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International Journal of Molecular... Jul 2020Stromal vascular fraction (SVF) containing adipose stem cells (ASCs) has been used for many years in regenerative plastic surgery for autologous applications, without... (Meta-Analysis)
Meta-Analysis
Systematic Review: Allogenic Use of Stromal Vascular Fraction (SVF) and Decellularized Extracellular Matrices (ECM) as Advanced Therapy Medicinal Products (ATMP) in Tissue Regeneration.
Stromal vascular fraction (SVF) containing adipose stem cells (ASCs) has been used for many years in regenerative plastic surgery for autologous applications, without any focus on their potential allogenic role. Allogenic SVF transplants could be based on the possibility to use decellularized extracellular matrix (ECM) as a scaffold from a donor then re-cellularized by ASCs of the recipient, in order to develop the advanced therapy medicinal products (ATMP) in fully personalized clinical approaches. A systematic review of this field has been realized in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. Multistep research of the PubMed, Embase, MEDLINE, Pre-MEDLINE, PsycINFO, CINAHL, Clinicaltrials.gov, Scopus database, and Cochrane databases has been conducted to identify articles and investigations on human allogenic ASCs transplant for clinical use. Of the 341 articles identified, 313 were initially assessed for eligibility on the basis of the abstract. Of these, only 29 met all the predetermined criteria for inclusion according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach, and 19 have been included in quantitative synthesis (meta-analysis). Ninety-one percent of the studies previously screened (284 papers) were focused on the in vitro results and pre-clinical experiments. The allogenic use regarded the treatment of perianal fistulas, diabetic foot ulcers, knee osteoarthritis, acute respiratory distress syndrome, refractory rheumatoid arthritis, pediatrics disease, fecal incontinence, ischemic heart disease, autoimmune encephalomyelitis, lateral epicondylitis, and soft tissue defects. The information analyzed suggested the safety and efficacy of allogenic ASCs and ECM transplants without major side effects.
Topics: Adipose Tissue; Animals; Extracellular Matrix; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regenerative Medicine; Tissue Engineering; Tissue Scaffolds; Transplantation, Homologous
PubMed: 32679697
DOI: 10.3390/ijms21144982 -
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 -
BJS Open Feb 2020
Systematic review and meta-analysis of endorectal advancement flap and ligation of the intersphincteric fistula tract for cryptoglandular and Crohn's high perianal fistulas.
PubMed: 32011811
DOI: 10.1002/bjs5.50249 -
Expert Opinion on Biological Therapy Mar 2020: Anti-Tumor Necrosis Factor-alpha (TNF-α) therapy, primarily infliximab and adalimumab, are now increasingly used to induce and maintain disease remission in the...
: Anti-Tumor Necrosis Factor-alpha (TNF-α) therapy, primarily infliximab and adalimumab, are now increasingly used to induce and maintain disease remission in the pediatric perianal Crohn's disease (CD) population, however, their optimal use has not yet been defined in the pediatric setting.: In accordance with a published protocol (PROSPERO no. CRD42019118838), we systematically and critically evaluated all published evidence on the efficacy and safety of anti-TNF-α in children with perianal CD, in the PubMed, MEDLINE, Embase, Cochrane and clinicalTrials.gov databases until October, 18, 2018. We included in our systematic review 29 articles yielding a total of 565 perianal CD patients aged between 9 months to 18 years.: According to low-quality evidence from small, uncontrolled and heterogeneous descriptive studies, and very few randomized controlled trial, nearly three-fifths children with perianal CD achieved remission with anti-TNF-α treatment and in approximately 40% remission was maintained after 12 months, with practically low discontinuation rate due to serious adverse events. More than half of the patients achieved complete fistula closure. There is still a need for more robust evidence adequately assessing the efficacy and safety of anti-TNF-α therapy in pediatric perianal CD, as well as in comparison with other therapies.
Topics: Adalimumab; Anemia; Clinical Trials as Topic; Crohn Disease; Humans; Infliximab; Outcome Assessment, Health Care; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 31971447
DOI: 10.1080/14712598.2020.1718096 -
Arquivos Brasileiros de Cirurgia... 2019Crohn's disease is a pathological condition that has different options of treatment, but there are patients who need other therapeutic approach, such as the use of...
BACKGROUND
Crohn's disease is a pathological condition that has different options of treatment, but there are patients who need other therapeutic approach, such as the use of adipose-derived mesenchymal stem cells.
AIM
Systematic literature review to determine the different ways of adipose-derived mesenchymal stem cells administration in humans with luminal refractory and perianal fistulizing Crohn's disease.
