The Italian Registry for Therapeutic Apheresis. A report from the Apheresis Study Group of the Italian Society of Nephrology

Many clinical indications and different technical issues have been reported on therapeutic apheresis: much criticism has also been recorded in several instances, mainly due to the lack of large clinical trials to validate collected data. A Registry where all the available data can be organized and analyzed therefore becomes a priority for all the professionals involved in apheresis. The purpose of this report is to describe the data submitted from 1994 to 2004 from 15,285 treatments on 1,477 patients from 44 Centers, including mainly, but not exclusively, Nephrological Units, collected by the Apheresis Study Group of the Italian Society of Nephrology in 15 Italian regions. Plasma exchange accounted for 56.2% of the procedures, and of these 50.4% were performed by filtration. Plasma treatment was used in 40.1% of procedures, namely with Protein A immunoadsorption (14.6%), LDL-Cholesterol dextran sulfate adsorption (9.7%), and semiselective cascade or double filtration (12.6%). Cell apheresis, limited to photopheresis, was used in 0.85% of cases, and whole blood treatment (direct adsorption lipoprotein, and molecular adsorption recirculating system) in 2.7%. The procedures analyzed here account for less than 20% of estimated therapeutic apheresis performed in Italy, according to the national survey of activity performed for year 2000 by the Italian Apheresis Society. Notwithstanding that the data are largely incomplete, they are sufficiently informative for a definite trend: plasma treatment with filtration on fractionation filters and adsorption must be used as often as possible, instead of plasma exchange, thus obtaining the most selective removals.     

Therapeutic peptides in inflammatory bowel disease

Introduction: Therapeutic peptides in inflammatory bowel diseases essentially comprise cytokines affecting immune response, growth factors and monoclonal antibodies directed against key targets of mucosal inflammation, in particular, tumor necrosis factor-α (TNF-α). The latter have revolutionized standard medical treatment which previously was restricted to mesalamine, corticosteroids or classical immunosuppressants.

Areas covered: We review current evidence of the use of the so-called biologicals, including the well-established TNF-α antagonists and novel peptides and monoclonal antibodies developed for these diseases. The focus is on controlled clinical trials and meta-analyses, if available. Limitations and biases of these studies are important but tend to be ignored. Safety is also an important issue with opportunistic infections and lymphoma as relevant risks. There is significant heterogeneity between different countries, guidelines and opinions within the scientific community regarding clinical indications, even apart from pharmacoeconomics and reimbursement.

Expert opinion: TNF blockers have greatly extended medical options in inflammatory bowel diseases. Their more or less extensive use in nearly all patients or only a few selected indications is a matter of debate. It proved difficult to reproduce this success with other antibody targets as well as with immunomodulatory cytokines and growth factors. The most promising novel peptide is vedolizumab, an antibody against α4β7 integrin.     

Apheresis: A cell-based therapeutic tool for the inflammatory bowel disease

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 non-pharmacological 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.     

Migraine,inflammatory bowel disease and celiac disease: A Mendelian randomization study

Objective

To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.

Background

Migraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition.

Methods

Linkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed.

Results

Migraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99–1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99–1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96–1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79–1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00–1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92–0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02–1.29, p = 0.025). However, the results were not significant after multiple testing correction.

Conclusions

We found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes.     

Granulomonocytapheresis as a cell-dependent treatment option for patients with inflammatory bowel disease: Concepts and clinical features for better therapeutic outcomes

Ulcerative colitis (UC) and Crohn's disease (CD) are major phenotypes of the chronic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms. The chronic nature of IBD means that patients require life-long medications, and this may lead to drug dependency, loss of response together with adverse side effects as additional morbidity factors. The efficacy of antitumour necrosis factor (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation and perpetuation of IBD. However, cytokines are released by myeloid lineage leucocytes like the CD14⁺CD16⁺ monocyte phenotype. Additionally in IBD, myeloid leucocytes are elevated with activation behavior, while lymphocytes are compromised. Therefore, patients' leucocytes appear logical targets of therapy. Adsorptive granulomonocytapheresis (GMA) with an Adacolumn uses carriers, which interact with the Fcγ receptor expressing leucocytes and deplete the elevated myeloid leucocytes, while the neutrophils, which re-enter the circulation via the Adacolumn outflow (≥40%) are phagocytosed by CD19 B-cells to become interleukin (IL)-10 producing Bregs or CD19^highCD1D^high B-cells. IL-10 is an anti-inflammatory cytokine. GMA has been applied to treat patients with IBD. The efficacy outcomes have been impressive as well as disappointing, the clinical response to GMA defines the patients' disease course and severity at entry. Efficacy outcomes in patients with deep ulcers together with extensive loss of the mucosal tissue are not encouraging, while patients without these features respond well and attain a favorable long-term disease course. Accordingly, for responder patients, GMA fulfills a desire to be treated without drugs.     

