BACKGROUND:Cardiovascular Disease is the leading cause of death in adult and pediatric patients with Chronic Kidney Disease (CKD) and its pathogenesis involves the interaction of multiple pathways. As Inflammatory mechanisms play a critical role in the vascular disease of CKD pediatric patients, there are several biomarkers related to inflammation strongly associated with this comorbidity.OBJECTIVE:This review provides available evidence on the link between several biomarkers and the pathophysiology of heart disease in patients with CKD.METHODS:The data were obtained independently by the authors, who carried out a comprehensive and non-systematic search in PubMed, Cochrane, Scopus, and SciELO databases. The search terms were "Chronic Kidney Disease", "Cardiovascular Disease", "Pediatrics", "Pathophysiology", "Mineral and Bone Disorder (MBD)", "Renin Angiotensin System (RAS)", "Biomarkers", "BNP", "NTproBNP", "CK-MB", "CXCL6", "CXCL16", "Endocan-1 (ESM-1)", "FABP3", "FABP4", h-FABP", "Oncostatin- M (OSM)", "Placental Growth Factor (PlGF)" and "Troponin I".RESULTS:The pathogenesis of CKD-mediated cardiovascular disease is linked to inflammatory biomarkers, which play a critical role in the initiation, maintenance, and progression of cardiovascular disease. There are several biomarkers associated with cardiovascular disease in pediatric patients, including BNP, NTproBNP, CK-MB, CXCL6, CXCL16, Endocan-1 (ESM-1), FABP3, FABP4, Oncostatin- M (OSM), Placental Growth Factor (PlGF), and Troponin I.CONCLUSION:The pathogenesis of CKD-mediated cardiovascular disease is not completely understood, but it is linked to inflammatory biomarkers. Further studies are required to elucidate the pathophysiological and potential role of these novel biomarkers.

Background C-reactive protein (CRP) is an inflammatory protein used in clinical practice to identify and monitor inflammatory and infectious processes. Recent data suggest CRP might be useful in guiding antibiotic therapy discontinuation among critical care patients. This meta-analysis analyzed the benefits and risks of CRP-guided protocols to guide antibiotic therapy in hospitalized patients in comparison with standard treatment. Methods Studies were searched in four databases: CENTRAL, Medline, Embase and LILACS. The search was performed until Jan 25th, 2023. The reference lists of the articles retrieved and related review studies were hand-screened to find eligible trials that might have been missed. Primary endpoints included the duration of antibiotic therapy for the index episode of infection. The secondary endpoint was the all-cause hospital mortality and infection relapses. The risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Random effects were used to pool the mean differences and odds ratio of individual studies. The protocol was registered in PROSPERO (CRD42021259977). Results The search strategy retrieved 5209 titles, out of which three studies met the eligibility criteria and were included in this meta-analysis. 727 adult patients were analyzed, of whom 278 were included in the intervention group and 449 were included in the control group. 55,7% of all patients were women. Meta-analysis indicated that experimental groups (CRP-guided) had a lower duration of antibiotic therapy (days) [MMD = -1.82, 95%IC -3.23; -0.40]; with no difference in mortality [OR = 1.19 95%IC 0.67–2.12] or in the occurrence of infection relapse [OR = 3.21 95%IC 0.85–12.05]. Conclusion The use of CRP-guided protocol reduces the total amount of time required for antibiotic therapy when compared to standard protocols of treatment in hospitalized patients with acute bacterial infection. We did not observe statistical differences regarding mortality and infection relapse rates.

Lowe syndrome (LS) is a rare disease (1:500,000) with X-linked recessive inheritance involving the kidneys, eyes, and nervous sys-tem. A Mexican 25-year-old male patient presented for diagnosis of multiple radiolucent lesions observed on routine radiographic examination. General aspects revealed cognitive delay, eye alterations, and kidney involvement, which support the diagnosis of LS. Radiolucent well-delimited lesions were observed in both mandibular angle and symphysis. Under general anesthesia, inci-sional biopsy and decompression were performed. Histological aspects led to diagnosing odontogenic keratocyst (OKC) for all lesions. The lesions in the right and left mandibular angles were decompressed, and the symphyseal lesion was enucleated. A 2-month follow-up shows the bone healing process. There are few reports detailing oral findings in LS. Here, we reported the first case of multiple OKC in a patient with LS. In addition, we performed a literature review on odontogenic lesions in patients affected by LS.

Background: The identification of vulnerable subgroups and risk factors associated with the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and coronavirus disease 2019 (COVID-19) is of utmost importance in a pandemic scenario. Potential interactions between renin-angiotensin system (RAS), immune markers and COVID-19 play a role in disease outcome in specific groups of patients. Objective: This review aimed to describe the particularities of the RAS and the immune system profile of particular subgroups of patients. Methods: This non-systematic review summarizes evidence on SARS-CoV-2 infection in specific subgroups of patients and possible relationships between immune system, RAS and the pathophysiology of COVID-19. Results: The RAS and the immune system exert a role in the pathogenesis and prognosis of COVID-19, mainly in cases of hypertension, diabetes, obesity and other chronic diseases. The overactivation of the ACE/Ang II/AT1R axis and the enhancement of inflammation contribute to deleterious effects of COVID-19. Likewise, pregnant women and elderly patients usually display immune responses that are less effective in withstanding exposition to viruses, while children are relatively protected against severe complications of COVID-19. Women, conversely, exhibit stronger antiviral responses and are less sensitive to the effects of increased Ang II. Future Perspectives: The recognition of vulnerable subgroups and risk factors for disease severity is essential to better understand the pandemic. Precision medicine tools, including proteomics and metabolomics approaches, identified metabolic patterns of the severe form of disease and might be the alternative to diagnose, evaluate and predict the prognosis and the efficiency of therapies.

