Patients with chronic inflammatory bowel diseases (IBD) have increased risk of developing intestinal and extraintestinal cancers. However, once a diagnosis of malignancy is made, the therapeutic ...management of Crohn's disease (CD) and ulcerative colitis (UC) can be challenging as major guidelines suggest discontinuing the ongoing immunosuppressant and biological therapies for at least 2-5 years after the end of cancer treatment. Recently, new molecules such as vedolizumab and ustekinumab have been approved for IBD and limited data exist on the real risk of new or recurrent cancer in IBD patients with prior cancer, exposed to immunosuppressants and biologic agents. Thus, a multidisciplinary approach and case-by-case management is the preferred choice. The primary aim of our review was to summarize the current evidence about the safety of reintroducing an immunosuppressant or biologic agent in patients with a history of malignancy and to compare the different available therapies, including gut-selective agents. The secondary aim was to evaluate the clinical course of the IBD patients under cancer treatment who do not receive any specific immunosuppressant treatment after the diagnosis of cancer.
The main goals of Ulcerative Colitis (UC) treatment are to both induce and maintain the clinical and endoscopic remission of disease, reduce the incidence of complications such as dysplasia and ...colorectal carcinoma and improve quality of life. Although a curative medical treatment for UC has not yet been found, new therapeutic strategies addressing specific pathogenetic mechanisms of disease are emerging. Notwithstanding these novel therapies, non-biological conventional drugs remain a mainstay of treatment. The aim of this review is to summarize current therapeutic strategies used as treatment for ulcerative colitis and to briefly focus on emerging therapeutic strategies, including novel biologic therapies and small molecules. To date, multiple therapeutic approaches can be adopted in UC and the range of available compounds is constantly increasing. In this era, the realization of well-designed comparative clinical trials, as well as the definition of specific therapeutic models, would be strongly suggested in order to achieve personalized management for UC patients.
Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional ...gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.
CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be ...detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape:
asymptomatic
,
neuro-symptomatic
, and
secondary
. The first,
asymptomatic CSF escape
, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression.
Neuro-symptomatic CSF escape
is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally,
secondary CSF escape
, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir.
Long-term transmission expansion planning has to face the energy transition in a restructured electricity market environment. Increased transmission capacity within and between Member States is ...likely to play an essential role in maintaining the secure and economic operation of the whole European power system and ensuring the integration of growing renewable generation. This paper proposes a novel iterative methodology aimed at assessing an optimal level of interconnection between relevant bidding zones, simultaneously investigating different potential alternatives. Starting from a reference grid, a multi-criteria analysis is adopted to select the additional transmission capacities to be tested in each iteration via network and market simulations in order to confirm that transmission expansion benefits outweigh the estimated realization costs. The proposed approach is applied to the Italian case in two contrasting energy scenarios for the mid-term 2030 and very-long-term 2040 horizons: different development strategies are derived, and the least regret criterion is applied to define the most cost-effective as the target development strategy for the Transmission System Operator (TSO). Furthermore, sensitivity analyses on relevant input data variation are performed to test the robustness of the results obtained.
Gluten-free diet (GFD) decreases the quality of life of celiac disease (CD) patients, who frequently ask to occasionally ingest gluten-containing food. We evaluated CD patients reporting voluntary ...and occasional transgressions to their GFD.
From October 2017 to September 2018, the patients reporting occasional and voluntary gluten ingestion (GFD-noncompliant) were prospectively enrolled. These patients underwent clinical examination, blood tests, duodenal biopsy, capsule enteroscopy (CE), and a validated food-frequency questionnaire (FFQ) assessing the frequency and quantity of gluten intake. Mortality was calculated and compared to the general population. A group of patients on strict GFD (GFD-adherent) acted as controls.
One thousand three hundred seventy-eight CD patients were evaluated during the study period. One hundred nine (8%) reported occasional (weekly or monthly) voluntary ingestion of gluten. The mean gluten intake was 185.2 ± 336.9 g/year, and the duration of their incorrect GFD was 8.6 ± 6.9 years. Among the noncompliant patients, 57% did not present any histological alteration; furthermore, the Marsh score profile was not different between compliant and noncompliant patients. Seventy percent did not present any alteration at CE. Seventy-five percent of patients reported no gastrointestinal symptoms after gluten ingestion. Twenty-three percent of patients in the GFD-noncompliant group presented positive tTG-IgA. No association was found between gluten intake, clinical symptoms, and biomarkers. Mortality was not different between the groups and the general population.
Our results are that in a real-life scenario, a group of CD patients on long-term gluten intake showed no significant clinical symptoms or small bowel damage, thus suggesting that a degree of tolerance towards gluten consumption can be reached.
