Clinical applications of the sustained-release dexamethasone implant for treatment of macular edema

Macular edema is one of the leading causes of vision loss among patients with retinal vein occlusion, diabetic retinopathy, and posterior chamber inflammatory disease. However, the treatment of macular edema is considerably limited by the difficulty in delivering effective doses of therapeutic agents into the vitreous cavity. In recent years, the development of a sustained-release dexamethasone intravitreal implant (Ozurdex®) has enabled more controlled drug release at a stable rate over a long period of time, with a potentially lower rate of adverse events. Clinical studies indicate that this dexamethasone implant is a promising new treatment option for patients with persistent macular edema resulting from retinal vein occlusion, diabetic retinopathy, and uveitis or Irvine-Gass syndrome

Random Topologies and the emergence of cooperation: the role of short-cuts

We study in detail the role of short-cuts in promoting the emergence of cooperation in a network of agents playing the Prisoner's Dilemma Game (PDG). We introduce a model whose topology interpolates between the one-dimensional euclidean lattice (a ring) and the complete graph by changing the value of one parameter (the probability p to add a link between two nodes not already connected in the euclidean configuration). We show that there is a region of values of p in which cooperation is largely enhanced, whilst for smaller values of p only a few cooperators are present in the final state, and for p \rightarrow 1- cooperation is totally suppressed. We present analytical arguments that provide a very plausible interpretation of the simulation results, thus unveiling the mechanism by which short-cuts contribute to promote (or suppress) cooperation

Structural Properties of Planar Graphs of Urban Street Patterns

Recent theoretical and empirical studies have focused on the structural properties of complex relational networks in social, biological and technological systems. Here we study the basic properties of twenty 1-square-mile samples of street patterns of different world cities. Samples are represented by spatial (planar) graphs, i.e. valued graphs defined by metric rather than topologic distance and where street intersections are turned into nodes and streets into edges. We study the distribution of nodes in the 2-dimensional plane. We then evaluate the local properties of the graphs by measuring the meshedness coefficient and counting short cycles (of three, four and five edges), and the global properties by measuring global efficiency and cost. As normalization graphs, we consider both minimal spanning trees (MST) and greedy triangulations (GT) induced by the same spatial distribution of nodes. The results indicate that most of the cities have evolved into networks as efficienct as GT, although their cost is closer to the one of a tree. An analysis based on relative efficiency and cost is able to characterize different classes of cities.Comment: 7 pages, 3 figures, 3 table

Temporary interruption of baricitinib: characterization of interruptions and effect on clinical outcomes in patients with rheumatoid arthritis

Background In clinical practice, temporary interruption of rheumatoid arthritis (RA) therapy is common for various reasons including side effects, non-compliance, or necessity for surgery. To characterize temporary interruptions of baricitinib and placebo-matched tablets in phase 3 studies of patients with moderate-to-severe rheumatoid arthritis (RA) and describe their impact on efficacy and safety. Methods During 4 baricitinib phase 3 studies, investigators documented timing, reason, and duration of investigator-initiated temporary interruptions of study drug. In 2 studies, patients recorded RA symptoms in daily diaries for 12 weeks. Post hoc analyses investigated changes in symptom scores during interruptions and resumption of treatment. Interruptions were evaluated for reoccurrence of adverse events or laboratory abnormalities after retreatment. Results Across the placebo-controlled studies, interruptions occurred in larger proportions of baricitinib- (2 mg, 18%; 4 mg, 18%) vs placebo-treated (9%) patients in only one study (bDMARD-inadequate responder patients, RA-BEACON). In the active comparator-controlled studies, the lowest rates of interruption were in the baricitinib monotherapy arm (9%) of RA-BEGIN (vs methotrexate monotherapy or combination therapy), and proportions were similar for baricitinib (10%) and adalimumab (9%) in RA-BEAM. Adverse events were the most common reason for interruption, but their reoccurrence after drug restart was infrequent. Most interruptions lasted ≤ 2 weeks. Daily diaries indicated modest symptom increases during interruption with return to pre-interruption levels or better after resumption. Interruptions had no impact on long-term efficacy outcomes. Conclusions Consistent with its pharmacologic properties, brief interruptions of baricitinib during phase 3 studies were associated with minor increases in RA symptoms that resolved following retreatment. This analysis provides useful information for clinicians, as temporary interruption of antirheumatic therapy is common in the care of patients with RA

Correction to: Temporary interruption of baricitinib: characterization of interruptions and effect on clinical outcomes in patients with rheumatoid arthritis

