Short-term clinical evaluation of teduglutide for patients with Crohn's disease on home parenteral support for postoperative short bowel syndrome with intestinal failure.

BACKGROUND & AIM: The short-term effects of teduglutide (TED) for short bowel syndrome with chronic intestinal failure (SBS-IF) in patients with Crohn's disease (CD) remain unknown. The aim of this study was to investigate the effects of TED in patients with CD on home parenteral support (PS) for SBS-IF. METHODS: We retrospectively investigated the medical records of patients with CD associated with SBS-IF who initiated TED between 2020 and 2021. The primary outcomes were the change in PS volume and proportion of patients with a reduction of PS volume by ≥ 20% at week 8. Secondary outcomes were the change in PS volume in patients with CD without/with colon in continuity and adverse events during the observation period. RESULTS: Eighteen patients with CD who underwent home PS for SBS-IF were included in this study. Two patients were excluded owing to intolerable abdominal pain or vomiting within 8 weeks (11%). Sixteen patients continued TED throughout the observation period. The median PS duration was 10.5 years. The median observation period was 22 weeks after starting TED. TED significantly reduced the PS volume from 15,825.0 mL/week to 10,700.0 mL/week (p = 0.0038), and the PS volume decreased by ≥ 20% in 7 patients (43.8%) at week 8. The PS volume was significantly reduced at week 4 (p = 0.0078) in 11 patients without colon in continuity but not in 5 patients with colon in continuity. Two patients successfully stopped home PS. No serious adverse events occurred. CONCLUSIONS: TED administration significantly reduced PS volume at week 8 in patients with CD associated with SBS-IF, and at week 4 in patients without colon in continuity.

Evaluation of discomfort during colonoscopy with conventional and ultrathin colonoscopes in ulcerative colitis patients.

BACKGROUND AND AIM: In patients with ulcerative colitis (UC), colonoscopy is an essential procedure for evaluating mucosal damage, and treatment outcomes. A new flexible ultrathin colonoscope (PCF-PQ260) has been developed to readily pass through tortuous and narrow lesions of the colon and cause minimum patient discomfort. The objective of the present study was to evaluate the comfort and performance of this new type of scope in UC patients who underwent colonoscopy for estimation of mucosal inflammation, basically without sedation. METHODS: In a prospective, single-center setting, among 107 UC patients who were to undergo colonoscopy, 84 eligible cases were randomly assigned to the new ultrathin flexible colonoscope, PCF-PQ260 (n = 42) or to a conventional colonoscope, PCF-Q260A (n = 42). Main outcome measure was patient pain level determined by visual analogue scale (VAS) with 0 = none, and 100 = extremely painful. Other outcomes were cecal intubation time, rate of complete intubation (to reach the cecum) and rate of procedural complications. RESULTS: VAS score was significantly lower in the new-scope group as compared with the conventional-scope group: mean ± SD, median (range): 19.3 ± 16.9, 14 (0-62) vs 32.0 ± 21.6, 31.8 (0-100, P = 0.005). However, cecal intubation rate (97.6%) and time (4 min) were similar in the two groups. There was no procedure-related serious complication in either group. CONCLUSION: The findings indicated that the flexible ultrathin colonoscope PCF-PQ260 has significantly better tolerability in UC patients compared to a conventional colonoscope.

Xilei san ameliorates experimental colitis in rats by selectively degrading proinflammatory mediators and promoting mucosal repair.

Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC.

Crohn's disease complicated by hepatitis B virus successfully treated with the use of adsorptive depletion of myeloid lineage leucocytes to suppress inflammatory cytokine profile.

BACKGROUND AIMS: In patients with inflammatory bowel disease infected with hepatitis B virus (HBV), immunosuppressive therapy required to suppress active inflammatory bowel disease may promote HBV reactivation. METHODS: A 27-year-old corticosteroid-naive woman with Crohn's disease (CD) activity index of 249.8 complicated by HBV infection was offered Entecavir to control HBV reactivation during immunosuppressive therapy for CD. The patient refused Entecavir, fearing that it might adversely affect her pregnancy outcome. Instead, we applied intensive granulocyte/monocyte adsorptive apheresis (GMA) at two sessions per week to deplete inflammatory cytokine-producing leucocytes as an immunosuppressive therapy in this case. RESULTS: GMA induced stable remission (CD activity index, I 105) and endoscopic improvement without HBV reactivation or safety concern. Furthermore, CD remission was paralleled by suppression of tumor necrosis factor and interleukin as measured in serum samples. CONCLUSIONS: Immunosuppressive therapy required to treat an active CD potentially can promote HBV reactivation and worsen liver function. In this study involving a CD case complicated by chronic HBV infection, intensive GMA as a non-pharmacologic treatment intervention was associated with clinical remission and endoscopic improvement without HBV reactivation. Furthermore, GMA was well-tolerated and was without any safety concern. However, suppression of tumor necrosis and interleukin-6by GMA in this clinical setting is potentially very interesting.

