Decoding Klebsiella pneumoniae in poultry chain: unveiling genetic landscape, antibiotic resistance, and biocide tolerance in non-clinical reservoirs.

The rise of antibiotic resistance in the food chain is influenced by the use of antimicrobial agents, such as antibiotics, metals, and biocides, throughout the entire farm-to-fork continuum. Besides, non-clinical reservoirs potentially contribute to the transmission of critical pathogens such as multidrug-resistant (MDR) Klebsiella pneumoniae. However, limited knowledge exists about the population structure and genomic diversity of K. pneumoniae circulating in conventional poultry production. We conducted a comprehensive characterization of K. pneumoniae across the whole chicken production chain (7 farms; 14 flocks + environment + meat, 56 samples; 2019-2022), exploring factors beyond antibiotics, like copper and quaternary ammonium compounds (QACs). Clonal diversity and adaptive features of K. pneumoniae were characterized through cultural, molecular (FT-IR), and whole-genome-sequencing (WGS) approaches. All except one flock were positive for K. pneumoniae with a significant increase (p < 0.05) from early (n = 1/14) to pre-slaughter (n = 11/14) stages, most (n = 6/7) persisting in chicken meat batches. Colistin-resistant K. pneumoniae rates were low (4%-n = 1/24 positive samples), while most samples carried MDR strains (67%-n = 16/24) and copper-tolerant isolates (63%-n = 15/24, with sil and pco gene clusters; MICCuSO4 ≥ 16 mM), particularly at pre-slaughter. Benzalkonium chloride consistently exhibited activity against K. pneumoniae (MIC/MBC range = 4-64 mg/L) from representative strains independently of the presence or absence of genes linked to QACs tolerance. A polyclonal K. pneumoniae population, discriminated by FT-IR and WGS, included various lineages dispersed throughout the chicken's lifecycle at the farm (ST29-KL124, ST11-KL106, ST15-KL19, ST1228-KL38), until the meat (ST1-KL19, ST11-KL111, ST6405-KL109, and ST6406-CG147-KL111), or over years (ST631-49 KL109, ST6651-KL107, ST6406-CG147-KL111). Notably, some lineages were identical to those from human clinical isolates. WGS also revealed F-type multireplicon plasmids carrying sil + pco (copper) co-located with qacEΔ1 ± qacF (QACs) and antibiotic resistance genes like those disseminated in humans. In conclusion, chicken farms and their derived meat are significant reservoirs for diverse K. pneumoniae clones enriched in antibiotic resistance and metal tolerance genes, some exhibiting genetic similarities with human clinical strains. Further research is imperative to unravel the factors influencing K. pneumoniae persistence and dissemination within poultry production, contributing to improved food safety risk management. This study underscores the significance of understanding the interplay between antimicrobial control strategies and non-clinical sources to effectively address the spread of antimicrobial resistance.

Raw meat-based diet for pets: a neglected source of human exposure to Salmonella and pathogenic Escherichia coli clones carrying mcr, Portugal, September 2019 to January 2020.

BackgroundThe pet industry is expanding worldwide, particularly raw meat-based diets (RMBDs). There are concerns regarding the safety of RMBDs, especially their potential to spread clinically relevant antibiotic-resistant bacteria or zoonotic pathogens.AimWe aimed to investigate whether dog food, including RMBD, commercially available in Portugal can be a source of Salmonella and/or other Enterobacteriaceae strains resistant to last-line antibiotics such as colistin.MethodsFifty-five samples from 25 brands (21 international ones) of various dog food types from 12 suppliers were screened by standard cultural methods between September 2019 and January 2020. Isolates were characterised by phenotypic and genotypic methods, including whole genome sequencing and comparative genomics.ResultsOnly RMBD batches were contaminated, with 10 of 14 containing polyclonal multidrug-resistant (MDR) Escherichia coli and one MDR Salmonella. One turkey-based sample contained MDR Salmonella serotype 1,4,[5],12:i:- ST34/cgST142761 with similarity to human clinical isolates occurring worldwide. This Salmonella exhibited typical antibiotic resistance (bla TEM + strA-strB + sul2 + tet(B)) and metal tolerance profiles (pco + sil + ars) associated with the European epidemic clone. Two samples (turkey/veal) carried globally dispersed MDR E. coli (ST3997-complexST10/cgST95899 and ST297/cgST138377) with colistin resistance (minimum inhibitory concentration: 4 mg/L) and mcr-1 gene on IncX4 plasmids, which were identical to other IncX4 circulating worldwide.ConclusionSome RMBDs from European brands available in Portugal can be a vehicle for clinically relevant MDR Salmonella and pathogenic E. coli clones carrying genes encoding resistance to the last-line antibiotic colistin. Proactive actions within the One Health context, spanning regulatory, pet-food industry and consumer levels, are needed to mitigate these public health risks.

