Inflammatory Bowel Disease(IBD)is a hallmark of leukocyte infiltration,followed by the release of cytokines and interleukins.Disease progression to Ulcerative Colitis(UC)or Crohn’s Disease(CD)remained largely incurab...Inflammatory Bowel Disease(IBD)is a hallmark of leukocyte infiltration,followed by the release of cytokines and interleukins.Disease progression to Ulcerative Colitis(UC)or Crohn’s Disease(CD)remained largely incurable.The genetic and environmental factors disrupt enteral bacteria in the gut,which hampers the intestinal repairing capability of damaged mucosa.Commonly practiced pharmacological therapies include 5-aminosalicylic acid with corticosteroids and tumor necrosis factor(TNF)-α.New interventions such as CDP571 and TNF-blocking RDP58 report the loss of patient response.This review discusses the non-pharmacologic selective granulocyte–monocyte-apheresis(GMA)and leukocytapheresis(LCAP)that have been proposed as treatment modalities that reduce mortality.GMA,an extracorporeal vein-to-vein technique,presents a strong safety profile case for its use as a viable therapeutic option compared to GMA's conventional medication safety profile.GMA reported minimal to no side effects in the pediatric population and pregnant women.Numerous studies report the efficacious nature of GMA in UC patients,whereas data on CD patients is insufficient.Its benefits outweigh the risks and are emerging as a favored nonpharmacological treatment option.On the contrary,LCAP uses a general extracorporeal treatment that entraps leukocytes and suppresses cytokine release.It has been deemed more efficacious than conventional drug treatments,the former causing better disease remission,and maintenance.Patients with UC/CD secondary to complications have responded well to the treatment.Side effects of the procedure have remained mild to moderate,and there is little evidence of any severe adverse event occurring in most age groups.LCAP decreases the dependence on steroids and immunosuppressive therapies for IBD.The review will discuss the role of GMA and LCAP.展开更多
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
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 prevents hospital admission, re-administration of steroids and surgery, and improves a quality of life of the patients, GMCAP may prove to be cost-effective.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
Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Leukocytapheresis is a novel nonphar- macologic approach for active UC, in which leuko...Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Leukocytapheresis is a novel nonphar- macologic approach for active UC, in which leukocytes are mechanically removed from the circulatory system. Current data indicate that leukocytapheresis is effica- cious in improving response and remission rates with excellent tolerability and safety in patients with UC. Corticosteroid therapy remains a mainstay in the treat- ment of active UC, however, long-term, high doses of corticosteroids usually produce predictable and po- tentially serious side effects. If leukocytapheresis can spare patients from exposure to corticosteroids, the risk of steroid-induced adverse events should be mini- mized. This may be of great benefit to patients because severe side effects of steroids seriously impair health- related quality of life. In this article, we reviewed cur- rent evidence on whether leukocytapheresis can avoid or reduce the use of corticosteroids in the manage- ment of patients with UC. Several studies have shown that leukocytapheresis was effective for steroid-nafve patients with active UC. Furthermore, both short-term and long-term studies have demonstrated the steroid- sparing effects of leukocytapheresis therapy in patients with UC. Although the evidence level is not striking, theavailable data suggest that leukocytapheresis can avoid or reduce the use of corticosteroids in the management of UC. Large, well-designed clinical trials are necessary to more accurately evaluate the steroid-sparing effects of leukocytapheresis in the management of UC.展开更多
For the optimal management of refractory ulcerative colitis(UC),secondary loss of response(LOR)and primary non-response to biologics is a critical issue.This article aimed to summarize the current literature on the us...For the optimal management of refractory ulcerative colitis(UC),secondary loss of response(LOR)and primary non-response to biologics is a critical issue.This article aimed to summarize the current literature on the use of cytapheresis(CAP)in patients with UC showing a poor response or LOR to biologics and discuss its advantages and limitations.Further,we summarized the efficacy of CAP in patients with UC showing insufficient response to thiopurines or immunomodulators(IM).Eight studies evaluated the efficacy of CAP in patients with UC with inadequate responses to thiopurines or IM.There were no significant differences in the rate of remission and steroid-free remission between patients exposed or not exposed to thiopurines or IM.Three studies evaluated the efficacy of CAP in patients with UC showing an insufficient response to biologic therapies.Mean remission rates of biologics exposed or unexposed patients were 29.4%and 44.2%,respectively.Fourteen studies evaluated the efficacy of CAP in combination with biologics in patients with inflammatory bowel disease showing a poor response or LOR to biologics.The rates of remission/response and steroid-free remission in patients with UC ranged 32%-69%(mean:48.0%,median:42.9%)and 9%-75%(mean:40.7%,median:38%),respectively.CAP had the same effectiveness for remission induction with or without prior failure on thiopurines or IM but showed little benefit in patients with UC refractory to biologics.Although heterogeneity existed in the efficacy of the combination therapy with CAP and biologics,these combination therapies induced clinical remission/response and steroid-free remission in more than 40%of patients with UC refractory to biologics on average.Given the excellent safety profile of CAP,this combination therapy can be an alternative therapeutic strategy for UC refractory to biologics.Extensive prospective studies are needed to understand the efficacy of combination therapy with CAP and biologics.