Impact of antimicrobial stewardship interventions on appropriateness of surgical antibiotic prophylaxis. How to improve

Background and Objectives: Surgical Site Infections (SSIs) are the most common healthcare-associated infections and represent a major clinical problem in terms of mortality, morbidity, length of stay and overall costs. The appropriateness of Surgical Antibiotic Prophylaxis (SAP) is a key component to reduce the SSIs while the inappropriateness is a major cause of some emerging infections and selection of antibiotic resistance, therefore increasing healthcare costs. For this reasons international and national guidelines have been developed to guide clinicians in the optimal use of SAP. The The overall compliance to these guidelines is poor, with a high heterogeneity and as a consequence there is no universally recognized intervention to improve the appropriateness of SAP. The antimicrobial stewardship program is a systematic approach to improve appropriateness of antimicrobial use, to optimize the treatment of infections and to minimize the adverse effects associated with antibiotic use, like antimicrobial resistance, toxicity and costs. We describe a successfully Antimicrobial Stewardship (AMS) intervention on SAP appropriateness. Material and Methods: The prospective study was conducted at “Santa Maria” tertiary hospital in Terni, Umbria, in 12 main surgical units and was organized in three subsequent phases . The hospital defined evidence-based guidelines for optimal use of SAP, approved a new workflow to optimize the process of ordering, dispensing, administering and documenting SAP and created a satellite pharmacy in the operative block . Phase 1: we analysed 2059 elective surgical cases from January to June 2018 for 3 SAP parameters of appropriateness: indication, choice, dose. Phase 2: in July 2018 an audit was performed to analyse the result ; we reviewed 1781 elective surgical procedures from July to December 2018 looking for the same 3 SAP parameters of appropriateness. Results: The comparative analysis between phase 1 and 2 has demonstrated that the correct indication has a significant improvement (p-value 0.00128), moving from 73.63% in phase 1 to 77.82% in phase 2. The choice of antibiotic has not shown any significant improvement (p-value 0.4863) . The correct dose significantly improved (p-value< 2.2 1016 ), rising from 71.75% in phase 1 to 86.19% in phase 2. The overall compliance had a significant improvement (p-value <5.6 1012) passing from 40.21% in tphase 1 to 51.15% in phase 2. Conclusions: Our prospective study demonstrated a model of succesfully antimicrobial stewardship intervention that improves appropriateness of SAP

Molecular pathways triggered by COVID-19 in different organs: ACE2 receptor-expressing cells under attack? A review

OBJECTIVE: In human pathology, SARS-CoV-2 utilizes multiple molecular pathways to determine structural and biochemical changes within the different organs and cell types. The clinical picture of patients with COVID-19 is characterized by a very large spectrum. The reason for this variability has not been clarified yet, causing the inability to make a prognosis on the evolution of the disease. MATERIALS AND METHODS: PubMed search was performed focusing on the role of ACE 2 receptors in allowing the viral entry into cells, the role of ACE 2 downregulation in triggering the tissue pathology or in accelerating previous disease states, the role of increased levels of Angiotensin II in determining endothelial dysfunction and the enhanced vascular permeability, the role of the dysregulation of the renin angiotensin system in COVID-19 and the role of cytokine storm. RESULTS: The pathological changes induced by SARS-CoV-2 infection in the different organs, the correlations between the single cell types targeted by the virus in the different human organs and the clinical consequences, COVID-19 chronic pathologies in liver fibrosis, cardiac fibrosis and atrial arrhythmias, glomerulosclerosis and pulmonary fibrosis, due to the systemic fibroblast activation induced by angiotensin II are discussed. CONCLUSIONS: The main pathways involved showed different pathological changes in multiple tissues and the different clinical presentations. Even if ACE2 is the main receptor of SARS-CoV-2 and the main entry point into cells for the virus, ACE2 expression does not always explain the observed marked inter-individual variability in clinical presentation and outcome, evidencing the complexity of this disorder. The proper interpretation of the growing data available might allow to better classifying COVID-19 in human pathology