POSEIDON: Peptidic Objects SEquence-based Interaction with cellular DOmaiNs: a new database and predictor.

Cell-penetrating peptides (CPPs) are short chains of amino acids that have shown remarkable potential to cross the cell membrane and deliver coupled therapeutic cargoes into cells. Designing and testing different CPPs to target specific cells or tissues is crucial to ensure high delivery efficiency and reduced toxicity. However, in vivo/in vitro testing of various CPPs can be both time-consuming and costly, which has led to interest in computational methodologies, such as Machine Learning (ML) approaches, as faster and cheaper methods for CPP design and uptake prediction. However, most ML models developed to date focus on classification rather than regression techniques, because of the lack of informative quantitative uptake values. To address these challenges, we developed POSEIDON, an open-access and up-to-date curated database that provides experimental quantitative uptake values for over 2,300 entries and physicochemical properties of 1,315 peptides. POSEIDON also offers physicochemical properties, such as cell line, cargo, and sequence, among others. By leveraging this database along with cell line genomic features, we processed a dataset of over 1,200 entries to develop an ML regression CPP uptake predictor. Our results demonstrated that POSEIDON accurately predicted peptide cell line uptake, achieving a Pearson correlation of 0.87, Spearman correlation of 0.88, and r2 score of 0.76, on an independent test set. With its comprehensive and novel dataset, along with its potent predictive capabilities, the POSEIDON database and its associated ML predictor signify a significant leap forward in CPP research and development. The POSEIDON database and ML Predictor are available for free and with a user-friendly interface at https://moreiralab.com/resources/poseidon/ , making them valuable resources for advancing research on CPP-related topics. Scientific Contribution Statement: Our research addresses the critical need for more efficient and cost-effective methodologies in Cell-Penetrating Peptide (CPP) research. We introduced POSEIDON, a comprehensive and freely accessible database that delivers quantitative uptake values for over 2,300 entries, along with detailed physicochemical profiles for 1,315 peptides. Recognizing the limitations of current Machine Learning (ML) models for CPP design, our work leveraged the rich dataset provided by POSEIDON to develop a highly accurate ML regression model for predicting CPP uptake.

A Review of the Lidocaine in the Perioperative Period.

This review analyzes the controversies surrounding lidocaine (LIDO), a widely recognized local anesthetic, by exploring its multifaceted effects on pain control in the perioperative setting. The article critically analyzes debates about lidocaine's efficacy, safety, and optimal administration methods. While acknowledging its well-documented analgesic attributes, the text highlights the ongoing controversies in its application. The goal is to provide clinicians with a comprehensive understanding of the current discourse, enabling informed decisions about incorporating lidocaine into perioperative protocols. On the other hand, emphasizes the common uses of lidocaine and its potential role in personalized medicine. It discusses the medication's versatility, including its application in anesthesia, chronic pain, and cardiovascular diseases. The text recognizes lidocaine's widespread use in medical practice and its ability to be combined with other drugs, showcasing its adaptability for individualized treatments. Additionally, it explores the incorporation of lidocaine into hyaluronic acid injections and its impact on pharmacokinetics, signaling innovative approaches. The discussion centers on how lidocaine, within the realm of personalized medicine, can offer safer and more comfortable experiences for patients through tailored treatments.

New Perspective for Drug-Drug Interaction in Perioperative Period.

In this review, we aim to discuss current information on drug interactions in the perioperative period. During this period, patients receive several drugs that may interact with each other and affect the efficacy and safety of the treatment. There are three types of drug interactions: pharmacodynamic, pharmacokinetic, and pharmaceutical. It is important to recognize that drug interactions may increase the toxicity of the drug or reduce its efficacy, increasing the risk of complications in the perioperative period. This review describes the most commonly used perioperative drugs approved by the FDA and some of the described interactions between them. Thoroughly reviewing a patient's medication list and identifying potential interactions are essential steps in minimizing risks. Additionally, vigilant monitoring of patients during and after surgery plays a pivotal role in early detection of any signs of drug interactions. This article emphasizes the significance of addressing DDIs in the perioperative period to ensure patient well-being and advocates for the implementation of careful monitoring protocols to promptly identify and manage potential interactions.

From Farm to Fork: Persistence of Clinically Relevant Multidrug-Resistant and Copper-Tolerant Klebsiella pneumoniae Long after Colistin Withdrawal in Poultry Production.

