The molecular landscape of colitis-associated carcinogenesis

In spite of the well-established histopathological phenotyping of IBD-associated preneoplastic and neoplastic lesions, their molecular landscape remains to be fully elucidated. Several studies have pinpointed the initiating role of longstanding/relapsing inflammatory insult on the intestinal mucosa, with the activation of different pro-inflammatory cytokines (TNF-\u3b1, IL-6, IL-10, IFN-\u3b3), chemokines and metabolites of arachidonic acid resulting in the activation of key transcription factors such as NF-\u3baB. Longstanding inflammation may also modify the intestinal microbiota, prompting the overgrowth of genotoxic microorganisms, which may act as further cancer promoters. Most of the molecular dysregulation occurring in sporadic colorectal carcinogenesis is documented in colitis-associated adenocarcinoma too, but marked differences have been established in both their timing and prevalence. Unlike sporadic cancers, TP53 alterations occur early in IBD-related carcinogenesis, while APC dysregulation emerges mainly in the most advanced stages of the oncogenic cascade. From the therapeutic standpoint, colitis-associated cancers are associated with a lower prevalence of KRAS mutations than the sporadic variant. Epigenetic changes, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, are significantly involved in colitis-associated cancer development and progression. The focus now is on identifying diagnostic and prognostic biomarkers, with a view to ultimately designing patient-tailored therapie

Morphologic Criteria of Lesion Activity in Neovascular Age-Related Macular Degeneration: A Consensus Article

Intravitreal antivascular endothelial growth factor drugs represent the current standard of care for neovascular age-related macular degeneration (nAMD). Individualized treatment regimens aim at obtaining the same visual benefits of monthly injections with a reduced number of injections and follow-up visits, and, consequently, of treatment burden. The target of these strategies is to timely recognize lesion recurrence, even before visual deterioration. Early detection of lesion activity is critical to ensure that clinical outcomes are not compromised by inappropriate delays in treatment, but questions remain on how to effectively monitor the choroidal neovascularization (CNV) activity. To assess the persistence/recurrence of lesion activity in patients undergoing treatment for nAMD, an expert panel developed a decision algorithm based on the morphological features of CNV. After evaluating all current retinal imaging techniques, the panel identified optical coherent tomography as the most reliable tool to ascertain lesion activity when funduscopy is not obvious

Porous silicon microparticles as efficient carriers for immunologic adjuvants

In this work we report a first-time combination of porous silicon (pSi) particles with the immunologic adjuvant Pam3CSK4, a TLR 1/2 agonist, as a tool for immunotherapy. pSi is a sponge-like biocompatible and biode gradable nanomaterial with high porosity, large surface-to-volume ratio and tunable surface, suitable for drug delivery applications. This study provides, by means of live-cell confocal microscopy, an insight about the time course of the interaction of free Pam3CSK4 vs vectorized by pSi microparticles with human dendritic cells (DCs). We found a delay in the ingestion of the agonist when carried by pSi microparticles. These findings were sup ported by the observation of the morphological changes related to the activation of DCs that occurred with a 5 h difference when treated with the vectorized ligand. These results provide the first demonstration of pSi as a conceivable candidate to deliver Pam3CSK4 to DCs paving the way towards immunotherapy practice

Statistical modeling of monthly rainfall variability in Soummam watershed of Algeria, between 1967 and 2018

AbstractThe monthly precipitations obtained during 51 years of measurement in 24 stations of Soummam watershed in Algeria were analyzed to describe rainfall trends and aridity state of the area using statistical modeling. The choice of distribution laws was justified by comparing fitting results of different distributions laws used in literature reviews. Hence, the p values proved that Generalized Extreme Value, Weibull (3) and Logistic the distribution law are more adequate to analyze rainfall frequencies in different part of the watershed. The diagnostic given by Q‐Q plot, P‐P plot and survival regression curve showed the period of wetness and dryness in the northeastern and the southwestern part of the watershed, respectively. Moreover, the study given by the De Martonne index explains the consequences of climate change by a new form of aridity in the watershed between 1994 and 2018.Recommendations for Resource Managers The annual rainfall of Soummam watershed has a moderate and irregular rainfall distribution between 1967 and 2018. Using distribution function on monthly rainfall in each bioclimatic floor to analyze the trend of rainfall frequency gives a spatio‐temporal description of climate in the area. Fitting by Kolmogorov‐Smirnov test allows us to choose generalized extreme value, Weibull (3) and Logistic for modeling monthly rainfall variability in each part of the watershed. The diagnostic obtained by P‐P plot, Q‐Q plot and survival regression curve proved a change of aridity in the northeastern and southwestern part of the watershed between 1994 and 2018

Minimal disease activity in patients with psoriatic arthritis treated with ustekinumab: results from a 24-week real-world study