Background and Aims Enteroscopy (wireless or wired) is the reference standard for small-bowel (SB) diseases, and it has been applied to detect SB malignancies in complicated celiac disease (CD) with ...heterogeneous results. The aim of this meta-analysis was to obtain a diagnostic yield (DY) by pooling the data of studies that investigated the use of enteroscopy to detect SB adverse events in CD. Methods We performed an online search for studies estimating the DY of wireless and wired enteroscopy in predicting the presence of SB premalignant and/or malignant lesions. The DerSimonian and Laird random-effects method was used to pool the arcsine-transformed proportions of patients with the events. Three meta-analyses were performed considering the following events: the presence of a malignancy, premalignant damage (ulcerative jejunoileitis UJ), or the presence of a malignancy or UJ. A subgroup analysis was performed after extracting (if possible) patients with refractory CD (RCD). Results Of the 529 titles initially resulting from the search, 10 studies on capsule enteroscopy (CE) and 3 on double-balloon or push enteroscopy met the inclusion criteria. Overall, 439 and 76 patients were enrolled in these studies using CE and enteroscopy, respectively. Twelve tumors and 47 UJs were found by CE versus 8 tumors and 13 UJs detected by wired enteroscopy. For malignancies the CE yield was 1.9% (95% CI, .5%-3.8%) and wired enteroscopy yield 8.7% (95% CI, 0%-21.2%); similarly, for UJ the DYs were 8.4% (95% CI, 2.1%-17.7%) and 16.7% (95% CI, 8.7%-26.3%); for either UJ or neoplasia the DYs were 13.0% (95% CI, 5.6%-22.5%) and 27.7% (95% CI, 14.8%-42.6%). For RCD the DYs of all enteroscopic techniques were 1.8% (95% CI, 0%-7.7%) for neoplasia, 22.3% (95% CI, 8.2%-39.7%) for UJ, and 27.5% (95% CI, 13.1%-44.2%) for either. Conclusions Enteroscopy is a powerful and efficient diagnostic tool for the detection of SB malignancies in complicated CD.
In this work, a deterministic approach is adopted to analyze the robustness of the timber roof of the Gaggiandre shipyard at the Arsenale of Venice. The capacity of the traditional timber truss to ...withstand the design loads as a result of the damage in the strut-tie node is evaluated according to the alternative load path method. Two layouts of the trusses are analyzed and compared: before and after the Austrian retrofitting intervention, performed in the late 1800s. For both configurations, robustness analyses are carried out by using linear 2D numerical models that consider the effective rotational capacity of the structural nodes in relation to the construction methods of the timber joints. For the configuration subject to the 19th-century restoration, the 3D response of the roof is also analyzed to verify the additional contribution provided by the longitudinal bracing system to the activation of alternative load paths (bridge effect). The results obtained with the different analyses are thoroughly evaluated, providing an indication of the deterministic robustness index of the roofing system based on different assumptions. The outcomes of this work allow to draw some general considerations on the method that could be used for the robustness assessment of historical wood systems.
The evaluation of the degree of inflammation and fibrosis, intrinsic elements in intestinal wall damage of Crohn's disease, is essential to individuate the extent of the lesions and the presence of ...strictures. This information will contribute to the choice of the appropriate therapeutic approach, the prediction of the response to therapy and the course of the disease. The accurate evaluation of the extent and severity of inflammation and/or fibrosis in Crohn's disease currently requires histopathological analysis of the intestinal wall. However, in clinical practice and research, transmural assessment of the intestinal wall with cross sectional imaging is increasingly used for this purpose. The B-mode ultrasonograhic characteristics of the intestinal wall, the assessment of its vascularization by color Doppler and I.V. contrast agents, and the evaluation of the mechanical and elastic properties by sonoelastography, may provide useful and accurate information on the severity and extent of inflammation and intestinal fibrosis in Crohn's disease. The purpose of this review is to provide an update on current sonographic methods to discriminate inflammation and fibrosis in Crohn's disease.
A subset of patients with celiac disease (CD) on a gluten-free diet (GFD) reported the persistence of functional gastrointestinal disorders. Foods containing fermentable, oligosaccharides, ...disaccharides, monosaccharides, and polyols (FODMAP) can trigger a broad range of gastrointestinal symptoms in sensitive individuals. We evaluated the effects of a low FODMAP diet (LFD) on gastrointestinal and psychological symptomatology in CD patients. A total of 50 celiac patients on GFDs and with persistence of gastrointestinal symptoms were included. The patients were randomly allocated to one of two dietary groups-one on a low FODMAP GFD (LF-GFD,
= 25) and the other on a regular GFD (R-GFD,
= 25)-for 21 days. Psychological symptomatology and quality of life were evaluated by the Symptom Checklist-90-R (SCL-90) and the Short Form (36) Health Survey (SF-36) questionnaires, respectively. Gastrointestinal symptomatology and general well-being were evaluated by visual analogue scale (VAS) scores. After 21 days, 21 and 23 patients completed the dietary treatment on LF-GFD and R-GFD, respectively. A reduced global SCL-90 index (
< 0.0003) was found in the LF-GFD group but not in the R-GFD one. However, the SF-36 scores did not differ between groups after treatment. The VAS for abdominal pain was much lower, and the VAS for fecal consistency enhanced after treatment in the LF-GFD group. General well-being increased in both groups but with a much higher improvement in the LF-GFD (
= 0.03). A short-term LFD regimen helps to improve the psychological health and gastrointestinal symptomatology with enhanced well-being of CD patients with persisting functional gastrointestinal symptomatology. The long-term clinical effects of LFD in particular subgroups of CD patients need further evaluation.
PDF
