Surgical site infection surveillance in knee and hip arthroplasty: optimizing an algorithm to detect high-risk patients based on electronic health records.

BACKGROUND: Surgical site infection (SSI) is an important cause of disease burden and healthcare costs. Fully manual surveillance is time-consuming and prone to subjectivity and inter-individual variability, which can be partly overcome by semi-automated surveillance. Algorithms used in orthopaedic SSI semi-automated surveillance have reported high sensitivity and important workload reduction. This study aimed to design and validate different algorithms to identify patients at high risk of SSI after hip or knee arthroplasty. METHODS: Retrospective data from manual SSI surveillance between May 2015 and December 2017 were used as gold standard for validation. Knee and hip arthroplasty were included, patients were followed up for 90 days and European Centre for Disease Prevention and Control SSI classification was applied. Electronic health records data was used to generate different algorithms, considering combinations of the following variables: ≥1 positive culture, ≥ 3 microbiological requests, antimicrobial therapy ≥ 7 days, length of hospital stay ≥ 14 days, orthopaedics readmission, orthopaedics surgery and emergency department attendance. Sensitivity, specificity, negative and predictive value, and workload reduction were calculated. RESULTS: In total 1631 surgical procedures were included, of which 67.5% (n = 1101) in women; patients' median age was 69 years (IQR 62 to 77) and median Charlson index 2 (IQR 1 to 3). Most surgeries were elective (92.5%; n = 1508) and half were hip arthroplasty (52.8%; n = 861). SSI incidence was 3.8% (n = 62), of which 64.5% were deep or organ/space infections. Positive culture was the single variable with highest sensitivity (64.5%), followed by orthopaedic reintervention (59.7%). Twenty-four algorithms presented 90.3% sensitivity for all SSI types and 100% for deep and organ/space SSI. Workload reduction ranged from 59.7 to 67.7%. The algorithm including ≥ 3 microbiological requests, length of hospital stay ≥ 14 days and emergency department attendance, was one of the best options in terms of sensitivity, workload reduction and feasibility for implementation. CONCLUSIONS: Different algorithms with high sensitivity to detect all types of SSI can be used in real life, tailored to clinical practice and data availability. Emergency department attendance can be an important variable to identify superficial SSI in semi-automated surveillance.

Evaluation of Seroprevalence and Risk Factors of Heartworm Infection for Dogs in Rio de Janeiro with Access to Veterinary Care.

Heartworm infection is a chronic disease with clinical signs and effects ranging from an asymptomatic condition to severe disease and death. The prevalence of heartworm disease in the state of Rio de Janeiro has been reported to be high (21.3%). The present study was conducted to evaluate the seroprevalence and risk factors of heartworm infection for the canine population with access to veterinary services in different areas of the state of Rio de Janeiro, Brazil. A total of 1787 canine blood samples were obtained from 135 practices across 8 different areas of Rio de Janeiro state (Rio de Janeiro municipality, São Gonçalo municipality, Niterói municipality, Baixada Fluminense, and the northern, southern, eastern, and mountainous areas) and tested for the presence of Dirofilaria immitis antigens and antibodies against several tick-borne disease pathogens using a commercial immunochromatography technique (Vetscan® Flex 4 Rapid Test; Zoetis; NJ USA). Pet owners reported living conditions, physical characteristics, demographics, and clinical signs for evaluation of risk factors for heartworm infection. Only two evaluated risk factors were shown to enhance the risk for D. immitis infection, including having a short hair coat vs. having a medium or long hair coat (OR 2.62) or positive for antibodies to tick-borne disease parasites (OR 3.83). Clinical signs reported for dogs with heartworm disease were typical for that condition. The overall prevalence of heartworm disease in the state was 8.2%, ranging from 2.4% in the mountainous region to 29.4% in the eastern area. It could not be determined if veterinarians were not diligent about dispensing heartworm preventatives or if poor levels of compliance by dog owners were responsible for higher infection rates in some areas of the state.

Differences in clinical outcomes of bloodstream infections caused by Klebsiella aerogenes, Klebsiella pneumoniae and Enterobacter cloacae: a multicentre cohort study.

BACKGROUND: Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study. METHODS: Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome. RESULTS: Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results. CONCLUSIONS: Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.

A Scalable Pseudonymization Tool for Rapid Deployment in Large Biomedical Research Networks: Development and Evaluation Study.

