A Crohn’s Disease Patient with Extraintestinal Manifestations: A Case Report

Crohn’s disease (CD) is a chronic debilitating inflammatory disease which mostly affect gastrointestinal tract, but due to its unique features, CD enables to affect extraintestinal organs. Pathophysiology of extraintestinal manifestations is still debatable as many experts propose immune-related hypotheses. It is still unpredictable which manifestation precedes another as studies ongoing. Diagnosing CD is difficult since no gold standards available, therefore clinicians must combine history taking, diagnostic modalities, and a good clinical judgement to diagnose CD. Treatment for CD is not only to treat disease activity, but also to prevent complications to preserve patients’ quality of life.

A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response

Micelles from amphiphilic polylactide-block-poly(N-acryloxysuccinimide-co-N-vinylpyrrolidone) (PLA-b-P(NAS-co-NVP)) block copolymers of 105 nm in size were characterized and evaluated in a vaccine context. The micelles were non-toxic in vitro (both in dendritic cells and HeLa cells). In vitro fluorescence experiments combined with in vivo fluorescence tomography imaging, through micelle loading with the DiR near infrared probe, suggested an efficient uptake of the micelles by the immune cells. The antigenic protein p24 of the HIV-1 was successfully coupled on the micelles using the reactive N-succinimidyl ester groups on the micelle corona, as shown by SDS-PAGE analyses. The antigenicity of the coupled antigen was preserved and even improved, as assessed by the immuno-enzymatic (ELISA) test. Then, the performances of the micelles in immunization were investigated and compared to different p24-coated PLA nanoparticles, as well as Alum and MF59 gold standards, following a standardized HIV-1 immunization protocol in mice. The humoral response intensity (IgG titers) was substantially similar between the PLA micelles and all other adjuvants over an extended time range (one year). More interestingly, this immune response induced by PLA micelles was qualitatively higher than the gold standards and PLA nanoparticles analogs, expressed through an increasing avidity index over time (>60% at day 365). Taken together, these results demonstrate the potential of such small-sized micellar systems for vaccine delivery.

Advances in Distant Diplomatics: A Stylometric Approach to Medieval Charters

The quantitative analysis of writing style (stylometry) is becoming an increasingly common research instrument in philology. When it comes to medieval texts, such a methodology might be able to help us disentangle the multiple authorial strata that can often be discerned in them (issuer, dictator, scribe, etc.). To deliver a proof of concept in 'distant diplomatics,' we have turned to a corpus of twelfth-century Latin charters from the Cambrai episcopal chancery. We subjected this collection to an (unsupervised) stylometric modelling procedure, based on lexical frequency extraction and dimension reduction. In the absence of a sizable 'ground truth' for this material, we zoomed in on a specific case study, namely the oeuvre of the previously identified dictator-scribe known as 'RogF/JeanE.' Our results offer additional support for the attribution of a diplomatic oeuvre to this individual and even allow us to enlarge it with additional documents. Our analysis moreover yielded the serendipitous discovery of another, previously unnoticed, oeuvre, which we tentatively attribute to a scribe-dictator 'JeanB.' We conclude that the large-scale stylometric analysis is a promising methodology for digital diplomatics. More efforts, however, will have to be invested in establishing gold standards for this method to realize its full potential.

Four points regarding reproducibility and external statistical validity: a comment on Walter et al.

Walter et al. (2021) present phase 1–2–3 trial data that show two doses of the BNT162b2 (Pfizer–BioN-Tech) Covid-19 vaccine were safe and effective in children aged 5–11 years. Given that millions of children in this age group are receiving the paediatric Pfizer COVID-19 vaccine, that there are potential risks, and that the balance of benefits over potential risks is more limited in children compared to adults due to low rates of serious disease (ATAGI 2021), gold standards ought to be applied to supporting data in terms of placebo-controlled disease endpoint efficacy trials, safety databases large enough to detect adverse events, and appropriate data sharing to enable reproduction and scrutiny of results. Four points are worthy of attention regarding the reproducibility and external statistical validity of the analysis reported in Walter et al. (2021). ‘External validity’ refers to the extent to which conclusions drawn from the data (and statistical tests thereof) are likely to correspond to, or be generalisable to, the real world (Campbell 1957). ‘Reproducibility’ refers to the ability of independent researchers to draw the same conclusions from the data (Kass et al. 2016).

