Activated platelets as a possible early marker to predict clinical efficacy of leukocytapheresis in severe ulcerative colitis patients

Background Leukocytapheresis (LCAP) is an effective adjunct for patients with active ulcerative colitis (UC). Because LCAP may have the potential to remove and modulate not only leukocytes but also platelets, we evaluated the correlation between activated platelets and the therapeutic response to LCAP. Methods Fourteen patients with severe UC received weekly LCAP for 5 consecutive weeks. Their average clinical activity index (CAI) and endoscopic index (EI) were 9.6 ± 3.4 and 10.9 ± 1.0, respectively. Their peripheral blood was sampled before and after every LCAP and stained with fluorescent antibodies to the activation-dependent surface antigens of platelets (CD63, CD62-P) prior to flow cytometry. Endoscopic evaluations were performed after the last LCAP. Results Clinical remission (CAI < 4) was induced in 50% of the patients (7/14) after 5 weeks, and there were no significant differences observed in clinical background between the responder group (RG) and the nonresponder group (NG). In the RG, the populations of CD63⁺ (P < 0.03) and CD62-P⁺ (P < 0.05) platelets were significantly decreased after the first LCAP, and their reduction ratio decreased gradually with repeated LCAP. A significant improvement of the EI score, especially mucosal damage, was achieved in RG (P < 0.04) but not in NG. Conclusions These results indicate that the therapeutic responses to LCAP were reflected in modulations of population and/or platelet functions, especially after the first session. The decrease of such activated platelets immediately after the first LCAP may be an early marker for predicting the response in patients with severe UC.     

Safety and efficacy of single‐needle leukocyte apheresis for treatment of ulcerative colitis

Leukocyte apheresis (LCAP) is a safe and effective treatment for active ulcerative colitis (UC) in Japan. Nevertheless, a limitation of LCAP is its requirement for two puncture sites (double‐needle [DN] apheresis), sometimes leading to problems with needle puncture. Single‐needle (SN) apheresis is useful in hemodialysis and reduces needle puncture pain. If SN apheresis were found to be useful in LCAP for UC, it may reduce patient burden. The aim of this study was to compare the safety and efficacy of SN apheresis with that of DN apheresis. Twenty‐four patients with active UC were retrospectively enrolled. They underwent either SN apheresis (n = 12) or conventional double‐needle (DN) apheresis (n = 12) at the Kurume University Hospital from February 2014 to March 2018. At each session, we recorded access problems defined by the time required to initiate apheresis and the frequency of puncture‐related problems, as well as blood circuit clotting, defined as clotting necessitating interruption of apheresis and changing of the circuit. Efficacy was assessed using partial Mayo scores. The number of apheresis sessions was comparable between SN and DN apheresis (9.0 ± 2.0 times vs 9.6 ± 1.4 times, mean ± SEM). SN significantly reduced the time required to start apheresis (10.0 ± 5.4 minutes vs 19.4 ± 11.9 minutes, P < .05) as well as needle puncture troubles (0.9% vs 11.5%, P < .05). SN had comparable frequency of blood clotting episodes (5.6% vs 8.7%). SN apheresis had similar clinical efficacy (P < .001 in SN and P < .01 in DN). The improvement and remission rates were comparable between groups. SN apheresis may be safe and effective and may reduce patient burden during UC treatment. Nevertheless, further comparative studies are needed.     

Gene Expression Analysis Using a High‐Resolution DNA Microarray of Peripheral Whole Blood Immediately Before and After Leukocytapheresis for Rheumatoid Arthritis

Leukocytapheresis (LCAP) is a safe, unique therapy pertaining to intractable rheumatoid arthritis (RA) even in cases of drug allergy or infectious states. To investigate how to represent LCAP efficacy, we have conducted gene expression analyses from the peripheral blood of RA patients treated with non‐woven polyethylene terephthalate filters. Peripheral blood samples were collected immediately before and after treatment from eight RA patients who received LCAP. Among these patients, all of them achieved 20% improvement in the core set of the American College of Rheumatology (ACR20), and thus, they were confirmed as LCAP responders. Gene expression analysis was done with a high‐resolution DNA microarray. The results of each of the two groups' gene expression values (immediately before and after LCAP) were calculated using Welch's t‐test. Calculations were performed with a statistical software R.basic package: if the P‐value was less than 0.05, this was seen as a significant change. In a comparison of 25 370 gene expressions, the number of genes showing a P‐value < 0.05 in the upregulating group was 2110, and in the downregulating group it was 1864. The results of pathway analysis using the MetaCore program indicate that gene groups work for cytoskeletal remodeling are upregulated, and genes related to immune responses, such as antigens presenting via major histocompatibility complex class I and II, are downregulated just after LCAP. These findings may relate to LCAP efficacy for RA patients, but this needs further investigation.     

