the last apheresis session, and at the time of endoscopic and clinical assessing. RESULTS: Increased expression of Fox P3 mRNA was found in all five patients who responded to cytapheresis with remission of clinical symptoms, mucosal inflammation and cutaneous lesions, and an increased frequency of circulating Tregs was found in four patients. These changes were not observed in the patient with UC who did no respond to GMA. Variations in TGF-β (mRNA) did not parallel that of FoxP3 mRNA. CONCLUSION: The clinical efficacy of GMA on IBD and related extra intestinal manifestations was associated with an expansion of circulating CD4+ CD25+ Tregs and higher expression of FoxP3 in CD4+ T cells. Accordingly, an elevated CD4+ CD25+ FoxP3 may be a valuable index of remission in patients with IBD and other chronic relapsing-remitting inflammatory conditions during treatment with GMA.展开更多
Background： Although many previous studies have confirmed that perioperative blood transfusion is associated with poor outcomes after liver transplantation （LT）, few studies described the influence of single-donor ...Background： Although many previous studies have confirmed that perioperative blood transfusion is associated with poor outcomes after liver transplantation （LT）, few studies described the influence of single-donor platelet apheresis transfusion in living donor LT （LDLT）. This study aimed to assess the effect of blood products on outcomes for LDLT recipients, focusing on apheresis platelets. Methods： This retrospective study included 126 recipients who underwent their first adult-to-adult LDLT. Twenty-four variables including consumption of blood products of 126 LDLT recipients were assessed for their link to short-term outcomes and overall survival. Kaplan-Meier survival curve and the log-rank test were used for recipient survival analysis. A multivariate Cox proportional-hazard model and a propensity score analysis were applied to adjust confounders after potential risk factors were identified by a univariate Cox analysis. Results： Patients who received apheresis platelet transfusion had a lower 90-day cumulative survival （78.9% vs. 94.2%, P = 0.009）, but had no significant difference in overall survival in the Cox model, compared with those without apheresis platelet transfusion. Units of apheresis platelet transfusion（hazard ratio[HR]=3.103,95% confidence interval[CI]：1.720–5.600,P〈0.001）and preoperative platelet count（HR=0.170,95% CI：0.040–0.730,P=0.017）impacted 90-day survival independently.Multivariate Cox regression analysis also found that units of red blood cell（RBC）transfusion（HR=1.036,95% CI：1.006–1.067,P=0.018）,recipient＇s age（HR=1.045,95% CI：1.005–1.086,P=0.025）,and ABO blood group comparison（HR=2.990,95% CI：1.341–6.669,P=0.007）were independent risk factors for overall survival after LDLT. Conclusions： This study suggested that apheresis platelets were only associated with early mortality but had no impact on overall survival in LDLT. Units of RBC, recipient＇s age, and ABO group comparison were independent predictors of long-term o展开更多
2023年4月美国血液分离学会(American Society for Apheresis,ASFA)发布了第9版《治疗性血液分离技术临床实践指南》。该指南基于目前已发表的文献,确定治疗性血液分离技术治疗疾病的证据质量及推荐强度,讨论了该技术在91种疾病(166种...2023年4月美国血液分离学会(American Society for Apheresis,ASFA)发布了第9版《治疗性血液分离技术临床实践指南》。该指南基于目前已发表的文献,确定治疗性血液分离技术治疗疾病的证据质量及推荐强度,讨论了该技术在91种疾病(166种适应证)中的临床应用。本文重点解读血浆净化技术,即血浆置换和免疫吸附技术在临床多学科中的应用。展开更多
AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis.METHODS: The ADAPT study was a prospective, open-label, multicenter study in pe...AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis.METHODS: The ADAPT study was a prospective, open-label, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric ulcerative colitis activity index (PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn<sup>®</sup> granulocyte, monocyte/macrophage adsorptive (GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint was the change in mean PUCAI between baseline and week 12; the secondary endpoint was improvement in PUCAI categorized as (Significant Improvement, PUCAI decrease of ≥ 35), Moderate Improvement (PUCAI decrease of 20 < 35), Small Improvement (PUCAI decrease of 10 < 20) or No change (PUCAI decrease of < 10).RESULTS: Twenty-five patients (mean age 13.5 years; mean weight 47.7 kg) were enrolled. In the intention-to-treat set (ITT), the mean value for PUCAI improvement was 22.3 [95%CI: 12.9-31.6; n = 21]. In the per-protocol (PP) set, the mean improvement was 36.3 [95%CI: 31.4-41.1; n = 8]. Significant Improvement was recorded for 9 out of 20 patients (45%); 5 out of 20 patients (25%) had Moderate Improvement and one patient (5%) had No Change in PUCAI score at week 12. In the PP set, six out of eight patients (75%) showed Significant Improvement; and in two out of eight patients (25%) Moderate Improvement was recorded. The endoscopic activity index (EAI) decreased by 3 points on average. Seven (7) out of 21 (33%) patients in ITT and 4 out of 8 (50%) patients in PP have used steroids during the clinical investigation. The mean steroid dosage for these patients in the ITT set decreased from a mean 12.4 mg to 10 mg daily on average from Baseline to week 12.CONCLUSION: Adacolumn<sup>®</sup> GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative 展开更多
Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime.Approximately 75%of these patients will also require immunosuppressive drugs(i.e.,thiopurines or b...Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime.Approximately 75%of these patients will also require immunosuppressive drugs(i.e.,thiopurines or biological agents)in the mid-term to avoid colectomy.Immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer,particularly in elderly and co-morbid patients,underlining the unmet need for safer alternative therapies.Granulocyte/monocytapheresis(GMA),a CE-marked,non-pharmacological procedure for the treatment of ulcerative colitis(among other immune-mediated diseases),remains the only therapy targeting neutrophils,the hallmark of pathology in ulcerative colitis.GMA has proven its efficacy in different clinical scenarios and shows an excellent and unique safety profile.In spite of being a first line therapy in Japan,GMA use is still limited to a small number of centres and countries in Europe.In this article,we aim to give an overview from a European perspective of the mechanism of action,recent clinical data on efficacy and practical aspects for the use of GMA in ulcerative colitis.展开更多
2019年6月美国血浆置换学会(American Society for Apheresis,ASFA)发布了第8版《治疗性单采术临床实践指南》。该指南基于目前已发表的文献,确定治疗性单采术治疗疾病的证据质量并得出推荐强度,讨论了治疗性单采术在84种疾病(157种适应...2019年6月美国血浆置换学会(American Society for Apheresis,ASFA)发布了第8版《治疗性单采术临床实践指南》。该指南基于目前已发表的文献,确定治疗性单采术治疗疾病的证据质量并得出推荐强度,讨论了治疗性单采术在84种疾病(157种适应证)中的临床应用。指南将治疗性单采术分为针对血液细胞的净化技术和针对血浆成分的净化技术两大类,血浆净化技术主要是指血浆置换和免疫吸附。本文重点解读血浆置换和免疫吸附在临床多学科的应用。展开更多
文摘Hypertriglyceridemic pancreatitis(HTGP) accounts for up to 10% of acute pancreatitis presentations in nonpregnant individuals and is the third most common cause of acute pancreatitis after alcohol and gallstones. There are a number of retrospective studies and case reports that have suggested a role for apheresis and insulin infusion in the acute inpatient setting. We report a case of HTGP in a male with hyperlipoproteinemia type Ⅲ who was treated successfully with insulin and apheresis on the initial inpatient presentation followed by bi-monthly outpatient maintenance apheresis sessions for the prevention of recurrent HTGP. We also reviewed the literature for the different inpatient and outpatient management modalities of HTGP. Given that there are no guidelines or randomized clinical trials that evaluate the outpatient management of HTGP, this case report may provide insight into a possible role for outpatient apheresis maintenance therapy.
文摘Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients’ disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much
文摘Active ulcerative colitis （UC） is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes/macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis （GMCAP） for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session （session time, 60 min） per week for five consecutive weeks （a total of five apheresis sessions） has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, doubleblind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs ￥145 000 （$1 300）. However, if this treatment p
文摘AIM: To investigate if the clinical efficacy of granulocytes and monocytes by adsorption (GMA) is associated with an increased frequency of peripheral regulatory T cells (Tregs), as these cells have proven to be successful in suppressing inflammatory bowel disease (IBD) in animal models. METHODS: We report four cases of corticosteroid- dependent ulcerative colitis (UC) and two Crohn’s disease (CD) cases with severe cutaneous lesions who received GMA therapy. The frequency of CD4+ CD25high (Tregs) in peripheral blood was analyzed by flow cytometry and the expression of FoxP3 and TGF beta in purified CD4+ T cells was determined by real time PCR prior to and one month after the last apheresis session, and at the time of endoscopic and clinical assessing. RESULTS: Increased expression of Fox P3 mRNA was found in all five patients who responded to cytapheresis with remission of clinical symptoms, mucosal inflammation and cutaneous lesions, and an increased frequency of circulating Tregs was found in four patients. These changes were not observed in the patient with UC who did no respond to GMA. Variations in TGF-β (mRNA) did not parallel that of FoxP3 mRNA. CONCLUSION: The clinical efficacy of GMA on IBD and related extra intestinal manifestations was associated with an expansion of circulating CD4+ CD25+ Tregs and higher expression of FoxP3 in CD4+ T cells. Accordingly, an elevated CD4+ CD25+ FoxP3 may be a valuable index of remission in patients with IBD and other chronic relapsing-remitting inflammatory conditions during treatment with GMA.