Concerns about colistin-resistant bacteria in animal food-environmental-human ecosystems prompted the poultry sector to implement colistin restrictions and explore alternative trace metals/copper feed supplementation. The impact of these strategies on the selection and persistence of colistin-resistant Klebsiella pneumoniae in the whole poultry production chain needs clarification. We assessed colistin-resistant and copper-tolerant K. pneumoniae occurrence in chickens raised with inorganic and organic copper formulas from 1-day-old chicks to meat (7 farms from 2019 to 2020), after long-term colistin withdrawal (>2 years). Clonal diversity and K. pneumoniae adaptive features were characterized by cultural, molecular, and whole-genome-sequencing (WGS) approaches. Most chicken flocks (75%) carried K. pneumoniae at early and preslaughter stages, with a significant decrease (P < 0.05) in meat batches (17%) and sporadic water/feed contamination. High rates (>50%) of colistin-resistant/mcr-negative K. pneumoniae were observed among fecal samples, independently of feed. Most samples carried multidrug-resistant (90%) and copper-tolerant (81%; silA and pcoD positive and with a MICCuSO4 of ≥16 mM) isolates. WGS revealed accumulation of colistin resistance-associated mutations and F type multireplicon plasmids carrying antibiotic resistance and metal/copper tolerance genes. The K. pneumoniae population was polyclonal, with various lineages dispersed throughout poultry production. ST15-KL19, ST15-KL146, and ST392-KL27 and IncF plasmids were similar to those from global human clinical isolates, suggesting chicken production as a reservoir/source of clinically relevant K. pneumoniae lineages and genes with potential risk to humans through food and/or environmental exposure. Despite the limited mcr spread due to the long-term colistin ban, this action was ineffective in controlling colistin-resistant/mcr-negative K. pneumoniae, regardless of feed. This study provides crucial insights into the persistence of clinically relevant K. pneumoniae in the poultry production chain and highlights the need for continued surveillance and proactive food safety actions within a One Health perspective. IMPORTANCE The spread of bacteria resistant to last-resort antibiotics such as colistin throughout the food chain is a serious concern for public health. The poultry sector has responded by restricting colistin use and exploring alternative trace metals/copper feed supplements. However, it is unclear how and to which extent these changes impact the selection and persistence of clinically relevant Klebsiella pneumoniae throughout the poultry chain. We found a high occurrence of copper-tolerant and colistin-resistant/mcr-negative K. pneumoniae in chicken flocks, regardless of inorganic and organic copper formulas use and a long-term colistin ban. Despite the high K. pneumoniae isolate diversity, the occurrence of identical lineages and plasmids across samples and/or clinical isolates suggests poultry as a potential source of human K. pneumoniae exposure. This study highlights the need for continued surveillance and proactive farm-to-fork actions to mitigate the risks to public health, relevant for stakeholders involved in the food industry and policymakers tasked with regulating food safety.

Systemic Anti-Inflammatory Effects of Intravenous Lidocaine in Surgical Patients: A Systematic Review and Meta-Analysis.

There has recently been increasing evidence that the use of perioperative intravenous lidocaine infusion possesses analgesic, opioid-sparing and anti-inflammatory effects in surgical patients. Although opioid-sparing and analgesic properties have been strongly supported, the anti-inflammatory features are not well established in elective surgery. Therefore, the aim of this systematic review is to examine the effect of perioperative intravenous lidocaine infusion on postoperative anti-inflammatory status in patients undergoing elective surgery. A search strategy was created to identify suitable randomised clinical trials (RCTs) in PubMed, Scopus, Web of Science and Clinicaltrials.gov databases until January 2023. RCTs that evaluated the effect of intravenous lidocaine infusion, compared with placebo, on adult patients who underwent elective surgery, in inflammatory markers response were included. Exclusion criteria consisted of paediatric patients, animal studies, non-RCT methodology, intervention without intravenous lidocaine, inadequate control group, duplicated samples, ongoing studies and lack of any relevant clinical outcome measures. The following inflammatory markers-interleukin (IL)-6, tumour necrosis factor (TNF)-α, IL-1RA, IL-8, IL-10, C-reactive protein (CRP), IL-1, IL-1ß, interferon (IFN)-γ, cortisol, IL-4, IL-17, high-mobility group protein B1 (HMGB1) and transforming growth factor (TGF)-ß-were evaluated as outcomes in this review. A total of 21 studies, including 1254 patients, were identified. Intravenous lidocaine infusion significantly reduced the change from IL-6 baseline levels at the end of surgery compared to a placebo (standardised mean difference [SMD]: -0.647, 95% confidence interval [CI]: -1.034 to -0.260). Usage of lidocaine was associated with a significant reduction in other postoperative pro-inflammatory markers, such as TNF-α, IL-1RA, IL-8, IL-17, HMGB-1 and CRP. There was no significant difference in other markers, such as IL-10, IL-1ß, IL-1, IFN-γ, IL-4, TGF-ß and cortisol. This systematic review and meta-analysis provide support for the administration of perioperative intravenous lidocaine infusion as an anti-inflammatory strategy in elective surgery.

