Use of point-of-care ultrasound to assess the severity of scorpion stings in hospitalized patients.

INTRODUCTION: Scorpionism is a public health problem, especially in tropical regions. In Brazil, the prevalence of envenomation by scorpions is high, and the average national lethality is around 0.16 percent. The Tityus serrulatus scorpion is the primary species of medical importance. However, objective tools to predict and define the severity of these envenomations are lacking. MATERIALS AND METHODS: This was an observational study conducted among patients aged 0-19 years with scorpionism. Patients were admitted to a reference hospital between December 2020 and May 2022. Point-of-care ultrasound was performed within 24 hours of the scorpion sting. RESULTS: Forty-nine patients were included, with a median age of 3.6 (interquartile range 2.3-5.3) years and a predominance of females (51 percent). Fifteen patients (30.6 percent) presented major life-threatening signs, 32 (65.3 percent) minor systemic manifestations, and two (4.1 percent) only local manifestations. Left ventricular dysfunction was identified in 13 patients (26.5 percent). Ten patients (20.4 percent) presented pattern B (visualization of three or more B lines in the evaluated quadrant) in at least one lung window. The sensitivity and specificity of cardiac and pulmonary ultrasound to identify the most severely ill patients were 86 percent and 94 percent, respectively. DISCUSSION: The changes found on point-of-care ultrasound were associated with life-threatening signs. All patients with class III envenomation were referred to the intensive care unit, showing the importance of early identification of this subgroup. The main limitations were the small sample size and the fact that admission to intensive care was not based on systematic criteria. CONCLUSIONS: Point-of-care ultrasound is able to identify early signs of pulmonary congestion and heart failure in scorpionism. It can be useful for the objective selection of patients who are at a higher risk of complications and death and who require intensive support; it may also be valuable for periodic reassessments. Point-of-care ultrasound is a valuable tool for identifying and monitoring severe cases of scorpionism.

Reduction of hospital length of stay through the implementation of SAFER patient flow bundle and Red2Green days tool: a pre-post study.

BACKGROUND: In 2018, the National Health System released the 'Guide to reducing long hospital stays' to stimulate improvement and decrease length of stay (LOS) in England hospitals. The SAFER patient flow bundle and Red2Green tool were described as strategies to be implemented in inpatient wards to reduce discharge delays. OBJECTIVE: To verify if implementing the SAFER patient flow bundle and Red2Green days tool is associated with LOS reduction in the internal medicine unit (IMU) wards of a university hospital in Brazil. METHODS: In this pre post study, we compared the LOS of patients discharged from the IMU wards in 2019, during the implementation of the SAFER bundle and Red2Green tool, to the LOS of patients discharged in the same period in 2018. The Diagnosis-Related Group Brazil algorithm compared groups according to complexity and resource requirements. In-hospital mortality, readmission rates, the number of hospital acquired conditions and the number and causes of inappropriate hospital days were also evaluated. RESULTS: Two hundred and eight internal medicine patients were discharged in 2018, and 252 were discharged in 2019. The median hospital LOS was significantly lower during the intervention period (14.2 days (IQR, 8-23) vs 19 days (IQR, 12-32); p<0.001). In-hospital mortality, 30-day mortality, readmission in 30 days and the number of hospital acquired conditions were the same between groups. Of the 3350 patient days analysed, 1482 (44.2%) were classified as green and 1868 (55.8%) as red. The lack of senior review was the most frequent cause of a red day (42.4%). CONCLUSION: The SAFER patient flow bundle and Red2Green days tool implementation were associated with a significant decrease in hospital LOS in a university hospital IMU ward. There is a considerable improvement opportunity for hospital LOS reduction by changing the multidisciplinary team's attitude during patient hospitalisation using these strategies.

Compartmentalized Regulation of Pulmonary and Systemic Inflammation in Critical COVID-19 Patients.