Univariate Analysis to Examine Predictors of Response to Leukocytapheresis in Ulcerative Colitis Patients

Leukocytapheresis (LCAP) is reportedly effective for the treatment of active ulcerative colitis (UC) and is a therapeutic option for steroid‐dependent or steroid‐resistant patients with UC. However, a consensus regarding the use of LCAP for UC patients has not yet been established. Therefore, we analyzed patients' records to identify predictors of response to LCAP therapy and subsequent recurrence. Between October 2001 and March 2011, we recruited 41 patients who had been diagnosed as having UC and had received LCAP therapy. Patients diagnosed with moderate to severe UC with left‐side or total colitis and received LCAP therapy for the first time were enrolled. We retrospectively performed a univariate analysis using the patients' medical records to identify factors affecting the therapeutic effect of LCAP. Body mass index exceeding 18.5 kg/m² was found to influence the therapeutic effect of LCAP. Male sex was correlated with a rapid response to LCAP treatment and the maintenance of remission. UC patients experiencing their first attack or had an elevated C‐reactive protein level prior to LCAP therapy exhibited a relatively long remission period. In the “after LCAP therapy” group, a low Rachmilewitz endoscopic score, low erythrocyte sedimentation rate, or high white blood cell count was associated with a long remission period. Our results suggest that LCAP should be performed for the treatment of early‐onset UC. LCAP can be expected to induce a long remission period, enabling mucosal healing, although the factors that affected the remission period did not influence the therapeutic effect and responsiveness.     

Leukocytapheresis therapy for steroid-naïve patients with active ulcerative colitis: its clinical efficacy and adverse effects compared with those of conventional steroid therapy

Background: Steroid administration currently plays a central role in the medical management of ulcerative colitis (UC); however, long‐term steroid usage causes adverse effects, which necessitates stoppage of drug intake, leading to worsening of the disease. A steroid‐sparing, well‐tolerated treatment is therefore required. As several investigators have reported the efficacy of leukocytapheresis (LCAP) combined with steroid therapy, we investigated the clinical usefulness and safety of LCAP for steroid‐naïve patients with active UC for comparison with those of conventional steroid therapy. Methods: Twenty‐nine Japanese patients with active UC without a history of steroid usage were selected to be treated with LCAP (n = 9) or prednisolone (PSL) (n = 20). LCAP administration continued for 10 weekly cycles. In the PSL group, patients with moderately severe disease received 0.5 mg/kg per day of PSL and those with severe disease 1.0 mg/kg per day. The PSL dosage was gradually tapered in accordance with improvement. Results: Eight (88.9%) of the LCAP group and 16 (80.0%) of the PSL group showed clinical improvement and three (33.3%) of the LCAP group and seven (35.0%) of the PSL group achieved remission. As for the treatment complications, three major adverse effects were observed in the PSL group, but none were observed in the LCAP group. Conclusion: The results of this study suggest that the efficacy and safety of LCAP are equivalent, and in terms of severe adverse effects, superior to those of steroid therapy. LCAP therapy may thus be a promising candidate therapy for steroid‐naïve patients with active UC. © 2005 Blackwell Publishing Asia Pty Ltd     