Enterococcus spp. from chicken meat collected 20 years apart overcome multiple stresses occurring in the poultry production chain: Antibiotics, copper and acids.

Poultry meat has been a vehicle of antibiotic resistant bacteria and genes. Yet, the diversity of selective pressures associated with their maintenance in the poultry-production chain remains poorly explored. We evaluated the susceptibility of Enterococcus spp. from chicken meat collected 20 years apart to antibiotics, metals, acidic pH and peracetic acid-PAA. Contemporary chicken-meat samples (n = 53 batches, each including a pool of neck skin from 10 single carcasses) were collected in a slaughterhouse facility using PAA as disinfectant (March-August 2018, North of Portugal). Broilers were raised in intensive farms (n = 29) using CuSO4 and organic acids as feed additives. Data were compared with that of 67 samples recovered in the same region during 1999-2001. All 2018 samples had multidrug resistant-MDR isolates, with >45 % carrying Enterococcus faecalis, Enterococcus faecium or Enterococcus gallinarum resistant to tetracycline, erythromycin, ampicillin, quinupristin-dalfopristin, ciprofloxacin, chloramphenicol or aminoglycosides. Resistance rates were similar (P > 0.05) to those of 1999-2001 samples for all but five antibiotics. The decrease of samples carrying vancomycin-resistant isolates from 46 % to 0 % between 1999-2001 and 2018 was the most striking difference. Isolates from both periods were similarly susceptible to acid pH [minimum-growth pH (4.5-5.0), minimum-survival pH (3.0-4.0)] and to PAA (MIC90 = 100-120 mg/L/MBC90 = 140-160 mg/L; below concentrations used in slaughterhouse). Copper tolerance genes (tcrB and/or cueO) were respectively detected in 21 % and 4 % of 2018 and 1999-2001 samples. The tcrB gene was only detected in E. faecalis (MICCuSO4 > 12 mM), and their genomes were compared with other international ones of chicken origin (PATRIC database), revealing a polyclonal population and a plasmid or chromosomal location for tcrB. The tcrB plasmids shared diverse genetic modules, including multiple antimicrobial resistance genes (e.g. to tetracyclines, chloramphenicol, macrolide-lincosamide-streptogramin B-MLSB, aminoglycosides, bacitracin, coccidiostats). When in chromosome, the tcrB gene was co-located closely to merA (mercury) genes. Chicken meat remains an important vehicle of MDR Enterococcus spp. able to survive under diverse stresses (e.g. copper, acid) potentially contributing to these bacteria maintenance and flux among animal-environment-humans.

How Anaesthesiology Helped to Fight the First Wave of the COVID-19 Pandemic in Portugal.

INTRODUCTION: The dissemination of the COVID-19 pandemic in Europe, namely in Portugal, demanded an organizational and clinical reaction from the Portuguese National Health Service. With the unpredictable impact of COVID-19 infected patients redefining hospital logistics, reducing non-priority elective care and extending the hospital capacity for critical care patients made mobilizing a significant part of human resources a priority. We conducted a national survey to monitor the contribution and the role of anaesthesiologists belonging to the 53 Portuguese National Health Service hospitals in the first wave fight against the pandemic. MATERIAL AND METHODS: This prospective cross-sectional observational study used a weekly survey sent to the Directors of the Anaesthesiology Departments of all Portuguese National Health Service hospitals, between the period of 13th April and 21st June 2020. Directors were asked about human resources, hospital logistics, anaesthetic activity and residency programs in their departments as well as contingency plans facing the impact of the pandemic growth in the PNHS. RESULTS: Contingency strategy for all Portuguese National Health Service hospitals planned for a total of 1524 level III critical care beds during the initial phases of the pandemic, an increase of 151% from the existing 607 level III critical care beds in Portugal in January 2020. This re-configuration effort of the Portuguese National Health Service was only possible due to the partial or total suspension of non-urgent elective activity that reached over 90% of these institutions in the first pandemic months (March and April) and the deployment of anaesthesiologists from their normal activities to the treatment of critical care patients. During the peak of the first pandemic wave, 209 anaesthesiology specialists and 170 trainees (22.9% of the total anaesthesiologist's staff in the Portuguese National Health Service) were deployed in critical care. There was an almost complete interruption of the residency program rotation in 70.4% of hospitals with anaesthesiology residents, between March and April 2020. CONCLUSION: During the first pandemic wave there was an effective and fast reorganisation of the Portuguese National Health Service in order to increase level III critical care beds, which might have contributed to the low mortality rates in Portugal. We believe that this could have also been a result of the contribution given by all public anaesthesiology departments.

