Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: the OnCovid Inflammatory Score

Background: Patients with cancer are particularly susceptible to SARS-CoV-2 infection. The systemic inflammatory response is a pathogenic mechanism shared by cancer progression and COVID-19. We investigated systemic inflammation as a driver of severity and mortality from COVID-19, evaluating the prognostic role of commonly used inflammatory indices in SARS-CoV-2-infected patients with cancer accrued to the OnCovid study. Methods: In a multicenter cohort of SARS-CoV-2-infected patients with cancer in Europe, we evaluated dynamic changes in neutrophil:lymphocyte ratio (NLR); platelet:lymphocyte ratio (PLR); Prognostic Nutritional Index (PNI), renamed the OnCovid Inflammatory Score (OIS); modified Glasgow Prognostic Score (mGPS); and Prognostic Index (PI) in relation to oncological and COVID-19 infection features, testing their prognostic potential in independent training (n=529) and validation (n=542) sets. Results: We evaluated 1071 eligible patients, of which 625 (58.3%) were men, and 420 were patients with malignancy in advanced stage (39.2%), most commonly genitourinary (n=216, 20.2%). 844 (78.8%) had ≥1 comorbidity and 754 (70.4%) had ≥1 COVID-19 complication. NLR, OIS, and mGPS worsened at COVID-19 diagnosis compared with pre-COVID-19 measurement (p<0.01), recovering in survivors to pre-COVID-19 levels. Patients in poorer risk categories for each index except the PLR exhibited higher mortality rates (p<0.001) and shorter median overall survival in the training and validation sets (p<0.01). Multivariable analyses revealed the OIS to be most independently predictive of survival (validation set HR 2.48, 95% CI 1.47 to 4.20, p=0.001; adjusted concordance index score 0.611). Conclusions: Systemic inflammation is a validated prognostic domain in SARS-CoV-2-infected patients with cancer and can be used as a bedside predictor of adverse outcome. Lymphocytopenia and hypoalbuminemia as computed by the OIS are independently predictive of severe COVID-19, supporting their use for risk stratification. Reversal of the COVID-19-induced proinflammatory state is a putative therapeutic strategy in patients with cancer

Determinants of enhanced vulnerability to coronavirus disease 2019 in UK patients with cancer: a European study

Despite high contagiousness and rapid spread, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to heterogeneous outcomes across affected nations. Within Europe (EU), the United Kingdom (UK) is the most severely affected country, with a death toll in excess of 100,000 as of January 2021. We aimed to compare the national impact of coronavirus disease 2019 (COVID-19) on the risk of death in UK patients with cancer versus those in continental EU. Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of patients with cancer consecutively diagnosed with COVID-19 in 27 centres from 27th February to 10th September 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline including oncological and COVID-19-specific therapy across UK and EU cohorts and evaluated the association of these factors with the risk of adverse outcomes in multivariable Cox regression models. Findings: Compared with EU (n = 924), UK patients (n = 468) were characterised by higher case fatality rates (40.38% versus 26.5%, p < 0.0001) and higher risk of death at 30 days (hazard ratio [HR], 1.64 [95% confidence interval {CI}, 1.36-1.99]) and 6 months after COVID-19 diagnosis (47.64% versus 33.33%; p < 0.0001; HR, 1.59 [95% CI, 1.33-1.88]). UK patients were more often men, were of older age and have more comorbidities than EU counterparts (p < 0.01). Receipt of anticancer therapy was lower in UK than in EU patients (p < 0.001). Despite equal proportions of complicated COVID-19, rates of intensive care admission and use of mechanical ventilation, UK patients with cancer were less likely to receive anti-COVID-19 therapies including corticosteroids, antivirals and interleukin-6 antagonists (p < 0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of the patient's age, gender, tumour stage and status; number of comorbidities; COVID-19 severity and receipt of anticancer and anti-COVID-19 therapy. Rates of permanent cessation of anticancer therapy after COVID-19 were similar in the UK and EU cohorts. Interpretation: UK patients with cancer have been more severely impacted by the unfolding of the COVID-19 pandemic despite societal risk mitigation factors and rapid deferral of anticancer therapy. The increased frailty of UK patients with cancer highlights high-risk groups that should be prioritised for anti-SARS-CoV-2 vaccination. Continued evaluation of long-term outcomes is warranted

Determinants of enhanced vulnerability to COVID-19 in UK cancer patients: a European Study