Critical COVID-19 has been associated with altered patterns of cytokines. Distinct inflammatory processes in systemic and pulmonary sites have been reported, but studies comparing these two sites are still scarce. We aimed to evaluate the profile of pulmonary and systemic cytokines and chemokines in critically ill COVID-19 patients. Levels of cytokines and chemokines were measured in plasma samples and minibronchoalveolar lavage of critical COVID-19 patients within 48 h and 5-8 days after intubation. Distinct inflammatory processes were observed in the lungs and blood, which were regulated separately. Survivor patients showed higher lung cytokine levels including IFN-γ, IL-2, IL-4, G-CSF, and CCL4, while nonsurvivors displayed higher levels in the blood, which included IL-6, CXCL8, CXCL10, CCL2, and CCL4. Furthermore, our findings indicate that high TNF and CXCL8 levels in the mini-BAL were associated with better lung oxygen exchange capacity, whereas high levels of IFN-γ in plasma were associated with worse lung function, as measured using the PaO2/FiO2 ratio. These results suggest that a robust and localized inflammatory response in the lungs is protective and associated with survival, whereas a systemic inflammatory response is detrimental and associated with mortality in critical COVID-19.

Morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis.

BACKGROUND: Fibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to study the ultrastructural characteristics and functional responses in human and mouse FLS. The objective of the study was to analyze ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with rheumatoid arthritis (RA) and from mice with collagen-induced arthritis (CIA). METHODS: FLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with CIA (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor-alpha (TNF-α) and IL-1ß. RESULTS: RA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well-developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1ß by CIA-FLSs than by RA-FLSs. CONCLUSION: This study provides a comprehensive understanding of the biology of RA-FLS and CIA-FLS. The differences and similarities in ultrastructural morphology and important inflammatory cytokines shown, contribute to future in vitro studies using RA-FLS and CIA-FLS, in addition, they indicate that the adoption of CIA-FLS for studies should take careful and be well designed, since they do not completely resemble human diseases.

Dysfunctional phenotype of systemic and pulmonary regulatory T cells associate with lethal COVID-19 cases.

Severe cases of COVID-19 present hyperinflammatory condition that can be fatal. Little is known about the role of regulatory responses in SARS-CoV-2 infection. In this study, we evaluated the phenotype of regulatory T cells in the blood (peripheral blood mononuclear cell) and the lungs (broncho-alveolar) of adult patients with severe COVID-19 under invasive mechanical ventilation. Our results show important dynamic variation on Treg cells phenotype during COVID-19 with changes in number and functional parameters from the day of intubation (Day 1 of intensive care unit admission) to Day 7. We observed that compared with surviving patients, non-survivors presented lower numbers of Treg cells in the blood. In addition, lung Tregs of non-survivors also displayed higher PD1 and lower FOXP3 expressions suggesting dysfunctional phenotype. Further signs of Treg dysregulation were observed in non-survivors such as limited production of IL-10 in the lungs and higher production of IL-17A in the blood and in the lungs, which were associated with increased PD1 expression. These findings were also associated with lower pulmonary levels of Treg-stimulating factors like TNF and IL-2. Tregs in the blood and lungs are profoundly dysfunctional in non-surviving COVID-19 patients.

Morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis

Abstract Background Fibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to study the ultrastructural characteristics and functional responses in human and mouse FLS. The objective of the study was to analyze ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with rheumatoid arthritis (RA) and from mice with collagen-induced arthritis (CIA). Methods FLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with CIA (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor-alpha (TNF-α) and IL-1β. Results RA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well- developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1β by CIA-FLSs than by RA-FLSs. Conclusion This study provides a comprehensive understanding of the biology of RA-FLS and CIA-FLS. The differences and similarities in ultrastructural morphology and important inflammatory cytokines shown, contribute to future in vitro studies using RA-FLS and CIA-FLS, in addition, they indicate that the adoption of CIA-FLS for studies should take careful and be well designed, since they do not completely resemble human diseases.

Psychometric Evaluation of the Cardiology Certification Exam of the Brazilian Society of Cardiology. / Avaliação Psicométrica da Prova de Título de Especialista em Cardiologia da Sociedade Brasileira de Cardiologia.