Background: The SARS-CoV-2 pandemic has demonstrated once again that rapid collaborative research is essential for the future of biomedicine. Large research networks are needed to collect, share, and reuse data and biosamples to generate collaborative evidence. However, setting up such networks is often complex and time-consuming, as common tools and policies are needed to ensure interoperability and the required flows of data and samples, especially for handling personal data and the associated data protection issues. In biomedical research, pseudonymization detaches directly identifying details from biomedical data and biosamples and connects them using secure identifiers, the so-called pseudonyms. This protects privacy by design but allows the necessary linkage and reidentification. Objective: Although pseudonymization is used in almost every biomedical study, there are currently no pseudonymization tools that can be rapidly deployed across many institutions. Moreover, using centralized services is often not possible, for example, when data are reused and consent for this type of data processing is lacking. We present the ORCHESTRA Pseudonymization Tool (OPT), developed under the umbrella of the ORCHESTRA consortium, which faced exactly these challenges when it came to rapidly establishing a large-scale research network in the context of the rapid pandemic response in Europe. Methods: To overcome challenges caused by the heterogeneity of IT infrastructures across institutions, the OPT was developed based on programmable runtime environments available at practically every institution: office suites. The software is highly configurable and provides many features, from subject and biosample registration to record linkage and the printing of machine-readable codes for labeling biosample tubes. Special care has been taken to ensure that the algorithms implemented are efficient so that the OPT can be used to pseudonymize large data sets, which we demonstrate through a comprehensive evaluation. Results: The OPT is available for Microsoft Office and LibreOffice, so it can be deployed on Windows, Linux, and MacOS. It provides multiuser support and is configurable to meet the needs of different types of research projects. Within the ORCHESTRA research network, the OPT has been successfully deployed at 13 institutions in 11 countries in Europe and beyond. As of June 2023, the software manages data about more than 30,000 subjects and 15,000 biosamples. Over 10,000 labels have been printed. The results of our experimental evaluation show that the OPT offers practical response times for all major functionalities, pseudonymizing 100,000 subjects in 10 seconds using Microsoft Excel and in 54 seconds using LibreOffice. Conclusions: Innovative solutions are needed to make the process of establishing large research networks more efficient. The OPT, which leverages the runtime environment of common office suites, can be used to rapidly deploy pseudonymization and biosample management capabilities across research networks. The tool is highly configurable and available as open-source software.

Ivabradine restores tonic cardiovascular autonomic control and reduces tachycardia, hypertension and left ventricular inflammation in post-weaning protein malnourished rats.

Malnutrition results in autonomic imbalance and heart hypertrophy. Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the left ventricles (LV) is linked to hypertrophied hearts and abnormal myocardium automaticity. Given that ivabradine (IVA) has emerging pleiotropic effects, in addition to the widely known bradycardic response, this study evaluated if IVA treatment could repair the autonomic control and cardiac damages in malnourished rats. AIM: Assess the impact of IVA on tonic cardiovascular autonomic control and its relationship with hemodynamics regulation, LV inflammation, and HCN gene expression in post-weaning protein malnutrition condition. MAIN METHODS: After weaning, male rats were divided into control (CG; 22 % protein) and malnourished (MG; 6 % protein) groups. At 35 days, groups were subdivided into CG-PBS, CG-IVA, MG-PBS and MG-IVA (PBS 1 ml/kg or IVA 1 mg/kg) received during 8 days. We performed jugular vein cannulation and electrode implant for drug delivery and ECG registration to assess tonic cardiovascular autonomic control; femoral cannulation for blood pressure (BP) and heart rate (HR) assessment; and LV collection to evaluate ventricular remodeling and HCN gene expression investigation. KEY FINDINGS: Malnutrition induced BP and HR increases, sympathetic system dominance, and LV remodeling without affecting HCN gene expression. IVA reversed the cardiovascular autonomic imbalance; prevented hypertension and tachycardia; and inhibited the LV inflammatory process and fiber thickening caused by malnutrition. SIGNIFICANCE: Our findings suggest that ivabradine protects against malnutrition-mediated cardiovascular damage. Moreover, our results propose these effects were not attributed to HCN expression changes, but rather to IVA pleiotropic effects on autonomic control and inflammation.

Real-life experience with inotersen at CEPARM, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is an inherited, progressive, and fatal disease still largely underdiagnosed. Mutations in the transthyretin (TTR) gene cause the TTR protein to destabilize, misfold, aggregate, and deposit in body tissues, which makes ATTRv a disease with heterogeneous clinical phenotype. OBJECTIVE: To describe the long-term efficacy and safety of inotersen therapy in patients with ATTRv peripheral neuropathy (ATTRv-PN). METHODS: Patients who completed the NEURO-TTR pivotal study and the NEURO-TTR OLE open-label extension study migrated to the present study and were followed-up for at least 18 more months to an average of 67 months and up to 76 months since day 1 of the inotersen therapy (D1-first dose of inotersen). Disease progression was evaluated by standard measures. RESULTS: Ten ATTRv-PN patients with Val30Met mutation were included. The mean disease duration on D1 was of 3 years, and the mean age of the patients was of 46.8 years. During an additional 18-month follow up, neurological function, based on the Neuropathy Impairment Score and the Polyneuropathy Disability Score, functionality aspects (Karnofsky Performance Status), and nutritional and cardiac aspects were maintained. No new safety signs have been noted. CONCLUSION: The treatment with inotersen was effective and well tolerated for the average of 67 months and up to 76 months. Our results are consistent with those of larger phase-III trials.