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 favoured by patients for its good safety profile. GMA in 21<sup>st</sup> century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.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
AIM: To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS: An op...AIM: To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI 6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk). Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn, Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life (IBDQ), and laboratory tests. RESULTS: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAI〈4, EI〈4). Quality of life (IBDQ) increased significantly (24 points, P〈0.01) at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. CONCLUSION: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/ monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.展开更多
AIM:To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA). METHODS:Sixty-nine ulcerative colitis patients (39 F,30 M) dependent upon/refractory to ...AIM:To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA). METHODS:Sixty-nine ulcerative colitis patients (39 F,30 M) dependent upon/refractory to steroids were treated with GMA. Steroid dependency,clinical activity index (CAI),C reactive protein (CRP) level,erythrocyte sedimentation rate (ESR),values at baseline,use of immunosuppressant,duration of disease,and age and extent of disease were considered for statistical analysis as predictive factors of clinical response. Univariate and multivariate logistic regression models were used. RESULTS:In the univariate analysis,CAI (P = 0.039) and ESR (P = 0.017) levels at baseline were singled out as predictive of clinical remission. In the multivariate analysis steroid dependency [Odds ratio (OR) = 0.390,95% Confidence interval (CI):0.176-0.865,Wald 5.361,P = 0.0160] and low CAI levels at baseline (4 < CAI <7) (OR = 0.770,95% CI:0.425-1.394,Wald 3.747,P = 0.028) proved to be effective as factors predicting clinical response. CONCLUSION:GMA may be a valid therapeutic option for steroid-dependent ulcerative colitis patients with mild-moderate disease and its clinical efficacy seems to persist for 12 mo.展开更多
The etiology and pathogenesis of inflammatory bowel disease(IBD),including ulcerative colitis and Crohn’s disease,are not fully understood so far.Therefore,IBD still remains incurable despite the fact that significan...The etiology and pathogenesis of inflammatory bowel disease(IBD),including ulcerative colitis and Crohn’s disease,are not fully understood so far.Therefore,IBD still remains incurable despite the fact that significant progress has been achieved in recent years in its treatment with innovative medicine.About 20 years ago,selective granulocyte and monocyte apheresis(GMA)was invented in Japan and later approved by the Japanese health authority for IBD treatment.From then on this technique was extensively used for IBD patients in Japan and later in Europe.Clinical trials from Japan and European countries have verified the effectiveness and safety of GMA therapy in patients with IBD.In 2013,GMA therapy was approved by China State Food and Drug Administration for therapeutic use for the Chinese IBD patients.However,GMA therapy has not been extensively used in China,although a few clinical studies also showed that it was effective in clinical and endoscopic induction of remission in Chinese IBD patients with a high safety profile.This article reviews past history,present clinical application as well as the future prospective of GMA therapy for patients with IBD.展开更多
Severe alcoholic hepatitis(AH) has a high mortality,and it is associated with encephalopathy,acute renal failure,sepsis,gastrointestinal bleeding,and endotoxemia.The 28-d mortality remains poor(34%-40%),because no eff...Severe alcoholic hepatitis(AH) has a high mortality,and it is associated with encephalopathy,acute renal failure,sepsis,gastrointestinal bleeding,and endotoxemia.The 28-d mortality remains poor(34%-40%),because no effective treatment has been established.Recently,corticosteroids(CS) have been considered effective for significantly improving the prognosis of those with AH,as it prevents the production of pro-inflammatory cytokines.However,CS are not always appropriate as an initial therapeutic option,such as in cases with an infection or resistance to CS.We describe a patient with severe AH complicated by a severe infection caused by the multidrug resistance bacteria(Pseudomonas aeruginosa),and was successfully treated with granulocytapheresis monotherapy without using CS.The experience of this case will provide understanding of the disease and information treating cases without using CS.展开更多