文摘Background： Although many previous studies have confirmed that perioperative blood transfusion is associated with poor outcomes after liver transplantation （LT）, few studies described the influence of single-donor platelet apheresis transfusion in living donor LT （LDLT）. This study aimed to assess the effect of blood products on outcomes for LDLT recipients, focusing on apheresis platelets. Methods： This retrospective study included 126 recipients who underwent their first adult-to-adult LDLT. Twenty-four variables including consumption of blood products of 126 LDLT recipients were assessed for their link to short-term outcomes and overall survival. Kaplan-Meier survival curve and the log-rank test were used for recipient survival analysis. A multivariate Cox proportional-hazard model and a propensity score analysis were applied to adjust confounders after potential risk factors were identified by a univariate Cox analysis. Results： Patients who received apheresis platelet transfusion had a lower 90-day cumulative survival （78.9% vs. 94.2%, P = 0.009）, but had no significant difference in overall survival in the Cox model, compared with those without apheresis platelet transfusion. Units of apheresis platelet transfusion（hazard ratio[HR]=3.103,95% confidence interval[CI]：1.720–5.600,P〈0.001）and preoperative platelet count（HR=0.170,95% CI：0.040–0.730,P=0.017）impacted 90-day survival independently.Multivariate Cox regression analysis also found that units of red blood cell（RBC）transfusion（HR=1.036,95% CI：1.006–1.067,P=0.018）,recipient＇s age（HR=1.045,95% CI：1.005–1.086,P=0.025）,and ABO blood group comparison（HR=2.990,95% CI：1.341–6.669,P=0.007）were independent risk factors for overall survival after LDLT. Conclusions： This study suggested that apheresis platelets were only associated with early mortality but had no impact on overall survival in LDLT. Units of RBC, recipient＇s age, and ABO group comparison were independent predictors of long-term o
文摘2023年4月美国血液分离学会(American Society for Apheresis,ASFA)发布了第9版《治疗性血液分离技术临床实践指南》。该指南基于目前已发表的文献,确定治疗性血液分离技术治疗疾病的证据质量及推荐强度,讨论了该技术在91种疾病(166种适应证)中的临床应用。本文重点解读血浆净化技术,即血浆置换和免疫吸附技术在临床多学科中的应用。
基金Supported by Otsuka Frankfurt Research Institute, the legal and financial sponsor for this clinical trial, Otsuka Pharmaceutical Europe Ltd. supported the realization of this paper
文摘AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis.METHODS: The ADAPT study was a prospective, open-label, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric ulcerative colitis activity index (PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn<sup>®</sup> granulocyte, monocyte/macrophage adsorptive (GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint was the change in mean PUCAI between baseline and week 12; the secondary endpoint was improvement in PUCAI categorized as (Significant Improvement, PUCAI decrease of ≥ 35), Moderate Improvement (PUCAI decrease of 20 < 35), Small Improvement (PUCAI decrease of 10 < 20) or No change (PUCAI decrease of < 10).RESULTS: Twenty-five patients (mean age 13.5 years; mean weight 47.7 kg) were enrolled. In the intention-to-treat set (ITT), the mean value for PUCAI improvement was 22.3 [95%CI: 12.9-31.6; n = 21]. In the per-protocol (PP) set, the mean improvement was 36.3 [95%CI: 31.4-41.1; n = 8]. Significant Improvement was recorded for 9 out of 20 patients (45%); 5 out of 20 patients (25%) had Moderate Improvement and one patient (5%) had No Change in PUCAI score at week 12. In the PP set, six out of eight patients (75%) showed Significant Improvement; and in two out of eight patients (25%) Moderate Improvement was recorded. The endoscopic activity index (EAI) decreased by 3 points on average. Seven (7) out of 21 (33%) patients in ITT and 4 out of 8 (50%) patients in PP have used steroids during the clinical investigation. The mean steroid dosage for these patients in the ITT set decreased from a mean 12.4 mg to 10 mg daily on average from Baseline to week 12.CONCLUSION: Adacolumn<sup>®</sup> GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative
文摘Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime.Approximately 75%of these patients will also require immunosuppressive drugs(i.e.,thiopurines or biological agents)in the mid-term to avoid colectomy.Immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer,particularly in elderly and co-morbid patients,underlining the unmet need for safer alternative therapies.Granulocyte/monocytapheresis(GMA),a CE-marked,non-pharmacological procedure for the treatment of ulcerative colitis(among other immune-mediated diseases),remains the only therapy targeting neutrophils,the hallmark of pathology in ulcerative colitis.GMA has proven its efficacy in different clinical scenarios and shows an excellent and unique safety profile.In spite of being a first line therapy in Japan,GMA use is still limited to a small number of centres and countries in Europe.In this article,we aim to give an overview from a European perspective of the mechanism of action,recent clinical data on efficacy and practical aspects for the use of GMA in ulcerative colitis.
文摘2019年6月美国血浆置换学会(American Society for Apheresis,ASFA)发布了第8版《治疗性单采术临床实践指南》。该指南基于目前已发表的文献,确定治疗性单采术治疗疾病的证据质量并得出推荐强度,讨论了治疗性单采术在84种疾病(157种适应证)中的临床应用。指南将治疗性单采术分为针对血液细胞的净化技术和针对血浆成分的净化技术两大类,血浆净化技术主要是指血浆置换和免疫吸附。本文重点解读血浆置换和免疫吸附在临床多学科的应用。