Questionnaire based assessment of patients' acceptability of leukocytapheresis for the treatment of inflammatory bowel disease.

The aim of the present study was to assess patients' acceptance of therapeutic leukocytapheresis known as cytapheresis (CAP) for the treatment of an active flare of inflammatory bowel disease (IBD). A questionnaire was sent to 155 IBD patients who had been treated with CAP for an active flare of IBD at the IBD center of Hyogo College of Medicine between January 2009 and July 2012. In the questionnaire, patients were asked to evaluate CAP including efficacy, safety, unfavorable features and their willingness to be retreated with CAP for a subsequent IBD flare-up. Seventy-eight percent (112 of 155 patients) including 86 with ulcerative colitis and 26 with Crohn's disease completed the questionnaire. The need for coming to hospital for CAP, needle pain during blood access, sparing time for CAP process were scored by 57%, 58%, and 58.9% of the patients, respectively as unfavorable. Patients highly favored the safety of CAP, the sum of very and relatively favorable was 89%, higher than for efficacy (68%). Seventy-two percent of patients favored retreatment with CAP. In binary logistic regression analysis, the levels of satisfaction for efficacy (P < 0.001), and inconvenience for CAP treatment time (P < 0.001) were highly significant factors for patients' willingness to be retreated. Bearing in mind that CAP is a non-pharmacologic treatment intervention, our analyses indicated that IBD patients favored high efficacy, as well as comfort of CAP or maintaining their normal social activity even during an active phase of the disease. Patient's acceptability for CAP appeared to be determined by the balance of these factors.

Looking for predictive factors of clinical response to adsorptive granulocyte and monocyte apheresis in patients with ulcerative colitis: markers of response to GMA.

BACKGROUND: Adsorptive granulocyte and monocyte apheresis (GMA) with an Adacolumn in patients with ulcerative colitis (UC) has been applied as a non-pharmacological treatment strategy, but the efficacy has been encouraging as well as discouraging, depending on patients' demography at entry. In this study, we looked for predictive factors for clinical response to GMA in patients with UC. METHODS: In a retrospective setting, 43 outpatients who had been treated with GMA for active UC were evaluated. Patients were divided into remission group and non-remission group based on Lichtiger's clinical activity index (CAI) before and after 10, once a week GMA sessions. The efficacy was analysed in relation to patients' demographic variables. To determine predictive factors that closely related to the response to GMA, receiver operating characteristic (ROC) curve, and multiple logistic regression analyses were applied. RESULTS: After 10 GMA sessions, the overall clinical remission rate (CAI < 4) was 53.5%. Multiple logistic regression and ROC analyses showed that the interval between relapse and the first GMA session was a significant and independent predictive factor for clinical response to GMA (P = 0.016); the clinical response was better in patients who received GMA immediately after a relapse and vice versa. Likewise, univariate analyses showed that, the duration of UC (P = 0.036) and the cumulative prednisolone (PSL) dose (P = 0.006) before the first GMA session were significantly greater in the GMA non-responder group as compared with the responder group. Additionally, a lower white blood cell (WBC) count at first GMA session was related to clinical response to GMA (P = 0.032). CONCLUSIONS: In this study, patients with a short duration of UC and low cumulative PSL dose seemed to respond well to GMA. However, we found that the best responders were patients who received GMA immediately after a clinical relapse. Additionally, GMA was effective in patients with low WBC count at the first GMA session. The findings of this study should spare medical cost and reduce morbidity time for many patients, relevant for decision making in clinical settings.

Adsorptive granulocyte/monocyte apheresis for the maintenance of remission in patients with ulcerative colitis: a prospective randomized, double blind, sham-controlled clinical trial.