BACKGROUND: The Cardiology Certification Exam is issued annually by the Brazilian Cardiology Society and set and applied by the Judging Committee for the Cardiologist Title (CJTEC). The psychometric analysis of the exam items using the Item Response Theory (IRT) may provide robust data that can help in the continuous improvement of this instrument. OBJECTIVES: To evaluate the psychometric properties of the 2019 Cardiology Certification Exam in relation to the IR parameters. METHODS: This was an observational study, with psychometric analysis of the 120 questions of the exam taken by 1,120 candidates for the title of Cardiologist in 2019. RESULTS: The IRT analysis revealed that 32.2% of the items had a "high" or "very high" discriminating power, 49.2% were categorized as "easy" or "very easy", and 41.5% showed a high probability of a correct guessing. Sixty-nine deficient items in terms of the IRT parameters were identified, which were then considered poorly effective in evaluating the candidate's ability. CONCLUSIONS: The psychometric analysis of the 2019 Cardiology Certification Exam by the IRT revealed a high percentage of easy questions, with nearly two thirds of the items with a high probability of correct guessing. These data may serve as a basis for a series of discussions and proposals for the elaboration of future certificate exams in Cardiology.

FUNDAMENTO: A Sociedade Brasileira de Cardiologia promove anualmente a prova para obtenção do título de especialista em Cardiologia, sendo a Comissão Julgadora do Título de Especialista em Cardiologia responsável pela sua organização e aplicação. A análise psicométrica dos itens de uma prova, por meio da Teoria de Resposta ao Item (TRI) pode fornecer informações robustas e contribuir para o aprimoramento contínuo dessa avaliação. OBJETIVOS: Avaliar as propriedades psicométricas da prova do Título de Especialista em Cardiologia no ano de 2019, em relação aos parâmetros da TRI. MÉTODOS: Estudo observacional, com a análise psicométrica das 120 questões da prova realizada por 1120 (mil cento e vinte) candidatos para a obtenção do título de especialista em Cardiologia, no ano de 2019. RESULTADOS: A análise da prova pela TRI mostrou 32,2% dos itens com poder de discriminação "alto" ou "muito alto", 49,2% dos itens categorizados como "fácil" ou "muito fácil" e 41,5% apresentavam alta probabilidade de acerto ao acaso . Foram identificados 69 itens com problemas em relação aos parâmetros da TRI e, portanto, com baixo poder de avaliar a proficiência do candidato. CONCLUSÕES: A análise psicométrica da prova de título de Especialista em Cardiologia pela TRI demonstrou um alto percentual de questões fáceis, com cerca de dois terços dos itens com alta probabilidade de acerto ao acaso. Esses dados poderão desencadear uma série de discussões e propostas para a construção das futuras provas em cardiologia.

Avaliação Psicométrica da Prova de Título de Especialista em Cardiologia da Sociedade Brasileira de Cardiologia / Psychometric Evaluation of the Cardiology Certification Exam of the Brazilian Society of Cardiology

Resumo Fundamento A Sociedade Brasileira de Cardiologia promove anualmente a prova para obtenção do título de especialista em Cardiologia, sendo a Comissão Julgadora do Título de Especialista em Cardiologia responsável pela sua organização e aplicação. A análise psicométrica dos itens de uma prova, por meio da Teoria de Resposta ao Item (TRI) pode fornecer informações robustas e contribuir para o aprimoramento contínuo dessa avaliação. Objetivos Avaliar as propriedades psicométricas da prova do Título de Especialista em Cardiologia no ano de 2019, em relação aos parâmetros da TRI. Métodos Estudo observacional, com a análise psicométrica das 120 questões da prova realizada por 1120 (mil cento e vinte) candidatos para a obtenção do título de especialista em Cardiologia, no ano de 2019. Resultados A análise da prova pela TRI mostrou 32,2% dos itens com poder de discriminação "alto" ou "muito alto", 49,2% dos itens categorizados como "fácil" ou "muito fácil" e 41,5% apresentavam alta probabilidade de acerto ao acaso . Foram identificados 69 itens com problemas em relação aos parâmetros da TRI e, portanto, com baixo poder de avaliar a proficiência do candidato. Conclusões A análise psicométrica da prova de título de Especialista em Cardiologia pela TRI demonstrou um alto percentual de questões fáceis, com cerca de dois terços dos itens com alta probabilidade de acerto ao acaso. Esses dados poderão desencadear uma série de discussões e propostas para a construção das futuras provas em cardiologia.