Introdução: A disseminação da pandemia por COVID-19 na Europa, designadamente em Portugal, exigiu uma resposta clínica e organizativa por parte do Serviço Nacional de Saúde português. Com o imprevisível impacto da COVID-19 nos doentes infectados, foi prioritário redefinir a logística hospitalar, reduzir a prestação de cuidados electivos não prioritários, e estender a capacidade hospitalar ao tratamento do doente crítico, mobilizando uma parte significativa dos recursos humanos. Utilizou-se um inquérito nacional que permitisse monitorizar a contribuição que os anestesiologistas pertencentes aos 53 hospitais do Serviço Nacional de Saúde tiveram no combate à COVID-19 durante a primeira vaga da pandemia. Material e Métodos: Estudo observacional transversal de tipo prospectivo, baseado num inquérito semanal enviado aos directores dos Serviços de Anestesiologia de todos os hospitais do Serviço Nacional de Saúde, entre 13 de abril e 21 de junho de 2020. Foi solicitada informação relativa aos recursos humanos, logística hospitalar, atividade assistencial, programa de formação pós-graduado, assim como plano de contingência face ao crescimento da pandemia. Resultados: O plano de contingência hospitalar nos hospitais do Serviço Nacional de Saúde previu um total de 1524 camas de cuidados intensivos de nível III, o que corresponde a um crescimento de 151% das 607 camas existentes em janeiro de 2020. Esta reconfiguração dos hospitais do Serviço Nacional de Saúde só foi possível devido à suspensão parcial ou total da atividade eletiva não prioritária que afectou mais de 90% das instituições hospitalares nos primeiros meses da pandemia (março e abril), e à mobilização dos anestesiologistas das suas atividades eletivas para o tratamento do doente crítico. Nos piores momentos, esta mobilização envolveu 209 especialistas e 170 internos de especialidade (22,9% do total destes profissionais nos hospitais do Serviço Nacional de Saúde). Por outro lado, registou-se uma interrupção quase total do programa de formação pós-graduada em mais de 70,4% dos hospitais com esta idoneidade formativa, de março a abril de 2020. Conclusão: Durante a primeira vaga da pandemia houve uma rápida reorganização do Serviço Nacional de Saúde que poderá ter contribuído para a baixa taxa de mortalidade em Portugal. Os autores acreditam que para esse resultado poderá ainda ter contribuído a ajuda dada pelos serviços de Anestesiologia do Serviço Nacional de Saúde.

Effects of dexmedetomidine in non-operating room anesthesia in adults: a systematic review with meta-analysis.

BACKGROUND: Dexmedetomidine (DEX) is an α2-adrenergic receptor agonist used for its sedative, analgesic, and anxiolytic effects. Non-Operating Room Anesthesia (NORA) is a modality of anesthesia that can be done under general anesthesia or procedural sedation or/and analgesia. In this particular setting, a level-2 sedation, such as the one provided by DEX, is beneficial. We aimed to study the effects and safety of DEX in the different NORA settings in the adult population. METHODS: A systematic review with meta-analysis of randomized controlled trials was conducted. Interventions using DEX only or DEX associated with other sedative agents, in adults (18 years old or more), were included. Procedures outside the NORA setting and/or without a control group without DEX were excluded. MEDLINE, ClinicalTrials.gov, Scopus, LILACS, and SciELO were searched. The primary outcome was time until full recovery. Secondary outcomes included hemodynamic and respiratory complications and other adverse events, among others. RESULTS: A total of 97 studies were included with a total of 6,706 participants. The meta-analysis demonstrated that DEX had a higher time until full recovery (95% CI = [0.34, 3.13] minutes, a higher incidence of hypotension (OR = 1.95 [1.25, 3.05], p = 0.003, I2 = 39%) and bradycardia (OR = 3.60 [2.29, 5.67], p < 0.00001, I2 = 0%), and a lower incidence of desaturation (OR = 0.40 [0.25, 0.66], p = 0.0003, I² = 60%). CONCLUSION: DEX in NORA procedures in adults was associated with a lower incidence of amnesia and respiratory effects but had a long time to recovery and more hemodynamic complications.