BACKGROUND/AIMS: Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse. METHODS: Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy. They were then randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal circulation without the GMA column every 4 weeks (Sham, n=11), or no additional intervention (Control, n=11). The primary endpoint was the rate of avoiding relapse (AR) over 48 weeks. RESULTS: At week 48, the AR rates in the True, Sham, and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were steroid-free, but no statistically significant difference was seen among the three arms. However, in patients who could taper their prednisolone dose to <20 mg/day during the remission induction therapy, the AR in the True group was better than in the Sham (p<0.03) or Control (p<0.05) groups. CONCLUSIONS: Monthly GMA may potentially prevent UC relapse in patients who have achieved remission through weekly GMA, especially in patients on <20 mg/day PSL at the start of the maintenance therapy.

Placebo controlled evaluation of Xilei San, a herbal preparation in patients with intractable ulcerative proctitis.

BACKGROUND AND AIM: Topical mesalamine or corticosteroid has shown efficacy in patients with ulcerative proctitis, but patients often become refractory to these interventions. Xilei San is a herbal preparation with evidence of anti-inflammatory effects. We evaluated the efficacy of topical Xilei San in ulcerative proctitis patients. METHODS: In a double blind setting, 30 patients with intractable ulcerative proctitis despite ≥ 4 weeks of topical mesalamine or corticosteroid were randomly assigned to True (n = 15) and placebo (n = 15). Patients in True received suppository Xilei San (0.1 g/dose per day of Xilei San), the other 15 received placebo suppository. The initial efficacy was evaluated on day 14. Primary endpoint of the trial was avoiding relapse during 180 days, relapse meant recurrence of active disease. Riley's index was applied for endoscopic and histological evaluations, while patients' quality of life was evaluated by an inflammatory bowel disease questionnaire. RESULTS: On day 14, the number of patients who achieved remission, clinical activity index ≤ 4 in True was significantly higher versus placebo (P < 0.04). Likewise, at day 180, an 81.8% of patients in True were without relapse versus 16.7% in placebo (P < 0.001). Further, significant endoscopic (P < 0.01), histological (P < 0.02) and inflammatory bowel disease questionnaire (P < 0.04) improvements were observed in True, but not in placebo. CONCLUSIONS: This is the first controlled investigation showing significant clinical and endoscopic efficacy for Xilei San in patients with intractable ulcerative proctitis. Topical Xilei San was well tolerated, and was without safety concerns.

Scheduled infliximab monotherapy to prevent recurrence of Crohn's disease following ileocolic or ileal resection: a 3-year prospective randomized open trial.

BACKGROUND: Infliximab (IFX) is effective for remission induction and maintenance of Crohn's disease (CD). This trial assessed the efficacy of scheduled maintenance IFX monotherapy to prevent postoperative CD recurrence. METHODS: Thirty-one CD patients who had ileocolic resection within the past 4 weeks were randomly assigned to scheduled IFX at 5 mg/kg intravenously every 8 weeks for 36 months (n = 15) or without IFX (control, n = 16). All patients were treated without immunomodulator or corticosteroid following surgery. The primary and secondary endpoints were remission rates at 12 and 36 months, defined as CD Activity Index (CDAI) ≤150, an International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score <2, and C-reactive protein (CRP) <0.3 mg/dL. Additionally, endoscopic recurrences at 12 and 36 months were evaluated. RESULTS: At 12 and 36 months, 100%, and 93.3% of patients in the IFX group were in remission (IOIBD <2), respectively vs. 68.8% and 56.3% in the control arm (P < 0.03). Similarly, 86.7% and 86.7% of patients in the IFX group maintained serological remission (CRP <0.3 mg/dL) vs. 37.5% and 37.5% in the control arm (P < 0.02). Further, the IFX group achieved higher endoscopic remission at 12 months, 78.6% vs. 18.8% (P = 0.004). However, in the Kaplan-Meier survival analysis the CDAI scores between the two arms were not significantly different either at 12 or at 36 months. No adverse event (AE) was observed. CONCLUSIONS: An early intervention with IFX monotherapy should prevent clinical, serological, and endoscopic CD recurrence following ileocolic resection. Thiopurine naivety and eliminating the initial loading dose of IFX might minimize serious AEs.

Optimal apheresis treatment volume for the efficacy and safety of leukocytapheresis with Cellsorba in patients with active ulcerative colitis.