Abstract Background The Cardiology Certification Exam is issued annually by the Brazilian Cardiology Society and set and applied by the Judging Committee for the Cardiologist Title (CJTEC). The psychometric analysis of the exam items using the Item Response Theory (IRT) may provide robust data that can help in the continuous improvement of this instrument. Objectives To evaluate the psychometric properties of the 2019 Cardiology Certification Exam in relation to the IR parameters. Methods This was an observational study, with psychometric analysis of the 120 questions of the exam taken by 1,120 candidates for the title of Cardiologist in 2019. Results The IRT analysis revealed that 32.2% of the items had a "high" or "very high" discriminating power, 49.2% were categorized as "easy" or "very easy", and 41.5% showed a high probability of a correct guessing. Sixty-nine deficient items in terms of the IRT parameters were identified, which were then considered poorly effective in evaluating the candidate's ability. Conclusions The psychometric analysis of the 2019 Cardiology Certification Exam by the IRT revealed a high percentage of easy questions, with nearly two thirds of the items with a high probability of correct guessing. These data may serve as a basis for a series of discussions and proposals for the elaboration of future certificate exams in Cardiology.

Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease.

Host immune responses contribute to dengue's pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, interferon (alpha and beta) receptor one knockout (KO), AnxA1 KO, and formyl peptide receptor 2 (FPR2) KO mice were infected with dengue virus (DENV) and treated with the AnxA1 mimetic peptide Ac2-26 for analysis. In addition, the effect of Ac2-26 on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. Whilst the absence of AnxA1 or its receptor FPR2 aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestationsatteanuated the symptoms of the disease. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease.

Transient Alterations in Streamwater Quality Induced by Pollution Incidents: Interim Losses Calculations and Compensation Alternatives Based on Habitat Equivalency Analysis.

Pollution incidents cause transient water quality alterations during the passage of contaminants' plume along watercourses, with plume passage period and contaminants' concentrations modelled by advection-dispersion equations. Despite being transient, water quality alterations can impose many impacts on the streamwater ecosystem services. This study proposes two frameworks based on Habitat Equivalency Analysis to be applied during assessments of streamwaters' pollution incidents and respective compensation panoramas: (1) Streamwater interim loss framework, to calculate interim loss debits caused by transient alterations in the streamwater quality; (2) Total credit framework, to calculate streamwater credits generated by improvements in selected watercourse's streamwater quality, produced by wastewater treatment plants in this study. The amount of credits calculated in the selected watercourses assists in the proposal of suitable compensatory remediation projects to offset interim losses. Frameworks' calculations are founded on IVA, a water quality index for protection of aquatic life and aquatic communities. Frameworks' calculations depend on three parameters: IVA, watercourses fluxes and the present value multiplier. The frameworks were calculated in ΔIVAxL, unit defined by multiplying sensed alterations in streamwater quality (as ΔIVA) and streamwater flux, in liters (L). The frameworks were applied to two major streamwater pollution incidents in Brazil, caused by the dam collapses of Mariana and Brumadinho, suggesting suitable compensatory remediations' projects for the respective streamwater interim losses. Depending on the selected project, Brumadinho compensation period varied from 2 to 5 years, with estimated costs in the 2020 Int.$ 5.7-18.7M range; Mariana compensation period varied from 8 to 20 years, with estimated costs in the 2020 Int.$ 16.7-58.1M range. Based on Brumadinho compensatory remediation projects, an average water pollution environmental damage value per interim loss was calculated, 1.17E-4 2020 Int.$/ΔIVAxL, which might be useful in comparing streamwater pollution evaluations around the world.

Performance of High Mobility Protein Group 1 and Interleukin-6 as Predictors of Outcomes Resulting from Variceal Bleeding in Patients with Advanced Chronic Liver Disease.

Variceal bleeding is a serious complication in cirrhotic patients and is related to increased expression of inflammatory mediators that accentuate circulatory dysfunction. The study aims to evaluate the performance of high mobility protein group 1 (HMG1) and interleukin-6 (IL-6) as predictors of acute kidney injury (AKI), infection and death in these patients. Fifty patients who were diagnosed with advanced chronic liver disease with variceal bleeding were included. The mean age was 52.8 ± 10.8 years, and 33 (66%) were male. Twenty-one (42%) patients were classified as Child-Pugh C, 21 (42%) Child-Pugh B and 8 (16%) Child-Pugh A. The mean HMG1 serum level was 2872.36 pg/mL ± 2491.94, and the median IL-6 serum level was 47.26 pg/mL (0-1102.4). In AKI, the serum level of HMG1 that performed best on the ROC curve was 3317.9 pg/mL. The IL-6 serum level was not associated with AKI. HMG1 and IL-6 cut-off values that better predicted infection were 3317.9 pg/mL and 72.9 pg/mL, and for mortality, the values were 2668 pg/mL and 84.5 pg/mL, respectively. In multivariate analysis, the variables that were associated with AKI and infection outcomes were model for end-stage liver disease and HMG1. Infections were related to the risk of death. Clinical and laboratory variables related to the outcomes were identified. Serum levels of HMG1 were associated with AKI and infection and had good performance in the ROC curve. IL-6 levels were not maintained in logistic regression outcomes but had good performance in infection and death outcomes. Such data will be useful for comparisons and possible future validations.

