Summary
Background
Management of recurrent Clostridium difficile‐associated disease (CDAD), particularly in elderly patients, remains clinically challenging. Faecal transplantation (FT) may restore ...normal microbiota and break the cycle of recurrent CDAD.
Aim
To critically appraise the clinical research evidence on the safety and effectiveness of FT compared with standard care in the treatment of patients with CDAD.
Methods
A comprehensive literature search was conducted by a research librarian to identify relevant studies published between 2000 and 2011. The Cochrane Library, PubMed, EMBASE, CINAHL, Biological s, BIOSIS Previews and Web of Science were searched using the following Medical Subject Headings (MeSH) terms and keywords, alone or in combination: Clostridium infections/Clostridium difficile/pseudomembranous/colitis/faeces/rectal/colon flora/gastrointestinal/nasogastric tube/enema/donor/transplant/infusion/bacteriotherapy/human probiotic infusion. Methodological quality of the included case series studies was assessed in terms of patient selection criteria, consecutive recruitment, prospective data collection, reporting of lost to follow‐up, and follow‐up rates.
Results
No controlled studies were found. Based on the weak evidence from seven full‐text case series studies of 124 patients with recurrent/refractory CDAD, FT appears to be a safe and effective procedure. In most cases (83%) symptoms improved immediately after the first FT procedure, and some patients stayed diarrhoea free for several months or years.
Conclusions
Although these results appear to be promising, the treatment effects of faecal transplantation cannot be determined definitively in the absence of a control group. Results from randomised controlled trials that compare faecal transplantation to oral vancomycin without or with a taper regimen will help to better define the role of faecal transplantation in the management of recurrent CDAD.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Aims: Isomalto-oligosaccharides (IMO) with α(1→6) and α(1→4) glucosidic linkages are produced by enzymatic conversion of starch. IMO are only partially digestible but data on their influence on ...intestinal microbiota are limited. It was the aim of this study to investigate the effect of IMO diet on intestinal microbiota and short-chain fatty acids production (SCFA) in rats. Methods and results: Three groups of F344 rats, each consisting of six animals, were fed IMO, inulin or a control diets for six weeks. A qualitative assessment of the intestinal microbiota was achieved by PCR-denaturing gradient gel electrophoresis (DGGE). Major bacterial taxa were quantified by quantitative PCR (qPCR), and SCFA were measured using gas chromatography. Quantitative PCR demonstrated that lactobacilli were one of the dominant bacterial taxa in faecal samples from rats. IMO increased the number of lactobacilli and the total number of intestinal bacteria in rats fed IMO compared with animals receiving control and inulin diets. Furthermore, PCR-DGGE with lactobacilli-specific primers showed an altered biodiversity of lactobacilli in rats fed IMO compared with control diet. Conclusions: IMO selectively stimulates lactobacilli and increases their diversity in rats. Significance and impact of study: Isomalto-oligosaccharides specifically stimulate growth of intestinal lactobacilli in a rat model system.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Background
The efficacy of adalimumab in maintaining remission in Crohn's disease patients may wane over time, leading to secondary loss of response that is often managed with dose ...escalation. However, the response to adalimumab dose escalation and long‐term outcomes after escalation have not been well evaluated.
Aims
To characterise the short‐ and long‐term clinical responses to adalimumab dose escalation for secondary loss of response.
Methods
A retrospective cohort study evaluating Crohn's disease out‐patients requiring adalimumab dose escalation for secondary loss of response from 2003 to 2013 was conducted. The primary outcome was the proportion of patients achieving symptomatic clinical response to dose escalation and subsequent development of tertiary loss of response. Duration of regained response was assessed by Kaplan–Meier analysis.
Results
Ninety‐two CD patients met inclusion criteria with mean duration of follow‐up of 170.2 weeks (±129.6 weeks). Disease distribution was predominantly ileal (37/92, 40.2%) or ileocolonic (43/92, 46.7%), with equal distribution of inflammatory (34.8%), stricturing (27.2%), and penetrating (38.0%) disease phenotypes. At 24 weeks post‐dose escalation, 74/92 (80.4%) patients had symptomatic clinical response. Among responders, median duration of sustained response was 69.2 weeks (IQR 29.4–107.1) but 42/74 (56.8%) responders experienced subsequent tertiary loss of response at a median time of 47.9 weeks (IQR 24.7–80.3). C‐reactive protein >10.0 mg/L at the time of dose escalation predicted tertiary loss of response in univariate analysis (OR 3.32, 95% CI: 1.18–9.37).