BACKGROUND: Leukocytapheresis (LCAP) is used as an adjunct therapy for patients with active ulcerative colitis (UC). Although, LCAP is routinely performed at 3,000 mL per session, we were interested to see that if this can be replaced with bodyweight (BW) adjusted volume. METHODS: In an open label prospective trial, the clinical response to BW adjusted LCAP (BWA-LCAP) was evaluated in 14 patients with active UC. Fourteen demography matched UC patients who had been treated with the routine 3,000 mL LCAP were randomly sampled from our database as a control group. All patients were given 10 weekly LCAP sessions. In the BWA-LCAP group, the processed blood volume (PBV) was set at 30 mL/kg × BW/session. Baseline demographic measures were not significantly different between the two groups. RESULTS: The average PBV in the BWA-LCAP group was 1971.0 ± 330.0 mL, range 1,020-2,460. In both groups, the average UC clinical disease activity index, the endoscopic index, and the concomitant prednisolone dosage were significantly and equally reduced during the course of 10 LCAP. Accordingly, at the end of the trial, no significant difference was seen in any outcome measure between the two groups. However, a significantly higher incidence of adverse event (AE) was observed in the routine 3,000 mL LCAP group as compared with the BWA-LCAP group (P < 0.01). CONCLUSIONS: The outcomes of this investigation showed that the therapeutic efficacy of LCAP based on 30 mL/kg × BW is similar to the routine 3,000 mL per session LCAP. However, BWA-LCAP should be favored if one is to see the full potential of LCAP without AE.

Relevance of the processed blood volume per granulocyte and monocyte apheresis session to its clinical efficacy in patients with ulcerative colitis.

Granulocyte/monocyte adsorption (GMA) has been introduced as an adjunct intervention for active ulcerative colitis (UC) patients. The processed blood volume (PV) per GMA session is an important factor for its efficacy because depletion of elevated/activated myeloid leukocytes is its main action. Hitherto, this aspect of GMA has been largely ignored. Thirty-three patients were enrolled for remission induction therapy with five weekly GMA sessions at a standard PV of 1800 mL, regardless of patients' bodyweight (BW). The patients were divided into three groups: high (H)BW (≥ 65 kg, n = 11), 50 kg ≤ medium (M)BW < 65 kg (n = 12), and low (L)BW (≤ 50 kg, n = 10). UC clinical activity index (CAI) was according to Lichtiger, and the clinical efficacies were evaluated at both one week post 3(rd) GMA (Week 4) and one week post 5(th) GMA (Week 6). The average BW was 70.9 ± 6.2 kg in HBW, 55.8 ± 4.5 kg in MBW, and 46.8 ± 1.2 kg in LBW, indicating the mean PV/BW in the three groups being 25.6 ± 2.12, 32.5 ± 2.50, and 38.7 ± 1.0 (mL/kg, P < 0.05), respectively. The LBW group consisted of female patients only. Significant improvements of CAI were seen before treatment at either Week 4 or Week 6 in all groups. A significantly higher remission rate was achieved in the LBW (80.0%) vs. MBW (33.3%) or HBW (27.3%) at Week 6 (P < 0.03). According to this GMA evaluation, the lower-limit of optimum PV/kg should be higher than 38.7 mL/kg for its potential clinical efficacy to be significantly greater than the routine GMA method. Additional BW-oriented GMA studies in larger and gender controlled cohorts of patients should strengthen our findings.

Immunoregulatory effects of adsorptive granulocyte and monocyte apheresis in patients with drug refractory Crohn's disease.

In Japan, adsorptive granulocyte/monocyte apheresis (GMA) is an approved treatment option in patients with active Crohn's disease (CD). However, there is inadequate knowledge regarding the mechanism(s) of therapeutic effects of this non-pharmacologic treatment strategy. Further, recently we have been interested in the regulatory T-cell (Treg) profile which has an essential immunoregulatory function. Thirteen CD patients were treated with a single GMA session. The mean CD activity index (CDAI) and duration of CD were 218.5 and 9.8 years, respectively. Eight healthy volunteers participated as a control group. From CD patients, whole blood was taken immediately before and after the GMA session directly from the GMA column inflow and outflow lines. Broad spectrum serum key cytokines and chemokines were measured by suspension-array and ELISA. At baseline, almost all assayed inflammatory cytokines were significantly elevated in CD patients. Treg-associated cytokines including IL-10 (P < 0.02) and transforming growth factor (TGF)-ß1 (P < 0.03), were higher in the GMA column outflow vs. inflow. In contrast, the Th1/Th2 balance, defined as IFN-γ/IL-10 was lower during hemofiltration (P = 0.05), potentially due to an elevated IL-10 (P < 0.02) because an elevation of pro-inflammatory IFN-γ (Th1) was not observed at the GMA column outflow. A single GMA session had a significant impact on the Treg profile. Treg-related cytokines like IL-10 and TGF-ß1 in the blood returning to the patients from the GMA column outflow were elevated, while pro-inflammatory cytokines like IFN-γ were not. This action of GMA is potentially very interesting in patients with immune disorders, like CD patients.