Emergency medicine in Brazil: historical perspective, current status, and future challenges.

BACKGROUND: Emergency medicine (EM) in Brazil has achieved critical steps toward its development in the last decades including its official recognition as a specialty in 2016. In this article, we worked in collaboration with the Brazilian Association of Emergency Medicine (ABRAMEDE) to describe three main aspects of EM in Brazil: (1) brief historical perspective; (2) current status; and (3) future challenges. MAIN TEXT: In Brazil, the first EM residency program was created in 1996. Only 20 years later, the specialty was officially recognized by national regulatory bodies. Prior to recognition, there were only 2 residency programs. Since then, 52 new programs were initiated. Brazil has now 54 residency programs in 16 of the 27 federative units. As of December 2020, 192 physicians have been board certified as emergency physicians in Brazil. The shortage of formal EM-trained physicians is still significant and at this point it is not feasible to have all Brazilian emergency care units and EDs staffed only with formally trained emergency physicians. Three future challenges were identified including the recognition of EM specialists in the house of Medicine, the need of creating a reliable training curriculum despite highly heterogeneous emergency care practice across the country, and the importance of fostering the development of academic EM as a way to build a strong research agenda and therefore increase the knowledge about the epidemiology and organization of emergency care. CONCLUSION: Although EM in Brazil has accomplished key steps toward its development, there are several obstacles before it becomes a solid medical specialty. Its continuous development will depend on special attention to key challenges involving recognition, reliability, and research.

Lung Ultrasound Can Predict the Clinical Course and Severity of COVID-19 Disease.

Coronavirus disease 2019 (COVID-19) compromises the lung in large numbers of people. The development of minimally invasive methods to determine the severity of pulmonary extension is desired. This study aimed to describe the characteristics of sequential lung ultrasound and to test the prognostic usefulness of this exam in a group of patients admitted to the hospital with COVID-19. We prospectively evaluated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to our hospital between April and August 2020. Bedside lung ultrasound exams were performed at three time points: at inclusion in the study, after 48 h and on the seventh day of follow-up. Lung ultrasound scores were quantified according to the aeration loss in each of eight zones scanned. Sixty-six participants were included: 42 (63.6%) in the intensive care unit and 24 (36.3%) in the ward. Lung ultrasound scores were higher in participants admitted to the intensive care unit than in those admitted to the ward at the time of inclusion (16 [13-17] vs. 10 [4-14], p < 0.001), after 48 h (15.5 [13-17] vs. 12.5 [8.2-14.7], p = 0.001) and on the seventh day (16 [14-17] vs. 7 [4.5-13.7], p < 0.001) respectively. Lung ultrasound score measured at the time of inclusion in the study was independently associated with the need for admission to the intensive care unit (odds ratio = 1.480; 95% confidence interval, 1.093-2.004; p = 0.011) adjusted by the Sequential Organ Failure Assessment score.

UHPLC for quality evaluation of genuine and illegal medicines containing sildenafil citrate and tadalafil.

