Abstract Backgrounds Healthcare-associated infections (HAIs) increase morbidity, mortality, and costs, necessitating effective prevention strategies. This study estimates the additional costs of HAIs in a university hospital in Rome, Italy Policlinico Tor Vergata (PTV), to inform policymakers, healthcare professionals, and researchers. Methods We conducted a retrospective cohort study, including all patients admitted or discharged in 2018. We applied propensity score matching (PSM) to balance study groups and then we analysed cost differences using the average treatment effect on the treated (ATT) approach. Costs were calculated using the Diagnosis Related Groups (DRGs) system. Outcome measures included the real reimbursement cost in euros and the relative cost increment using adjusted logarithmic transformation. Results 12,033 patients were included: 6,653(55%) female, 5,380 (45%) male, with a median age of 67. In total, 1,212 (10.1%) infected patients were compared to 10,821 (89.9%) non-infected patients. Predominant infections were urinary tract infections (UTI) (48.8%) and blood stream infections (BSI) (34.4%), while Staphylococcus spp. (37.5%) and Enterococcus spp. (36.4%) were the most common pathogens. The propensity score analysis showed a 59.7% (95% CI: 48.8% to 71.3%) cost increase for infected patients. They incurred an additional €4,988 (95% CI: €4,173 to €5,804) in costs. Subgroup analyses revealed cost variations across infection sites and pathogens, with Klebsiella P. having the greatest economic impact at €7,586 (95% CI: €5,301 to €9,871) and BSI also at €9,719 (95% CI: €8,137 to €11,307). Conclusions This study highlights the significant additional cost burden of HAIs in the PTV. Interventions with an equal or lower cost per HAI averted can be considered cost-effective. Public health actions, including enhancing infection prevention, developing or revising policies, and strengthening surveillance systems, should be prioritised to address ongoing HAI challenges. Key messages • Our study reveals a significant 59.7% cost increase (€4,988in our hospital) for HAI patients, highlighting the need for cost-effective prevention strategies in healthcare settings. • Findings emphasise the importance of enhancing infection prevention measures, policy development, and strengthening surveillance systems to reduce HAI-associated costs.
BackgroundHealthcare-associated infections (HCAIs) burden healthcare globally. Amid the SARS-CoV-2 pandemic, intensified infection control measures, such as mask usage and hand hygiene, were implemented. This study aimed to assess the efficacy of these measures in preventing HCAIs among hospitalized patients.MethodsUsing the PICO framework, the study focused on hospitalized patients and the effectiveness of anti-COVID-19 measures in preventing HCAIs. A systematic review of literature published in 2020-2021-2022 was conducted, examining interventions such as mask usage, hand hygiene, and environmental cleaning.ResultsThis systematic review analyzed 42 studies: 2 in 2020, 21 in 2021 and 19 in 2022. Most studies were from high-income countries (28). Most studies (30 out of 42) reported a reduction in HCAIs after implementing anti-COVID-19 measures Gastrointestinal infections and respiratory tract infections showed significant reduction unlike bloodstream infections and urinary tract infections. Some wards, like cardiology and neurology, experienced reduced HCAIs, unlike intensive care units and coronary care units. We observed an increase in studies reporting no effect of hygiene measures on HCAIs in 2022, eventually indicating a shift in effectiveness over time.DiscussionAnti-COVID-19 measures have shown selective efficacy in preventing HCAIs. The study emphasizes the need for context-specific strategies and increased focus on regions with limited resources. Continued research is essential to refine infection control practices, especially in high-risk settings.
Supplementary Figure 6 from Therapeutic Effectiveness of Recombinant Cancer Vaccines Is Associated with a Prevalent T-Cell Receptor α Usage by Melanoma-specific CD8<sup>+</sup> T Lymphocytes
Abstract The development of effective anti-tumor immune responses is normally constrained by low avidity, tumor-specific cytotoxic T lymphocytes (CTL) which are unable to eradicate the tumor. Therefore, new strategies to rescue anti-tumor activity of low avidity melanoma-specific CTL in vivo may improve immunotherapy efficacy. To boost the in vivo effectiveness of low avidity CTL we immunized mice bearing metastatic lung melanoma with artificial Antigen Presenting Cells (aAPC), made by covalently coupling pepMHC-Ig dimers and B7.1-Ig molecules to magnetic beads. aAPC treatment induced significant tumor reduction in a mouse telomerase antigen system and complete tumor eradication in a mouse TRP-2 antigen system, when low avidity CTL specific for these antigens were adoptively transferred. In addition, in an in vivo treatment model of subcutaneous melanoma, aAPC injection also augmented the activity of adoptively transferred CTL and significantly delayed tumor growth. In vivo tumor clearance due to aAPC administration correlated with in situ proliferation of the transferred CTL. In vitro studies showed that aAPC effectively stimulated cytokine release and TCR down-regulation in low avidity CTL. Therefore, in vivo aAPC administration represents a potentially novel approach to improve adoptive immunotherapy of cancer.