Effects of dexmedetomidine in non-operating room anesthesia in adults: a systematic review with meta-analysis

Abstract Background: Dexmedetomidine (DEX) is an α2-adrenergic receptor agonist used for its sedative, analgesic, and anxiolytic effects. Non-Operating Room Anesthesia (NORA) is a modality of anesthesia that can be done under general anesthesia or procedural sedation or/and analgesia. In this particular setting, a level-2 sedation, such as the one provided by DEX, is beneficial. We aimed to study the effects and safety of DEX in the different NORA settings in the adult population. Methods: A systematic review with meta-analysis of randomized controlled trials was conducted. Interventions using DEX only or DEX associated with other sedative agents, in adults (18 years old or more), were included. Procedures outside the NORA setting and/or without a control group without DEX were excluded. MEDLINE, ClinicalTrials.gov, Scopus, LILACS, and SciELO were searched. The primary outcome was time until full recovery. Secondary outcomes included hemodynamic and respiratory complications and other adverse events, among others. Results: A total of 97 studies were included with a total of 6,706 participants. The meta-analysis demonstrated that DEX had a higher time until full recovery (95% CI = [0.34, 3.13] minutes, a higher incidence of hypotension (OR = 1.95 [1.25, 3.05], p = 0.003, I2 = 39%) and bradycardia (OR = 3.60 [2.29, 5.67], p < 0.00001, I2 = 0%), and a lower incidence of desaturation (OR = 0.40 [0.25, 0.66], p = 0.0003, I2 = 60%). Conclusion: DEX in NORA procedures in adults was associated with a lower incidence of amnesia and respiratory effects but had a long time to recovery and more hemodynamic complications..

Personalized Medicine for Classical Anesthesia Drugs and Cancer Progression.

In this review, we aim to discuss the use and effect of five different drugs used in the induction of anesthesia in cancer patients. Propofol, fentanyl, rocuronium, sugammadex, and dexamethasone are commonly used to induce anesthesia and prevent pain during surgery. Currently, the mechanisms of these drugs to induce the state of anesthesia are not yet fully understood, despite their use being considered safe. An association between anesthetic agents and cancer progression has been determined; therefore, it is essential to recognize the effects of all agents during cancer treatment and to evaluate whether the treatment provided to the patients could be more precise. We also highlight the use of in silico tools to review drug interaction effects and safety, as well as the efficacy of the treatment used according to different subgroups of patients.

The Gupta Perioperative Risk for Myocardial Infarct or Cardiac Arrest (MICA) Calculator as an Intraoperative Neurologic Deficit Predictor in Carotid Endarterectomy.

BACKGROUND: Patients undergoing carotid endarterectomy (CEA) may experiment intraoperative neurologic deficits (IND) during carotid cross-clamping. This work aimed to assess the impact of the Gupta Perioperative Myocardial Infarct or Cardiac Arrest (MICA) risk calculator in the IND. METHODS: From January 2012 to April 2021, patients undergoing CEA with regional anaesthesia for carotid stenosis with IND and consecutively control operated patients without IND were selected. A regressive predictive model was created, and a receiver operating characteristic (ROC) curve was applied for comparison. A multivariable dependence analysis was conducted using a classification and regression tree (CRT) algorithm. RESULTS: A total of 97 out of 194 included patients developed IND. Obesity showed aOR = 4.01 (95% CI: 1.66-9.67) and MICA score aOR = 1.21 (1.03-1.43). Higher contralateral stenosis showed aOR = 1.29 (1.08-1.53). The AUROC curve was 0.656. The CRT algorithm differentiated obese patients with a MICA score ≥ 8. Regarding non-obese patients, the model identified the presence of contralateral stenosis ≥ 55% with a MICA ≥ 10. CONCLUSION: MICA score might play an additional role in stratifying patients for IND in CEA. Obesity was determined as the best discrimination factor, followed by a score ≥ 8. A higher ipsilateral stenosis degree is suggested to have a part in avoiding procedure-related IND. Larger studies might validate the benefit of MICA score regarding the risk of IND.

SYNPRED: prediction of drug combination effects in cancer using different synergy metrics and ensemble learning.

