POEMS Syndrome: Real World Experience in Diagnosis and Systemic Therapy - 108 Patients Multicenter Analysis

POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases analyzing clinical features and therapeutic modes. We compare our results with the available literature. This is the first description with such wide use of proteasome inhibitors in first line treatment. POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present a retrospective real world experience of 108 patients with POEMS. We analyzed the clinical features and therapeutic interventions. Regarding clinical features, our findings demonstrated that skin lesions, thrombocythemia and polycythemia were present less frequently than reported previously. Regarding clinical interventions, this is one of the largest analyses of front line treatment in POEMS and the first one to include frequent utilization of proteasome inhibitors (37%). Bortezomib monotherapy was the most effective therapy achieving complete remission/very good partial remissions (CR/VGPR) in 69% of patients. Thirty percent of patients proceeded to planned autologous stem cell transplant (ASCT) as part of the front-line treatment resulting in statistically superior progression-free (PFS) and overall survival (OS) compared to non-ASCT treated patients (P= .003). In multivariate analysis, anemia, thrombocytopenia, and as age over 60 were associated with a negative impact on patient outcomes

Mortality Following Clostridioides difficile Infection in Europe : A Retrospective Multicenter Case-Control Study

We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in nine hospitals from seven European countries. A total of 624 patients were included, of which 415 were deceased (cases) and 209 were still alive 90 days after a CDI diagnosis (controls). The most common antibiotics used previously in both groups were β-lactams; previous exposure to fluoroquinolones was significantly (p = 0.0004) greater in deceased patients. Multivariate logistic regression showed that the factors independently related with death during CDI were older age, inadequate CDI therapy, cachexia, malignancy, Charlson Index, long-term care, elevated white blood cell count (WBC), C-reactive protein (CRP), bacteraemia, complications, and cognitive impairment. In addition, older age, higher levels of WBC, neutrophil, CRP or creatinine, the presence of malignancy, cognitive impairment, and complications were strongly correlated with shortening the time from CDI diagnosis to death. CDI prevention should be primarily focused on hospitalised elderly people receiving antibiotics. WBC, neutrophil count, CRP, creatinine, albumin and lactate levels should be tested in every hospitalised patient treated for CDI to assess the risk of a fatal outcome

Sports events and interaction among spectators: examining antecedents of spectators’ value creation

Research question: Spectating at sports events comprises on-pitch and off-pitch benefits. Value may also derive from spectator-to-spectator interaction, however, we do not know whether all types of interaction have similar effects on value creation and subsequent word-of-mouth (WOM) behaviours. We investigate two types of spectator-to-spectator interaction – between known/familiar others, and between unknown-others. We study their effects within a framework grounded in Customer Dominant Logic and sport value framework, integrating on-pitch sport performance, off-pitch service quality, overall satisfaction, team identification and WOM intention. Research methods: Hypotheses were tested using a survey of 1002 spectators of a British Premier League football club. Respondents were asked about the last game they attended. Data were analysed using Structural Equations Modelling and PROCESS analysis. Results and findings: Customer-to-customer interaction was antecedent to overall satisfaction and team identification. Satisfaction and team identification led to WOM intention, with team identification having greater effect. Evaluation of on-pitch performance (the football match) influenced overall satisfaction more than off-pitch service quality. The study contributes to knowledge in finding that customer-to-customer interaction with familiar accompaniers influenced satisfaction more than interaction with anonymous-other spectators. However, the latter contributed more to team identification and indirectly to WOM. Implications: The study highlights the importance to sports events organisers of facilitating customer-to-customer interaction. While promotion of many sports events focuses on game performance, this study highlights the importance of promoting the social benefits of attendance in increasing positive WOM. Suggestions are made, including provision of social media platforms within events to promote interaction among spectators

Human Induced Pluripotent Stem Cells Differentiation into Oligodendrocyte Progenitors and Transplantation in a Rat Model of Optic Chiasm Demyelination

BACKGROUND: This study aims to differentiate human induced pluripotent stem cells (hiPSCs) into oligodendrocyte precursors and assess their recovery potential in a demyelinated optic chiasm model in rats. METHODOLOGY/PRINCIPAL FINDINGS: We generated a cell population of oligodendrocyte progenitors from hiPSCs by using embryoid body formation in a defined medium supplemented with a combination of factors, positive selection and mechanical enrichment. Real-time polymerase chain reaction and immunofluorescence analyses showed that stage-specific markers, Olig2, Sox10, NG2, PDGFRα, O4, A2B5, GalC, and MBP were expressed following the differentiation procedure, and enrichment of the oligodendrocyte lineage. These results are comparable with the expression of stage-specific markers in human embryonic stem cell-derived oligodendrocyte lineage cells. Transplantation of hiPSC-derived oligodendrocyte progenitors into the lysolecithin-induced demyelinated optic chiasm of the rat model resulted in recovery from symptoms, and integration and differentiation into oligodendrocytes were detected by immunohistofluorescence staining against PLP and MBP, and measurements of the visual evoked potentials. CONCLUSIONS/SIGNIFICANCE: These results showed that oligodendrocyte progenitors generated efficiently from hiPSCs can be used in future biomedical studies once safety issues have been overcome

