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EClinicalMedicine Mar 2023Onset of effect of advanced therapies is an important parameter due to symptom load and risk of disease complications in moderate-to-severe ulcerative colitis (UC), but...
BACKGROUND
Onset of effect of advanced therapies is an important parameter due to symptom load and risk of disease complications in moderate-to-severe ulcerative colitis (UC), but comparative data are lacking. Therefore, we aimed to assess the comparative onset of efficacy of biological therapies and small molecules for this patient population.
METHODS
In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to 24 August 2022, for randomised controlled trials or open-label studies assessing the efficacy of biologics or small molecule drugs within the first six weeks of treatment in adults with UC. The co-primary outcomes were the induction of clinical response and clinical remission at week 2. Network meta-analyses was conducted under the Bayesian framework. This study is registered with PROSPERO: CRD42021250236.
FINDINGS
The systematic literature search identified 20,406 citations, of which 25 studies comprising 11,074 patients fulfilled the eligibility criteria. Upadacitinib ranked highest for induction of clinical response and clinical remission at week 2 and was significantly superior to all agents but tofacitinib, which ranked second highest. Although the rankings remained consistent, no differences between upadacitinib and biological therapies were demonstrated in the sensitivity analyses of partial Mayo clinic score response or resolution of rectal bleeding at week 2. Tumor necrosis factor-α (TNF) inhibitors were significantly superior to vedolizumab and ustekinumab for patient-reported outcome-2 (PRO-2) remission at week 2 in bio-naïve patients. Filgotinib 100 mg, ustekinumab, and ozanimod ranked lowest across all endpoints.
INTERPRETATION
In this network meta-analysis, we found upadacitinib to be significantly superior to all agents but tofacitinib for the induction of clinical response and clinical remission two weeks after treatment initiation. In contrast, ustekinumab and ozanimod ranked lowest. Our findings help to establish the evidence regarding the onset of efficacy of advanced therapies.
FUNDING
None.
PubMed: 36864986
DOI: 10.1016/j.eclinm.2023.101866 -
Alimentary Pharmacology & Therapeutics Oct 2014The management of perianal Crohn's fistulas represents a significant challenge. A combination of medical and surgical therapy, guided by radiology, is often required. (Review)
Review
BACKGROUND
The management of perianal Crohn's fistulas represents a significant challenge. A combination of medical and surgical therapy, guided by radiology, is often required.
AIM
To review systematically the literature to assess fistula healing rates with medical treatment (anti-TNF-α therapies ± immunomodulators) or surgical treatment alone, compared with combined medical and surgical treatment in fistulising perianal Crohn's disease (CD).
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Two independent reviewers searched the literature.
RESULTS
Twenty-four articles were included. The total population was 1139 patients; 460 (40%) received single treatment with either medical or surgical therapy, and 679 (60%) received combined medical and surgical therapy. Eight studies compared single and combination therapy, with a total population of 797 patients (single therapy: n = 448, combination therapy: n = 349). In the single therapy group, 191/448 were in complete remission (43%). This was lower than the healing rate of the combination therapy group 180/349 (52%). No response to therapy was noted in 34% (153/448) of the single therapy group compared with 23% (80/349) of the combination group.
CONCLUSIONS
Combined surgical and medical (anti-TNF-α ± immunomodulators) therapy may have additional beneficial effects on perianal fistula healing in patients with Crohn's disease, compared with surgery or medical therapy alone. A well-designed Crohn's perianal fistula clinical trial is required in a multidisciplinary medical and surgical setting, with clearly defined end points of clinical (and likely patient reported outcomes) and radiological healing.