HLA‐DR genotypes in Chinese patients with ulcerative colitis

OBJECTIVE: To study HLA‐DR genotypes and to analyze the relationship between HLA‐DR genotypes, antineutrophil cytoplasmic antibodies (ANCA) and clinical classification of ulcerative colitis (UC) in Chinese patients. METHODS: Eighty UC patients and 123 healthy subjects were enrolled in the study. Serum ANCA was detected by using indirect immunofluorescence and HLA‐DR was genotyped by using the polymerase chain reaction with sequence‐specific primers (PCR‐SSCP). RESULTS: The positive rate of ANCA in UC patients was 55%, but 0.0% in the controls. The HLA‐DR2 and DR15 positive rates in the UC patients were 58.8 and 40%, respectively, which were significantly greater than 30.1 and 17.9% in the controls (P < 0.05). In the UC patients, the DR15‐positive rate was significantly higher, but the DR16‐positive rate was significantly lower in the ANCA‐positive group than in the ANCA‐negative group (52.3 vs 25.0%; 9.1 vs 30.6%, P < 0.05). The HLA‐DR2 and DR15‐positive rates in chronic persistent UC patients were significantly greater than those in the incipient or chronic recrudescent type of UC (84.2 vs 50.0 or 51.4%; 63.2 vs 29.2 or 35.1%, P < 0.05). CONCLUSIONS: In Chinese UC patients, the positive rates of HLA‐DR2 and ANCA were significantly higher compared with healthy controls. The increase in the DR2‐positive rate was associated with the increase in the DR15‐positive rate in ANCA‐positive UC patients, and was associated with the increase in the DR16 gene positive rate in ANCA‐negative UC patients. In general, HLA‐DR genotypes are related to the clinical classification of ulcerative colitis.     

Efficacy of High‐Throughput Leukocytapheresis for Rheumatoid Arthritis With a Reduced Response to Infliximab

Infliximab (INF), a tumor necrosis factor‐alpha (TNF‐α) inhibitor, is an effective drug for patients with rheumatoid arthritis (RA). However, some patients receive no clinical benefit, or the agents gradually lose their effect. Five sessions of high‐throughput leukocytapheresis (LCAP) were given at a frequency of once a week using a Cellsorba CS‐180S to four patients with a reduced response to INF. The clinical response to LCAP was evaluated using the 28‐joint disease activity score with C‐reactive protein (DAS28‐CRP) and with the erythrocyte sedimentation rate (DAS28‐ESR). DAS28‐CRP decreased significantly from 5.8 ± 0.6 before LCAP to 3.9 ± 0.7 (P = 0.0182) at 1–2 weeks after completion of five sessions of LCAP, and DAS28‐ESR decreased significantly from 6.4 ± 0.6 to 4.6 ± 0.5 (P = 0.0267). Moreover, all patients had a moderate response according to the European League Against Rheumatism (EULAR) response criteria. The effect of LCAP continued for at least 6 months after its completion in all patients, with no changes in any of their concomitant drugs, and the effect was maintained for at least 1 year in three of the four patients. These results indicate that LCAP is a useful treatment for RA patients with a reduced response to INF.     

Antibody levels correlate with creatine kinase levels and strength in anti–3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase–associated autoimmune myopathy

Objective

Autoantibodies recognizing 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) are found in patients with statin‐associated immune‐mediated necrotizing myopathy and, less commonly, in statin‐unexposed patients with autoimmune myopathy. The main objective of this study was to define the association of anti‐HMGCR antibody levels with disease activity.

Methods

Anti‐HMGCR levels, creatine kinase (CK) levels, and strength were assessed in anti‐HMGCR–positive patients. Associations of antibody level with CK level and strength at visit 1 were analyzed in 55 patients, 40 of whom were exposed to statins. In 12 statin‐exposed and 5 statin‐unexposed patients with serum from 5 serial visits, the evolution of antibody levels, CK levels, and strength was investigated.

Results

Antibody levels were associated with CK levels (P < 0.001), arm strength (P < 0.05), and leg strength (P < 0.05) at visit 1, but these associations were only significant among statin‐exposed patients in stratified analyses. With immunosuppressive treatment over 26.2 ± 12.6 months (mean ± SD), antibody levels declined (P < 0.05) and arm abduction strength improved (P < 0.05) in the 17 patients followed up longitudinally. The separate analysis showed that statin‐exposed patients developed decreased antibody levels (P < 0.01), decreased CK levels (P < 0.001), improved arm strength (P < 0.05), and improved hip flexion strength (P < 0.05) with treatment. Anti‐HMGCR antibody levels did not normalize in any patient.