One of the highest incidences of illegal drug products is related to phosphodiesterase-5 inhibitors, used in treatment of erectile dysfunction, including those containing sildenafil citrate and tadalafil. In this context, comprehensive evaluation of the quality of genuine and illegal medicines was performed. A simple and rapid ultra-high performance liquid chromatography (UHPLC-UV) method to quantify sildenafil and tadalafil in the presence of six degradation products was developed and validated. Sildenafil and tadalafil were submitted to forced degradation. The separation was carried out on a Kinetex C18 (50 × 2.1 mm; 1.7 µm) column with mobile phase composed of acetonitrile and aqueous triethylamine solution. The calibration curves were linear in the range of 14-126 µg mL-1 for sildenafil citrate and 4-36 µg mL-1 for tadalafil and the method proved to be selective, precise, accurate and robust. Sildenafil degraded in oxidative media, whereas tadalafil degraded in acidic, alkaline and oxidative environment. The chemical structures and the mechanisms for the formation of the main degradation products were proposed by UHPLC coupled to tandem mass spectrometry. The UHPLC-UV method was applied in the pharmaceutical analysis of genuine and seized medicines. Some of them did not meet quality standards, mainly due to contents below specifications and the large variation on contents between units within a batch.

Clinical Frailty Scale em idosos atendidos no Serviço Hospitalar de Emergência: a fragilidade basal é um bom preditor de mortalidade em 90 dias? / Clinical Frailty Scale in older adults admitted at Emergency Department: is baseline frailty a good predictor of Ninety-Day Mortality?

Resumo Objetivo Avaliar a capacidade da Clinical Frailty Scale (CFS) em predizer a mortalidade em até 90 dias e outros desfechos desfavoráveis em idosos admitidos em um Serviço Hospitalar de Emergência (SHE). Método Estudo de coorte prospectivo que incluiu idosos admitidos e que permaneceram por pelo menos uma noite no SHE de um hospital público terciário. O grau de fragilidade basal foi avaliado através da CFS e sua pontuação, o preditor estudado, por meio da curva Receiver Operator Characteristics (ROC). Analisou-se como desfecho primário a mortalidade em 90 dias. Considerou-se como desfechos secundários: mortalidade em 180 dias, declínio funcional, readmissão no SHE, reinternação e necessidade de atenção domiciliar. Resultados 206 participantes foram incluídos. Dos 127 idosos frágeis, 40 (31,5%) faleceram até o 90º dia comparado a 5 (6,3%) do grupo não frágil (p<0,001). Após ajuste para variáveis demográficas e clínicas, a fragilidade manteve-se no modelo como um preditor independente de mortalidade em 90 dias da admissão. A acurácia obtida pela curva ROC (AUROC) para predição de mortalidade em 90 dias foi de 0,81. Para mortalidade em 180 dias foi 0,80; para necessidade de atenção domiciliar, 0,77; e para reinternação, 0,65. Para os demais desfechos estudados, a acurácia não foi significativa. Conclusão A fragilidade basal medida pela CFS é um bom preditor de mortalidade em 90 e 180 dias e de necessidade de atenção domiciliar em idosos admitidos no SHE. Sua aplicação nesse cenário pode auxiliar na tomada de decisões clínicas.

Abstract Objective To evaluate the ability of the Clinical Frailty Scale (CFS) to predict 90-day mortality and other poor outcomes in older adults admitted at a Hospital Emergency Department (ED). Method This is a prospective cohort study including older adults admitted at ED of a Public Hospital who spent at least one night in it. The degree of baseline frailty was assessed through the CFS, and its score was the predictor studied, through the Receiver Operator Characteristics (ROC) curve analysis. We analyzed 90-day mortality as a primary outcome. The following outcomes were considered as secondary ones: mortality, functional decline, readmittance to ED, readmission and need for home care. Results 206 participants were included. Of the 127 frail older adults, 40 (31.5%) died before the 90th day compared to 5 (6.3%) in the non-frail group (p<0.001). After adjustment for demographic and clinical variables, frailty remained in the model as an independent predictor of 90-day mortality. The accuracy obtained by the ROC curve (AUROC) for predicting 90-day mortality was 0.81. For 180-day mortality, 0.80, for the need for home care, 0.77 for readmission, 0.65. For the other outcomes studied, the accuracy was not significant. Conclusion Baseline frailty measured by the CFS is a good predictor of 90 and 180-day mortality and needing for home care in older adults admitted to ED. Its application in this setting might help clinical decision-making.

