Summary
Background
A link between histone deacetylases (HDACs) and intestinal inflammation has been established. HDAC inhibitors that target gut‐selective inflammatory pathways represent a potential ...new therapeutic strategy in patients with refractory inflammatory bowel diseases (IBD).
Aims
To review the use of selective HDAC inhibitors to treat gut inflammation and to highlight potential improvements in selectivity/sensitivity by additional targeting of HDAC‐regulating microRNAs (miRNAs).
Methods
Original articles and reviews have been identified using PubMed search terms: ‘histone deacetylase’, ‘HDAC inhibitor’, ‘inflammatory bowel disease’, ‘gut inflammation,’ and ‘microRNA and HDAC’.
Results
The use of butyrate in distal colitis provided the first evidence that inhibition of HDACs decreases intestinal inflammation in IBD. HDAC inhibitors, such as valproic acid, vorinostat and givinostat, reduce inflammation and tissue damage in experimental murine colitis. Potential mechanisms of action for HDAC inhibitors include increased apoptosis, reduction of pro‐inflammatory cytokine release, regulation of transcription factors and modulation of HDAC‐regulatory miRNAs. HDAC2, HDAC3, HDAC6, HDAC9 and HDAC10 isoforms seem to be specifically involved in chronic intestinal inflammation, justifying the use of selective inhibitors as new therapeutic strategies in IBD. Controlling miRNAs for these isoforms can be identified.
Conclusions
The pro‐inflammatory influence of HDACs in the gut has been confirmed, but mostly in murine studies. Considerably more human data are required to permit development of selective HDAC inhibitors for IBD treatment. Inhibition of key HDAC isoforms in combination with modulation of HDAC‐regulatory miRNAs has potential as a novel therapeutic approach.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Psoriasis is an emerging paradoxical side effect in patients with inflammatory bowel disease (IBD) when treated with anti‐TNF alpha. Patients with severe skin lesions unresponsive ...to topical therapy need to withdraw from treatment.
Aim
To estimate the incidence of paradoxical psoriasis in a large cohort of IBD patients treated with anti‐TNF alpha and to analyse its clinical correlates.
Methods
A retrospective cohort study on all IBD patients who started anti‐TNF alpha at our IBD Centre from January 2008 to December 2013 was performed. Proportional hazards regression models were used to estimate the association between each predictor and time to the development of psoriasis. Time‐dependent predictors were updated at each available time point.
Results
Four hundred and two patients were included. Participants contributed a total of 839 person‐years of follow‐up, during which 42 incident cases of psoriasis were recorded, with an incidence rate of five per 100 person‐years. Cox‐regression survival analysis revealed smoking as independent predictor of psoriasis (HR: 2.37, 95% CI: 1.36–4.48; P = 0.008). Conversely, concomitant immunosuppressive therapy was inversely related to psoriasis (HR: 0.33, 95% CI: 0.12–0.92; P = 0.03).
Conclusions
Paradoxical psoriasis is a relevant side effect of anti‐TNF alpha therapy, with an incidence rate of five per 100 person‐years. Smoking is confirmed as the main risk factor for developing lesions. The combination therapy with anti‐TNF alpha plus immunosuppressants is associated with a reduced risk of paradoxical psoriasis.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
The chronic and progressive evolution of Inflammatory Bowel Diseases (IBD), with its prototypical fluctuating trend, creates a condition of psycho-social discomfort, impacting the ...quality of life in terms of personal, working, and interpersonal.
Aims
In this article, we want to identify the nature and extent of the research evidence on the life experiences, the perceived engagement, the psychological, social care and welfare needs of people affected by IBD across the lifecycle.
Methods
Following the approach set out by Arksey and O’Malley and the PRISMA extension for scoping reviews, we conducted a scoping review in March 2019 and closed the review with an update in October 2019. It was performed using electronic databases covering Health and Life Sciences, Social Sciences and Medical Sciences, such as PubMed, Medline, Embase, Scopus, Cochrane, Web of Science, PsycInfo.