METHODS
It was conducted a search for articles (from 2008 to 2018) on PubMed and ScienceDirect databases using the keywords Crohn's disease, fistulizing Crohn's disease, luminal Crohn's disease and transplantation of mesenchymal stem cells or mesenchymal stem cells or stromal cells. Thirteen publications were selected for analysis.
RESULTS
Only one study referred to the luminal Crohn´s disease. The number of cells administered was variable, occurring mainly through subcutaneous adipose tissue by liposuction. It could be highlighted the autologous transplant with exclusive infusion of mesenchymal stem cells. The procedures involved in pre-transplant were mainly curettage, setons placement and stitching with absorbable suture, and conducting tests and drug treatment for luminal Crohn´s disease. During transplant, the injection of mesenchymal stem cells across the fistula path during the transplant was mainly on the intestinal tract wall.
CONCLUSION
Although the use of mesenchymal stem cells is promising, the transplant on the luminal region should be more investigated. The injection of mesenchymal stem cells, exclusively, is more explored when compared to treatment with other products. The preparation of the fistulizing tract and the location of cell transplantation involve standardized health care in most studies.
Topics: Adipose Tissue; Crohn Disease; Humans; Mesenchymal Stem Cell Transplantation; Rectal Fistula
PubMed: 31859918
DOI: 10.1590/0102-672020190001e1465 -
Advances in Therapy Dec 2019Despite the fact that perianal fistulas are associated with significant morbidity and impaired quality of life, their prevalence in Europe is unknown. The aim of this...
INTRODUCTION
Despite the fact that perianal fistulas are associated with significant morbidity and impaired quality of life, their prevalence in Europe is unknown. The aim of this study was to estimate the prevalence of perianal fistulas in Europe, overall and according to etiology.
METHODS
Two independent literature reviews were performed using different search strategies to maximize the identification of potentially relevant studies. Data from relevant articles were used to estimate the prevalence of perianal fistulas in Europe. The robustness of the estimate was evaluated using data from a large population-based database from the UK.
RESULTS
A total of 26 studies provided epidemiological data on perianal fistulas, of which 16 provided suitable data to estimate the prevalence. Estimations using these data yielded a total prevalence of 1.69 per 10,000 population. Cryptoglandular infection and Crohn's disease (CD) were the predominant etiologies, with prevalence rates at 0.86 and 0.76 per 10,000 population, respectively. Comparison of prevalence data from the UK population-based database with the European population resulted in a standardized prevalence estimate of all perianal fistulas of 1.83 per 10,000 population, confirming the robustness of the literature-based estimate.
CONCLUSION
Although in terms of incidence cryptoglandular fistulas were clearly predominant, the prevalence of fistulas in CD and cryptoglandular infection appeared more balanced. This is due to the longer duration and higher frequency of relapses of fistulas in CD. The estimated prevalence implies that perianal fistulas meet the criteria to be considered as a rare condition in Europe (prevalence less than 5 per 10,000 population).
FUNDING
This study was funded by Takeda Pharmaceutical U.S.A., Inc. and TiGenix SAU.
Topics: Adult; Europe; Female; Humans; Incidence; Male; Middle Aged; Prevalence; Quality of Life; Rectal Fistula; Recurrence; Time Factors; Treatment Outcome; Young Adult
PubMed: 31656013
DOI: 10.1007/s12325-019-01117-y -
Central European Journal of Urology 2019The purpose of this study was to determine the effectiveness and harms of periprostatic block compared with other interventions in patients with clinically suspected... (Review)
Review
INTRODUCTION
The purpose of this study was to determine the effectiveness and harms of periprostatic block compared with other interventions in patients with clinically suspected prostate cancer who underwent transrectal biopsy to diminish pain.
MATERIAL AND METHODS
We included only clinical trials which involved male adults older than 18 years-old suspected of having prostate cancer. The intervention performed was a periprostatic block and the comparators were topical anesthetics, sedatives, placebo/no intervention or combined therapies. The primary outcome was perianal or perineal pain and serious adverse effects (SAE). Literature search was conducted in MEDLINE, EMBASE, LILACS, CENTRAL and non-published literature from inception to March 2019. We performed a network meta-analysis in R.
RESULTS
We included 43 studies in the meta-analysis. Thirteen studies compared periprostatic block vs. placebo/no intervention (the most frequent). Most of the studies had an unclear risk of bias for selection, performance and detection bias and low risk for attrition, reporting and other bias. Periprostatic block (lidocaine) + intrarectal gel (lidocaine + prilocaine) vs. periprostatic block (lidocaine) showed an RR -0.9 (95%CI - 1.9 to 0.074); intrarectal gel (lidocaine) vs. periprostatic block (lidocaine) had a RR 0.77 (95%CI 0.14 to 1.4); placebo/no intervention vs. periprostatic block (lidocaine) + intrarectal gel (lidocaine+prilocaine) RR 3 (95%CI 1.9 to 4); intrarectal gel (lidocaine) versus periprostatic block (lidocaine) + intrarectal gel (lidocaine + prilocaine) RR 1.7 (95%CI 0.64 to 2.7).