Conclusion

In the entire cohort, initial anti‐HMGCR levels correlated with indicators of disease activity; with immunosuppressive treatment, antibody levels declined and arm strength improved. Statin‐exposed patients had significant improvements in CK levels and strength whereas statin‐unexposed patients did not, suggesting a phenotypic difference between statin‐exposed and statin‐unexposed anti‐HMGCR–positive patients.

     

Population‐based cases control study of inflammatory bowel disease risk factors

Background and Aim: The rapid increase in inflammatory bowel disease (IBD) incidence confirms the importance of environment in its etiology. We aimed to assess the role of childhood and other environmental risk factors in IBD. Methods: A population‐based case‐control study was carried out in Canterbury, New Zealand. Participants comprised 638 prevalent Crohn's disease (CD) cases, 653 prevalent ulcerative colitis (UC) cases and 600 randomly‐selected sex and age matched controls. Exposure rates to environmental risk factors were compared. Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (CI) are presented. Results: A family history of IBD (CD OR 3.06 [2.18–4.30], UC OR 2.52 [1.90–3.54]), cigarette smoking at diagnosis (CD OR 1.99 [1.48–2.68], UC OR 0.67 [0.48–0.94]), high social class at birth (CD and UC trend, P < 0.001) and Caucasian ethnicity (CD OR 2.04 [1.05–4.38], UC OR 1.47 [1.01–2.14]) were significantly associated with IBD. City living was associated with CD (P < 0.01). Being a migrant was associated with UC (UC OR 1.40 [1.14–2.01]). Having a childhood vegetable garden was protective against IBD (CD OR 0.52 [0.36–0.76], UC OR 0.65 [0.45–0.94]) as was having been breast‐fed (CD OR 0.55 [0.41–0.74], UC OR 0.71 [0.52–0.96]) with a duration‐response effect. Appendicectomy, tonsillectomy, infectious monomucleosis and asthma were more common in CD patients than controls (P < 0.01). Conclusions: The importance of childhood factors in the development of IBD is confirmed. The duration‐response protective association between breast‐feeding and subsequent development of IBD requires further evaluation, as does the protective effect associated with a childhood vegetable garden.     

Therapeutic Plasma Exchange in Neuromyelitis Optica Spectrum Disorders and Related Disorders in Resource‐Limited Settings: Outcomes in a Multiethnic Single‐Center Population

We evaluated therapeutic plasma exchange (TPE) efficiency in treatment of a single relapse in steroid‐refractory patients with neuromyelitis optica spectrum disorders (NMOSD) in a multi‐ethnic resource‐limited setting. This was a historical cohort study on the clinical outcomes post‐TPE in a multiethnic cohort of 53 steroid‐refractory NMOSD patients at a single Malaysian tertiary center. Primary outcomes, assessed both pre‐ and post‐TPE, were Medical Research Council scale of muscle power, Modified Rankin Scale, Expanded Disability Status Scale (EDSS), and visual acuity. Secondary outcomes were ambulatory status and target neurological deficit (TND)‐based TPE response. Significant improvements in Medical Research Council, Modified Rankin Scale, EDSS, and visual acuity (P < 0.001) were observed at 1‐month post‐TPE with further improvement of EDSS at 6 months (EDSSΔ6) post‐TPE (P < 0.001). At 6 months post‐TPE, 87% of patients has successful TND‐based TPE response and 69.8% were ambulating without support. Patients with anti‐aquaporin 4 seronegativity (P = 0.004), myelitis and brainstem features at first relapse (P = 0.004), longer cord lesions (P = 0.030), higher pre‐TPE EDSS of ≥8 (P = 0.018) and delayed TPE initiation of >14 days (P = 0.047) were significantly associated with improved EDSSΔ6. TND‐based TPE response was significant in absence of cord atrophy (P = 0.030). TPE is an effective treatment for steroid‐refractory acute relapses of NMOSD in a multiethnic Malaysian population despite its resource‐limited setting. The predictive factors of EDSSΔ6 improvement were anti‐aquaporin 4 seronegativity, longer cord lesions, and higher pre‐TPE EDSS. Absence of cord atrophy was predictive of better TND‐based TPE response. Unexpectedly, our study showed that delayed TPE initiation of more than 14 days and up to 60 days may also be beneficial.     