BACKGROUND: In cancer research, high-throughput screening technologies produce large amounts of multiomics data from different populations and cell types. However, analysis of such data encounters difficulties due to disease heterogeneity, further exacerbated by human biological complexity and genomic variability. The specific profile of cancer as a disease (or, more realistically, a set of diseases) urges the development of approaches that maximize the effect while minimizing the dosage of drugs. Now is the time to redefine the approach to drug discovery, bringing an artificial intelligence (AI)-powered informational view that integrates the relevant scientific fields and explores new territories. RESULTS: Here, we show SYNPRED, an interdisciplinary approach that leverages specifically designed ensembles of AI algorithms, as well as links omics and biophysical traits to predict anticancer drug synergy. It uses 5 reference models (Bliss, Highest Single Agent, Loewe, Zero Interaction Potency, and Combination Sensitivity Score), which, coupled with AI algorithms, allowed us to attain the ones with the best predictive performance and pinpoint the most appropriate reference model for synergy prediction, often overlooked in similar studies. By using an independent test set, SYNPRED exhibits state-of-the-art performance metrics either in the classification (accuracy, 0.85; precision, 0.91; recall, 0.90; area under the receiver operating characteristic, 0.80; and F1-score, 0.91) or in the regression models, mainly when using the Combination Sensitivity Score synergy reference model (root mean square error, 11.07; mean squared error, 122.61; Pearson, 0.86; mean absolute error, 7.43; Spearman, 0.87). Moreover, data interpretability was achieved by deploying the most current and robust feature importance approaches. A simple web-based application was constructed, allowing easy access by nonexpert researchers. CONCLUSIONS: The performance of SYNPRED rivals that of the existing methods that tackle the same problem, yielding unbiased results trained with one of the most comprehensive datasets available (NCI ALMANAC). The leveraging of different reference models allowed deeper insights into which of them can be more appropriately used for synergy prediction. The Combination Sensitivity Score clearly stood out with improved performance among the full scope of surveyed approaches and synergy reference models. Furthermore, SYNPRED takes a particular focus on data interpretability, which has been in the spotlight lately when using the most advanced AI techniques.

High diversity of pathogenic Escherichia coli clones carrying mcr-1 among gulls underlines the need for strategies at the environment-livestock-human interface.

The expansion of mcr-carrying bacteria is a well-recognized public health problem. Measures to contain mcr spread have mainly been focused on the food-animal production sector. Nevertheless, the spread of MCR producers at the environmental interface particularly driven by the increasing population of gulls in coastal cities has been less explored. Occurrence of mcr-carrying Escherichia coli in gull's colonies faeces on a Portuguese beach was screened over 7 months. Cultural, molecular and genomic approaches were used to characterize their diversity, mcr plasmids and adaptive features. Multidrug-resistant mcr-1-carrying E. coli were detected for 3 consecutive months. Over time, multiple strains were recovered, including zoonotic-related pathogenic E. coli clones (e.g. B2-ST131-H22, A-ST10 and B1-ST162). Diverse mcr-1 genetic environments were mainly associated with ST2/ST4-HI2 (ST10, ST131, ST162, ST354 and ST4204) but also IncI2 (ST12990) plasmids or in the chromosome (ST656). Whole-genome sequencing revealed enrichment of these strains on antibiotic resistance, virulence and metal tolerance genes. Our results underscore gulls as important spreaders of high-priority bacteria and genes that may affect the environment, food-animals and/or humans, potentially undermining One-Health strategies to reduce colistin resistance.

The Patient Perspective Regarding Ambulatory Surgery: An Observational Study.

INTRODUCTION: Due to the advances in anesthetics and surgery, ambulatory surgery plays an increasingly important role. This regimen, despite showing several advantages, still instills fear in patients. The aim of this was to evaluate the level of knowledge and the perspective of patients regarding ambulatory surgery. MATERIAL AND METHODS: A prospective study was carried out for two months in patients with pre-anesthetic consultation at a University Hospital Center. Demographic information, educational level, and previous ambulatory surgery were surveyed. Patients' level of knowledge about surgery, satisfaction, and the perceived advantages and fears regarding this regimen were evaluated. The analysis was performed with SPSS, and p < 0.05 was considered statistically significant. RESULTS: Two hundred and fifty-one patients were included. One hundred and twenty-eight (51%) patients disclosed having knowledge about ambulatory surgery. The main advantages perceived by patients were more peaceful recovery (44.7%), avoiding being surrounded by other patients (43.1%), and avoiding infection (37.2%). The main fears shown by patients were poor pain control (20.7%), having other health problems (13.1%), and poor control of nausea or vomiting (10%). CONCLUSION: Patients may benefit from being more informed about the ambulatory surgical regimen in order to decrease their fears and increase their acceptance of the regimen. Providing more information to patients may result in increased satisfaction with this regimen.