Cells and Mediators of Inflammation as Effectors of Epithelial Repair in the Inflamed Intestine

Mucosal and histological healing have become the gold standards for assessing the efficacy of therapy in patients living with inflammatory bowel diseases (IBD). Despite these being the accepted goals in therapy, the mechanisms that underlie the healing of the mucosa after an inflammatory insult are not well understood, and many patients fail to meet this therapeutic endpoint. Here we review the emerging evidence that mediators (e.g. prostaglandins, cytokines, proteases, reactive oxygen and nitrogen species) and innate immune cells (e.g. neutrophils and monocytes/macrophages), that are involved in the initiation of the inflammatory response, are also key players in the mechanisms underlying mucosal healing to resolve chronic inflammation in the colon. The dual function mediators comprise an inflammation/repair program that returns damaged tissue to homeostasis. Understanding details of the dual mechanisms of these mediators and cells may provide the basis for the development of drugs that can help to stimulate epithelial repair in patients affected by IBD.

Studies on the combinations of some herbals with various chemical entities as a potent antifungal agents

A widespread increase in the prevalence of fungal infections has been documented in recent decades. Candida albicans infections, which are frequently refractory and linked with high morbidity and mortality, place a significant burden on public health, despite the fact that existing antifungal medicines are restricted and associated with toxicity. Fungi are one of the most underappreciated killers, as evidenced by the fact that Amphotericin B and other commercially available antifungal therapies are still recognized as gold standards. The majority of commonly used antifungal medications have toxicity, effectiveness, and cost disadvantages. As a result of these limitations, there is a growing demand for the development of a novel antifungal medication treatment that acts selectively on new targets while having the fewest adverse effects. Natural goods, whether as pure phytocompounds or regulated plant extracts, give prospects for the development of lead compounds that may subsequently be turned into diverse synthetic medications with the appropriate alterations. These herbs can also be used as a component of a herbal synthetic combination, lowering the minimum required dose of the synthetic medicine (when taken singly) and reducing the risk of adverse effects. The goal of this research is to reduce the minimum required concentrations of today's antifungal medications by mixing them with a few less well-known herbal extracts while maintaining their efficacy.

91. Gaps and Opportunities in Antimicrobial Stewardship Programs in Asia: A Survey of 10 Countries

Background Most studies on hospital antimicrobial stewardship (AMS) status and practices are conducted in the west, and there is a lack of such data from Asian countries. The objective of this survey was to determine existing AMS practices and gaps, and challenges in implementing AMS programs in secondary and tertiary acute-care hospitals in 10 Asian countries. Methods A 70-item questionnaire was disseminated to hospitals fulfilling inclusion criteria and responses were collected from 10 April 2020 to 9 April 2021. The survey, specific to the Asian hospital setting, enquired about hospital leadership support for AMS; AMS team membership and training; AMS interventions; AMS monitoring and reporting; hospital infrastructure; and education. These were subdivided into core and supplementary components, adapted from the Transatlantic Taskforce on Antimicrobial Resistance set of core and supplementary indicators for hospital AMS programs, and the US Centers for Disease Control and Prevention checklist for core elements of hospital AMS programs. Results A total of 349 hospitals from Cambodia, India, Indonesia, Japan, Malaysia, Pakistan, Philippines, Taiwan, Thailand and Vietnam responded. Overall, only 47 hospitals fulfilled all 12 core components, and there were inter-country differences in terms of performance. The hospitals generally did well in terms of the AMS team (ie, comprising at least a physician leader responsible for AMS activities, a pharmacist, and infection control and microbiology personnel), and access to a timely and reliable microbiology service, with mean positive response rates (PRR) of ≥ 80% for these indicators (Figure 1). In the core components of AMS program interventions, and AMS monitoring and reporting, the lower mean PRR ( > 60%) revealed that Asia has wider gaps in these areas versus gold standards. Although many hospitals had formal hospital leadership statements to support AMS (mean PPR 85.6%), this was not always matched by allocated financial support for AMS activities (mean PPR 57.1%). Figure 1 Conclusion For all core components of an AMS program, most Asian hospitals participating in this survey fell short of international gold standards. Inter-country differences in gaps highlight that country-specific solutions are needed to improve current standards in AMS. Disclosures Tetsuya Matsumoto, MD; PhD, MSD (Speaker's Bureau)Pfizer (Speaker's Bureau)