ANTECEDENTES: Amiloidose hereditária por transtirretina (ATTRv) é uma doença hereditária, progressiva e fatal ainda largamente subdiagnosticada. Mutações no gene transtirretina (TTR) promovem desestabilização, desdobramento, agregação e depósito da proteína TTR em tecidos do corpo, o que faz da ATTRv uma doença de fenótipo clínico heterogêneo. OBJETIVO: Descrever a eficácia e segurança da terapia com inotersena no longo prazo em pacientes com neuropatia periférica ATTRv (ATTRv-PN). MéTODOS: Pacientes que completaram o estudo pivotal NEURO-TTR e o estudo de extensão aberta NEURO-TTR OLE migraram para este estudo e foram acompanhados por no mínimo 18 meses adicionais, em média por 67 meses, e por até 76 meses, desde o dia 1 da terapia com inotersena (D1­primeira dose de inotersena). A progressão da doença foi avaliada por medidas padronizadas. RESULTADOS: Dez pacientes com ATTRv-PN com mutação Val30Met foram incluídos. A duração média da doença no D1 era de 3 anos, e a média de idade dos pacientes era de 46,8 anos. Durante o período de acompanhamento adicional de 18 meses, a função neurológica, baseada no Neuropathy Impairment Score e no Polyneuropathy Disability Score, os aspectos de funcionalidade (Karnofsky Performance Status), nutricional e cardíacos estavam mantidos. Não se observou nenhum novo sinal de segurança. CONCLUSãO: O tratamento com inotersena foi eficaz e bem tolerado por 67 meses em média, e por até 76 meses. Nossos resultados são consistentes com os de estudos maiores de fase III.

A systematic review on the excess health risk of antibiotic-resistant bloodstream infections for six key pathogens in Europe.

BACKGROUND: Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined. OBJECTIVES: We evaluated pathogen-specific excess health burden of drug-resistant bloodstream infections (BSIs) in Europe. METHODS: A systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase, and grey literature for the period January 1990 to May 2022. STUDY ELIGIBILITY CRITERIA: Studies that reported burden data for six key drug-resistant pathogens: carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, third-generation cephalosporin or CR Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Excess health outcomes compared with drug-susceptible BSIs or uninfected patients. For MRSA and third-generation cephalosporin E. coli and K. pneumoniae BSIs, five or more European studies were identified. For all others, the search was extended to high-income countries. PARTICIPANTS: Paediatric and adult patients diagnosed with drug-resistant BSI. INTERVENTIONS: Not applicable. ASSESSMENT OF RISK OF BIAS: An adapted version of the Joanna-Briggs Institute assessment tool. METHODS OF DATA SYNTHESIS: Random-effect models were used to pool pathogen-specific burden estimates. RESULTS: We screened 7154 titles, 1078 full-texts and found 56 studies on BSIs. Most studies compared outcomes of drug-resistant to drug-susceptible BSIs (46/56, 82.1%), and reported mortality (55/56 studies, 98.6%). The pooled crude estimate for excess all-cause mortality of drug-resistant versus drug-susceptible BSIs ranged from OR 1.31 (95% CI 1.03-1.68) for CR P. aeruginosa to OR 3.44 (95% CI 1.62-7.32) for CR K. pneumoniae. Pooled crude estimates comparing mortality to uninfected patients were available for vancomycin-resistant Enterococcus and MRSA BSIs (OR of 11.19 [95% CI 6.92-18.09] and OR 6.18 [95% CI 2.10-18.17], respectively). CONCLUSIONS: Drug-resistant BSIs are associated with increased mortality, with the magnitude of the effect influenced by pathogen type and comparator. Future research should address crucial knowledge gaps in pathogen- and infection-specific burdens to guide development of novel interventions.

Real-life experience with inotersen at CEPARM, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro / Experiência de vida-real com inotersena no CEPARM, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro

Abstract Background Hereditary transthyretin amyloidosis (ATTRv) is an inherited, progressive, and fatal disease still largely underdiagnosed. Mutations in the transthyretin (TTR) gene cause the TTR protein to destabilize, misfold, aggregate, and deposit in body tissues, which makes ATTRv a disease with heterogeneous clinical phenotype. Objective To describe the long-term efficacy and safety of inotersen therapy in patients with ATTRv peripheral neuropathy (ATTRv-PN). Methods Patients who completed the NEURO-TTR pivotal study and the NEURO-TTR OLE open-label extension study migrated to the present study and were followed-up for at least 18 more months to an average of 67 months and up to 76 months since day 1 of the inotersen therapy (D1-first dose of inotersen). Disease progression was evaluated by standard measures. Results Ten ATTRv-PN patients with Val30Met mutation were included. The mean disease duration on D1 was of 3 years, and the mean age of the patients was of 46.8 years. During an additional 18-month follow up, neurological function, based on the Neuropathy Impairment Score and the Polyneuropathy Disability Score, functionality aspects (Karnofsky Performance Status), and nutritional and cardiac aspects were maintained. No new safety signs have been noted. Conclusion The treatment with inotersen was effective and well tolerated for the average of 67 months and up to 76 months. Our results are consistent with those of larger phase-III trials.