Topics: Combined Modality Therapy; Crohn Disease; Humans; Immunologic Factors; Rectal Fistula; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 25115149
DOI: 10.1111/apt.12906 -
JGH Open : An Open Access Journal of... Jun 2020Perianal fistulas are a common and debilitating manifestation of Crohn's disease. Since the advent of biological agents, patient outcomes appear to have improved. While... (Review)
Review
Perianal fistulas are a common and debilitating manifestation of Crohn's disease. Since the advent of biological agents, patient outcomes appear to have improved. While rates of clinical response and remission are well characterized in literature, magnetic resonance imaging (MRI) outcomes remain less so. This is despite previous studies demonstrating the persistence of fistula tracts on MRI, in spite of clinical healing, suggesting radiological markers of improvement may be more accurate. The aims of this study were to systematically review the literature for all studies reporting on MRI outcomes following biological therapy and to compare rates of radiological healing to clinical remission. A search was performed according to the Preferred Reporting Items For Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Nine articles were included, with a total sample size of 259 patients. Of these 259 patients, 47% achieved clinical remission following induction therapy and 42% following a median of 52 weeks' maintenance therapy. Out of the 259 patients, 7% achieved radiological healing in the short term and 25% in the long term. The odds ratio of MRI clinical healing was 0.10 (95% confidence interval [CI], 0.02-0.39) and 0.43 (95% CI, 0.26-0.71), respectively, at those corresponding time points. MRI healing of perianal fistulizing Crohn's, while arguably a more accurate assessment of treatment response, is significantly less common than clinical remission. Heterogeneity exists in the definition of radiological and clinical response, leading to variation in reported rates. Further studies, directly comparing the long-term outcomes of patients achieving clinical remission and MRI healing are required, to better inform the role of MRI follow up in clinical practice.
PubMed: 32514434
DOI: 10.1002/jgh3.12295 -
Evidence Report/technology Assessment Nov 2010The purpose of this report is to systematically examine the possible causal mechanism(s) that may explain the association between alcohol (ethanol) consumption and the... (Review)
Review
OBJECTIVES
The purpose of this report is to systematically examine the possible causal mechanism(s) that may explain the association between alcohol (ethanol) consumption and the risk of developing breast and colorectal cancers.
DATA SOURCES
We searched 11 external databases, including PubMed® and Embase, for studies on possible mechanisms. These searches used Medical Subject Headings and free text words to identify relevant evidence.
REVIEW METHODS
Two reviewers independently screened search results, selected studies to be included, and reviewed each trial for inclusion. We manually examined the bibliographies of included studies, scanned the content of new issues of selected journals, and reviewed relevant gray literature for potential additional articles.
RESULTS
Breast Cancer. Five human and 15 animal studies identified in our searches point to a connection between alcohol intake and changes in important metabolic pathways that when altered may increase the risk of developing breast cancer. Alterations in blood hormone levels, especially elevated estrogen-related hormones, have been reported in humans. Several cell line studies suggest that the estrogen receptor pathways may be altered by ethanol. Increased estrogen levels may increase the risk of breast cancer through increases in cell proliferation and alterations in estrogen receptors. Human studies have also suggested a connection with prolactin and with biomarkers of oxidative stress. Of 15 animal studies, six reported increased mammary tumorigenesis (four administered a co-carcinogen and two did not). Other animal studies reported conversion of ethanol to acetaldehyde in mammary tissue as having a significant effect on the progression of tumor development. Fifteen cell line studies suggested the following mechanisms: Increased hormonal receptor levels. Increased cell proliferation. A direct stimulatory effect. DNA adduct formation. Increase cyclic adenosine monophosphate (camp). Change in potassium channels. Modulation of gene expression. Colorectal Cancer. One human tissue study, 19 animal studies (of which 12 administered a co-carcinogen and seven did not), and 10 cell line studies indicate that ethanol and acetaldehyde may alter metabolic pathways and cell structures that increase the risk of developing colon cancer. Exposure of human colonic biopsies to acetaldehyde suggests that acetaldehyde disrupts epithelial tight junctions. Among 19 animal studies the mechanisms considered included: Mucosal damage after ethanol consumption. Increased degradation of folate. Stimulation of rectal carcinogenesis. Increased cell proliferation. Increased effect of carcinogens. Ten cell line studies suggested: Folate uptake modulation. Tumor necrosis factor modulation. Inflammation and cell death. DNA adduct formation. Cell differentiation. Modulation of gene expression. One study used a combination of animal and cell line and suggested intestinal cell proliferation and disruption of cellular signals as possible mechanisms.
CONCLUSIONS
Based on our systematic review of the literature, many potential mechanisms by which alcohol may influence the development of breast or colorectal cancers have been explored but the exact connection or connections remain unclear. The evidence points in several directions but the importance of any one mechanism is not apparent at this time.