Comparison of the efficacy of granulocyte and monocyte/macrophage adsorptive apheresis and leukocytapheresis in active ulcerative colitis patients: a prospective randomized study

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with recurring inflammation of the colorectal mucosa. Recently, cytapheresis has emerged as a new treatment for patients with UC. Removal methods are mainly performed with beads [granulocyte and monocyte/macrophage adsorptive apheresis (GMCAP)] or filters [leukocytapheresis (LCAP)]. Both treatments have been reported to be effective for active UC. There have been few trials, however, comparing the efficacy of GMCAP and LCAP. In this study, we prospectively evaluated the efficacy of LCAP and GMCAP for the treatment of active UC. METHODS: Thirty-nine patients [18 male, 21 female; mean age 38.7 years; duration of disease 6 years; clinical activity index (CAI) >6 points] with moderate-to-severe active UC were randomly assigned to the LCAP (n=21) or GMCAP group (n=17). Adacolumn (cellulose acetate beads; Japan Immunoresearch Laboratories, Takasaki, Japan) for GMCAP and Cellsorba EX (polyethylene phthalate fibers; Asahi Medical Co. Ltd, Tokyo, Japan) for LCAP were used for leukocyte removal. Patients received two sessions of cytapheresis in the first week, followed by four weekly administrations. Steroid doses were tapered if patients achieved clinical improvement. When the CAI score had decreased by 5 points or more, the patient was considered to have improved. RESULTS: Thirteen patients in the GMCAP group and 14 in the LCAP group achieved clinical improvement. No significant difference was found in clinical response and clinical course between LCAP and GMCAP. Hemoglobin levels were significantly decreased immediately after one session of cytapheresis in the LCAP group. No severe adverse effects were observed in any of the patients. No significant differences were observed in any clinical parameters predictive of a response to either LCAP or GMCAP. But in all patients receiving cytapheresis, a high CAI score was a significant risk factor for treatment failure. All of the cytapheresis nonresponders had CAI scores >or=16. CONCLUSION: Both GMCAP and LCAP were effective treatments for active UC. Patients with severe UC and a high CAI score were, however, refractory to treatment.     

Lifestyle Educational Program Strongly Increases Compliance to Nonpharmacologic Intervention in Hypertensive Patients: A 2‐Year Follow‐Up Study

J Clin Hypertens (Greenwich). 2012;14:767–772. ©2012 Wiley Periodicals, Inc. The authors investigated the efficacy of a lifestyle educational program, organized in small group meetings, in improving the outcome of a nonpharmacologic intervention. One hundred and eighty‐eight hypertensive patients with stable blood pressure (BP) levels and drug therapy in the previous 6 months were randomly divided into educational care (EC) and usual care (UC) groups. They were followed at 3‐month intervals up to 2 years. In addition to the visits in an outpatient clinic, patients in the EC program participated in small group meetings in order to improve their knowledge of the disease and reinforce their motivation for treatment. At baseline, EC and UC groups were similar for age, sex, body mass index (BMI), blood pressure (BP) levels, and pharmacologic treatment. Patients in the EC group had significantly reduced total energy, total and saturated fats, and sodium intake. Physical activity was significantly increased in the EC group as well. At the end of the 1‐year follow‐up, BMI (P<.001), visceral fat (P<.001), and BP (P<.001) were significantly lower in the EC group compared with the UC group. Pharmacologic treatment during the study was similar for all classes of drugs apart from diuretics whose dose was higher in the UC group at the end of the study.     

Efficacy and Safety of Adsorptive Granulocyte and Monocyte Apheresis in Elderly and Pregnant Patients With Ulcerative Colitis

In patients with active ulcerative colitis (UC), adsorptive granulocyte/monocyte apheresis (GMA) is expected to promote remission. We conducted a retrospective cohort study to evaluate the efficacy and safety of GMA in patients with active UC. Twenty‐one UC patients including five pregnant or lactating mothers and four elderly patients (aged >60 years) received up to 10 GMA sessions. UC severity was evaluated at baseline and after GMA therapy according to Lichtiger's Clinical Activity Index (CAI). We defined clinical remission as CAI ≤4. Overall, the median CAI score after GMA therapy had decreased from 9 to 4 (P < 0.001). The clinical remission rate was 62%, but in the elderly and pregnant or lactating mothers, the remission rates were 100% and 60%, respectively. No severe adverse effects were seen in this study. Our results may support GMA as an effective and safe treatment for active UC patients, including elderly patients and pregnant cases.     