Open-label, uncontrolled trial of bowel sterilization and repopulation with normal bowel flora for treatment of inflammatory bowel disease

In this open-label, uncontrolled study, six patients with inflammatory bowel disease (IBD) (2 with ulcerative colitis, 1 with collagenous colitis, 1 with Crohn's disease, and 2 with indeterminate type) were treated with bowel decontamination using mechanical cleansing and antibiotics followed by repopulation with 12 strains of colonic bacteria from normal donors. One patient relapsed after 13 months following treatment with an antibiotic for an upper respiratory infection. One patient remains in full clinical remission after 18 months, and another patient after 32 months; the other three patients' symptoms did not change with treatment. No evidence of toxicity from treatments was observed. None of the patients who were in remission required therapy for IBD.     

炎症性肠病的营养相关疾病

炎症性肠病（IBD）中的溃疡性结肠炎和克罗恩病都属于病因不清,病情反复发作的以肠道受累为主的炎症性疾病。这样的疾病特点使得大多数患者历经数十年的病痛困扰,在漫长的病史中不论疾病的活动程度如何,甚至在疾病的缓解期营养不良的情况都是十分常见的。营养不良的情况包括蛋白质能量营养不足、超重、维生素、矿物质和微量元素的缺乏等。与IBD患者的营养不良相关的因素众多,如肠道吸收功能不良、肠道溃疡和炎症引发的营养素丢失、小肠细菌过度生长、糖皮质激素类药物的使用和饮食限制。营养支持治疗对于IBD患者至关重要,尤其是对维持儿童期IBD患者正常的生长发育、诱导活动期CD患者的临床缓解、减少IBD患者围手术期并发症等都是至关重要的。     

5-氨基水杨酸在炎症性肠病中的合理应用

5-氨基水杨酸（5-ASA）是临床应用最早、不良反应最少、使用最多的治疗炎症性肠病（IBD）的药物,但实际应用中仍存在诸多不规范的情况。本文从5-ASA用于IBD治疗的发展史和治疗机制、5-ASA在IBD中的合理应用、5-ASA对IBD相关结直肠癌的预防作用以及5-ASA的不良反应4个方面介绍其在IBD中的应用,旨在全面了解5-ASA在IBD治疗中的作用,使其更合理、规范地应用于临床。     

Symptom burden: A forgotten area of measurement in inflammatory bowel disease

Inflammatory bowel disease (IBD) collectively known as Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the digestive tract. Periods of active and inactive disease are common along the trajectory of this illness. A range of symptoms such as fatigue, diarrhoea and abdominal pain are experienced and are often very debilitating in nature resulting in significance interference in daily life. Despite this, to date, research in the area of symptoms remains an underexplored topic. This paper aims to discuss current approaches to symptom assessment in IBD and the potential to measure symptom burden in further research, in order to gain a greater understanding into the experiences of individuals with IBD.     

Drug-resistant bullous pemphigoid and inflammatory bowel disease in a pediatric case successfully treated by plasma exchange and extracorporeal photochemotherapy

Bullous pemphigoid (BP) is an autoimmune skin disease that occurs mainly in elderly patients; onset of BP is rare in childhood. Inflammatory bowel diseases (IBD), by contrast, have a pediatric onset in 25% of presenting cases, requiring expert multidisciplinary management. Here we report a pediatric case of IBD (involving stomach, duodenum, ileum, and colon-rectum) associated with a disseminated form of drug-resistant BP successfully treated by plasma exchange (PEX), extracorporeal photochemotherapy (ECP), and corticosteroid therapy. The addition of PEX and ECP to standard treatment induced no severe side effects, prompted a rapidly achieved complete and long-term remission, and allowed dose tapering of the immunosuppressive drugs over an 18-month follow-up.     

