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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 -
Arquivos de Gastroenterologia 2023Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome.
BACKGROUND
Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome.
OBJECTIVE
Thus, the aim of this study was to assess whether sex influences the response to treatment for these patients.
METHODS
This systematic review (PROSPERO CRD42022319629) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. We selected articles published in English, Spanish, Portuguese, and Italian between 2010 and 2020 in the PubMed and Science Direct databases. According to the PICO acronym, prospective studies in patients older than 18 years with the objective of treating fistulizing perianal Crohn's disease were selected. Studies in pediatric populations, retrospective, without treatment objectives, and that included only rectovaginal fistulas or a single sex were excluded. Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale.
RESULTS
Of the 1887 articles found, 33 were included. Most studies used anti-TNF drugs as treatment (n=11). Ten studies had subgroup analyses; of them, the two studies reporting sex differences used infliximab and adalimumab as treatment and showed that women had a longer fistula closure time than men.
CONCLUSION
This systematic review showed that few data corroborate the difference between sexes in the treatment of fistulizing perianal Crohn's disease, possibly having a greater relationship with the phenotype. However, considering the lack of results, further studies with this objective and with standardization of fistulas and response assessment methods are needed.
Topics: Child; Humans; Male; Female; Crohn Disease; Retrospective Studies; Prospective Studies; Tumor Necrosis Factor Inhibitors; Rectal Fistula; Treatment Outcome; Infliximab
PubMed: 38018554
DOI: 10.1590/S0004-2803.230402023-28 -
Journal of Crohn's & Colitis Apr 2024Fistulas are a debilitating complication of Crohn's disease [CD]. We conducted a systematic review to assess the efficacy of medical therapies for fistulizing CD. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fistulas are a debilitating complication of Crohn's disease [CD]. We conducted a systematic review to assess the efficacy of medical therapies for fistulizing CD.
METHODS
MEDLINE, Embase, and CENTRAL were searched on May 26, 2022, for randomized controlled trials [RCTs] of pharmacological therapy in adults with fistulizing CD. The primary outcome was induction and maintenance of fistula response. Pooled risk ratios [RRs] and 95% confidence intervals [CIs] were calculated. GRADE was used to assess the certainty of evidence.
RESULTS
Thirty-eight RCTs were included. Nineteen trials [50%] exclusively involved perianal fistula. The remaining studies included some participants with non-perianal fistula. Pooled RRs for anti-tumour necrosis factor [TNF] agents were not statistically significant for induction [RR 1.36, 95% CI 0.97-1.91] or maintenance of fistula response [RR 1.48, 95% CI 0.97-2.27]. However, in a sensitivity analysis of studies with fistula response as the primary outcome, anti-TNFs were superior to placebo for induction [RR 1.94, 95% CI 1.10-3.41] and maintenance [RR 1.88, 95% CI 1.23-2.88] of fistula response. Oral small molecules [RR 2.56, 95% CI 1.18-5.53] and mesenchymal stem cell [MSC] therapy [RR 1.26, 95% CI 1.01-1.57] were effective for induction of fistula response. Ustekinumab was associated with maintenance of fistula response [RR 1.80, 95% CI 1.04-3.11]. Vedolizumab was not superior to placebo. The certainty of evidence ranged from very low to moderate.
CONCLUSION
Very low- to moderate-certainty evidence suggests that anti-TNF therapy, oral small molecules, ustekinumab, and MSCs are effective for perianal fistulizing CD. Dedicated fistula studies evaluating biologics and small molecules are needed.
Topics: Humans; Crohn Disease; Rectal Fistula; Gastrointestinal Agents; Intestinal Fistula; Randomized Controlled Trials as Topic
PubMed: 37933849
DOI: 10.1093/ecco-jcc/jjad185 -
The American Journal of Gastroenterology Sep 2023Rapidity of symptom resolution informs treatment choice in patients with moderate-severe ulcerative colitis (UC). We conducted a systematic review and network... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Rapidity of symptom resolution informs treatment choice in patients with moderate-severe ulcerative colitis (UC). We conducted a systematic review and network meta-analysis comparing early symptomatic remission with approved therapies.
METHODS
Through a systematic literature review to December 31, 2022, we identified randomized trials in adult outpatients with moderate-severe UC treated with approved therapies (tumor necrosis factor α antagonists, vedolizumab, ustekinumab, janus kinase inhibitors, or ozanimod), compared with each other or placebo, reporting rates of symptomatic remission (based on partial Mayo score, with resolution of rectal bleeding and near-normalization of stool frequency) at weeks 2, 4, and/or 6. We performed random-effects network meta-analysis using a frequentist approach and estimated relative risk (RR) and 95% confidence interval values.