Clinical characteristics and long‐term prognosis of elderly onset ulcerative colitis

Background and Aim

The aim of this study was to investigate the clinical characteristics and prognosis of patients with elderly onset ulcerative colitis (EOUC), a new growing subgroup of UC.

Methods

This study retrospectively analyzed 3060 South Korean UC patients diagnosed between 1977 and 2014. The clinical characteristics and prognosis of EOUC, defined as UC in those aged ≥ 60 years at diagnosis, were compared with those of non‐EOUC (NEOUC).

Results

Among the 3060 patients, 226 were diagnosed with EOUC (7.4%, median age at diagnosis 65.9 years [interquartile range, 62.9–68.7 years], 58.4% male). The frequency of EOUC increased from 3.9% in the interval 1977–1999 to 9.7% in the interval 2008–2014 (P < 0.001). There were more ex‐smokers in the EOUC than in the NEOUC group (44.2% vs 19.9%, P < 0.001). In the EOUC group, extensive colitis at diagnosis, and the maximum extent thereof, was less than in the NEOUC group (13.7% vs 22.6%, P = 0.002, and 34.5% vs 42.5%, P = 0.011, respectively). The 10‐year cumulative colectomy rate was significantly higher in the EOUC than in the NEOUC group (12.6% vs 7.7%, P = 0.015). UC‐related and all‐cause mortality were higher in the EOUC than in the NEOUC group (3.5% vs 0.6%, P < 0.001, and 12.4% vs 1.8%, P < 0.001, respectively).

Conclusion

Elderly onset ulcerative colitis patients are likely to exhibit distinct features both at diagnosis and during follow‐up. It is necessary to pay more attention to, and to conduct further studies on, this particular group of patients.     

Coronary intervention with 4‐French catheters

Objectives: We sought to determine whether 4‐Fr percutaneous coronary intervention (PCI) is associated with technical difficulties that might have an unfavorable impact on procedural parameters. Background: Four‐Fr PCI is often associated with difficulties in catheter manipulation, which may lead to greater time consumption and increased dye usage when compared with PCI employing larger guiding catheters. Methods: From July 2007 to March 2009, 62 patients underwent 4‐Fr PCI. Procedural characteristics were compared between patients who underwent 4‐Fr PCI in 2007 (early phase: 31 lesions in 26 patients) and those underwent in 2008 or later (later phase: 40 lesions in 36 patients). Results: Ad‐hoc coronary intervention (3% vs. 23%, P < 0.05) and deep‐vessel intubation (46% vs. 91%, P < 0.05) were observed less frequently in the late phase than the early phase. Fluoroscopy time (8 ± 6 min vs. 17 ± 15 min, P < 0.05) and the amount of contrast dye used (64 ± 33 mL vs. 90 ± 46 mL, P < 0.05) were significantly reduced in the late phase than the early phase. No access site‐related complications were observed in patients in either phase. Conclusions: The performance of 4‐Fr PCI requires a certain learning curve, following which a reduction in fluoroscopy time and use of contrast dye may be achieved. This improvement in procedural parameters and the low incidence of access site‐related complications might allow 4‐Fr PCI to serve as a minimally invasive approach for the treatment of coronary artery diseases. © 2009 Wiley‐Liss, Inc.     