Introdução: Com os avanços observados a nível anestésico e cirúrgico, a cirurgia em regime de ambulatório tem cada vez mais expressão. Este regime, apesar das várias vantagens para os doentes, acarreta também vários receios. Os objetivos deste estudo foram avaliar o nível de conhecimento e a perspetiva dos doentes sobre a cirurgia em ambulatório. Material e Métodos: Estudo prospetivo decorrido durante dois meses em doentes com consulta pré-anestésica num Centro Hospitalar Universitário. Foi inquirida informação demográfica, nível educacional e existência de cirurgia prévia em regime de ambulatório. Foram avaliados o nível de conhecimento dos doentes, a satisfação, as vantagens e receios relativos à cirurgia em regime de ambulatório. A análise foi feita com SPSS (v 27.0) e p < 0,05 foi considerado como estatisticamente significativo. Resultados: Foram incluídos 251 doentes. Destes, 128 (51%) doentes demostraram ter conhecimento sobre a cirurgia de ambulatório. As principais vantagens percebidas pelos doentes foram ter uma recuperação mais sossegada (44,7%), evitar estar rodeado de outros doentes (43,1%) e evitar infeção (37,2%). Os principais receios mostrados pelos doentes foram o mau controlo da dor (20,7%) e de náuseas/vómitos (10%) e ter outros problemas de saúde (13,1%). Conclusão: Os doentes poderão beneficiar de ser mais informados sobre o regime cirúrgico em ambulatório de forma a diminuir os seus receios e aumentar a sua satisfação. Investir na informação do doente poderá aumentar a aceitação do regime de ambulatório.

Revised cardiac score index is a predictor of long-term outcomes after carotid endarterectomy.

Background: Cardiac complications represent the main cause of mortality after non-cardiac surgery and the Revised Cardiac Risk Index (RCRI) was created to estimate the perioperative risk of these events. It considers history of ischaemic heart disease, congestive heart failure, diabetes requiring preoperative insulin, stroke or transient ischaemic attack and renal impairment. We aim to describe the accuracy of the RCRI for predicting perioperative major adverse cardiovascular events (MACE) - a composite of heart failure, ischemic events and all-cause death. Also, the authors aimed to review the score for better prediction of cardiovascular outcomes. Patients and methods: From January 2012 to January 2020, patients who underwent Carotid endarterectomy (CEA) with regional anaesthesia (RA) were selected. RCRI was calculated for each case. Estimated and reported cardiovascular complications were compared using multivariate logistic regression and cox proportional hazards. An alternative and optimized carotid-RCRI (CtRCRI) was obtained. Overall predictive accuracy was assessed and compared by measuring model discrimination. Adjustments for overfitting and evaluation of the new model were performed by bootstrap. Results: 186 patients were selected, of which 80% were male with a mean age of 70.0±9.05 years old. The median follow-up was 50 months, interquartile range 21-69 months. None of the scores were able to predict MACE in the perioperative period. Both were associated with 30-day Clavien-Dindo ≥2 (p=0.022 and p=0.041, respectively). Regarding long-term prognosis, both were able to predict MACE (RCRI: hazard ratio (HR) 3.54 (95% confidence interval [CI] 1.04-11.48) vs. CtRCRI: HR 2.08 (95%CI 1.08-3.98) and all-cause mortality (RCRI: HR 3.33, 95%CI 0.99-11.11 vs. CtRCRI: HR 1.57, 95%CI 1.14-7.04). Conclusions: RCRI and CtRCRI did not predict MACE in the perioperative period but are good predictors of 30-day complications (Clavien-Dindo ≥2). Both RCRI and CtRCRI have good prognostic value as predictors of long-term cardiovascular events.

From farm to fork: Colistin voluntary withdrawal in Portuguese farms reflected in decreasing occurrence of mcr-1-carrying Enterobacteriaceae from chicken meat.

Expansion of mcr-carrying Enterobacteriaceae (MCR-E) is a well-recognized problem affecting animals, humans and the environment. Ongoing global control actions involve colistin restrictions among food-animal production, but their impact on poultry-derived products is largely unknown, justifying comprehensive farm-to-fork studies. Occurrence of MCR-E among 53 chicken-meat batches supplied from 29 Portuguese farms shortly after colistin withdrawal was evaluated. Strains (FT-IR/MLST/WGS), mcr plasmids and their adaptive features were characterized by cultural, molecular and genomic approaches. We found high rates of chicken-meat batches (80%-100% - 4 months; 12% - the last month) with multiple MDR + mcr-1-carrying Escherichia coli (Ec-including ST117 and ST648-Cplx) and Klebsiella pneumoniae (Kp-ST147-O5:K35) clones, some of them persisting over time. The mcr-1 was located in the chromosome (Ec-ST297/16-farms) or dispersed IncX4 (Ec-ST602/ST6469/5-farms), IncHI2-ST2/ST4 (Ec-ST533/ST6469/5 farms and Kp-ST147/6-farms) or IncI2 (Ec-ST117/1-farm) plasmids. WGS revealed high load and diversity in virulence, antibiotic resistance and metal tolerance genes. This study supports colistin withdrawal potential efficacy in poultry production and highlights both poultry-production chain as a source of mcr-1 and the risk of foodborne transmission to poultry-meat consumers. Finally, in the antibiotic reduction/replacement context, other potential co-selective pressures (e.g., metals-Cu as feed additives) need to be further understood to guide concerted, effective and durable actions under 'One Health' perspective.