The CD4+CD28null and the regulatory CD4+CD25High T-cell phenotypes in patients with ulcerative colitis during active and quiescent disease, and following colectomy.

The CD4+CD25High T-cell phenotype has an essential immunoregulatory role, while the CD4+CD28null T-cell reflects immune pathology. We investigated the profiles of the CD4+CD25High and the CD4+CD28null T-cell phenotypes in patients with ulcerative colitis (UC) during active and quiescent phases as well as following colectomy. Fifty-nine UC patients, 34 active (UCa) and 25 quiescent (UCq) together with 19 healthy controls (HC) were included. Ten of 34 UCa patients underwent colectomy due to unremitting UC (UCo). Immunohistochemical phenotypic of the peripheral blood lymphocytes bearing CD4, CD25 or CD28 was done for analyzes by a multiparameter fluorescence activated cell sorting technique. The expression of the CD4+CD25High phenotype was higher in UCq (P<0.01) or UCo (P<0.01) group vs UCa group. Further, the expression of the CD4+CD28null phenotype in UCa or UCo group was higher than in the HC group (P<0.05). However, the expression of the CD4+CD28null phenotype up to 12 months after colectomy was not significantly different from the levels in the same patients during acute phase. Our impression is that a high CD4+CD25High T-cell reflects alleviation of inflammation, while the expression of the CD4+CD28null T-cell phenotype is an etiologic feature in UC patients, and is maintained after removing the affected colon.

Selective depletion of peripheral granulocyte/monocyte enhances the efficacy of scheduled maintenance infliximab in Crohn's disease.

BACKGROUND: This is the first report on a case of Crohn's disease (CD), who was successfully maintained with a combination of infliximab (IFX) and selective depletion of granulocytes/monocytes by adsorption (GMA). CASE: A 33-year-old female with CD activity index (CDAI) 294.2 responded to iv IFX (5mg/kg) administered at weeks 0, 2, and 6 in combination with 3000 mg/day oral 5-aminosalicylic acid (5-ASA; CDAI = 118). Then IFX at 8 week intervals was given as maintenance therapy. Two weeks before the 5th scheduled IFX, the patient worsened with an increase in stool frequency and a rise in CDAI. GMA was administered at weeks 5, 6, and 7 after her 6th iv IFX. Her CDAI decreased from 166.2 to 126.3 and 111.9 before 2nd and 3rd GMA sessions. She received her 7th iv IFX while the CDAI was 83.6. GMA course was repeated before 8th and 9th IFX. The patient remained in stable clinical and endoscopic remission without experiencing any serious side effect. After achieving mucosal healing, the patient decided to cease IFX therapy while continuing with GMA. CONCLUSIONS: IFX appears to induce and maintain remission of CD, but it may lose its efficacy after repeated administration. GMA is safe and by selectively depleting elevated/activated leukocytes may be a useful adjunct for IFX efficacy.

Cytapheresis in patients with severe ulcerative colitis after failure of intravenous corticosteroid: a long-term retrospective cohort study.

BACKGROUND/AIMS: Cytapheresis (CAP) is a novel strategy for ulcerative colitis (UC). However, there is insufficient data on the long-term outcome of UC patients who achieve remission by CAP. This study involved patients with severe UC who refracted to intravenous (iv) corticosteroid. METHODS: Forty-seven UC patients who had received CAP therapy for the first time within 1 year after UC diagnosis were followed for 36 months. One of the inclusion criteria was a clinical activity index (CAI) of >/=7 points at the end of a 2-week iv course of corticosteroid therapy. CAP therapy consisted of ten sessions over 10 weeks. RESULTS: CAP induced clinical remission (CAI/=12, n=25) than for moderately severe UC at entry (7

Hyperthermic stimulation of blood increases the immunological effects of granulocyte and monocyte adsorption in vitro: relevance to extracorporeal immunomodulation.