Introduction: Vasculitis associated with anti-neutrophil cytoplasm antibodies (ANCA) can be grouped with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MAP), and eosinophilic granulomatosis with pol...Introduction: Vasculitis associated with anti-neutrophil cytoplasm antibodies (ANCA) can be grouped with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MAP), and eosinophilic granulomatosis with polyangiitis (EGPA). Diagnosis of these rare pathologies is based on clinical presentation, the positivity of ANCA, and, if possible, histological proof of vasculitis. Our study describes a series of six cases of ANCA-associated vasculitis where due to the severity of symptoms apheresis sessions were started from the beginning of the therapy. Patients and methods: We conducted a retrospective, single-center observational, monocentric study on all patients treated by apheresis for ANCA vasculitis in the period January 01, 2016 to December 01, 2019. Results: We identified six cases of ANCA vasculitis treated by apheresis over a 3-year period. The mean age was 61 ± 19 years;M/F gender ratio was 1:1. Initial renal damage in all patients was rapidly progressive glomerulonephritis. Inflammatory syndrome occurred in all patients with average CRP of 82 mg/L. All patients had positive ANCA at diagnosis. Four patients required renal replacement therapy at the time of diagnosis. The induction regimen consisted of rituximab associated with IV boluses of methylprednisolone. The apheresis techniques used were the same for all patients, i.e. plasmapheresis. Outcomes were favorable for five patients;only one patient became dependent on hemodialysis. No mortality occurred. Conclusion: This study analyzed practices for the management of patients with ANCA vasculitis. No patient was treated with cyclophosphamide as a first approach but rituximab instead. Plasmapheresis was given because of symptoms severity at initial diagnosis.展开更多
Background:The prognosis of focal segmental glomerulosclerosis patients with nephrotic syndrome is estimated to be 10%-20%in 5 years and 30%-50%in 10 years,leading to end-stage kidney disease.The response rate with st...Background:The prognosis of focal segmental glomerulosclerosis patients with nephrotic syndrome is estimated to be 10%-20%in 5 years and 30%-50%in 10 years,leading to end-stage kidney disease.The response rate with steroid therapy is 40%-60%.Therapeutic low-density lipoprotein-apheresis(LDL-A)may be effective in patients with steroid resistance.Information regarding the long-term prognosis of patients with focal segmental glomerulosclerosis receiving this therapy is scarce.Methods:We investigated the effectiveness of treatment in 50 patients with primary focal segmental glomerulosclerosis diagnosed between 1961 and 2017 at Kanazawa University Hospital and related facilities.The patients were observed at least 12 months after biopsy or until end-stage kidney disease occurrence or death.Results:LDL-A was performed in four patients who presented with steroidresistant nephrotic syndrome(two patients had concurrent acute renal failure for which hemodialysis was performed).In comparison with 17 patients who did not receive LDL-A after 1989,the LDL-A group had higher urinary protein excretion(13.7 vs.5.2 g/day,P=0.053)and serum creatinine(4.11 vs.1.65 mg/dL)levels at onset,and a numerically higher remission rate(75.0%vs.58.7%)compared with the nonlipoprotein-apheresis group.Conclusion:Therapeutic LDL-A can be performed for critical cases and may improve the remission rate.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 outcomes.展开更多
文摘Inflammatory Bowel Disease(IBD)is a hallmark of leukocyte infiltration,followed by the release of cytokines and interleukins.Disease progression to Ulcerative Colitis(UC)or Crohn’s Disease(CD)remained largely incurable.The genetic and environmental factors disrupt enteral bacteria in the gut,which hampers the intestinal repairing capability of damaged mucosa.Commonly practiced pharmacological therapies include 5-aminosalicylic acid with corticosteroids and tumor necrosis factor(TNF)-α.New interventions such as CDP571 and TNF-blocking RDP58 report the loss of patient response.This review discusses the non-pharmacologic selective granulocyte–monocyte-apheresis(GMA)and leukocytapheresis(LCAP)that have been proposed as treatment modalities that reduce mortality.GMA,an extracorporeal vein-to-vein technique,presents a strong safety profile case for its use as a viable therapeutic option compared to GMA's conventional medication safety profile.GMA reported minimal to no side effects in the pediatric population and pregnant women.Numerous studies report the efficacious nature of GMA in UC patients,whereas data on CD patients is insufficient.Its benefits outweigh the risks and are emerging as a favored nonpharmacological treatment option.On the contrary,LCAP uses a general extracorporeal treatment that entraps leukocytes and suppresses cytokine release.It has been deemed more efficacious than conventional drug treatments,the former causing better disease remission,and maintenance.Patients with UC/CD secondary to complications have responded well to the treatment.Side effects of the procedure have remained mild to moderate,and there is little evidence of any severe adverse event occurring in most age groups.LCAP decreases the dependence on steroids and immunosuppressive therapies for IBD.The review will discuss the role of GMA and LCAP.