Topics: Alcohol Drinking; Animals; Breast Neoplasms; Cell Proliferation; Colorectal Neoplasms; Estrogens; Ethanol; Female; Humans; Male; Mammary Neoplasms, Animal; Oxidative Stress; Prolactin; Receptors, Estrogen; Risk
PubMed: 23126574
DOI: No ID Found -
International Journal of Surgery Case... 2020Colonic volvulus is defined as a torsion of a part of the colon causing large bowel obstruction by strangulation which may lead to ischemia and then necrosis. The...
INTRODUCTION
Colonic volvulus is defined as a torsion of a part of the colon causing large bowel obstruction by strangulation which may lead to ischemia and then necrosis. The synchronous occurrence of a sigmoid colon and transverse colon volvulus is exceptional. We describe a case of synchronous sigmoid and transverse volvulus in a patient with a qualitative systematic review of this condition.
PRESENTATION OF THE CASE
This is a 74-year-old patient with a history of chronic constipation, who consulted for bowel obstruction. Plain abdominal radiography showed diffuse gas distension of the colon with the absence of rectal gas. An exploratory laparotomy was performed and showed sigmoid colon volvulus associated with synchronous transverse colon volvulus without bowel necrosis. A left hemicolectomy with loop colostomy was performed. The restoration of bowel continuity was done 3 weeks. The post-operative course was uneventful.
DISCUSSION
The occurrence of a simultaneous sigmoid and transverse colonic volvulus is an exceptional situation. Due to the rarity of this clinical entity, the literature concerning its description is sparse and the treatment options are poorly codified. There are no guidelines in the treatment and a tailored approach should be used for each patient.
CONCLUSION
The dual location of strangulation makes this situation a major surgical emergency with a high risk of gangrene and septic shock. Colectomy with delayed anastomosis should be preferred in the treatment.
PubMed: 32979829
DOI: 10.1016/j.ijscr.2020.09.027 -
International Journal of Molecular... Mar 2024Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD includes Crohn's disease and ulcerative colitis as the main entities. IBD is a debilitating condition that can lead to life-threatening complications, involving possible malignancy and surgery. The available therapies aim to achieve long-term remission and prevent disease progression. Biologics are bioengineered therapeutic drugs that mainly target proteins. Although they have revolutionized the treatment of IBD, their potential therapeutic benefits are limited due to large interindividual variability in clinical response in terms of efficacy and toxicity, resulting in high rates of long-term therapeutic failure. It is therefore important to find biomarkers that provide tailor-made treatment strategies that allow for patient stratification to maximize treatment benefits and minimize adverse events. Pharmacogenetics has the potential to optimize biologics selection in IBD by identifying genetic variants, specifically single nucleotide polymorphisms (SNPs), which are the underlying factors associated with an individual's drug response. This review analyzes the current knowledge of genetic variants associated with biological agent response (infliximab, adalimumab, ustekinumab, and vedolizumab) in IBD. An online literature search in various databases was conducted. After applying the inclusion and exclusion criteria, 28 reports from the 1685 results were employed for the review. The most significant SNPs potentially useful as predictive biomarkers of treatment response are linked to immunity, cytokine production, and immunorecognition.
Topics: Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Biological Products; Biomarkers
PubMed: 38612528
DOI: 10.3390/ijms25073717 -
Acta Bio-medica : Atenei Parmensis Dec 2018Shiga-toxin Escherichia coli productor (STEC) provokes frequently an important intestinal damage that may be considered in differential diagnosis with the onset of...
BACKGROUND
Shiga-toxin Escherichia coli productor (STEC) provokes frequently an important intestinal damage that may be considered in differential diagnosis with the onset of Inflammatory Bowel Disease (IBD). The aim of this work is to review in the current literature about Hemolytic Uremic Syndrome (HUS) and IBD symptoms at the onset, comparing the clinical presentation and symptoms, as the timing of diagnosis and of the correct treatment of both these conditions is a fundamental prognostic factor. A focus is made about the association between typical or atypical HUS and IBD and a possible renal involvement in patient with IBD (IgA-nephropathy).
METHODS
A systematic review of scientific articles was performed consulting the databases PubMed, Medline, Google Scholar, and consulting most recent textbooks of Pediatric Nephrology.