Extracorporeal granulocyte and monocyte/macrophage adsorption (GMA) using an adacolumn filled with cellulose acetate beads as GMA carriers selectively depletes excess and activated myeloid leucocytes from the circulation and has been used as a non-pharmacologic adjunct therapy in patients with inflammatory bowel disease (IBD). In this study we applied hyperthermic stimulation of blood during exposure to the GMA carriers with the aim of enhancing the release of anti-inflammatory substances from leucocytes. In blood from patients with Crohn's disease (CD) and healthy controls (HC), incubation with the carriers was associated with a striking increase in the release of interleukin-1 receptor antagonist (IL-1ra, a powerful anti-inflammatory cytokine) independent of hyperthermic stimulation, while in the blood from both CD and HC, the release of heat shock protein70 (Hsp70, a cytoprotective protein) was increased by two fold. The present data indicate that hyperthermic stimulation of blood at 43 degrees C or exposure to cellulose acetate carriers is a simple strategy to generate substances of therapeutic potential from blood, especially in patients with IBD. These observations are very interesting in the context of extracorporeal immunomodulation in patients with immune pathology.

Multiple POU-binding motifs, recognized by tissue-specific nuclear factors, are important for Dll1 gene expression in neural stem cells.

We cloned the 5'-flanking region of the mouse homolog of the Delta gene (Dll1) and demonstrated that the sequence between nucleotide position -514 and -484 in the 5'-flanking region of Dll1 played a critical role in the regulation of its tissue-specific expression in neural stem cells (NSCs). Further, we showed that multiple POU-binding motifs, located within this short sequence of 30bp, were essential for transcriptional activation of Dll1 and also that multiple tissue-specific nuclear factors recognized these POU-binding motifs in various combinations through differentiation of NSCs. Thus, POU-binding factors may play an important role in Dll1 expression in developing NSCs.

Detection of specific IgE antibodies to nafamostat mesilate as an indication of possible adverse effects of leukocytapheresis using nafamostat mesilate as anticoagulant.

The aim was to determine whether adverse effects of leukocytapheresis (LCAP) are related to nafamostat mesilate (NM) as an anticoagulant. Anti-NM IgE were detected in inflammatory bowel disease (IBD) patients who were administrated LCAP in our institute. Forty-nine patients (ulcerative colitis (UC)/Crohn's disease (CD): 30/19) were evaluated. Anti-NM IgE was measured by the ELISA method. Total IgE level and eosinophil count was tested concurrently. We retrospectively checked the presence of allergic symptoms and medications used concurrently with LCAP. Anti-NM IgE were present in six symptomatic patients (6/49; 12.2%) whose adverse effects were highly suspected to be from NM. However, 21 patients showed anti NM IgE-negative, in spite of the fact that their adverse effects were also highly suspected to be from NM. Through the detection of anti-NM IgE alone we could not estimate the relevance of NM as an anticoagulant to the adverse effects of LCAP.

Granulocyte and monocyte adsorptive apheresis for patients with chronic hepatitis C virus infection: a report on six cases with high plasma viremia.

Granulocytes and monocytes/macrophages (GM) are known to constitute extra-hepatic sites for hepatitis C virus (HCV) replication and dissemination. Accordingly, we thought that selective GM adsorptive apheresis (GMA) might contribute to the treatment of HCV in patients with high viremia (HCV-RNA > 100 kIU/mL). Of six patients (three males and three females), mean age 62.2 years, five had not responded to interferon-alpha (INF-alpha) and one was INF-alpha naïve. Each patient received five GMA sessions, once a week for 5 weeks. The two antecubital veins were used as blood access and return lines and the apheresis was performed at 30 mL/min for 60 min. Treatment efficacy was assessed by monitoring changes in plasma HCV-RNA and aminotransferase. Granulocyte and monocyte/macrophage adsorptive apheresis was well tolerated. During each GMA, there was on average a 52.9% fall in plasma HCV-RNA, but HCV-RNA increased again during the time before the next GMA. There was no marked change in either aminotransferase during GMA. Furthermore, beyond the last GMA, HCV-RNA increased together with worsening aminotransferase in three of six patients. In conclusion, it would appear that GMA can partially reduce plasma HCV and GMA at a frequency of one session/week for 5 consecutive weeks but that this was inadequate to induce a sustained decrease in plasma HCV-RNA in patients with high viremia without simultaneous administration of antiviral medications. The most effective frequency of GMA needs to be determined in future clinical studies.