Is the in vivo

The OneDosePlusTM system, based on MOSFET solid-state radiation detectors and a handheld dosimetry reader, has been used to evaluate intra-fraction movements of patients with breast and prostate cancer. METHODS: An Action Threshold (AT), defined as the maximum acceptable discrepancy between measured dose and dose calculated with the Treatment Planning System (TPS) (for each field) has been determined from phantom data. To investigate the sensitivity of the system to direction of the patient movements, fixed displacements have been simulated in phantom. The AT has been used as an indicator to establish if patients move during a treatment session, after having verified the set-up with 2D and/or 3D images. Phantom tests have been performed matching different linear accelerators and two TPSs (TPS1 and TPS2). RESULTS: The ATs have been found to be very similar (5.0% for TPS1 and 4.5% for TPS2). From statistical data analysis, the system has been found not sensitive enough to reveal displacements smaller than 1 cm (within two standard deviations). The ATs applied to in vivo treatments showed that among the twenty five patients treated for breast cancer, only four of them moved during each measurement session. Splitting data into medial and lateral field, two patients have been found to move during all these sessions; the others, instead, moved only in the second part of the treatment. Patients with prostate cancer have behaved better than patients with breast cancer. Only two out of twenty five moved in each measurement session. CONCLUSIONS: The method described in the paper, easily implemented in the clinical practice, combines all the advantages of in vivo procedures using the OneDosePlusTM system with the possibility of detecting intra-fraction patient movements

MALIGNITÀ DEL MELANOMA CUTANEO DEL CANE: SIGNIFICATO DELL’ESPRESSIONE IMMUNOISTOCHIMICA DI SURVIVINA E Β-CATENINA

Recent investigations highlighted the controversial role of the Wnt/β-catenin pathway in human cutaneous melanoma (CM), where β-catenin activation seems to both inhibit melanocyte migration and invasion and contribute to metastasis development. Survivin has been proposed as a valid prognostic marker and a promising therapeutic target for invasive and metastatic melanomas. Our aim was to investigate the aberrant expression of survivin and β-catenin in canine cutaneous melanocytic tumours, in order to understand the association of the expression of these molecules with features of malignancy. 10 cutaneous melanocytomas and 7 CM were investigated by immunohistochemistry using specific antibodies. A semi-quantitative method was used to analyse the results, that were related to histopathological features, evaluated in haematoxilin-eosin stained slides. A low nuclear β-catenin expression was found in the majority of the cases evaluated, and an overexpression of nuclear survivin was observed in melanoma cases compared to melanocytomas. The low nuclear β-catenin expression would confirm considerations arisen from similar results obtained in human melanocytic tumours, indicating an important role of deregulation of Wnt/β-catenin homeostasis, rather than a direct oncogenetic role of the pathway. The overexpression of nuclear survivin in malignant forms would indicate survivin as a possible useful prognostic marker and therapeutic target in canine melanoma patients. [...

Vitamin D Status Modulates Inflammatory Response in HIV+ Subjects: Evidence for Involvement of Autophagy and TG2 Expression in PBMC

Conflicting results on the involvement of vitamin D deficiency in inflammatory and immune response in HIV+ subjects are reported. We aimed to characterize the possible influence of vitamin D status on changes in expression of tissue transglutaminase gene (TGM2) and other genes involved in inflammatory response and autophagy in peripheral blood mononuclear cells (PBMC) from HIV+ subjects. HIV+ subjects (n = 57) under antiretroviral therapy (ART) and healthy controls (n = 40) were enrolled. mRNA levels of 1-alpha-hydroxylase (CYP27B1), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), TGM2, microtubule-associated protein 1A/1B-light chain 3 (LC3), autophagy-related 5 homolog (ATG5), and Beclin 1 (BECN1) were quantified by real-time PCR. In HIV+ subjects, 25(OH)D3 plasma levels were negatively correlated with time since HIV diagnosis. In PBMC from HIV+ subjects, increases in gene expression of TNF-α and IFN-γ in comparison to controls were observed. The highest increase in TNF-α transcripts was observed in HIV+ subjects with deficient 25(OH)D3 levels. Autophagy-related genes LC3, ATG5, and BECN1 were down-regulated in HIV+ subjects. Moreover, TGM2 transcripts were up-regulated in PBMC from HIV+ subjects with 25(OH)D3 deficiency. Changes observed in PBMC from HIV+ subjects appeared to be dependent on vitamin D status. The present results suggest that vitamin D deficiency is associated with changes in the expression of markers of inflammation and autophagy, resulting in immune cell dysfunction