Resumo Antecedentes Amiloidose hereditária por transtirretina (ATTRv) é uma doença hereditária, progressiva e fatal ainda largamente subdiagnosticada. Mutações no gene transtirretina (TTR) promovem desestabilização, desdobramento, agregação e depósito da proteína TTR em tecidos do corpo, o que faz da ATTRv uma doença de fenótipo clínico heterogêneo. Objetivo Descrever a eficácia e segurança da terapia com inotersena no longo prazo em pacientes com neuropatia periférica ATTRv (ATTRv-PN). Métodos Pacientes que completaram o estudo pivotal NEURO-TTR e o estudo de extensão aberta NEURO-TTR OLE migraram para este estudo e foram acompanhados por no mínimo 18 meses adicionais, em média por 67 meses, e por até 76 meses, desde o dia 1 da terapia com inotersena (D1-primeira dose de inotersena). A progressão da doença foi avaliada por medidas padronizadas. Resultados Dez pacientes com ATTRv-PN com mutação Val30Met foram incluídos. A duração média da doença no D1 era de 3 anos, e a média de idade dos pacientes era de 46,8 anos. Durante o período de acompanhamento adicional de 18 meses, a função neurológica, baseada no Neuropathy Impairment Score e no Polyneuropathy Disability Score, os aspectos de funcionalidade (Karnofsky Performance Status), nutricional e cardíacos estavam mantidos. Não se observou nenhum novo sinal de segurança. Conclusão O tratamento com inotersena foi eficaz e bem tolerado por 67 meses em média, e por até 76 meses. Nossos resultados são consistentes com os de estudos maiores de fase III.

Predictors of clinical evolution of SARS-CoV-2 infection in hematological patients: A systematic review and meta-analysis.

Main aim of this systematic review is to quantify the risk and identify predictors of clinical evolution of SARS-CoV-2 in hematological patients compared to different control populations. Two independent reviewers screened the literature assessing clinical outcomes of SARS-CoV-2 infection in adult patients with active hematological malignancies published up to June 2021. Primary outcome was COVID-19 related mortality, secondary outcomes were hospital and intensive-care admission, mechanical ventilation (MV), and thromboembolic events. Variables related to study setting, baseline patients' demographic, comorbidities, underlying hematological disease, ongoing chemotherapy, COVID-19 presentation, and treatments were extracted. A total of 67 studies including 10,061 hematological patients and 111,143 controls were included. Most of the studies were retrospective cohorts (51 studies, 76%) and only 19 (13%) provided data for a control group. A significant increased risk of clinical progression in the hematological population compared to the controls was found in terms of COVID-19 related mortality (OR, 2.12; 95% CI, 1.77-2.54), hospitalization (OR, 1.98; 95% CI, 1.15-3.43), intensive-care admission (OR, 1.77; 95% CI, 1.38-2.26), and MV (OR, 2.17; 95% CI, 1.71-2.75). The risk remained significantly higher in the subgroup analysis comparing hematological patients versus solid cancer. Meta-regression analysis of uncontrolled studies showed that older age, male sex, and hypertension were significantly related to worse clinical outcomes of COVID-19 in hematological population. Older age and hypertension were found to be associated also to thromboembolic events. In conclusion, hematological patients have a higher risk of COVID-19 clinical progression compared to both the general population and to patients with solid cancer.

Harmonization and standardization of data for a pan-European cohort on SARS- CoV-2 pandemic.

The European project ORCHESTRA intends to create a new pan-European cohort to rapidly advance the knowledge of the effects and treatment of COVID-19. Establishing processes that facilitate the merging of heterogeneous clusters of retrospective data was an essential challenge. In addition, data from new ORCHESTRA prospective studies have to be compatible with earlier collected information to be efficiently combined. In this article, we describe how we utilized and contributed to existing standard terminologies to create consistent semantic representation of over 2500 COVID-19-related variables taken from three ORCHESTRA studies. The goal is to enable the semantic interoperability of data within the existing project studies and to create a common basis of standardized elements available for the design of new COVID-19 studies. We also identified 743 variables that were commonly used in two of the three prospective ORCHESTRA studies and can therefore be directly combined for analysis purposes. Additionally, we actively contributed to global interoperability by submitting new concept requests to the terminology Standards Development Organizations.

Clinical outcome in solid organ transplant recipients affected by COVID-19 compared to general population: a systematic review and meta-analysis.