CONCLUSIONS
The blockage of the periprostatic plexus in the performance of a transrectal ultrasound-guided prostatic biopsy, alone or in combination with intrarectal analgesia or sedation, is an effective method to reduce pain.
PubMed: 31482018
DOI: 10.5173/ceju.2019.1874 -
JGH Open : An Open Access Journal of... Jun 2019Perianal fistulas in Crohn's disease (CD) represent a highly debilitating and difficult-to-treat condition. Given emerging supportive evidence, we conducted a systematic... (Review)
Review
Perianal fistulas in Crohn's disease (CD) represent a highly debilitating and difficult-to-treat condition. Given emerging supportive evidence, we conducted a systematic review and meta-analysis of all trials/observational studies to establish the safety and efficacy of local injections of mesenchymal stem cells (MSCs). The PRISMA-P statement was applied for planning and reporting, and MEDLINE, EMBASE, Web of Science, Cochrane, CINAHL, ClinicalTrials.gov database, and ECCO 2017 proceedings were searched for published observational studies and one-arm and randomized clinical trials (RCTs). Safety was assessed in terms of acute local/systemic events, long-term events, and relatedness with MSC treatment. Efficacy was evaluated in terms of external and/or radiological closure of fistula tracks. After a review of 211 citations, 23 studies, including 696 participants, were evaluated. Four were RCTs with a total of 483 patients. Overall, fistula closure occurred in 80% of MSC-treated patients. In RCTs, this rate was 64% in the MSC arm and 37% in the control arm (relative risk (RR) = 1.54). Radiological response occurred in 83% of MSC-treated patients. Treatment-related adverse events occurred in 1% of MSC-treated patients, with severe treatment-related adverse events reaching 0% over a median follow-up of 6 months. In RCTs, treatment-related adverse events occurred in 13% in the MSC arm and 24% in the control arm (RR = 0.65). The relapse rate was 0. These results suggest that a local MSC injection is safe and efficacious. Further clinical trials with standardized end-points are required to ensure the timely implementation of this new therapy in the management of perianal CD.
PubMed: 31276044
DOI: 10.1002/jgh3.12141 -
BJS Open Jun 2019High perianal fistulas require sphincter-preserving surgery because of the risk of faecal incontinence. The ligation of the intersphincteric fistula tract (LIFT)... (Comparative Study)
Comparative Study Meta-Analysis
Systematic review and meta-analysis of endorectal advancement flap and ligation of the intersphincteric fistula tract for cryptoglandular and Crohn's high perianal fistulas.
BACKGROUND
High perianal fistulas require sphincter-preserving surgery because of the risk of faecal incontinence. The ligation of the intersphincteric fistula tract (LIFT) procedure preserves anal sphincter function and is an alternative to the endorectal advancement flap (AF). The aim of this study was to evaluate outcomes of these procedures in patients with cryptoglandular and Crohn's perianal fistulas.
METHODS
A systematic literature search was performed using MEDLINE, Embase and the Cochrane Library. All RCTs, cohort studies and case series (more than 5 patients) describing one or both techniques were included. Main outcomes were overall success rate, recurrence and incontinence following either technique. A proportional meta-analysis was performed using a random-effects model.
RESULTS
Some 30 studies comprising 1295 patients were included (AF, 797; LIFT, 498). For cryptoglandular fistula (1098 patients), there was no significant difference between AF and LIFT for weighted overall success (74·6 (95 per cent c.i. 65·6 to 83·7) 69·1 (53·9 to 84·3) per cent respectively) and recurrence (25·6 (4·7 to 46·4) 21·9 (14·8 to 29·0) per cent) rates. For Crohn's perianal fistula (64 patients), no significant differences were observed between AF and LIFT for overall success rate (61 (45 to 76) 53 per cent respectively), but data on recurrence were limited. Incontinence rates were significantly higher after AF compared with LIFT (7·8 (3·3 to 12·4) 1·6 (0·4 to 2·8) per cent).
CONCLUSION
Overall success and recurrence rates were not significantly different between the AF and LIFT procedure, but continence was better preserved after LIFT.
Topics: Adult; Anal Canal; Crohn Disease; Cutaneous Fistula; Digestive System Surgical Procedures; Fecal Incontinence; Female; Humans; Ligation; Male; Middle Aged; Rectal Fistula; Recurrence; Surgical Flaps; Treatment Outcome
PubMed: 31183438
DOI: 10.1002/bjs5.50129 -
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