Background In clinical practice, temporary interruption of rheumatoid arthritis (RA) therapy is common for various reasons including side effects, non-compliance, or necessity for surgery. To characterize temporary interruptions of baricitinib and placebo-matched tablets in phase 3 studies of patients with moderate-to-severe rheumatoid arthritis (RA) and describe their impact on efficacy and safety. Methods During 4 baricitinib phase 3 studies, investigators documented timing, reason, and duration of investigator-initiated temporary interruptions of study drug. In 2 studies, patients recorded RA symptoms in daily diaries for 12 weeks. Post hoc analyses investigated changes in symptom scores during interruptions and resumption of treatment. Interruptions were evaluated for reoccurrence of adverse events or laboratory abnormalities after retreatment. Results Across the placebo-controlled studies, interruptions occurred in larger proportions of baricitinib- (2 mg, 18%; 4 mg, 18%) vs placebo-treated (9%) patients in only one study (bDMARD-inadequate responder patients, RA-BEACON). In the active comparator-controlled studies, the lowest rates of interruption were in the baricitinib monotherapy arm (9%) of RA-BEGIN (vs methotrexate monotherapy or combination therapy), and proportions were similar for baricitinib (10%) and adalimumab (9%) in RA-BEAM. Adverse events were the most common reason for interruption, but their reoccurrence after drug restart was infrequent. Most interruptions lasted ≤ 2 weeks. Daily diaries indicated modest symptom increases during interruption with return to pre-interruption levels or better after resumption. Interruptions had no impact on long-term efficacy outcomes. Conclusions Consistent with its pharmacologic properties, brief interruptions of baricitinib during phase 3 studies were associated with minor increases in RA symptoms that resolved following retreatment. This analysis provides useful information for clinicians, as temporary interruption of antirheumatic therapy is common in the care of patients with RA

NetMe 2.0: a web-based platform for extracting and modeling knowledge from biomedical literature as a labeled graph

Motivation: The rapid increase of bio-medical literature makes it harder and harder for scientists to keep pace with the discoveries on which they build their studies. Therefore, computational tools have become more widespread, among which network analysis plays a crucial role in several life-science contexts. Nevertheless, building correct and complete networks about some user-defined biomedical topics on top of the available literature is still challenging. Results: We introduce NetMe 2.0, a web-based platform that automatically extracts relevant biomedical entities and their relations from a set of input texts—i.e. in the form of full-text or abstract of PubMed Central’s papers, free texts, or PDFs uploaded by users—and models them as a BioMedical Knowledge Graph (BKG). NetMe 2.0 also implements an innovative Retrieval Augmented Generation module (Graph-RAG) that works on top of the relationships modeled by the BKG and allows the distilling of well-formed sentences that explain their content. The experimental results show that NetMe 2.0 can infer comprehensive and reliable biological networks with significant Precision–Recall metrics when compared to state-of-the-art approaches

Markov Chain Methods For Analyzing Complex Transport Networks

We have developed a steady state theory of complex transport networks used to model the flow of commodity, information, viruses, opinions, or traffic. Our approach is based on the use of the Markov chains defined on the graph representations of transport networks allowing for the effective network design, network performance evaluation, embedding, partitioning, and network fault tolerance analysis. Random walks embed graphs into Euclidean space in which distances and angles acquire a clear statistical interpretation. Being defined on the dual graph representations of transport networks random walks describe the equilibrium configurations of not random commodity flows on primary graphs. This theory unifies many network concepts into one framework and can also be elegantly extended to describe networks represented by directed graphs and multiple interacting networks.Comment: 26 pages, 4 figure

Pathological features and outcomes of incidental renal cell carcinoma in candidate solid organ donors

Background: We report the findings of a single Italian center in the evaluation of renal lesions in deceased donors from 2001 to 2017. In risk evaluation, we applied the current Italian guidelines, which include donors with small (< 4 cm, stage pT1a) renal carcinomas in the category of non-standard donors with a negligible risk of cancer transmission. Methods: From the revision of our registries, 2,406 donors were considered in the Emilia Romagna region of Italy; organs were accepted from 1,321 individuals for a total of 3,406 organs. Results: The evaluation of donor safety required frozen section analysis for 51 donors, in which a renal suspicious lesion was detected by ultrasound. Thirty-two primary renal tumors were finally diagnosed: 26 identified by frozen sections and 6 in discarded kidneys. The 32 tumors included 13 clear cell renal cell carcinomas (RCCs), 6 papillary RCCs, 6 angiomyolipomas, 5 oncocytomas, 1 chromophobe RCC, and 1 papillary adenoma. No cases of tumor transmission were recorded in follow-up of the recipients. Conclusion: Donors with small RCCs can be accepted to increase the donor pool. Collaboration in a multidisciplinary setting is fundamental to accurately evaluate donor candidate risk assessment and to improve standardized protocols for surgeons and pathologists