An orally available, small-molecule interferon inhibits viral replication

Most acute hepatitis C virus (HCV) infections become chronic and some progress to liver cirrhosis or hepatocellular carcinoma. Standard therapy involves an interferon (IFN)-α-based regimen, and efficacy of therapy has been significantly improved by the development of protease inhibitors. However, several issues remain concerning the injectable form and the side effects of IFN. Here, we report an orally available, small-molecule type I IFN receptor agonist that directly transduces the IFN signal cascade and stimulates antiviral gene expression. Like type I IFN, the small-molecule compound induces IFN-stimulated gene (ISG) expression for antiviral activity in vitro and in vivo in mice, and the ISG induction mechanism is attributed to a direct interaction between the compound and IFN-α receptor 2, a key molecule of IFN-signaling on the cell surface. Our study highlights the importance of an orally active IFN-like agent, both as a therapy for antiviral infections and as a potential IFN substitute

Investigating the Genetic Diversity of H5 Avian Influenza Viruses in the United Kingdom from 2020–2022

Publication history: Accepted - 27 April 2023; Published - 26 June 2023.Since 2020, the United Kingdom and Europe have experienced annual epizootics of high-pathogenicity avian influenza virus (HPAIV). The first epizootic, during the autumn/winter of 2020–2021, involved six H5Nx subtypes, although H5N8 HPAIV dominated in the United Kingdom. While genetic assessments of the H5N8 HPAIVs within the United Kingdom demonstrated relative homogeneity, there was a background of other genotypes circulating at a lower degree with different neuraminidase and internal genes. Following a small number of detections of H5N1 in wild birds over the summer of 2021, the autumn/winter of 2021–2022 saw another European H5 HPAIV epizootic that dwarfed the prior epizootic. This second epizootic was dominated almost exclusively by H5N1 HPAIV, although six distinct genotypes were defined. We have used genetic analysis to evaluate the emergence of different genotypes and proposed reassortment events that have been observed. The existing data suggest that the H5N1 viruses circulating in Europe during late 2020 continued to circulate in wild birds throughout 2021, with minimal adaptation, but then went on to reassort with AIVs in the wild bird population. We have undertaken an in-depth genetic assessment of H5 HPAIVs detected in the United Kingdom over two winter seasons and demonstrate the utility of in-depth genetic analyses in defining the diversity of H5 HPAIVs circulating in avian species, the potential for zoonotic risk, and whether incidents of lateral spread can be defined over independent incursions of infections from wild birds. This provides key supporting data for mitigation activities.This work was funded by the Department for Environment, Food, and Rural Affairs (Defra) (United Kingdom) and the Devolved Administrations of Scotland and Wales through the following programs of work: SV3400, SV3032, SV3006, and SE2213. Funding for diagnostic testing in Northern Ireland was provided by the Department for Agriculture, Environment, and Rural Affairs (DAERA). The writing and data analysis for the manuscript were also supported in part by the DELTA-FLU project funded by the European Union’s Horizon 2020 research and innovation program under grant agreement no. 727922. A.C.B., J.J., and I.H.B. were also partly funded by the BBSRC/Defra-funded research initiative FluMAP (BB/X006204/1)

Investigating the role of customers’ perceptions of employee effort and justice in service recovery

Purpose: The purpose of this paper is, first, to identify the relationship, if any, between customers’ perceptions of justice (functional element) and employee effort (symbolic element) and their effects on satisfaction and loyalty in the context of service recovery and, second, to determine the impact of cross-cultural differences on these relationships. Design/methodology/approach: Survey data from actual customers were gathered in three countries (n = 414) and analyzed using structural equation modeling to test the proposed hypotheses. Findings: The results demonstrate the role of the constructs of perceived employee effort and perceived justice in influencing post-recovery satisfaction and loyalty across cultures. While perceived justice is valued across cultures, customers from feminine (masculine) cultures require more (less) employee effort to influence post-recovery satisfaction positively. Customers from low (high) uncertainty cultures are more (less) willing to give the provider another chance after a service recovery. Research limitations/implications: The study shows that both functional and symbolic elements of service recovery are important determinants of customer satisfaction and loyalty and that their influence can be significant in a cross-cultural context. Practical implications: International service managers must consider the nature of cultural differences in their markets to develop and implement tailored recovery strategies that can result in satisfied customers. Originality/value: This study is the first to integrate the functional and symbolic elements of service recovery, their impact on customers’ behavioral responses and the influence of cultural variations