RESULTS
On network meta-analysis, upadacitinib was more effective than all agents in achieving symptomatic remission at weeks 2 (range of RR, 2.85-6.27), 4 (range of RR, 1.78-2.37), and 6 (range of RR, 1.84-2.79). Tumor necrosis factor α antagonists and filgotinib, but not ustekinumab and vedolizumab, were more effective than ozanimod in achieving symptomatic remission at week 2, but not at weeks 4 and 6. With approximately 10% placebo-treated patients achieving symptomatic remission at 2 weeks, we estimated 68%, 22%, 23.7%, 23.9%, 22.2%, 18.4%, 15.7%, and 10.9% of upadacitinib-, filgotinib-, infliximab-, adalimumab-, golimumab-, ustekinumab-, vedolizumab-, and ozanimod-treated patients would achieve early symptomatic remission, ustekinumab and vedolizumab achieving rapid remission only in biologic-naïve patients.
DISCUSSION
In a systematic review and network meta-analysis, upadacitinib was most effective in achieving early symptomatic remission, whereas ozanimod was relatively slower acting.
Topics: Adult; Humans; Colitis, Ulcerative; Tumor Necrosis Factor-alpha; Network Meta-Analysis; Adalimumab; Ustekinumab; Treatment Outcome
PubMed: 36976548
DOI: 10.14309/ajg.0000000000002263 -
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 -
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 -
Plastic and Reconstructive Surgery Jun 2021The treatment of locally advanced or recurrent anorectal cancer requires radical surgery such as extralevator abdominoperineal resection and pelvic exenteration. Larger...
BACKGROUND
The treatment of locally advanced or recurrent anorectal cancer requires radical surgery such as extralevator abdominoperineal resection and pelvic exenteration. Larger defects require flap reconstruction. The authors evaluated outcomes of different perineal reconstruction techniques.
METHODS
A systematic search was performed in the PubMed, Embase, and Cochrane databases. Studies reporting outcomes on perineal flap reconstruction in patients with anal or colorectal cancer were included. Data on patient characteristics, surgical details, perineal and donor-site complications, revision surgery, mortality, and quality of life were extracted. Articles were assessed using the Group Reading Assessment and Diagnostic Evaluation approach.
RESULTS
The authors included 58 mainly observational studies comprising 1988 patients. Seventy-three percent of patients had rectal cancer. The majority of 910 abdominoperineal resection patients underwent reconstruction with rectus abdominis flaps (91 percent). Dehiscence (15 to 32 percent) and wound infection (8 to 16 percent) were the most common complications. Partial flap necrosis occurred in 2 to 4 percent and flap loss occurred in 0 to 2 percent. Perineal herniation was seen in 6 percent after gluteal flap reconstruction and in 0 to 1 percent after other types of reconstruction. Donor-site complications were substantial but were reported inconsistently.
CONCLUSIONS
Clinical outcome data on perineal reconstruction after exenterative surgery are mostly of very low quality. Perineal reconstruction after pelvic exenteration is complex and requires a patient-tailored approach. Primary defect size, reconstruction aims, donor-site availability, and long-term morbidity should be taken into account. This review describes the clinical outcomes of four flap reconstruction techniques. Shared clinical decision-making on perineal reconstruction should be based on these present comprehensive data.
Topics: Colorectal Neoplasms; Humans; Pelvic Exenteration; Perineum; Quality of Life; Surgical Flaps; Surgical Wound; Treatment Outcome
PubMed: 33973948
DOI: 10.1097/PRS.0000000000007976 -
Journal of Vascular and Interventional... Aug 2021To assess the efficacy and safety of a catheter-directed hemorrhoidal dearterialization technique for the management of hemorrhoidal bleeding. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To assess the efficacy and safety of a catheter-directed hemorrhoidal dearterialization technique for the management of hemorrhoidal bleeding.
MATERIALS AND METHODS
A systematic review and meta-analysis of pubmed, cochrane, and scopus databases was conducted according to the preferred reporting items for systematic reviews and meta-Analysis (PRISMA) guidelines. Clinical studies reporting on catheter-directed hemorrhoidal dearterialization for rectal bleeding were analyzed.
RESULTS
Fourteen studies (n = 362) were identified. The mean maximum follow-up duration was 12.1 months (SD, 7.31; range, 1-28; median, 12), and the mean length of hospital stay was 1.5 days (SD, 1.1; range, 0-2.5). The mean technical success was 97.8% (SD, 3.5), and the mean clinical success was 78.9% (SD, 10.5). A statistically significant reduction in the french bleeding score before and after embolization was noted (P = .004). In subgroup analysis, when the coils-only group was compared with the coils and particles group, the average rebleeding rate was 21.5% (n = 111; SD, 18.2; range, 0%-44%) versus 10.05% (N = 108; SD, 4.8; range, 5%-15.7%), respectively (P < .0001). No bowel ischemia/necrosis or anorectal complications were reported.
CONCLUSIONS
The current preliminary clinical evidence suggests that catheter-directed hemorrhoidal dearterialization is an effective and safe procedure for the treatment of hemorrhoidal bleeding. The standardization of the technique and the generation of higher level evidence will be required to compare this minimally invasive procedure with more invasive surgical options for patients with grades I-III hemorrhoids and chronic bleeding.
Topics: Catheters; Hemorrhoidectomy; Hemorrhoids; Humans; Ligation; Rectum; Treatment Outcome
PubMed: 33971251
DOI: 10.1016/j.jvir.2021.03.548 -
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 -
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