BACKGROUND: A significant increased risk of complications and mortality in immunocompromised patients affected by COVID-19 has been described. However, the impact of COVID-19 in solid organ transplant (SOT) recipients is an issue still under debate, due to conflicting evidence that has emerged from different observational studies. OBJECTIVES: We performed a systematic review with a meta-analysis to assess the clinical outcome in SOT recipients with COVID-19 compared with the general population. DATA SOURCES: PubMed-MEDLINE and Scopus were independently searched until 13 October 2021. STUDY ELIGIBILITY CRITERIA: Prospective or retrospective observational studies comparing clinical outcome in SOT recipients versus general populations affected by COVID-19 were included. The primary endpoint was 30-day mortality. PARTICIPANTS: Participants were patients with confirmed COVID-19. INTERVENTIONS: Interventions reviewed were SOTs. METHODS: The quality of the included studies was independently assessed with the Risk of Bias in Non-randomized Studies of Interventions tool for observational studies. The meta-analysis was performed by pooling ORs retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity. RESULTS: A total of 3501 articles were screened, and 31 observational studies (N = 590 375; 5759 SOT recipients vs. 584 616 general population) were included in the meta-analyses. No difference in 30-day mortality rate was found in the primary analysis, including studies providing adjustment for confounders (N = 17; 3752 SOT recipients vs. 159 745 general population; OR: 1.13; 95% CI, 0.94-1.35; I2 = 33.9%). No evidence of publication bias was reported. A higher risk of intensive care unit admission (OR: 1.56; 95% CI, 1.03-2.63) and occurrence of acute kidney injury (OR: 2.50; 95% CI, 1.81-3.45) was found in SOT recipients. CONCLUSIONS: No increased risk in mortality was found in SOT recipients affected by COVID-19 compared with the general population when adjusted for demographic and clinical features and COVID-19 severity.

Enzyme immunoassays (EIA) for serodiagnosis of human leptospirosis: specific IgG3/IgG1 isotyping may further inform diagnosis of acute disease.

The laborious microscopic agglutination test (MAT) is the gold standard serologic test for laboratory diagnosis of leptospirosis. We developed EIA based serologic assays using recombinant proteins (rLigA, rLigB, rLipL32) and whole-cell extracts from eight Leptospira serovars as antigen and assessed the diagnostic performance of the new assay within each class, against MAT positive (MAT+) human sera panels from Portugal/PT (n = 143) and Angola/AO (n = 100). We found that a combination of recombinant proteins rLigA, rLigB and rLipL32 correctly identified antigen-specific IgG from patients with clinical and laboratory confirmed leptospirosis (MAT+) with 92% sensitivity and ~ 97% specificity (AUC 0.974) in serum from the provinces of Luanda (LDA) and Huambo (HBO) in Angola. A combination of whole cell extracts of L. interrogans sv Copenhageni (LiC), L. kirschneri Mozdok (LkM), L. borgpetersenii Arborea (LbA) and L. biflexa Patoc (LbP) accurately identified patients with clinical and laboratory confirmed leptospirosis (MAT+) with 100% sensitivity and ~ 98% specificity for all provinces of Angola and Portugal (AUC: 0.997 for AO/LDA/HBO, 1.000 for AO/HLA, 0.999 for PT/AZ and 1.000 for PT/LIS). Interestingly, we found that MAT+ IgG+ serum from Angola had a significantly higher presence of IgD and that IgG3/IgG1 isotypes were significantly increased in the MAT+ IgG+ serum from Portugal. Given that IgM/IgD class and IgG3/IgG1 specific isotypes are produced in the earliest course of infection, immunoglobulin G isotyping may be used to inform diagnosis of acute leptospirosis. The speed, ease of use and accuracy of EIA tests make them excellent alternatives to the laborious and expensive MAT for screening acute infection in areas where circulating serovars of pathogenic Leptospira are well defined.

Enterovirus D: A Small but Versatile Species.

Enteroviruses (EVs) from the D species are the causative agents of a diverse range of infectious diseases in spite of comprising only five known members. This small clade has a diverse host range and tissue tropism. It contains types infecting non-human primates and/or humans, and for the latter, they preferentially infect the eye, respiratory tract, gastrointestinal tract, and nervous system. Although several Enterovirus D members, in particular EV-D68, have been associated with neurological complications, including acute myelitis, there is currently no effective treatment or vaccine against any of them. This review highlights the peculiarities of this viral species, focusing on genome organization, functional elements, receptor usage, and pathogenesis.

Lasting effects of ketamine and isoflurane administration on anxiety- and panic-like behavioral responses in Wistar rats.

In clinical and laboratory practice, the use of anesthetics is essential in order to perform surgeries. Anesthetics, besides causing sedation and muscle relaxation, promote several physiological outcomes, such as psychotomimetic alterations, increased heart rate, and blood pressure. However, studies depicting the behavioral effect induced by ketamine and isoflurane are conflicting. In the present study, we assessed the behavioral effects precipitated by ketamine and isoflurane administration. We have also evaluated the ketamine effect on cell cytotoxicity and viability in an amygdalar neuronal primary cell culture. Ketamine (80 mg/kg) caused an anxiogenic effect in rats exposed to the elevated T-maze test (ETM) 2 and 7 days after ketamine administration. Ketamine (40 and 80 mg/kg) administration also decreased panic-like behavior in the ETM. In the light/dark test, ketamine had an anxiogenic effect. Isoflurane did not change animal behavior on the ETM. Neither ketamine nor isoflurane changed the spontaneous locomotor activity in the open field test. However, isoflurane-treated animals explored less frequently the OF central area seven days after treatment. Neither anesthetic caused oxidative damage in the liver. Ketamine also reduced cellular metabolism and led to neuronal death in amygdalar primary cell cultures. Thus, our work provides evidence that ketamine and isoflurane induce pronounced long lasting anxiety-related behaviors in male rats.