炎症性肠病患者肠内营养支持治疗与护理进展

目的 营养不良是炎症性肠病的常见临床表现,而营养支持是目前炎症性肠病患者重要的辅助疗法。近年来,关于肠内营养对炎症性肠病的治疗作用得到了广泛的关注,故围绕肠内营养在炎症性肠病中的应用这一要点展开综述。方法 检索近几年国内外关于炎症性肠病的营养支持及肠内营养的文献,并作总结分析。结果 肠内营养能改善炎症性肠病患者的营养状况,此外,肠内营养能诱导活动期克罗恩病缓解并维持缓解期。结论 肠内营养不仅能改善炎症性肠病患者的营养状况,对炎症性肠病的诱导缓解和维持缓解均起着重要的作用,而且具有安全、便捷、经济等优点,恰当地使用肠内营养能为炎症性肠病患者带来许多益处。     

炎症性肠病病人自我管理研究进展

介绍了炎症性肠病病人自我管理的定义和意义,从心理因素、治疗因素、社会因素3方面阐述了影响炎症性肠病病人自我管理的因素,提出了健康教育、心理干预、社会支持等干预措施,并指出了目前该领域研究的局限性.     

炎症性肠病病情活动监测指标的临床价值

目的探讨髓过氧化物酶(MPO)和超氧化物歧化酶(SOD)作为炎症性肠病(IBD)病情活动临床监测指标的价值。方法分别观察了IBD活动组患者15例[其中活动期溃疡性结肠炎(UC)10例,活动期克罗恩病(CD)5例],IBD非活动组患者15例(其中缓解期UC10例,缓解期CD5例)和12例对照组患者的结肠黏膜病理变化,按Oshitani评分标准和d'Haens评分标准进行UC和CD组织学评分,测定结肠黏膜MPO和SOD活性。结果IBD活动组、IBD非活动组病理组织评分均比对照组高(8±5 vs 3±1)、(5±2 vs 3±1)(P<0.01),IBD活动组病理组织评分亦较IBD非活动组高(8±5 vs 5±2)(P<0.01);IBD活动组、IBD非活动组肠黏膜MPO活性均较对照组高[(3.55±0.38)U/g vs(1.52±0.24)U/g、(2.28±0.30)U/g vs(1.52±0.24)U/g](P<0.01),IBD活动组MPO活性较IBD非活动组高[(3.55±0.38)U/g vs(2.28±0.30)U/g](P<0.01);IBD活动组、IBD非活动组肠黏膜SOD活性均较对照组低[(104.58±18.91)U/mg vs(212.44±14.22)U/mg、(170.91±13.57)U/mg vs(212.44±14.22)U/mg](P<0.01),IBD活动组SOD活性较IBD非活动组低[(104.58±18.91)U/mg vs(170.91±13.57)U/mg](P<0.01)。结论MPO活性与IBD病情活动程度呈正相关,SOD活性与IBD病情活动程度呈负相关,两者可作为IBD病情活动的临床监测指标。     

炎症性肠病患者的营养支持治疗

溃疡性结肠炎和克罗恩病等炎症性肠病患者常伴有营养不良及生长发育障碍。营养支持治疗在炎症性肠病治疗中占有重要地位。应常规对炎症性肠病患者进行营养风险筛查,并采用适当方法进行营养评定,以便及时进行营养支持。肠内营养支持作为儿童克罗恩病患者诱导缓解和维持治疗的首选,在成人患者中作为药物的替代治疗。有多种营养制剂,不同患者对不同的营养制剂反应不同,需选择合适的制剂,进行个体化治疗,才能发挥营养制剂的最大效用。     

炎症性肠病患者用药依从性现况及其影响因素调查

目的调查炎症性肠病患者用药依从性现况及影响因素。方法采用Morisky用药依从性问卷、克罗恩病与溃疡性结肠炎知识问卷、炎症性肠病患者用药信念问卷对141例炎症性肠病患者进行调查。结果炎症性肠病患者用药依从性总分为(6.03±1.12)分,用药依从性好22例,占15.60%;依从性中等66例,占46.81%;依从性差53例,占37.56%;患者的年龄、疾病类型、疾病活动性、疾病知识、用药信念是其用药依从性的主要影响因素。结论炎症性肠病患者用药依从性整体不佳,护理人员应重视患者的用药管理和评估,根据依从性影响因素的不同给予针对性的健康指导与干预,提高用药依从性,促进健康行为,从而改善生活质量。