Electrocautery, diathermy, and surgical energy devices: are surgical teams at risk during the COVID-19 pandemic?

OBJECTIVE: The aim of the study was to provide a rapid synthesis of available data to identify the risk posed by utilizing surgical energy devices intraoperatively due to the generation of surgical smoke, an aerosol. Secondarily it aims to summarize methods to minimize potential risk to operating room staff. SUMMARY BACKGROUND DATA: Continuing operative practice during the coronavirus disease-19 (COVID-19) pandemic places the health of operating theatre staff at potential risk. SARS-CoV2 is transmitted through inhaled droplets and aerosol particles, thus posing an inhalation threat even at considerable distance. Surgical energy devices generate an aerosol of biological particular matter during use. The risk to healthcare staff through use of surgical energy devices is unknown. METHODS: This review was conducted utilizing a rapid review methodology to enable efficient generation and dissemination of information useful for concurrent clinical practice. RESULTS: There are conflicting stances on the use of energy devices and laparoscopy by different surgical governing bodies and societies. There is no definitive evidence that aerosol generated by energy devices may carry active SARS-CoV2 virus. However, investigations of other viruses have demonstrated aerosolization through energy devise use. Measures to reduce potential transmission include appropriate personal protective equipment, evacuation and filtration of surgical plume, limiting energy device use if appropriate, and adjusting endoscopic and laparoscopic practice (low CO2 pressures, evacuation through ultrafiltration systems). CONCLUSIONS: The risk of transmission of SARS-CoV2 through aerosolized surgical smoke associated with energy device use is not fully understood, however transmission is biologically plausible. Caution and appropriate measures to reduce risk to healthcare staff should be implemented when considering intraoperative use of energy devices

Gut microbiota modulation of chemotherapy efficacy and toxicity

Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation. The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds

Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling

Activating mutations in genes of the Ras-mitogen-activated protein kinase (MAPK) pathway occur in approximately 30% of all human cancers; however, mutation of Ras alone is rarely sufficient to induce tumour development. Scribble is a polarity regulator recently isolated from a Drosophila screen for events that cooperate with Ras mutation to promote tumour progression and cell invasion. In mammals, Scribble regulates directed cell migration and wound healing in vivo; however, no role has been identified for mammalian Scribble in oncogenic transformation. Here we show that in human epithelial cells expressing oncogenic Ras or Raf, loss of Scribble promotes invasion of cells through extracellular matrix in an organotypic culture system. Further, we show that the mechanism by which this occurs is in the regulation of MAPK signalling by Scribble. The suppression of MAPK signalling is a highly conserved function of Scribble as it also prevents Raf-mediated defects in Drosophila wing development. Our data identify Scribble as an important mediator of MAPK signalling and provide a molecular basis for the observation that Scribble expression is decreased in many invasive human cancers. © 2008 Macmillan Publishers Limited All rights reserved

Antimicrobial use in European acute care hospitals: results from the second point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use, 2016 to 2017

Antimicrobial agents used to treat infections are life-saving. Overuse may result in more frequent adverse effects and emergence of multidrug-resistant microorganisms. In 2016-17, we performed the second point-prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals. We included 1,209 hospitals and 310,755 patients in 28 of 31 European Union/European Economic Area (EU/EEA) countries. The weighted prevalence of antimicrobial use in the EU/EEA was 30.5% (95% CI: 29.2-31.9%). The most common indication for prescribing antimicrobials was treatment of a community-acquired infection, followed by treatment of HAI and surgical prophylaxis. Over half (54.2%) of antimicrobials for surgical prophylaxis were prescribed for more than 1 day. The most common infections treated by antimicrobials were respiratory tract infections and the most commonly prescribed antimicrobial agents were penicillins with beta-lactamase inhibitors. There was wide variation of patients on antimicrobials, in the selection of antimicrobial agents and in antimicrobial stewardship resources and activities across the participating countries. The results of the PPS provide detailed information on antimicrobial use in European acute care hospitals, enable comparisons between countries and hospitals, and highlight key areas for national and European action that will support efforts towards prudent use of antimicrobials

