Patients with inflammatory bowel disease (IBD) treated with biologic and/or immunosuppressant drugs are at increased risk for opportunistic infections. Seroprevalence studies can confirm the ...diagnosis of SARS-CoV-2 infections as well as the associated risk factors. This is a descriptive study which primary endpoints were to highlight the prevalence of SARS-CoV-2 antibodies in a cohort of IBD patients in March 2021, and to analyze seroconversion in patients with known COVID-19 infection and its relationship with IBD treatments. Patients filled in a questionnaire about symptoms of COVID-19 infection and clinical information about their IBD. All included patients were tested for SARS-CoV-2 antibodies. 392 patients were included. Among patients with clinical infection, 69 patients (17,65%) were IgG-positive, 286 (73,15%) IgG-negative and 36 (9,21%) indeterminate. In relation to seroconversion among patients under biologic treatment, 13 patients of the 23 with a previous positive CRP developed antibodies (56.5%). However, when the influence of immunosuppressive treatment on the probability of developing antibodies was analyzed, no significant differences were seen between those patients with or without treatment (77.8% vs. 77.1%, p = 0.96). In our cohort of IBD patients, after one year of pandemic, there were 18.64% IgG positive patients, a higher prevalence than the general population (15.7%).
BACKGROUND:Autologous adipose-derived stem cells may represent a novel approach for the management of complex fistula-in-ano. After successful phase I and II clinical trials, a phase III trial was ...performed to investigate the safety and efficacy.
DESIGN:In this multicenter, randomized, single-blind, add-on clinical trial, 200 adult patients from 19 centers were randomly assigned to receive 20 million stem cells (group A, 64 patients), 20 million adipose-derived stem cells plus fibrin glue (group B, 60 patients), or fibrin glue (group C, 59 patients) after closure of the internal opening. Fistula healing was defined as reepithelization of the external opening and absence of collection >2 cm by MRI. If the fistula had not healed at 12 weeks, a second dose (40 million stem cells in groups A and B) was administered. Patients were evaluated at 24 to 26 weeks (primary end point) and at 1 year (long-term follow-up).
RESULTS:All results are according to the “blinded evaluator” assessment. After 24 to 26 weeks, the healing rate was 39.1%, 43.3%, 37.3% in groups A, B, and C (p = 0.79). At 1 year, the healing rates were 57.1%, 52.4%, and 37.3 % (p = 0.13). On analysis of the subpopulation treated at the technique’s pioneer center, healing rates were 54.55%, 83.33%, and 18.18%, at 24 to 26 weeks (p < 0.001). No SAEs were reported.
CONCLUSIONS:In treatment of complex fistula-in-ano, a dose of 20 or 60 million adipose-derived stem cells alone or in combination with fibrin glue was considered a safe treatment, achieving healing rates of approximately 40% at 6 months and of more than 50% at 1-year follow-up. It was equivalent to fibrin glue alone. No statistically significant differences were found when the 3 groups where compared. Clinical trials registrationwww.clinicaltrials.gov, identifier NCT00475410; Sponsor, Cellerix SA.
Background and Aim
Biological therapies may be changing the natural history of inflammatory bowel diseases (IBDs), reducing the need for surgical intervention. We aimed to assess whether the ...availability of anti‐TNF agents impacts the need for early surgery in Crohn's disease (CD) and ulcerative colitis (UC).
Methods
Retrospective, cohort study of patients diagnosed within a 6‐year period before and after the licensing of anti‐TNFs (1990–1995 and 2007–2012 for CD; 1995–2000 and 2007–2012 for UC) were identified in the ENEIDA Registry. Surgery‐free survival curves were compared between cohorts.
Results
A total of 7370 CD patients (2022 in Cohort 1 and 5348 in Cohort 2) and 8069 UC patients (2938 in Cohort 1 and 5131 in Cohort 2) were included. Immunosuppressants were used significantly earlier and more frequently in both CD and UC post‐biological cohorts. The cumulative probability of surgery was lower in CD following anti‐TNF approval (16% and 11%, 22% and 16%, and 29% and 19%, at 1, 3, and 5 years, respectively P < 0.0001), although not in UC (3% and 2%, 4% and 4%, and 6% and 5% at 1, 3, and 5 years, respectively; P = 0.2). Ileal involvement, older age at diagnosis and active smoking in CD, and extensive disease in UC, were independent risk factors for surgery, whereas high‐volume IBD centers (in both CD and UC) and immunosuppressant use (in CD) were protective factors.
Conclusions
Anti‐TNF availability was associated with a reduction in early surgery for CD (driven mainly by earlier and more widespread immunosuppressant use) but not in UC.
The usefulness of local collagenase in therapeutic approaches to solid tumors has been tested recently. In this study, we evaluate the safety and efficacy of intraperitoneal collagenase associated or ...not to mitomycin for treatment of colorectal peritoneal metastases in an experimental rat model. Using a fixed-dose procedure, we found that a dose of collagenase of 37 IU/mL administered for 15 min with a hyperthermia pump at 37.5 °C, both in isolation or associated to sequential treatment with intraperitoneal mitomycin, led to a macroscopic decrease in tumor volume as evaluated by the modified peritoneal cancer index (mPCI). Concerning the safety of the procedure, the animals showed no physiological or behavioral disorders during 8 weeks of follow-up. Local treatment for peritoneal metastases of colorectal origin with intraperitoneal collagenase has proved safe and effective in an experimental murine model. Therefore, the stroma-first approach by enzymatic breakdown of collagen from the tumor's extracellular matrix provides a new therapeutic target for colorectal peritoneal metastases.