Evaluation of the Biomarkers HMGB1 and IL-6 as Predictors of Mortality in Cirrhotic Patients with Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) affects from 20% to 50% of cirrhotic patients, and the one-month mortality rate is 60%. The main cause of AKI is bacterial infection, which worsens circulatory dysfunction through the release of HMGB1 and IL-6. OBJECTIVES: To evaluate HMGB1 and IL-6 as biomarkers of morbidity/mortality. METHODS: Prospective, observational study of 25 hospitalised cirrhotic patients with AKI. Clinical and laboratory data were collected at the time of diagnosis of AKI, including serum HMGB1 and IL-6. RESULTS: The mean age was 55 years; 70% were male. Infections accounted for 13 cases. The 30-day and three-month mortality rates were 17.4% and 30.4%, respectively. HMGB1 levels were lower in survivors than in nonsurvivors at 30 days (1174.2 pg/mL versus 3338.5 pg/mL, p = 0.035), but not at three months (1540 pg/mL versus 2352 pg/mL, p = 0.243). Serum IL-6 levels were 43.3 pg/mL versus 153.3 pg/mL (p = 0.061) at 30 days and 35.8 pg/mL versus 87.9 pg/mL (p = 0.071) at three months, respectively. The area under the ROC curve for HMGB1 was 0.842 and 0.657, and that for IL-6 was 0.803 and 0.743 for discriminating nonsurvivors at 30 days and three months, respectively. In multivariate analysis, no biomarker was independently associated with mortality. CONCLUSION: HMGB1 levels were associated with decreased survival in cirrhotics. Larger studies are needed to confirm our results.

Duration of antibiotic therapy in critically ill patients: a randomized controlled trial of a clinical and C-reactive protein-based protocol versus an evidence-based best practice strategy without biomarkers.

BACKGROUND: The rational use of antibiotics is one of the main strategies to limit the development of bacterial resistance. We therefore sought to evaluate the effectiveness of a C-reactive protein-based protocol in reducing antibiotic treatment time in critically ill patients. METHODS: A randomized, open-label, controlled clinical trial conducted in two intensive care units of a university hospital in Brazil. Critically ill infected adult patients were randomly allocated to (i) intervention to receive antibiotics guided by daily monitoring of CRP levels and (ii) control to receive antibiotics according to the best practices for rational use of antibiotics. RESULTS: One hundred thirty patients were included in the CRP (n = 64) and control (n = 66) groups. In the intention-to-treat analysis, the median duration of antibiotic therapy for the index infectious episode was 7.0 (5.0-8.8) days in the CRP and 7.0 (7.0-11.3) days in the control (p = 0.011) groups. A significant difference in the treatment time between the two groups was identified in the curve of cumulative suspension of antibiotics, with less exposure in the CRP group only for the index infection episode (p = 0.007). In the per protocol analysis, involving 59 patients in each group, the median duration of antibiotic treatment was 6.0 (5.0-8.0) days for the CRP and 7.0 (7.0-10.0) days for the control (p = 0.011) groups. There was no between-group difference regarding the total days of antibiotic exposure and antibiotic-free days. CONCLUSIONS: Daily monitoring of CRP levels may allow early interruption of antibiotic therapy in a higher proportion of patients, without an effect on total antibiotic consumption. The clinical and microbiological relevance of this finding remains to be demonstrated. TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT02987790. Registered 09 December 2016.

Circulating levels of High-mobility group box 1 protein and nucleosomes are associated with outcomes after liver transplant.

BACKGROUND: Liver transplantation (LT) can be associated with early complications, such as allograft dysfunction and acute kidney injury, which contribute significantly to morbidity and mortality. High-mobility group box 1 protein (HMGB1) has been identified as mediator in ischemia-reperfusion injury. Nucleosomes are complexes formed by DNA and histone proteins, and histones contribute to organs failure and death during sepsis. METHODS: HMGB1 and nucleosome plasma levels were measured, by enzyme-linked immunosorbent assays, during LT and in the first 48 post-operative hours in 22 LT patients. The association between HMGB1 and nucleosome levels and the complications and survival within 6 months after LT were investigated. RESULTS: We observed peak HMGB1 and nucleosome levels after graft reperfusion. HMGB1 and nucleosome levels were associated with the occurrence of acute kidney injury, early allograft dysfunction, and early survival after LT. Nucleosome levels after graft reperfusion were associated with the occurrence of systemic inflammatory response syndrome. CONCLUSIONS: HMGB1 and nucleosome levels increased after liver reperfusion in human LT setting and were associated with early complications and survival. New studies are necessary to explore their role as early markers of hepatocellular injury in human LT and the risk of graft and organs dysfunction and death.