Desafios e adaptações da extensão universitária em tempos de pandemia: relato de experiência / Challenges and adaptations of university extension in pandemic times: experience report / Retos y adaptaciones de laExtensión universitaria en tiempos de pandemia: informe de experiencia

Introdução:A crise pelo novo Coronavírus tem influenciadodiversos setores, dentre eles o da educação superior, pois as atividades realizadas dentro da universidade estão, desde março de 2020, sendo remanejadas e readaptadas para o modelo on-line, dentre elas a extensão universitária.Objetivo:Opresente artigotemo objetivo dedescrever a vivência deum projeto de extensão universitária desenvolvido para estimular a adoção de hábitos alimentares saudáveis e que migrou suas atividades para o ambiente virtual, mostrando como foram os desafios e adaptações nesse novo cenário global.Metodologia:Trata-se de um estudo descritivo, do tipo relato de experiência. Asatividades adaptadas à nova realidade que serão aqui mencionadas ocorreram no primeiro semestre de 2020, iniciando no mês de maio e finalizando em julho. As postagens para as redes sociais Facebook®e Instagram®foram realizadas uma vez por semana, por dois acadêmicos do curso de Nutrição e bolsistas do projeto, tendo sempre o auxílio das professoras responsáveis. Resultados:A utilização das redes sociais Facebook®e Instagram®ajudaramnosso projeto a desempenhar suas atividades de forma remotae obter um alcance maior de pessoas beneficiadascom as publicações. Conclusão:Apesar das dificuldades iniciais de planejamento de cronograma, temas abordados e o alcance do público-alvo, conseguimos reestruturar bem o projeto ao novo formato. Conseguimos perceber,com a elaboração dos materiais para as publicações e os retornos recebidos,que tivemos a capacidade de influenciar positivamentea vida das pessoas, buscando trazer assuntos pertinentes e com embasamento científico, em linguagem de fácil entendimento,para assim, mesmo que remotamente, tentar melhorar a qualidade de vida da população. Reforçamosa importância das redes sociais para o aumento do número de indivíduosbeneficiados pelo projetode extensãoduranteo período pandêmico (AU).

Introduction:The crisis with the new Coronavirus has influenced several sectors, including higher education, since the activities carried out within the university are, since March 2020, being relocated and readapted for the online model, among them the university extension. Objective:This article aims to describe the experience of a university extension project developed to encourage the adoption of healthy eating habits and which migrated its activities to the virtual environment, showing how the challenges and adaptations were in this new global scenario. Methodology:This is a descriptive, experience report type study. The activities adapted to the new reality that will be mentioned here took place in the first half of 2020, starting in May and ending in July. The posts for the social networks Facebook® and Instagram® were made once a week, by two students of the Nutrition course and scholarship students of the project, always with the help of the responsible teachers. Results:The use of the social networks Facebook® and Instagram® helped our project to carry out its activities remotely and obtain a greater reach of people who benefit from the publications. Conclusion:Despite the initial difficulties in planning the schedule, topics covered and the reach of the target audience, we managed to restructure the project well to the new format. We were able to realize, with the preparation of the materials for the publications and the feedback received, that we had the ability to positively influence people's lives, seeking to bring pertinent and scientifically based matters, in language that is easy to understand, so that even remotely try to improve the quality of life of the population. We reinforce the importance of social networks for increasing the number of individuals benefited by the extension project during the pandemic period (AU).

Introducción:La crisis con el nuevo Coronavirus ha influido en varios sectores, entre ellos la educación superior, ya que las actividades que se llevan a cabo dentro de la universidad están, desde marzo de 2020, siendo reubicadas y readaptadas para el modelo online, entre ellos la extensión universitaria. Objetivo:Este artículo tiene como objetivo describir la experiencia de un proyecto de extensión universitaria desarrollado para incentivar la adopción de hábitos alimentarios saludables y que migró sus actividades al entorno virtual, mostrando cómo fueron los desafíos y adaptaciones en este nuevo escenario global. Metodología:Se trata de un estudio descriptivo tipo relato de experiencia. Las actividades adaptadas ala nueva realidad que aquí mencionaremos tuvieron lugar en el primer semestre de 2020, comenzando en mayo y finalizando en julio. Las publicaciones para las redes sociales Facebook® e Instagram® fueron realizada una veza la semana, por dos alumnos del curso de Nutrición y becarios del proyecto, siempre con la ayuda de los profesores responsables. Resultados:El uso de las redes sociales Facebook® e Instagram® ayudó a nuestro proyecto a realizar sus actividades de forma remota y obtener un mayor alcance de personas que se benefician de las publicaciones. Conclusión:A pesar de las dificultades iniciales en la planificación del cronograma, los temas tratados y el alcance de la audiencia objetivo, logramos reestructurar bien el proyecto al nuevo formato. Pudimos darnos cuenta, con la elaboración de los materiales para las publicaciones y la retroalimentación recibida, que teníamos la capacidad de influir positivamente en la vida de las personas, buscando traer asuntos pertinentes y con base científica, en un lenguaje fácil de entender, de manera que, incluso de forma remota, tratar de mejorar la calidad de vida de la población. Reforzamos la importancia de las redes sociales para incrementar el número de personas beneficiadas por el proyecto de extensión durante el período pandémico (AU).