a pilot study, 2013

Introduction After recognition of European outbreaks of Clostridium difficile infections (CDIs) associated with the emergence of PCR ribotype 027/NAP1 in 2005, CDI surveillance at country level was encouraged by the European Centre for Disease Prevention and Control (ECDC) [1]. In 2008, an ECDC-supported European CDI survey (ECDIS) identified large intercountry variations in incidence rates and distribution of prevalent PCR ribotypes, with the outbreak-related PCR ribotype 027 being detected in 5% (range: 0–26) of the characterised isolates [2]. The surveillance period was limited to one month and the representation of European hospitals was incomplete; however, this has been the only European (comprising European Union (EU)/European Economic Area (EEA) and EU candidate countries) CDI surveillance study. The authors highlighted the need for national and European surveillance to control CDI. Yet, European countries were found to have limited capacity for diagnostic testing, particularly in terms of standard use of optimal methods and absence of surveillance protocols and a fully validated, standardised and exchangeable typing system for surveillance and/or outbreak investigation. As of 2011, 14 European countries had implemented national CDI surveillance, with various methodologies [3]. National surveillance systems have since reported a decrease in CDI incidence rate and/or prevalence of PCR ribotype 027 in some European countries [4-8]. However, CDI generally remains poorly controlled in Europe [9], and PCR ribotype 027 continues to spread in eastern Europe [10-12] and globally [13]. In 2010, ECDC launched a new project, the European C. difficile Infection Surveillance Network (ECDIS-Net), to enhance surveillance of CDI and laboratory capacity to test for CDI in Europe. The goal of ECDIS- Net was to establish a standardised CDI surveillance protocol suitable for application all over Europe in order to: (i) estimate the incidence rate and total infection rate of CDI (including recurrent CDI cases) in European acute care hospitals; (ii) provide participating hospitals with a standardised tool to measure and compare their own incidence rates with those observed in other participating hospitals; (iii) assess adverse outcomes of CDI such as complications and death; and (iv) describe the epidemiology of CDI concerning antibiotic susceptibility, PCR ribotypes, presence of tcdA, tcdB and binary toxins and detect new emerging types at local, national and European level. The primary objectives of the present study were to: (i) test the pilot protocol for the surveillance of CDI in European acute care hospitals developed by ECDIS-Net (methodology, variables and indicators); (ii) assess the feasibility and workload of collecting the required hospital data, case- based epidemiological and microbiological data; and (iii) evaluate the quality of data collected, whether in the presence or absence of existing national CDI surveillance activities. A secondary aim was to assess the relationship between patient and microbiological characteristics and in-hospital outcome of CDI to confirm the added value of collecting detailed epidemiological and microbiological data on CDI at European level

Standardised surveillance of Clostridium Difficile Infection in European acute care hospitals: A pilot study, 2013

Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillance for acute care hospitals: a ‘minimal’ option (aggregated hospital data), a ‘light’ option (including patient data for CDI cases) and an ‘enhanced’ option (including microbiological data on the first 10 CDI episodes per hospital). A total of 37 hospitals in 14 European countries tested these options for a three-month period (between 13 May and 1 November 2013). All 37 hospitals successfully completed the minimal surveillance option (for 1,152 patients). Clinical data were submitted for 94% (1,078/1,152) of the patients in the light option; information on CDI origin and outcome was complete for 94% (1,016/1,078) and 98% (294/300) of the patients in the light and enhanced options, respectively. The workload of the options was 1.1, 2.0 and 3.0 person-days per 10,000 hospital discharges, respectively. Enhanced surveillance was tested and was successful in 32 of the hospitals, showing that C. difficile PCR ribotype 027 was predominant (30% (79/267)). This study showed that standardised multicountry surveillance, with the option of integrating clinical and molecular data, is a feasible strategy for monitoring CDI in Europe

The mTORC1 inhibitor everolimus prevents and treats Eμ-Myc lymphoma by restoring oncogene-induced senescence

MYC deregulation is common in human cancer. IG-MYC translocations that are modeled in EμMyc mice occur in almost all cases of Burkitt lymphoma as well as in other B-cell lymphoproliferative disorders. Deregulated expression of MYC results in increased mTOR complex 1 (mTORC1) signaling. As tumors with mTORC1 activation are sensitive to mTORC1 inhibition, we used everolimus, a potent and specific mTORC1 inhibitor, to test the requirement for mTORC1 in the initiation and maintenance of EμMyc lymphoma. Everolimus selectively cleared premalignant B cells from the bone marrow and spleen, restored a normal pattern of B-cell differentiation, and strongly protected against lymphoma development. Established EμMyc lymphoma also regressed after everolimus therapy. Therapeutic response correlated with a cellular senescence phenotype and induction of p53 activity. Therefore, mTORC1-dependent evasion of senescence is critical for cellular transformation and tumor maintenance by MYC in B lymphocytes

Optical spectroscopy shows that the normal state of URu2_2Si2_2 is an anomalous Fermi liquid

Fermi showed that electrons, as a result of their quantum nature, form a gas of particles where the temperature and density follow the so called Fermi distribution. In a metal, as shown by Landau, that despite their strong Coulomb interaction with each other and the positive background ions, the electrons continue to act like free quantum mechanical particles but with enhanced masses. This state of matter, the Landau-Fermi liquid, is recognized experimentally by an electrical resistivity that is proportional to the square of the absolute temperature plus a term proportional to the square of the frequency of the applied field. Calculations show that, if electron-electron scattering dominates the resistivity in a Landau Fermi liquid, the ratio of the two terms, $b$ has the universal value of {\em b} = 4. We find that in the normal state of the heavy Fermion metal URu$_2$Si$_2$, instead of the Fermi liquid value of 4 the coefficient $b$ =1 $\pm$ 0.1. This unexpected result implies that the electrons in this material are experiencing a unique scattering process. This scattering is intrinsic and we suggest that, the uranium $f$ electrons do not hybridize to form a coherent Fermi liquid but instead act like a dense array of elastic impurities, interacting incoherently with the charge carriers. This behavior is not restricted to URu$_2$Si$_2$. Fermi liquid like states with $b \neq$ 4 have been observed in a number of disparate systems but the significance of this result has not been recognized.Comment: 5 pages, 6 figure