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 prevents hospital admission, re-administration of steroids and surgery, and improves a quality of life of the patients, GMCAP may prove to be cost-effective.
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Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Leukocytapheresis is a novel nonphar- macologic approach for active UC, in which leukocytes are mechanically removed from the circulatory system. Current data indicate that leukocytapheresis is effica- cious in improving response and remission rates with excellent tolerability and safety in patients with UC. Corticosteroid therapy remains a mainstay in the treat- ment of active UC, however, long-term, high doses of corticosteroids usually produce predictable and po- tentially serious side effects. If leukocytapheresis can spare patients from exposure to corticosteroids, the risk of steroid-induced adverse events should be mini- mized. This may be of great benefit to patients because severe side effects of steroids seriously impair health- related quality of life. In this article, we reviewed cur- rent evidence on whether leukocytapheresis can avoid or reduce the use of corticosteroids in the manage- ment of patients with UC. Several studies have shown that leukocytapheresis was effective for steroid-nafve patients with active UC. Furthermore, both short-term and long-term studies have demonstrated the steroid- sparing effects of leukocytapheresis therapy in patients with UC. Although the evidence level is not striking, theavailable data suggest that leukocytapheresis can avoid or reduce the use of corticosteroids in the management of UC. Large, well-designed clinical trials are necessary to more accurately evaluate the steroid-sparing effects of leukocytapheresis in the management of UC.
文摘For the optimal management of refractory ulcerative colitis(UC),secondary loss of response(LOR)and primary non-response to biologics is a critical issue.This article aimed to summarize the current literature on the use of cytapheresis(CAP)in patients with UC showing a poor response or LOR to biologics and discuss its advantages and limitations.Further,we summarized the efficacy of CAP in patients with UC showing insufficient response to thiopurines or immunomodulators(IM).Eight studies evaluated the efficacy of CAP in patients with UC with inadequate responses to thiopurines or IM.There were no significant differences in the rate of remission and steroid-free remission between patients exposed or not exposed to thiopurines or IM.Three studies evaluated the efficacy of CAP in patients with UC showing an insufficient response to biologic therapies.Mean remission rates of biologics exposed or unexposed patients were 29.4%and 44.2%,respectively.Fourteen studies evaluated the efficacy of CAP in combination with biologics in patients with inflammatory bowel disease showing a poor response or LOR to biologics.The rates of remission/response and steroid-free remission in patients with UC ranged 32%-69%(mean:48.0%,median:42.9%)and 9%-75%(mean:40.7%,median:38%),respectively.CAP had the same effectiveness for remission induction with or without prior failure on thiopurines or IM but showed little benefit in patients with UC refractory to biologics.Although heterogeneity existed in the efficacy of the combination therapy with CAP and biologics,these combination therapies induced clinical remission/response and steroid-free remission in more than 40%of patients with UC refractory to biologics on average.Given the excellent safety profile of CAP,this combination therapy can be an alternative therapeutic strategy for UC refractory to biologics.Extensive prospective studies are needed to understand the efficacy of combination therapy with CAP and biologics.
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 favoured by patients for its good safety profile. GMA in 21<sup>st</sup> century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.
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AIM: To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI 6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk). Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn, Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life (IBDQ), and laboratory tests. RESULTS: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAI〈4, EI〈4). Quality of life (IBDQ) increased significantly (24 points, P〈0.01) at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. CONCLUSION: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/ monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.
文摘AIM:To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA). METHODS:Sixty-nine ulcerative colitis patients (39 F,30 M) dependent upon/refractory to steroids were treated with GMA. Steroid dependency,clinical activity index (CAI),C reactive protein (CRP) level,erythrocyte sedimentation rate (ESR),values at baseline,use of immunosuppressant,duration of disease,and age and extent of disease were considered for statistical analysis as predictive factors of clinical response. Univariate and multivariate logistic regression models were used. RESULTS:In the univariate analysis,CAI (P = 0.039) and ESR (P = 0.017) levels at baseline were singled out as predictive of clinical remission. In the multivariate analysis steroid dependency [Odds ratio (OR) = 0.390,95% Confidence interval (CI):0.176-0.865,Wald 5.361,P = 0.0160] and low CAI levels at baseline (4 < CAI <7) (OR = 0.770,95% CI:0.425-1.394,Wald 3.747,P = 0.028) proved to be effective as factors predicting clinical response. CONCLUSION:GMA may be a valid therapeutic option for steroid-dependent ulcerative colitis patients with mild-moderate disease and its clinical efficacy seems to persist for 12 mo.