Background: Despite high contagiousness and rapid spread, SARS-CoV-2 has led to heterogeneous outcomes across affected nations. Within Europe, the United Kingdom (UK) is the most severely affected country, with a death toll in excess of 100.000 as of January 2021. We aimed to compare the national impact of COVID-19 on the risk of death in UK cancer patients versus those in continental Europe (EU). / Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of cancer patients consecutively diagnosed with COVID-19 in 27 centres from February 27 to September 10, 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline, including oncological and COVID-19 specific therapy across UK and EU cohorts and evaluated the association of these factors with the risk adverse outcome in multivariable Cox regression models. / Findings: Compared to EU (n=924), UK patients (n=468) were characterised by higher case fatality rates (40.38% versus 26.5%, p<0.0001), higher risk of death at 30 days (hazard ratio, HR 1.64 [95%CI 1.36-1.99]) and 6 months after COVID-19 diagnosis (47.64% versus 33.33%, p<0.0001, HR 1.59 [95%CI 1.33-1.88]). UK patients were more often males, of older age and more co-morbid than EU counterparts (p<0.01). Receipt of anticancer therapy was lower in UK versus EU patients (p<0.001). Despite equal proportions of complicated COVID-19, rates of intensive care admission and use of mechanical ventilation, UK cancer patients were less likely to receive anti-COVID-19 therapies including corticosteroids, anti-virals and interleukin-6 antagonists (p<0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of patient’s age, gender, tumour stage and status, number of co-morbidities, COVID-19 severity, receipt of anticancer and anti-COVID-19 therapy. Rates of permanent cessation of anticancer therapy post COVID-19 were similar in UK versus EU. / Interpretation: UK cancer patients have been more severely impacted by the unfolding of the COVID-19 pandemic despite societal risk mitigation factors and rapid deferral of anticancer therapy. The increased frailty of UK cancer patients highlights high-risk groups that should be prioritised for anti-SARS-CoV-2 vaccination. Continued evaluation of long-term outcomes is warranted

Lean rules extraction methodology for lean PSS design via key performance indicators monitoring

Lean PSS (Product-Service System) design comprises a promising strategy for delivering sustainable PSS offerings, considering several well-established lean practices. However, automated ways to apply lean practices and more specifically lean rules in industry are limited. This work proposes a methodology for improving the leanness of PSS design, by combining real-time KPI monitoring with lean principles and practices. Through a correlation of typical wastes with the metrics used in the calculation of KPIs, the Total Leanness Index (TLI) of the procedures is defined. Based on automatically identified trade-off values for TLI, lean rules are extracted to improve the performance of PSS lifecycle phases. The proposed lean rules extraction methodology (LeanREM) is validated through a case study of power waste reduction and the concurrently maintenance time decrease in a mould-making company

PSS Design Considering Feedback from the Entire Product-service Lifecycle and Social Media

In the globally competitive market landscape, companies, in order to remain sustainable, must shift their focus towards constantly improving their PSS offerings by incorporating lean thinking approaches. PSS are complex, dynamic, and multi-dimensional systems, which are supported by appropriate infrastructure and networks. At the same time, PSS require robust engineering methods and tools for their design, which allow multi-dimensional exchange of knowledge between the designers and the relevant stakeholders across the value chain. Currently, enabling technologies such as Cloud technology, social media and networking, knowledge management, and context sensitivity present new possibilities to enhance the knowledge exchange and the collaborative process of PSS design. These technologies allow the gathering and analysis of big volumes of data from scattered heterogeneous IT systems and, at the same time, allow PSS design improvements by processing the experiences of the business customers, consumers, designers, shop-floor, and provide feedback to the design phase. However, a number of challenges are encountered during the gathering, visualization, monitoring, and assessment of related data, such as the lack of context sensitivity. Simultaneously, PSS evaluation approaches are still immature and there is limited work that correlates the impact of the entire PSS lifecycle with the performance assessment of the PSS design. The present work includes a review of the aforementioned technologies from academic, market, and industrial perspectives. Based on an extensive literature review and on constructive discussions with three European SMEs, several barriers and limitations of adopting the aforementioned technologies in practice are identified. Finally, a conceptual eco-innovative framework for lean PSS design is presented, explaining how these technologies could be combined for the improvements of PSS design and evaluation procedures

Definition of a PSS Engineering Environment: from the Theoretical Methodology to the Platform Implementation

The recent years have seen an increasing interest from the companies to differentiate themselves from competitors by enriching their portfolio with new product related services. The introduction of the Product Service System (PSS) worsened the companies’ economic performance since the proposed PSSs were not designed using methodologies and tools created to make them sustainable. In order to overcome this problem, the DIVERSITY project proposes a new methodology that considers the entire product life cycle, from the identification of the customer’s need to the PSS’ conceptualization, design and market performance monitoring. This paper aims at explaining the DIVERSITY methodology and the engineering platform derived from it highlighting the characteristics and functions of each tool

The Product Service System Lean Design Methodology (PSSLDM): Integrating product and service components along the whole PSS lifecycle

Nowadays manufacturers companies are increasingly compelled to navigate towards servitization. Different methods and approaches were proposed in literature to support them to switch from traditional product-based business model to product service systems (PSSs). However, new knowledge, capabilities and skills were needed to consistently develop PSSs, since they need a joint focus on both customer’s perspective and company’s internal performance and at the same time a proper support for the integration of product and service design. The purpose of this paper is to propose the Product Service Systemn Lean Design Methodology (PSSLDM), a structured methodology to develop PSSs along their entire lifecycle