A multicenter survey of re‐treatment with pegylated interferon plus ribavirin combination therapy for patients with chronic hepatitis C in Japan

Aim: This study aimed to clarify the factors associated the efficacy of re‐treatment with pegylated interferon (PEG IFN) plus ribavirin combination therapy for patients with chronic hepatitis C who had failed to respond to previous treatment. Methods: One hundred and forty‐three patients who had previously shown relapse (n = 79), non‐response (n = 34) or intolerance (n = 30) to PEG IFN plus ribavirin were re‐treated with PEG IFN plus ribavirin. Results: Twenty‐five patients with intolerance to previous treatment completed re‐treatment and the sustained virological response (SVR) rates were 55% and 80% for hepatitis C virus (HCV) genotype 1 and 2, respectively. On re‐treatment of the 113 patients who completed the previous treatment, the SVR rates were 48% and 63% for genotype 1 and 2, respectively. Relapse after previous treatment and a low baseline HCV RNA level on re‐treatment were associated with SVR in genotype 1 (P < 0.001). Patients with the interleukin‐28B major genotype responded significantly better and earlier to re‐treatment, but the difference in the SVR rate did not reach a significant level between the major and minor genotypes (P = 0.09). Extended treatment of 72 weeks raised the SVR rate among the patients who attained complete early virological response but not rapid virological response with re‐treatment (72 weeks, 73%, 16/22, vs 48 weeks, 38%, 5/13, P < 0.05). Conclusion: Relapse after previous treatment and a low baseline HCV RNA level have predictive values for a favorable response of PEG IFN plus ribavirin re‐treatment for HCV genotype 1 patients. Re‐treatment for 72 weeks may lead to clinical improvement for genotype 1 patients with complete early virological response and without rapid virological response on re‐treatment.     

Leukocytapheresis in ulcerative colitis: results of a multicenter double-blind prospective case-control study with sham apheresis as placebo treatment

OBJECTIVE: Leukocytapheresis (LCAP) is a method of therapeutic apheresis that removes peripheral leukocytes. Previous studies showed that in patients with ulcerative colitis (UC), LCAP was more effective than high-dose steroid therapy, and it had few adverse effects. We investigated LCAP in a multicenter study using active and sham devices in a double-blind study in order to elucidate the placebo effect of extracorporeal treatment including anticoagulant medication. METHODS: Twenty-five patients with active UC of severe or moderately severe grade were enrolled and assigned to the active group or the sham group. Six patients were excluded from the study and 19 (10 in the active group and nine in the sham group) were evaluated. LCAP (treatment using an active device or a sham device) was performed once a week for 5 wk, followed by two additional sessions during the next 4 wk at 2-wk intervals. Steroids and other medications were continued at the same dosage for 4 wk, which included a 2-wk pre-observation period and the first 2 wk after the start of the LCAP treatment. New medications or increase in the dosage of previous medication were prohibited until evaluation was conducted. RESULTS: The clinical activity index (CAI) value of UC, indicated that the active group showed a significantly greater improvement (80%, 8/10) than the sham group (33%, 3/9; p<0.05). Adverse effects were observed in five patients (one in the active group and four in the sham group). None of these effects was severe and none of the sessions was terminated as a consequence of the adverse effects. CONCLUSION: The results confirmed that LCAP is a safe and effective therapeutic option for patients with active UC.     

AC13, a C‐terminal fragment of apolipoprotein A‐I,is a candidate biomarker for microscopic polyangiitis

Objective

Microscopic polyangiitis (MPA) is necrotizing vasculitis of unknown etiology. We analyzed the serum peptide profile of MPA to find a biomarker for this disease.

Methods

Serum peptides from 33 patients with MPA, 7 with granulomatosis with polyangiitis (Wegener's), 7 with Churg‐Strauss syndrome, 6 with giant cell arteritis, and 25 with systemic lupus erythematosus (SLE) were comprehensively analyzed by mass spectrometry. Peptide function on human microvascular endothelial cells (HMVECs) was examined by enzyme‐linked immunosorbent assay and real‐time polymerase chain reaction.