PurposeThis paper investigates whether short-time work (STW) schemes were successful in their objective of maintaining employment and keeping workers employed within the same firms after the onset of ...the financial and economic crisis in 2008.Design/methodology/approachSpanish longitudinal administrative data has been used, making it possible to identify short-time work (STW) participation not only of workers but also of employers and allowing to know the future labour market status of participants and non-participants. Accordingly, treatment and control groups are defined, and Propensity Score Matching models estimated. The dependent variable is measured as the probability that an individual remained employed with the same employer in the future (one, two and three years) after implementation of a STW arrangement.FindingsOur results suggest that treated individuals are about 5 percentage points less likely to remain working with the same employer one year later than similar workers, and this negative effect of participation increases over time. Thus, STW schemes would not have the assumed effect of preventing unemployment by keeping the participants employed relative to non-participants.Research limitations/implicationsAs our analysis is based on the comparison of the employment trajectories of participant and non-participant workers in firms that have used STW arrangements, our findings cannot be interpreted as the job saving effects of either macro or micro studies carried out previously.Practical implicationsThe analysis carried out in the paper is complementary to the country-level and firm-level approaches that have been used in the empirical literature.Originality/valueWe adopt a worker-level approach. This is novel since no previous study has focused attention on the impact of STW participation on the subsequent labour market status of workers.
Anal fistula is a challenging condition both for surgeons and patients. Recurrent fistula, Crohn’s disease, or autoimmune disorders add further complexity to this situation. Numerous clinical trials ...have now demonstrated that cell-based therapy appears to be a good complement to fistulous surgery. As in any new treatment, especially that involving living cells, appropriate application is paramount to achieve optimal outcomes. As stem cell-based treatments are gaining a strong foothold in fistula management worldwide, we herein aim to share our mesenchymal stem cell surgical protocol. With the goal of optimizing results of this emerging therapy, we have improved and refined our protocol over the past 17 years of working with stem cells in clinical trials. The protocol consists of nine reproducible steps for mesenchymal stem cell application inside the fistulous tract, and has proven to be safe and effective in several studies, including international phase III clinical trials.
This paper uses data from the European Survey on Income and Living Conditions to offer new empirical evidence on how wage differentials are influenced by the changing economic conditions, that is, ...before and after the 2008–2010 recession, and shaped by the different institutional frameworks of European Union countries. We examine whether wage changes are homogeneous across groups of workers, as they are classified by their contractual relationship and working time, and by the heterogeneity in institutions that regulate and affect the labour market. Results obtained by estimating ordinary least squares and quantile regressions confirm the existence of contract and working time wage gaps and allow to estimate their different magnitudes along the wage distribution, and their rise during the recession. The impact of labour market institutions on shaping them is diverse, with more intervention of the government in the setting of the minimum wage and stricter regulation for atypical contracts reducing the wage gaps and producing larger positive effects for low-wage employees.
The study of circulating tumor DNA (ctDNA) plays a pivotal role in advancing precision oncology, providing valuable information for individualized patient care and contributing to the ongoing effort ...to improve cancer diagnosis, treatment, and management. However, its applicability in pseudomyxoma peritonei (PMP) remains unexplored. In this multicenter retrospective study involving 21 PMP patients, we investigated ctDNA presence in peripheral blood using three distinct methodologies. Despite mucinous tumor tissues exhibiting KRAS and GNAS mutations, ctDNA for these mutations was undetectable in blood samples. In this pilot study, circulating tumor DNA was not detected in blood when the tumor harbored mutations of known significance. In the future, a study with a larger sample size is needed to confirm these findings and to determine whether ctDNA could identify patients at risk for early recurrence and/or systemic metastases.
The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the ...factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.
This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.
A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.
The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.
The aims of this study were to determine the prevalence of fatigue in patients with inflammatory bowel disease IBD, to identify the factors associated with fatigue and its severity, to assess the ...impact of fatigue on quality of life QoL, and to evaluate the relationship between fatigue and sleep disorders.
This was a prospective multicentre study conducted at 22 Spanish centres. Consecutive patients followed at IBD Units were included. Fatigue was evaluated with the Fatigue Severity Scale FSS and the Fatigue Impact Scale FIS. Quality of life and sleep quality were assessed using the IBD Questionnaire-Short Form IBDQ-9 and the Pittsburgh Sleep Quality Index PSQI, respectively.
A total of 544 consecutive adult IBD patients were included 50% women, mean age 44 years, 61% Crohn's disease. The prevalence of fatigue was 41% (95% confidence interval CI = 37-45%). The variables associated with an increased risk of fatigue were: anxiety OR = 2.5, 95% CI = 1.6-3.7, depression OR = 2.4, 95% CI = 1.4-3.8, presence of extraintestinal manifestations EIMs OR = 1.7, 95% CI = 1.1-2.6, and treatment with systemic steroids OR = 2.8, 95% CI = 1.4-5.7. The presence of EIMs regression coefficient, RC = 8.2, 95% CI = 2.3-14.2, anxiety RC = 25.8, 95% CI = 20.0-31.5, depression RC = 30.6, 95% CI = 24.3-37.0, and sleep disturbances RC = 15.0, 95% CI = 9.3-20.8 were associated with severity of fatigue. Patients with fatigue had a significantly decreased IBDQ-9 score p < 0.001.
The prevalence of fatigue in IBD patients is remarkably high and has a negative impact on QoL. Therapy with systemic steroids is associated with an increased risk of fatigue. The severity of fatigue is associated with anxiety, depression, sleep disorders, and the presence of EIMs. Fatigue was not associated with anaemia, disease activity or anti-TNF therapy.
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