RESULTS
In STEC-associated HUS, that accounts for 90% of cases of HUS in children, the microangiopathic manifestations are usually preceded by gastrointestinal symptoms. Initial presentation may be considered in differential diagnosis with IBD onset. The transverse and ascending colon are the segments most commonly affected, but any area from the esophagus to the perianal area can be involved. The more serious manifestations include severe hemorrhagic colitis, bowel necrosis and perforation, rectal prolapse, peritonitis and intussusception. Severe gastrointestinal involvement may result in life-threatening complications as toxic megacolon and transmural necrosis of the colon with perforation, as in Ulcerative Colitis (UC). Transmural necrosis of the colon may lead to subsequent colonic stricture, as in Crohn Disease (CD). Perianal lesions and strictures are described. In some studies, intestinal biopsies were performed to exclude IBD. Elevation of pancreatic enzymes is common. Liver damage and cholecystitis are other described complications. There is no specific form of therapy for STEC HUS, but appropriate fluid and electrolyte management (better hyperhydration when possible), avoiding antidiarrheal drugs, and possibly avoiding antibiotic therapy, are recommended as the best practice. In atypical HUS (aHUS) gastrointestinal manifestation are rare, but recently a study evidenced that gastrointestinal complications are common in aHUS in presence of factor-H autoantibodies. Some report of patients with IBD and contemporary atypical-HUS were found, both for CD and UC. The authors conclude that deregulation of the alternative complement pathway may manifest in other organs besides the kidney. Finally, searching for STEC-infection, or broadly for Escherichia coli (E. coli) infection, and IBD onset, some reviews suggest a possible role of adherent invasive E. coli (AIEC) on the pathogenesis of IBD.
CONCLUSIONS
The current literature shows that gastrointestinal complications of HUS are quite exclusive of STEC-associated HUS, whereas aHUS have usually mild or absent intestinal involvement. Severe presentation as toxic megacolon, perforation, ulcerative colitis, peritonitis is similar to IBD at the onset. Moreover, some types of E. coli (AIEC) have been considered a risk factor for IBD. Recent literature on aHUS shows that intestinal complications are more common than described before, particularly for patients with anti-H factor antibodies. Moreover, we found some report of patient with both aHUS and IBD, who benefit from anti-C5 antibodies injection (Eculizumab).
Topics: Acute Kidney Injury; Anemia, Hemolytic; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Apoptosis; Atypical Hemolytic Uremic Syndrome; Combined Modality Therapy; Contraindications, Drug; Diagnosis, Differential; Diarrhea; Escherichia coli Infections; Gastrointestinal Hemorrhage; Granuloma; Hemolytic-Uremic Syndrome; Humans; Inflammatory Bowel Diseases; Necrosis; Shiga-Toxigenic Escherichia coli; Thrombocytopenia
PubMed: 30561409
DOI: 10.23750/abm.v89i9-S.7911 -
World Journal of Gastroenterology Nov 2018To systematically review the literature on epidemiology, disease burden, and treatment outcomes for Crohn's disease (CD) patients with complex perianal fistulas.
AIM
To systematically review the literature on epidemiology, disease burden, and treatment outcomes for Crohn's disease (CD) patients with complex perianal fistulas.
METHODS
PubMed, Embase, and Cochrane were searched for relevant articles (published 2000-November 2016) and congress abstracts (published 2011-November 2016).
RESULTS
Of 535 records reviewed, 62 relevant sources were identified (mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14% (follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment (failure and relapse rates, respectively: medical, 12%-73% and 0%-41%; surgical: 0%-100% and 11%-20%; combined medical/surgical: 0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies (1 of infliximab; 3 of surgical interventions) have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD.
CONCLUSION
Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to anti-tumour necrosis factor-α agents, as evidenced by high failure and relapse rates.
Topics: Adipose Tissue; Combined Modality Therapy; Cost of Illness; Crohn Disease; Cutaneous Fistula; Drainage; Humans; Immunosuppressive Agents; Quality of Life; Rectal Fistula; Recurrence; Stem Cell Transplantation; Stem Cells; Treatment Failure; Tumor Necrosis Factor-alpha
PubMed: 30479468
DOI: 10.3748/wjg.v24.i42.4821 -
Frontiers in Oncology 2023There is controversy about the outcomes of prophylactic ileostomy the specimen extraction site (SES) after laparoscopic rectal cancer surgery (LRCS). We, therefore,...