Conclusions
In patients with Crohn's disease, adalimumab dose escalation is effective for recapturing symptomatic response after secondary loss of response, but more than half will eventually experience a tertiary loss of response.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Ustekinumab is a monoclonal antibody targeting interleukins‐12 and ‐23, with efficacy in Crohn's disease (CD) demonstrated in clinical trials.
Aim
To assess the real‐world ...clinical, endoscopic and radiographic response and remission outcomes achieved with ustekinumab in medically‐refractory CD.
Methods
A retrospective multicentre cohort study was performed on CD patients receiving ustekinumab between 2011 and 2016. The primary outcome was achievement of clinical and objective steroid‐free response and remission at 3, 6 and 12 months. Clinical response and remission were defined by reduction in Harvey Bradshaw Index (HBI) of ≥3 points and an HBI ≤4 points respectively. Objective response was defined by improvement in endoscopic or radiographic CD, as assessed by ileocolonoscopy, contrast‐enhanced ultrasound or CT/MR enterography. Objective remission was defined by endoscopic mucosal healing or complete resolution of inflammatory parameters on radiographic assessment.
Results
A total of 167 CD patients were treated with ustekinumab. 95.2% (159/167) previously failed anti‐TNF therapy. Median follow‐up was 45.6 weeks (IQR: 24.4–88.9). At 3 months, clinical response was achieved in 38.9% (65/167) and remission in 15.0% (25/167) of patients. At 6 months, clinical response was achieved in 60.3% (91/151) and remission in 25.2% (38/151) of patients. At 12 months, clinical response was achieved in 59.5% (66/111) and remission in 27.9% (31/111) of patients. Endoscopic or radiographic response was demonstrated in 54.5% (67/123) at 6 months and 55.8% (48/86) of patients at 12 months.
Conclusions
Ustekinumab is an effective therapeutic option for inducing and maintaining clinical, endoscopic and radiographic response in patients with Crohn's disease failing anti‐TNF therapy.
Linked ContentThis article is linked to Khorrami and Gisbert paper. To view this article visit https://doi.org/10.1111/apt.14053.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background and aims:Bacteroides vulgatus induces colitis in gnotobiotic HLA-B27 transgenic (TG) rats while broad spectrum antibiotics prevent and treat colitis in specific pathogen free (SPF) TG rats ...although disease recurs after treatment ends. Lactobacilli treat human pouchitis and experimental colitis. We investigated if Lactobacillus rhamnosus GG (L GG) can prevent colitis in TG rats monoassociated with B vulgatus and if L GG or Lactobacillus plantarum 299v (LP 299v) can treat established colitis in SPF TG rats and prevent recurrent disease after antibiotics were stopped. Methods: Germfree B27 TG rats were monoassociated with B vulgatus for four weeks following two weeks of colonisation with L GG or no bacteria. SPF B27 TG rats received oral vancomycin and imipenem for two weeks, or water alone, followed by four weeks of treatment with oral L GG, LP 299v, or water only. Disease activity was quantified by blinded gross and histological scores, caecal myeloperoxidase (MPO) activity, and levels of interleukin (IL)-1β, tumour necrosis factor (TNF), transforming growth factor β, and IL-10. Results:L GG did not prevent colitis in B vulgatus co-associated TG rats or treat established disease in SPF rats. However, L GG but not LP 299v prevented colitis relapse in antibiotic treated rats with reduced gross and histological scores, caecal MPO, IL-1β, and TNF whereas caecal IL-10 was increased. Conclusions:L GG does not prevent colitis in gnotobiotic TG rats or treat established disease in SPF rats, but is superior to LP 299v in the prevention of recurrent colitis. These studies suggest that antibiotics and probiotic agents provide synergistic therapeutic effects, perhaps mediated by altered immunomodulation with selective activity of different lactobacillus species.
In preterm infants with Respiratory Distress Syndrome (RDS), Less Invasive Surfactant Administration (LISA) has been established to reduce the need of mechanical ventilation and might improve ...survival rates without bronchopulmonary dysplasia. The aim of this study was to investigate whether NICU care has changed after introduction of less invasive surfactant administration (LISA), with regard to diagnostic and therapeutic procedures in the first week of life.