Carbapenemase-producing Klebsiella pneumoniae intra-abdominal infection successfully treated with ceftazidime/avibactam plus tigecycline.

Ceftazidime/avibactam combines ceftazidime with a new beta-lactam that successfully that inhibits Amber Class A and D carbapenemases. We report a clinical case of a 61 year-old man with a carbapenemase-producing Klebsiella pneumoniae intra-abdominal infection after an elective abdominal hernia repair. The infection was successfully managed with multiple abdominal surgeries, drainage and combined antibiotic therapy with ceftazidime/avibactam plus tigecycline.

Pleural aspergillosis in a patient with recurrent spontaneous pneumothorax: The challenge of an optimal therapeutic approach.

Pleural aspergillosis (PA) is a rare but potentially fatal disease. Most cases are secondary to bronchopleural fistulae or pleural intervention and can occur in the absence of immunosuppression. We report a case of PA in a young patient after pleurodesis for recurrent pneumothorax. Clinical resolution was achieved with systemic and local antifungal therapy combined with surgical debridement. Hepatotoxicity led to a switch from voriconazole to isavuconazole, with a successful outcome.

The route of infection with Leptospira interrogans serovar Copenhageni affects the kinetics of bacterial dissemination and kidney colonization.

The goal of this study was to characterize how natural routes of infection affect the kinetics of pathogenic Leptospira dissemination to blood and kidney. C3H/HeJ mice were sublethally infected with L. interrogans serovar Copenhageni FioCruz L1-130 (Leptospira) through exposure of a dermis wound and through oral and nasal mucosa, in comparison to uninfected mice and to mice infected via standard intraperitoneal inoculation. In striking contrast to oral mucosa inoculation, transdermal and nasal mucosa infections led to weight loss, renal colonization and inflammation, as previously observed for conjunctival and intraperitoneal infections. However, the timing at which Leptospira gained access to blood, as well as Leptospira' colonization of the kidney and shedding in urine, differed from intraperitoneal infection. Furthermore, a comparative analysis of transcription of pro-inflammatory mediators in kidney and total immunoglobulin isotyping in serum from infected mice, showed increased innate immune response markers (KC, MIP-2, TNF-α) and lower Th1 associated IFN-γ in kidney, as well as lower Th1 associated IgG2a in mice infected through the nasal mucosa as compared to intraperitoneal infection. We conclude that the route of infection affects the timing at which Leptospira gains access to blood for dissemination, as well as the dynamics of colonization and inflammation of the kidney.

Role of TLR4 in Persistent Leptospira interrogans Infection: A Comparative In Vivo Study in Mice.

Toll-Like Receptor (TLR) 4, the LPS receptor, plays a central role in the control of leptospirosis and absence of TLR4 results in lethal infection in mice. Because human TLR4 does not sense the atypical leptospiral-LPS, we hypothesized that TLR4/MD-2 humanized transgenic mice (huTLR4) may be more susceptible to leptospirosis than wild-type mice, and thus may constitute a model of acute human leptospirosis. We infected huTLR4 mice, which express human TLR4 but not murine TLR4, with a high dose of L. interrogans serovar Copenhageni FioCruz (Leptospira) in comparison to C57BL/6J wild-type (WT) and, as a control, a congenic strain in which the tlr4 coding sequences are deleted (muTLR4Lps-del). We show that the huTLR4 gene is fully functional in the murine background. We found that dissemination of Leptospira in blood, shedding in urine, colonization of the kidney and overall kinetics of leptospirosis progression is equivalent between WT and huTLR4 C57BL/6J mice. Furthermore, inflammation of the kidney appeared to be subdued in huTLR4 compared to WT mice in that we observed less infiltrates of mononuclear lymphocytes, less innate immune markers and no relevant differences in fibrosis markers. Thus, huTLR4 mice showed less inflammation and kidney pathology, and are not more susceptible to leptospirosis than WT mice. This study is significant as it indicates that one intact TLR4 gene, be it mouse or human, is necessary to control acute leptospirosis.