Results
We identified 95 peer-reviewed articles published from 2009 to 2019, that allowed to detection the main needs in children (psychological, need to be accepted, physical activity, feeding, parent style, support, social needs), adolescents (to understand, physical and psychological needs, protection, relational, gratitude, respect, and engagement) and adults (information, medical, psychological, social, work-related, practical, future-related, engagement). Although the literature confirms that the majority of the IBD units have planned provision for the different types of transitions, the quality and appropriateness of these services have not been assessed or audited for all the kinds of challenges across the life cycle.
Conclusions
The literature shows the relevance of organizing a flexible, personalized health care process across all the critical phases of the life cycle, providing adequate benchmarks for comparison in a multidisciplinary perspective and ensuring continuity between hospital and territory.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Aminosalicylates are the mainstay of therapy to prevent relapse of quiescent ulcerative colitis. The rationale for using probiotics is based on the evidence implicating intestinal ...bacteria in the pathogenesis of this disorder.
Aim
To evaluate the efficacy of Lactobacillus GG alone or in combination with mesalazine vs. mesalazine as maintenance treatment in ulcerative colitis.
Patients and methods
187 ulcerative colitis patients with quiescent disease were randomized to receive Lactobacillus GG 18 × 109 viable bacteria/day (65 patients), mesalazine 2400 mg/day (60 patients) or Lactobacillus GG + mesalazine (62 patients). Disease activity index, endoscopic and histological scores were determined at 0, 6 and 12 months and in case of relapse. The primary end point was to evaluate sustained remission.
Results
Overall analysis showed no difference in relapse rate at 6 (P = 0.44) and 12 months (P = 0.77) among the three treatment groups. However, the treatment with Lactobacillus GG seems to be more effective than standard treatment with mesalazine in prolonging the relapse‐free time (P < 0.05).
Conclusions
Lactobacillus GG seems to be effective and safe for maintaining remission in patients with ulcerative colitis, and it could represent a good therapeutic option for preventing relapse in this group of patients.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
We described a case of IPEX syndrome successfully controlled with dupilumab, an anti-IL4 receptor alpha subunit inhibitor. IPEX syndrome is a rare and generally fatal genetic disorder characterized ...by immune dysregulation, polyendocrinopathy and enteropathy, mostly diagnosed in early childhood. Nonetheless, cases reported in the last 20 years demonstrated that IPEX clinical spectrum encompasses more than the classical triad of early-onset intractable diarrhea, type 1 diabetes and eczema. Atypical cases of IPEX include patients with late-onset of symptoms, single-organ involvement, mild disease phenotypes or rare clinical features. A 21-year-old caucasian man presented with immune dysregulation (hypereosinophilia and elevated IgE), protein-losing enteropathy, polyendocrinopathy (thyroiditis, osteoporosis, delayed puberty), weight loss, eczema manifestations and celiac disease. IPEX syndrome was diagnosed because of the presence of a hemizygous mutation in FOXP3 gene (c.543C>T (p.S181S) in the exon 5). During the course of the disease, the patient developed erosive proctitis, pyoderma gangrenosum, and erythema nodosum. Symptoms improved only after enteral and parenteral corticosteroid therapy and the patient soon developed steroid-dependence. Notwithstanding various therapies including azathioprine, sirolimus, tacrolimus, adalimumab, vedolizumab, the patient failed to achieve a good control of symptoms without steroids. Almost exclusive enteral nutrition with a hypoallergenic, milk-protein free, amino acid-based food for special medical purposes. He continued to lose weight (BMI 14.5 kg/m2) with a consequent high limitation of physical activity and a progressive worsening of the quality of life. In consideration of the poor response to conventional immunosuppressants and the presence of type 2 inflammatory manifestations, treatment with dupilumab at an initial dose of 600 mg, followed by a maintenance dose of 300 mg every other week, according to atopic dermatitis labeled dose, was started and combined to oral budesonide 6 mg/day and 6-mercaptopurine 75 mg/day. The patient experienced a rapid improvement in bowel and skin symptoms, leading to a progressive tapering of steroids. By our knowledge, this is the first report of IPEX syndrome successfully treated by antiIL-4/IL-13 therapy. In this case dupilumab demonstrated to be an effective, safe and steroid-sparing option.