Which site is better for prophylactic ileostomy after laparoscopic rectal cancer surgery? By the specimen extraction site or new site: A systematic review and meta-analysis.
BACKGROUND
There is controversy about the outcomes of prophylactic ileostomy the specimen extraction site (SES) after laparoscopic rectal cancer surgery (LRCS). We, therefore, performed a meta-analysis to determine the efficacy and safety of stoma through the SES versus new site (NS).
METHODS
All relevant studies from 1997 to 2022 were searched in the PubMed, EMBASE, Cochrane Library, CNKI, VIP databases. This meta-analysis was performed using RevMan software 5.3 for statistical analysis.
RESULTS
7 studies with 1736 patients were included. The present meta-analysis noted that prophylactic ileostomy SES was associated with a higher risk of overall stoma-related complications, especially parastomal hernia (OR, 2.39, 95% CI 1.43-4.00; p=0.0008). No statistical difference was found in terms of wound infection, ileus, stoma edema, stoma prolapse, stoma necrosis, stoma infection, stoma bleeding, stoma stenosis, skin inflammation around the stoma, stoma retraction and postoperative pain score on postoperative day 1 and 3 between SES group and NS group. However, prophylactic ileostomy SES was associated with lesser blood loss (MD = -0.38, 95% CI: -0.62 - -0.13; p=0.003), shorter operation time(MD = -0.43, 95% CI: -0.54 - -0.32 min; p<0.00001), shorter post-operative hospital stay (MD = -0.26, 95% CI: -0.43 - -0.08; p=0.004), shorter time to first flatus(MD = -0.23, 95% CI: -0.39 - -0.08; p=0.003) and lower postoperative pain score on postoperative day 2.
CONCLUSION
Prophylactic ileostomy SES after LRCS reduces new incision, decreases operative time, promotes postoperative recovery, and improves cosmetic outcomes, but may increase the incidence of parastomal hernias. The vast majority of parastomal hernias can be repaired by closing the ileostomy, therefore SES remain an option for temporary ileostomy after LRCS.
PubMed: 36874091
DOI: 10.3389/fonc.2023.1116502 -
Journal of Clinical Medicine Oct 2019The preclinical studies in vivo provide means of characterizing physiologic interactions when our understanding of such processes is insufficient to allow replacement... (Review)
Review
The preclinical studies in vivo provide means of characterizing physiologic interactions when our understanding of such processes is insufficient to allow replacement with in vitro systems and play a pivotal role in the development of a novel therapeutic drug cure. Chemically induced colitis models are relatively easy and rapid to develop. The 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis model is one of the main models in the experimental studies of inflammatory bowel disease (IBD) since inflammation induced by TNBS mimics several features of Crohn's disease. This review aims to summarize the existing literature and discuss different protocols for the induction of chronic model of TNBS-induced colitis. We searched MEDLINE via Pubmed platform for studies published through December 2018, using MeSH terms (Crohn Disease.kw) OR (Inflammatory Bowel Diseases.kw) OR (Colitis, Ulcerative.kw) AND (trinitrobenzenesulfonic acid.kw) AND (disease models, animal.kw) AND (mice.all). The inclusion criteria were original articles, preclinical studies in vivo using mice, chronic model of colitis, and TNBS as the inducer of colitis and articles published in English. Chronic TNBS-induced colitis is made with multiple TNBS intrarectal administrations in an average dose of 1.2 mg using a volume lower than 150 μL in 50% ethanol. The strains mostly used are Balb/c and C57BL/6 with 5-6 weeks. To characterize the preclinical model the parameters more used include body weight, stool consistency and morbidity, inflammatory biomarkers like interferon (IFN)-γ, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10, presence of ulcers, thickness or hyperemia in the colon, and histological evaluation of the inflammation. Experimental chronic colitis is induced by multiple rectal instillations of TNBS increasing doses in ethanol using Balb/c and C57BL/6 mice.
PubMed: 31581545
DOI: 10.3390/jcm8101574