Infants with gestational age < 32 weeks who received surfactant by LISA (June 2014 - December 2017, n = 169) were retrospectively compared to infants who received surfactant after intubation (January 2012 - May 2014, n = 155). Local protocols on indication for surfactant, early onset sepsis, blood transfusions and enteral feeding did not change between both study periods. Besides, as secondary outcome complications of prematurity were compared. Data was collected from electronic patient files and compared by univariate analysis through Students T-test, Mann Whitney-U test, Pearson Chi-Square test or Linear by Linear Association.
All baseline characteristics of both groups were comparable. Compared to controls, LISA patients received a higher total surfactant dose (208 vs.160 mg/kg; p < 0.001), required redosing more frequently (32.5% vs. 21.3%; p = 0.023), but needed less mechanical ventilation (35.5% vs. 76.8%; p < 0.001). After LISA, infants underwent fewer X-rays (1.0 vs. 3.0, p < 0.001), blood gas examinations (3.0 vs. 5.0, p < 0.001), less inotropic drugs (9.5% vs. 18.1%; p = 0.024), blood transfusions (24.9% vs. 41.9%, p = 0.003) and had shorter duration of antibiotic therapy for suspected early onset sepsis (3.0 vs. 5.0 days, p < 0.001). Moreover, enteral feeding was advanced faster (120 vs. 100 mL/kg/d, p = 0.048) at day seven. There were no differences in complications of prematurity.
The introduction of LISA is associated with significantly fewer diagnostic and therapeutic procedures in the first week of life, which emphasizes the beneficial effects of LISA.
Oral administration of DSS has been reported to induce an acute and chronic colitis in mice. The aim of our study was to evaluate if the chronic phase of DSS‐induced colitis was characterized by a ...Th1/Th2 response and how this would relate to mucosal regeneration. Swiss Webster mice were fed 5% DSS in their drinking water for 7 days, followed by 2–5 weeks consumption of water. Control mice received only water. The animals were killed at 3 and 6 weeks after induction. Their colons were isolated for histology and immunohistochemistry, using specific MoAbs for T and B cells, macrophages, interferon‐gamma (IFN‐γ), IL‐4 and IL‐5. Colons were scored for inflammation, damage and regeneration. Two weeks after stopping DSS the colonic epithelium had only partially healed. Total colitis scores were still increased, especially in the distal colon, which was due to more inflammation, damage and less regeneration. In areas of incomplete colonic healing the basal parts of the lamina propria contained macrophages and CD4+ T cells. These CD4+ T cells showed a focal increase of IFN‐γ and IL‐4 staining compared with control animals. These findings were still observed 5 weeks after stopping DSS in some mice, albeit less extensive. Chronic DSS‐induced colitis is characterized by focal epithelial regeneration and a Th1 as well as Th2 cytokine profile. We postulate that chronic immune activation mediated by both populations of Th cells can interfere with colonic healing and can play a role in the pathogenesis of chronic colitis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Intestinal microflora play a critical role in the initiation and perpetuation of chronic inflammatory bowel diseases. In genetically susceptible hosts, bacterial colonization results in rapid-onset ...chronic intestinal inflammation. Nevertheless, the intestinal and systemic immune response to faecal bacteria and antigen exposure into a sterile intestinal lumen of a post-weaned animal with a mature immune system are not understood clearly. This study examined the effects of faecal bacteria and antigen exposure on the intestinal mucosal and systemic immune system in healthy axenic mice. Axenic wild-type mice were inoculated orally with a crude faecal slurry solution derived from conventionally raised mice and were analysed prior to and then at days 3, 7, 14 and 28 post-treatment. Ingestion of faecal slurry resulted in a transient, early onset of proinflammatory interferon (IFN)-γ, tumour necrosis factor (TNF)-α and interleukin (IL)-17 response that was maximal at day 3. In contrast, the transient release of the anti-inflammatory cytokines IL-10 and IL-4 occurred later and was maximal at day 7. Both responses subsided by day 14. This early cytokine imbalance was associated with a brief rise in colonic and caecal histopathological injury score at day 7. The bacterial antigen-specific systemic response was found to follow the intestinal immune response with a maximal release of both pro- and anti-inflammatory cytokines at day 7. Thus, first exposure of healthy axenic wild-type mice to normal faecal flora and antigens results in an early proinflammatory cytokine response and transient colonic inflammation that then resolves in conjunction with a subsequent anti-inflammatory cytokine profile.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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