Summary
Background
Severe ulcerative colitis is a life‐threatening disorder, despite i.v. glucocorticoids treatment. Infliximab has been proposed as a safe rescue therapy.
Aim
To evaluate short‐ and ...long‐term effectiveness and safety of infliximab in severe refractory ulcerative colitis.
Methods
Eighty‐three patients with severe ulcerative colitis (i.v. glucocorticoids treatment‐refractory) were treated with infliximab in 10 Italian Gastroenterology Units. Patients underwent one or more infusions according to the choice of treating physicians. Short‐term outcome was colectomy/death 2 months after the first infusion. Long‐term outcome was survival free from colectomy. Safety data were recorded.
Results
Twelve patients (15%) underwent colectomy within 2 months. One died of Legionella pneumophila infection 12 days after infliximab. Early colectomy rates were higher in patients receiving one infusion (9/26), compared with those receiving two/more infusions (3/57, P = 0.001, OR = 9.53).
Seventy patients who survived colectomy and did not experience any fatal complications were followed‐up for a median time of 23 months; 58 patients avoided colectomy during the follow‐up. Forty‐two patients were maintained on immunosuppressive drugs. No clinical features were associated with outcomes.
Conclusions
Infliximab is an effective and relatively safe therapy to avoid colectomy and maintain long‐term remission for patients with severe refractory ulcerative colitis. In the short term, two or more infusions seem to be more effective than one single infusion.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The spread of COVID-19 pandemic forced the national healthcare system to reorganize almost all surgical services, in order to maintain an adequate therapeutic offer. At General Surgery department of ...Fondazione Policlinico Gemelli in Rome, surgical procedures were progressively reduced to provide beds and personnel for COVID-19. The aim of our study was to analyze the effect of one year of COVID-19 pandemic on Inflammatory Bowel Disease (IBD) surgery in a cohort of patients and evaluate post-operative short-term complications.
Our team retrospectively analyzed the records of IBD patients who were referred to an IBD-related resective surgery from January 2020 to December 2020. These patients were compared to a comparable group of IBD patients who were operated from January 2019 to December 2019.
A total of 160 patients were included in the study. Median age was 44 (range 15-77). Patients were referred for Ulcerative colitis (23.1%) and Crohn's disease (76.9%). Eighty-three patients underwent surgery from January 2020 to December 2020, which constitutes a 4.6% increase in the number of patients compared to the same period in 2019. Median post-operative hospital stay increased (7 days in 2019 vs. 6 days in 2020). Laparoscopic was the most frequently performed procedure during both periods (49% in 2019 and 59% in 2020). Complication rates, reported as Clavien-Dindo score 3 or 4, slightly decreased in 2020 (6.5 in 2019 vs. 4.8 in 2020). PCR test for detection of COVID-19 infection was conducted in all the patients before the hospitalization. Two patients out of 70 were tested positive for COVID-19 and their surgeries were rescheduled.
There was no significant reduction in IBD resective surgeries at our center in 2020, nor a deterioration of the outcomes. A reduction of other elective surgical procedures had to be carried out and adequate protective measures for both patients and healthcare workers were established.
Mepolizumab (MEP) is the first anti Interleukin (IL)-5 add-on therapy approved for the treatment of severe refractory eosinophilic asthma.
We describe here the case of a 49 years-old woman with ...Aspirin-exacerbated respiratory disease (AERD), chronic rhinosinusitis, nasal polyposis and eosinophilic gastroenteritis successfully treated with MEP. Several laboratory and clinical items improved during therapy; moreover MEP showed to be useful as steroid sparing agent.
This case supports that the use of mepolizumab can be effective also in other eosinophilic conditions different from asthma and this opens to new therapeutic perspectives.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
The following review is a compilation of the recent advances and knowledge on the behaviour of the most frequently used compounds to treat inflammatory bowel disease in an organism.
...Results
It considers clinical aspects of each entity and the pharmacokinetic/pharmacodynamic relationship supported by the use of plasma monitoring, tissue concentrations, and certain aspects derived from pharmacogenetics.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
PDF