Ações de educação alimentar e nutricional com grupos em vulnerabilidade social: relato de experiência / Food and nutritional education actions with social vulnerability groups: experience report / Accionesde educación alimentaria y nutricional con grupos en vulnerabilidad social: informe de experiencia

Introdução:O aumento da incidência de doenças crônicas não transmissíveis evidencia a necessidade de ações educativas que promovam melhora na qualidade de vida, diminuição da insegurança alimentar e prevenção de agravos nutricionais. Objetivo:Relatar a experiência de um projeto de extensão universitária desenvolvido para estimular a adoção de hábitos alimentares saudáveis e transmitir demais informações relevantes para a autonomia alimentar. Metodologia:O projeto de extensão vinculado ao curso de Nutrição promoveu aplicação de oficinas no decorrer do ano de 2019, realizadas por acadêmicos supervisionados por professores. Os beneficiados foram frequentadores do Centro de Arte e Lazer e Centro de Referência de Assistência Social do município de Itajaí-SC, sendo estes idosos e indivíduos em vulnerabilidade social, respectivamente. Contaram com participação de acadêmicos bolsistas, voluntários e estagiários de Nutrição em Saúde Coletiva, proporcionando a interface ensino e extensão. Os temas abordados foram adaptados de acordo com as demandas de cada local e público específico. Resultados:As oficinas desenvolvidasoportunizaram a vivência de educação alimentar e nutricional a acadêmicos de nutrição, proporcionando ampliação do conhecimento teórico e prático obtido na Universidade com troca de experiências com a comunidade. Conclusão:A oportunidade de atuação em uma extensão universitária proporciona experiências únicas que não são adquiridas dentro da sala de aula. Ela estreita os laços entre universitários e a comunidade, tornando os acadêmicos profissionais aptos a praticar a empatia e sensibilidade social, tão importante ao profissional da saúde. Ainda, favorece a autonomia do indivíduo em relação a alimentação saudável e melhora da qualidade de vida (AU).

Introduction:The increased incidence of noncommunicable chronic diseases highlights the need for educational actionsthat promote improved quality of life, decreased food insecurity and prevention of nutritional disorders. Objective:Report the experience of a university extension project developed to encourage the adoption of healthy eating habits and transmit other relevant information for food autonomy. Methodology: The extension project linked to the Nutrition course promoted workshops in 2019, conducted by academics supervised by teachers. The beneficiaries were attendees of the Art and Leisure Center and Reference Center for Social Assistance in the city of Itajaí-SC, being these elderly and individuals in social vulnerability, respectively. Participated by scholarship scholars, volunteers and trainees of Collective Health Nutrition, providing the interface teachingand extension. The topics addressed were adapted according to the demands of each specific location and audience. Results:The developedworkshopsprovided the opportunity to experiencefood and nutrition education to students of the nutrition course, and through practice, provided the expansion of theoretical knowledge obtained at the university with the exchange of experiences with the community. Conclusions:The opportunity to work ata university extension provides unique experiences that are not gained within the classroom. It tightens ties between college students and the community, making academics professionals able to practice the empathy and social sensitivity that is so important to the health worker. Still, it favors the autonomy of the individual in relation to healthy eating and improvement of quality of life (AU).

Introducción: Texto das conclusõe El aumento en la incidencia de enfermedades crónicas no transmisibles resalta la necesidad de acciones educativas que promuevan la mejora de la calidad de vida, la disminución de la inseguridad alimentaria y la prevención de problemas nutricionales. Objetivo: Informar sobre la experiencia de un proyecto de extensión universitaria desarrollado para fomentar la adopción de hábitos alimenticios saludables y transmitir otra información relevante para la autonomía alimentaria.Metodología: El proyecto de extensión vinculado al curso de Nutrición promovió la aplicación de talleres a lo largo de 2019, realizados por académicos supervisados por maestros. Los beneficiarios asistieron al Centro de Arte y Ocio y al Centro de Referencia de Asistencia Social en el municipio de Itajaí-SC, siendo estos ancianos e individuos en vulnerabilidad social, respectivamente. Contaban con la participación de becarios, voluntarios y pasantes de Nutrición en Salud Pública,brindando la interfaz de enseñanza y extensión. Los temas cubiertos fueron adaptados de acuerdo a las demandas de cada ubicación y audiencia específica. Resultados: Los talleres desarrollados brindaron la oportunidad de experimentar la educación alimentaria y nutricional para estudiantes de nutrición, proporcionando una expansión del conocimiento teórico y práctico obtenido en la Universidad con un intercambio de experiencias con la comunidad. Conclusiones: la oportunidad de trabajar en una extensión universitaria proporciona experiencias únicas que no se adquieren dentro del aula. Aprieta los lazos entre los estudiantes universitarios y la comunidad, haciendo que los académicos profesionales puedan practicar la empatía y la sensibilidad social, tan importantes para los profesionales de la salud. Aún así, favorece la autonomía del individuo en relación con una alimentación saludable y la mejora de la calidad de vida (AU).