Acute Lymphoblastic Leukaemia (ALL) remains the most frequent cause of cancer-related mortality in children and novel therapies are needed for the treatment of relapsed/refractory childhood ALL. One approach is the targeting of ALL blasts with the Pseudomonas immunotoxin CAT-8015. Although CAT-8015 has potent anti-leukaemia activity, with a 32 % objective response rate in a phase 1 study of childhood ALL, haemolytic-uremic syndrome (HUS) and vascular leak syndrome (VLS), major dose-limiting toxicities, have limited the use of this therapeutic approach in children. Investigations into the pathogenesis of CAT-8015-induced HUS/VLS are hindered by the lack of an adequate model system that replicates clinical manifestations, but damage to vascular endothelial cells (ECs) and blood cells are believed to be major initiating factors in both syndromes. Since there is little evidence that murine models replicate human HUS/VLS, and CAT-8015-induced HUS/VLS predominantly affects children, we developed human models and used novel methodologies to investigate CAT-8015 interactions with red blood cells (RBCs) from paediatric ALL patients and ECs of excised human mesenteric arteries. We provide evidence that CAT-8015 directly interacts with RBCs, mediated by Pseudomonas toxin. We also show correlation between the electrical properties of the RBC membrane and RBC susceptibility to CAT-8015-induced lysis, which may have clinical implication. Finally, we provide evidence that CAT-8015 is directly cytototoxic to ECs of excised human mesenteric arteries. In conclusion, the human models we developed constitutes the first, and very important, step in understanding the origins of HUS/VLS in immunotoxin therapy and will allow further investigations of HUS/VLS pathogenesis.
TB-12. ARGININE AUXOTROPHY IN PAEDIATRIC CNS TUMOURS: THE RATIONALE FOR THERAPEUTIC ARGININE DEPLETION AS A NOVEL ANTI-CANCER THERAPY Madhumita Dandapani1, Carmela De Santo2, and Francis Mussai1,2; Birmingham Childrens Hospital NHS Foundation Trust, Birmingham, UK; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK BACKGROUND: Despite significant improvements in survival of children with cancer, certain brain tumours have poor outcomes, particularly in the relapse setting. Therefore novel therapeutic strategies are needed. We have identified that some cancers are dependent on arginine for survival due to the absence of arginine recycling enzymes (arginine auxotrophism) and that this arginine addiction can be targeted. There is no published data thus far on arginine auxotrophy in paediatric CNS tumours. AIM: To examine the levels of gene expression of key enzymes involved in the synthesis and recycling of arginine in CNS tumours. METHODS: Using the R2 genomics platform,we analysed the expression of arginoscuccinate synthetase 1 (ASS1); ornithine transcarbamylase (OTC); arginosuccinate lyase (ASL), Arginase 1 and 2 isoforms and the cationic transporters CAT1 and CAT2 in a range of published CNS tumour datasets. Arginine auxotrophy was defined normal or high expression of ASS and low expression of OTC, compared to normal brain tissue and the housekeeping gene GAPDH. RESULTS: High grade glioma, diffuse intrinsic pontine glioma, ependymoma and medulloblastoma had high ASS and very low OTC expression levels compared to normal brain strongly suggesting arginine auxotrophism. Interesting all CNS tumours studied had high ASL expression. CONCLUSION: Several difficult to treat CNS tumours have the molecular features of arginine dependence. Therapeutic arginine depletion (using recombinant arginase BCT-100) may be a novel strategy for treatment of these tumours within the context of an early phase clinical trial. Neuro-Oncology 18:iii169–iii173, 2016. doi:10.1093/neuonc/now084.9 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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