Progressive failure analysis of shallow foundations on soils with strain-softening behaviour

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Seismic displacement analysis of homogeneous slopes: a review of existing simplified methods with reference to Italian seismicity.

The simplified displacement-based procedures for seismic slope stability represent a good-working balance between simplicity and reliability, since both slope ductility (i.e. the capacity of sustain permanent displacements) and deformability (basically affecting the asynchronous slope motion) are accounted for. In this paper the procedure proposed by Bray & Rathje (1998) is reviewed with particular reference to Italian seismicity on a set of subsoil models, representative of the different soil classes specified by Italian and European codes. The relationship expressing the decrease of the equivalent acceleration with increasing earthquake/soil frequency ratio is then obtained by means of dynamic 1D site response analyses. Statistical correlations between calculated Newmark displacements, significant ground motion parameters and the ratio of seismic load resistance to peak demand are then derived and compared to similar relationships proposed in literature

Respiratory Tract Infections in Inflammatory Bowel Disease Patients Taking Vedolizumab: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The ongoing COVID-19 pandemic has raised concerns about the risk of SARS-CoV-2 infection in patients with Crohn's disease (CD) and patients with ulcerative colitis (UC) taking immunosuppressants or biologics. We conducted a systematic review and meta-analysis to assess the risk of respiratory infections in patients with inflammatory bowel disease (IBD) treated with vedolizumab. We searched PubMed, EMBASE and Scopus to identify randomized controlled trials (RCT) comparing vedolizumab to placebo in patients with IBD. Outcomes were the rate of respiratory tract infections (RTI), upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) among patients receiving vedolizumab as compared with placebo. Pooled rates were reported as Odds Ratios (OR) with 95% Confidence Interval (CI). Eight RCT involving 3,287 patients (1873 CD and 1415 UC) were analyzed; 2,493 patients received vedolizumab and 794 received placebo. The rates of RTI and URTI were statistically higher in vedolizumab-treated patients compared to placebo [OR = 1.63; 95% CI (1.07-2.49); OR = 1.64 95% CI (1.07-2.53) respectively]. UC patients, but not CD patients, receiving vedolizumab had a higher risk to develop RTI and URTI [OR = 1.98; 95% CI (1.41-2.77); OR = 2.02; 95% CI (1.42-2.87)] compared to placebo-treated patients. The number of LRTI was small in both treatment groups. Data confirm the good safety profile of vedolizumab even though RTI were more frequent in patients receiving vedolizumab and the risk of URTIs was significantly higher in patients with UC

Interleukin-34 promotes tumorigenic signals for colon cancer cells

Colorectal carcinoma (CRC) is one of the most common forms of malignancy in the Western world. Accumulating evidence indicates that colon carcinogenesis is tightly controlled by tumour-associated immune cells and stromal cells, which can either stimulate or suppress CRC cell growth and survival, mainly via the production of cytokines. Interleukin-34 (IL-34), a cytokine known to regulate mainly monocyte/macrophage survival and function, is highly produced within the CRC microenvironment by several cell types, including cancer cells, tumour-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), and regulates the pro-tumoural functions of such cells. In this article, we summarize the available data supporting the multiple effects of IL-34 in human CRC

Involvement of smad7 in inflammatory diseases of the gut and colon cancer

In physiological conditions, the human intestinal mucosa is massively infiltrated with various subsets of immune cells, the activity of which is tightly regulated by several counter-regulatory factors. One of these factors is transforming growth factor-beta 1 (TGF-beta 1), a cytokine produced by multiple cell types and targeting virtually all the intestinal mucosal cells. Binding of TGF-beta 1 to its receptors triggers Smad2/3 signaling, thus culminating in the attenuation/suppression of immune-inflammatory responses. In patients with Crohn's disease and patients with ulcerative colitis, the major human inflammatory bowel diseases (IBD), and in mice with IBD-like colitis, there is defective TGF-beta 1/Smad signaling due to high levels of the intracellular inhibitor Smad7. Pharmacological inhibition of Smad7 restores TGF-beta 1 function, thereby reducing inflammatory pathways in patients with IBD and colitic mice. On the other hand, transgenic over-expression of Smad7 in T cells exacerbates colitis in various mouse models of IBD. Smad7 is also over-expressed in other inflammatory disorders of the gut, such as refractory celiac disease, necrotizing enterocolitis and cytomegalovirus-induced colitis, even though evidence is still scarce and mainly descriptive. Furthermore, Smad7 has been involved in colon carcinogenesis through complex and heterogeneous mechanisms, and Smad7 polymorphisms could influence cancer prognosis. In this article, we review the data about the expression and role of Smad7 in intestinal inflammation and cancer

Difficult Biliary Stones: A Comprehensive Review of New and Old Lithotripsy Techniques

Biliary stones represent the most common indication for therapeutic endoscopic retrograde cholangiopancreatography. Many cases are successfully managed with biliary sphincterotomy and stone extraction with balloon or basket catheters. However, more complex conditions secondary to the specific features of stones, the biliary tract, or patient's needs could make the stone extraction with the standard techniques difficult. Traditionally, mechanical lithotripsy with baskets has been reported as a safe and effective technique to achieve stone clearance. More recently, the increasing use of endoscopic papillary large balloon dilation and the diffusion of single-operator cholangioscopy with laser or electrohydraulic lithotripsy have brought new, safe, and effective therapeutic possibilities to the management of such challenging cases. We here summarize the available evidence about the endoscopic management of difficult common bile duct stones and discuss current indications of different lithotripsy techniques