文摘The etiology and pathogenesis of inflammatory bowel disease(IBD),including ulcerative colitis and Crohn’s disease,are not fully understood so far.Therefore,IBD still remains incurable despite the fact that significant progress has been achieved in recent years in its treatment with innovative medicine.About 20 years ago,selective granulocyte and monocyte apheresis(GMA)was invented in Japan and later approved by the Japanese health authority for IBD treatment.From then on this technique was extensively used for IBD patients in Japan and later in Europe.Clinical trials from Japan and European countries have verified the effectiveness and safety of GMA therapy in patients with IBD.In 2013,GMA therapy was approved by China State Food and Drug Administration for therapeutic use for the Chinese IBD patients.However,GMA therapy has not been extensively used in China,although a few clinical studies also showed that it was effective in clinical and endoscopic induction of remission in Chinese IBD patients with a high safety profile.This article reviews past history,present clinical application as well as the future prospective of GMA therapy for patients with IBD.
文摘Severe alcoholic hepatitis(AH) has a high mortality,and it is associated with encephalopathy,acute renal failure,sepsis,gastrointestinal bleeding,and endotoxemia.The 28-d mortality remains poor(34%-40%),because no effective treatment has been established.Recently,corticosteroids(CS) have been considered effective for significantly improving the prognosis of those with AH,as it prevents the production of pro-inflammatory cytokines.However,CS are not always appropriate as an initial therapeutic option,such as in cases with an infection or resistance to CS.We describe a patient with severe AH complicated by a severe infection caused by the multidrug resistance bacteria(Pseudomonas aeruginosa),and was successfully treated with granulocytapheresis monotherapy without using CS.The experience of this case will provide understanding of the disease and information treating cases without using CS.
文摘Introduction: Vasculitis associated with anti-neutrophil cytoplasm antibodies (ANCA) can be grouped with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MAP), and eosinophilic granulomatosis with polyangiitis (EGPA). Diagnosis of these rare pathologies is based on clinical presentation, the positivity of ANCA, and, if possible, histological proof of vasculitis. Our study describes a series of six cases of ANCA-associated vasculitis where due to the severity of symptoms apheresis sessions were started from the beginning of the therapy. Patients and methods: We conducted a retrospective, single-center observational, monocentric study on all patients treated by apheresis for ANCA vasculitis in the period January 01, 2016 to December 01, 2019. Results: We identified six cases of ANCA vasculitis treated by apheresis over a 3-year period. The mean age was 61 ± 19 years;M/F gender ratio was 1:1. Initial renal damage in all patients was rapidly progressive glomerulonephritis. Inflammatory syndrome occurred in all patients with average CRP of 82 mg/L. All patients had positive ANCA at diagnosis. Four patients required renal replacement therapy at the time of diagnosis. The induction regimen consisted of rituximab associated with IV boluses of methylprednisolone. The apheresis techniques used were the same for all patients, i.e. plasmapheresis. Outcomes were favorable for five patients;only one patient became dependent on hemodialysis. No mortality occurred. Conclusion: This study analyzed practices for the management of patients with ANCA vasculitis. No patient was treated with cyclophosphamide as a first approach but rituximab instead. Plasmapheresis was given because of symptoms severity at initial diagnosis.
文摘Background:The prognosis of focal segmental glomerulosclerosis patients with nephrotic syndrome is estimated to be 10%-20%in 5 years and 30%-50%in 10 years,leading to end-stage kidney disease.The response rate with steroid therapy is 40%-60%.Therapeutic low-density lipoprotein-apheresis(LDL-A)may be effective in patients with steroid resistance.Information regarding the long-term prognosis of patients with focal segmental glomerulosclerosis receiving this therapy is scarce.Methods:We investigated the effectiveness of treatment in 50 patients with primary focal segmental glomerulosclerosis diagnosed between 1961 and 2017 at Kanazawa University Hospital and related facilities.The patients were observed at least 12 months after biopsy or until end-stage kidney disease occurrence or death.Results:LDL-A was performed in four patients who presented with steroidresistant nephrotic syndrome(two patients had concurrent acute renal failure for which hemodialysis was performed).In comparison with 17 patients who did not receive LDL-A after 1989,the LDL-A group had higher urinary protein excretion(13.7 vs.5.2 g/day,P=0.053)and serum creatinine(4.11 vs.1.65 mg/dL)levels at onset,and a numerically higher remission rate(75.0%vs.58.7%)compared with the nonlipoprotein-apheresis group.Conclusion:Therapeutic LDL-A can be performed for critical cases and may improve the remission rate.
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 outcomes.