Results

A total of 102 serum peptides were detected from the 78 patients. One of the peptides, peptide 1,523, showed significantly higher ion intensity in MPA (mean ± SD 46.8 ± 39.3 arbitrary units [AU]) than in the other systemic vasculitides (14.1 ± 12.2 AU) (P < 0.05) or in SLE (17.0 ± 12.1 AU) (P < 0.05). In MPA, peptide 1,523 showed significantly higher ion intensity before treatment than 1 week (P < 0.05) and 6 weeks (P < 0.05) after the initiation of treatment. Peptide 1,523 was identified as 13 C‐terminal amino acid residues of apolipoprotein A‐I (Apo A‐I) and was designated “AC13.” Validation of AC13 ion intensity using another MPA cohort (n = 14) similarly showed significantly higher ion intensity (90.1 ± 167.9 AU) compared to 14 patients with rheumatoid arthritis (8.6 ± 5.4 AU) (P < 0.01) and 14 healthy subjects (11.8 ± 6.1 AU) (P < 0.01). Serum concentrations of Apo A‐I and high‐density lipoprotein cholesterol were down‐regulated in MPA before treatment and returned to their normal ranges 6 weeks after the initiation of treatment (both P < 0.01). Stimulation of HMVECs with AC13 significantly up‐regulated secretion of interleukin‐6 (IL‐6) (P < 0.05) and IL‐8 (P < 0.01).

Conclusion

AC13, a candidate biomarker for MPA, may be useful for monitoring disease activity and may exacerbate vascular inflammation through up‐regulation of proinflammatory cytokines.

     

Prevalence and short‐term outcome of acute kidney injury in patients with acute‐on‐chronic liver failure: A meta‐analysis

Acute kidney injury (AKI) in patients with acute‐on‐chronic liver failure (ACLF) is a distinct syndrome to that in patients with cirrhosis, yet is less characterized. The aim of this meta‐analysis was to investigate the impact of AKI on outcome of ACLF. We searched PubMed, Web of Science and Cochrane Library for original articles that evaluated the impact of AKI on outcome of ACLF from 2011 to 2019. Odds ratio (OR) with 95% confidence interval (CI) for 1‐month and 3‐month mortality was calculated. The response rate of vasoconstrictor for hepatorenal syndrome (HRS)‐AKI was assessed. Eight relevant articles with 3610 patients were included. The prevalence of AKI in ACLF patients was 41% (95% CI 32%‐50%). The presence of AKI was significantly associated with 1‐month mortality of ACLF (OR 3.98, 95% CI 3.09‐5.12; P < .001) and 3‐month mortality (OR 4.98, 95% CI 3.59‐6.92; P < .001). Additionally, patients with AKI stage ≥2 showed a higher 3‐month mortality than stage 1 (OR 3.89, 95% CI 2.60‐5.82; P < .001), and those of stage 3 had a higher mortality than stage ≤2 (OR 3.77, 95% CI 2.10‐6.77; P < .001). The pooled response rate of vasoconstrictors was 32% (95% CI 26%‐37%). This meta‐analysis indicated that about 40% of ACLF patients complicated with AKI and the presence of AKI substantially increased the short‐term mortality, together with a poor response rate of vasoconstrictors for HRS‐AKI.     

Clinical Effects of Pulse High‐Volume Hemofiltration on Severe Acute Pancreatitis Complicated With Multiple Organ Dysfunction Syndrome

To evaluate the effects of pulse high‐volume hemofiltration (PHVHF) on severe acute pancreatitis (SAP) with multiple organ dysfunction syndrome (MODS). Thirty patients were divided into two groups: PHVHF group and continuous venovenous hemofiltration (CVVH) group. They were evaluated in terms of clinical symptoms, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, simplified acute physiology (SAPS) II score and biochemical changes. The levels of IL‐6, IL‐10 and TNF‐α in plasma were assessed by ELISA before and after treatment. The doses of dopamine used in shock patients were also analyzed. In the two groups, symptoms were markedly improved after treatment. Body temperature (BT), breath rate (BR), heart rate (HR), APACHE II score, SOFA score, SAPS II score, serum amylase, white blood cell count and C‐reactive protein were decreased after hemofiltration (P < 0.05). The PHVHF group was superior to the CVVH group, especially in APACHE II score, CRP (P < 0.01), HR, temperature, SOFA score and SAPS II score (P < 0.05). The doses of dopamine for shock patients were also decreased in the two groups (P < 0.05), with more reduction in the PHVHF group than the CVVH group (P < 0.05). The levels of IL‐6, IL‐10 and TNF‐α decreased (P < 0.05) in the PHVHF group more significantly than the CVVH group (P < 0.01). PHVHF appears to be superior to CVVH in the treatment of SAP with MODS.