Precision medicine and machine learning towards the prediction of the outcome of potential celiac disease

Potential Celiac Patients (PCD) bear the Celiac Disease (CD) genetic predisposition, a significant production of antihuman transglutaminase antibodies, but no morphological changes in the small bowel mucosa. A minority of patients (17%) showed clinical symptoms and need a gluten free diet at time of diagnosis, while the majority progress over several years (up to a decade) without any clinical problem neither a progression of the small intestine mucosal damage even when they continued to assume gluten in their diet. Recently we developed a traditional multivariate approach to predict the natural history, on the base of the information at enrolment (time 0) by a discriminant analysis model. Still, the traditional multivariate model requires stringent assumptions that may not be answered in the clinical setting. Starting from a follow-up dataset available for PCD, we propose the application of Machine Learning (ML) methodologies to extend the analysis on available clinical data and to detect most influent features predicting the outcome. These features, collected at time of diagnosis, should be capable to classify patients who will develop duodenal atrophy from those who will remain potential. Four ML methods were adopted to select features predictive of the outcome; the feature selection procedure was indeed capable to reduce the number of overall features from 85 to 19. ML methodologies (Random Forests, Extremely Randomized Trees, and Boosted Trees, Logistic Regression) were adopted, obtaining high values of accuracy: all report an accuracy above 75%. The specificity score was always more than 75% also, with two of the considered methods over 98%, while the best performance of sensitivity was 60%. The best model, optimized Boosted Trees, was able to classify PCD starting from the selected 19 features with an accuracy of 0.80, sensitivity of 0.58 and specificity of 0.84. Finally, with this work, we are able to categorize PCD patients that can more likely develop overt CD using ML. ML techniques appear to be an innovative approach to predict the outcome of PCD, since they provide a step forward in the direction of precision medicine aimed to customize healthcare, medical therapies, decisions, and practices tailoring the clinical management of PCD children

p 206intensive first line fir c fox c association of triplet chemotherapy plus cetuximab in ras wild type metastatic colorectal cancer patients preliminary phase ii data and individual limiting toxicity syndromes prediction by pharmacogenomic biomarkers

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Direct peroral cholangioscopy in the management of difficult biliary stones: a new tool to confirm common bile duct clearance. Results of a preliminary study

Background and aims: Endoscopic sphincterotomy (ES) with stone extraction is the standard treatment for choledocholithiasis. After stone retrieval, balloon-occluded cholangiography is generally performed to confirm bile duct clearance but can miss residual stones particularly in patients with residual small-sized stones, a large bile duct or pneumobilia. In addition, difficult common bile duct (CBD) stones requiring advanced endoscopic techniques for retrieval are a potential risk factor for choledocholithiasis recurrence. Methods: We performed a retrospective evaluation of a prospectively maintained procedures database. From July 2016 to December 2017, all patients with difficult CBD stones who underwent endoscopic retrograde cholangiopancreatography (ERCP) with papillary balloon dilation-assisted stone retrieval and subsequent direct per-oral cholangioscopy (DPOC) using standard gastroscopes to confirm CBD clearance were analyzed. Results: Thirty-six patients who underwent ERCP and DPOC were included. Technical success, defined as deep intubation of CBD with hepatic hilum visualization, was achieved in 31 of 36 patients (86%). During DPOC, residual CBD stones were visualized and removed in 7 of 31 patients (22.5%). After a mean of 241 +/- 56 days of follow-up post-DPOC, no serious adverse events were reported, and there was no evidence or suspicion of recurrent choledocholithiasis. Conclusions: Direct per-oral cholangioscopy immediately following difficult CBD stone removal was safe, feasible and accurate. In this setting, DPOC at the time of ERCP appears to be a very useful tool to achieve complete clearance of choledocholithiasis.info:eu-repo/semantics/publishedVersio

Malignant gastric outlet obstruction: Which is the best therapeutic option?

Malignant gastric outlet obstruction (MGOO) is a clinical condition characterized by the mechanical obstruction of the pylorus or the duodenum due to tumor compression/infiltration, with consequent reduction or impossibility of an adequate oral intake. MGOO is mainly secondary to advanced pancreatic or gastric cancers, and significantly impacts on patients' survival and quality of life. Patients suffering from this condition often present with intractable vomiting and severe malnutrition, which further compromise therapeutic chances. Currently, palliative strategies are based primarily on surgical gastrojejunostomy and endoscopic enteral stenting with self-expanding metal stents. Several studies have shown that surgical approach has the advantage of a more durable relief of symptoms and the need of fewer re-interventions, at the cost of higher procedure-related risks and longer hospital stay. On the other hand, enteral stenting provides rapid clinical improvement, but have the limit of higher stent dysfunction rate due to tumor ingrowth and a subsequent need of frequent re-interventions. Recently, a third way has come from interventional endoscopic ultrasound, through the development of endoscopic ultrasound-guided gastroenterostomy technique with lumen-apposing metal stent. This new technique may ideally encompass the minimal invasiveness of an endoscopic procedure and the long-lasting effect of the surgical gastrojejunostomy, and brought encouraging results so far, even if prospective comparative trial are still lacking. In this Review, we described technical aspects and clinical outcomes of the above-cited therapeutic approaches, and discussed the open questions about the current management of MGOO