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease affecting around 40% of psoriasis patients. Minimal disease activity (MDA) criteria have been proposed to identify a state of low disease activity, one of the principal goals of treatment for psoriatic disease. This study investigated treatment with ustekinumab (UST) in the context of a real-world setting. Thirty-four PsA patients who had failure or inadequate response to conventional synthetic disease-modifying antirheumatic drugs or to anti-tumour necrosis factor alpha were enrolled. Demographic and clinical features, MDA criteria, and the impact of psoriatic skin manifestations on patients' quality of life (QoL) using the dermatology life quality index (DLQI) questionnaire were evaluated at baseline and after 24-week treatment. Adverse events were recorded. At week 24, 70.5% of patients (n = 24) achieved MDA. A sub-analysis of dermatological indices of the MDA criteria showed that the psoriasis area severity index score was significantly improved and body surface area was significantly decreased at 24 weeks compared with that at baseline (both p < 0.001). For the rheumatologic indexes, tender joint count, swollen joint count, and tender entheseal points were all significantly improved at 24 weeks of therapy (all p < 0.01 vs. baseline). Mean DLQI value decreased approximately fourfold, and there were no safety concerns. The achievement of MDA as well as the significant improvement in DLQI and lack of adverse events in the context of a real-life setting shown here confirms the efficacy and safety of UST in PsA

Increased Carotid Thickness in Subjects with Recently-Diagnosed Diabetes from Rural Cameroon

PMCID: PMC3423396This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Potential predictive role of chemotherapy-induced changes of soluble CD40 ligand in untreated advanced pancreatic ductal adenocarcinoma

Pancreas ductal adenocarcinoma lacks predictive biomarkers. CD40 is a member of the tumor necrosis factor superfamily. CD40-sCD40L interaction is considered to contribute to the promotion of tumor cell growth and angiogenesis. The aim of the present study was to investigate the role of serum sCD40L as a predictor in metastatic pancreatic cancer. We evaluated 27 consecutive pancreatic cancer patients treated with FOLFIRINOX (21 patients) or gemcitabine plus nab-paclitaxel combination (six patients). The sCD40L level was measured in serum by enzyme-linked immunosorbent assay at baseline, at first evaluation (all patients), and at time to progression (18 patients). The radiological response was evaluated according to the Response Evaluation Criteria in Solid Tumors, Version 1.1. The Wilcoxon signed-rank test was used to compare pre-post treatment sCD40L levels with respect to clinical response, while Pearson's correlation coefficient was used for the correlation between sCD40L and CA19.9 pre- and post-treatment. The Kruskal-Wallis test was also conducted for further comparisons. We observed a statistically significant reduction in the sCD40L level after 3 months of treatment in patients with partial response (11,718.05\ub17,097.13 pg/mL vs 4,689.42\ub15,409.96 pg/mL; P&lt;0.01). Conversely, in patients with progressive disease, the biomarker statistically increased in the same time (9,351.51\ub17,356.91 pg/mL vs 22,282.92\ub111,629.35 pg/mL; P&lt;0.01). This trend of sCD40L was confirmed in 18 patients at time to progression after the first evaluation. No differences were recorded within the stable disease group. Moreover, there was a positive correlation between the sCD40L and CA19.9 pre-post treatment variation percentage (Pearson's correlation coefficient =0.52; P&lt;0.05). Our data suggest a possible predictive role of sCD40L in pancreatic cancer patients, similar to CA19.9

Rare histotypes of epithelial biliary tract tumors: A literature review

Adenocarcinoma represents the most frequent biliary tract cancer. However, other rare histotypes can be found in the biliary tract, such as cholangiolocellular carcinoma, cholangiocarcinoma with ductal plate malformation pattern, adenosquamous carcinoma, mucinous carcinoma, signet ring cell carcinoma, clear cell carcinoma, mucoepidermoid carcinoma, lymphoepithelioma-like carcinoma, and sarcomatous cholangiocarcinoma. These cancer types account for less than 10 % of all the already rare biliary tract tumors. Yet, they represent a relevant issue in everyday clinical practice, given the lack of therapeutic recommendations and the overall scarcity of data, mainly deriving from isolated small center-specific cohorts of patients.The shifts of such histotypes from the most common ones reflect genetic and molecular differences, determine changes in clinical aggressiveness, and suggest a possible variability in sensitivity to the standard treatments of biliary adenocarcinomas. The consistency and degree of these variables are still to be solidly demonstrated and investigated. Therefore, this paper aims to review the current literature concerning very infrequent and rare epithelial biliary tract cancers, focusing our attention on the clinical, molecular, and immunohistochemical features of these tumors

Pseudopapillary tumor in pediatric age: clinical and surgical management

BACKGROUND:Solid pseudopapillary tumors of the pancreas are rare exocrine pancreatic tumors. Through a review of pediatric cases in a single Institution, we present the clinical and surgical management of this neoplasm.METHODS:We retrospectively reviewed the clinical charts of patients treated at our unit between 1995 and 2009 for SPT. Clinical and surgical management were analyzed and reported.RESULTS:During the study period 11 patients underwent surgery for pseudopapillary tumor. Five patients were treated with duodenum-preserving pancreatic head resection and six patients with splenopancreasectomy with a Roux-en-Y pancreatic jejunostomy. Patients did not show recurrence and are currently disease free. Blood tests, Ultrasound, Computed tomography and Magnetic Resonance Imaging were not useful to preoperatively identify the nature of the pancreatic masses.CONCLUSION:Solid pseudopapillary tumor is a rare condition that should be taken into account for the differential diagnosis of pancreatic masses in pediatric age. Due to its favourable prognosis, surgical removal should be planned and done following the intraoperative findings