The last decade was crucial for our understanding of the renin-angiotensin-aldosterone system (RAAS) as a two-axis, counter-regulatory system, divided into the classical axis, formed by angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the angiotensin type 1 receptor (AT1R), and the alternative axis comprising angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) (Ang-(1-7)), and the Mas receptor. Breakthrough discoveries also took place, with other RAAS endopeptides being described, including alamandine and angiotensin A. In this review, we characterize the two RAAS axes and the role of their components in pediatric kidney diseases, including childhood hypertension (HTN), pediatric glomerular diseases, congenital abnormalities of the kidney and urinary tract (CAKUT), and chronic kidney disease (CKD). We also present recent findings on potential interactions between the novel coronavirus, SARS-CoV-2, and components of the RAAS, as well as potential implications of coronavirus disease 2019 (COVID-19) for pediatric kidney diseases.

Abstract It is a study of Financial Impact Analysis, where the financial consequences arising from the possibility of inclusion of the dentist in the Intensive Care Units (ICU), within the reality of the Unified Health System (SUS), were evaluated in Brazil. It was based on a quick review of the literature and economic evaluation with reference to the year 2018. Information on costs and hospitalizations were collected from the official databases of the Ministry of Health, the Federal Council of Medicine and the Union of Dentists of the State of São Paulo. Only the direct medical costs related to the hospitalizations were calculated. Scenarios were simulated for a time horizon of 1 year (2018) and a sensitivity analysis was made for a more optimistic scenario (values 20% lower) and another less optimistic (values 20% higher). On average, the presence of a dentist in the ICU reduces the development of pneumonia cases by 56% and 8.18 days, which represents a savings of 34.92% in hospitalization costs in the evaluated scenario. In Brazil, when hiring dentists in all ICUs, each avoided case would contribute to savings of R$ 7,949.45 (1US$ = R$ 4,02 in 30/10/2019), ranging from R$ 6,359.56 to R$ 9,539.35 in the optimistic and pessimistic scenarios, respectively, where each case avoided is higher than the dentist's monthly salary. It would be necessary to spend R$ 142,060,140.00 on hiring the dentist to cover the ICUs, making the final savings more than 865 million reais. It is concluded that the inclusion of the Dental Surgeon (DS) in ICU teams would have a positive economic impact, with savings in hospitalization costs from the perspective of SUS. The COVID-19 pandemic in Brazil, depending on the State's action in containment strategies, could require 2.17 times more in the bests of scenarios where the action of total suppression would be used. Such a situation requires emergency measures, and the role of the dentist is a strategy that can support the health system. Key messages Dental care in the ICU is an important and cost-effectiveness strategy for the control of microorganisms that act in the evolution of the pneumonia nosocomial. Such a situation requires emergency measures, and the role of the dentist is a strategy that can support the health system.

Background and importanceOutpatient parenteral antimicrobial therapy (OPAT) has significantly increased since the implementation in 2015 of a hospital at home (HAH) unit. This increase was largely due to the versatility of once daily OPAT administration, advances in vascular access and infusion devices, and high acceptance by patients and healthcare professionals. The implementation also decreased cost, and improved safety and efficacy in a large number of infectious diseases.1 In 2018, an OPAT working group at a HaH unit was formed to optimise intravenous antimicrobial (IA) therapy, developing therapeutic protocols, and improving OPAT administration procedures at the patient‘s home.Aim and objectivesTo assess the importance of integrating a pharmacist into the HaH OPAT working group to optimise parenteral antimicrobial therapy.Material and methodsA bibliographic review and analysis of summary of products characteristics of IA therapy in the hospital was carried out to evaluate the properties, dosage, dose, administration routes and stability after reconstitution and/or dilution. Assessment of patient profiles treated with OPAT at the HaH during the first semester of 2017 was done and identification of the main differences compared with patients admitted to the conventional medicine service who refused to be admitted to the HaH during the same period.ResultsThe literature review allowed the development of a summary table with the most relevant information: reconstitution, dilution, stability, administration routes, incompatibilities, interactions and alerts. In April 2018, HaH therapeutic protocols were implemented according to IA selection and administration routes, as well as the use of programmable infusion devices that allow continuous or intermittent infusion according to the stability of each IA. An assessment was made 6 months after the implementation of these measures, demonstrating that the use of third generation cephalosporins were successfully substituted with second generation cephalosporins in 30% of patients.Conclusion and relevanceThe literature review contributed towards optimising the selection and use of IA, promoting its rational use, a fact proven by the decrease in third generation cephalosporin use. Study of the routes of administration and stability after reconstitution and/or dilution allowed minimisation of adverse effects. Therefore, the integration of a pharmacist into the HaH OPAT working group contributed towards increasing the effectiveness of OPAT and patient safety.References and/or acknowledgements1. Chung E, et al. Development and implementation of a pharmacist-managed OPAT program. Scholarship and Professional Work 2016:229. No conflict of interest.

Introduction: Chronic Kidney Disease (CKD) may cause great impacts on areas of occupational performance of children and adolescents on hemodialysis. The identification of these occupations can guide the practice of occupational therapy, enabling specific interventions as well as the creation of policies and guidelines in the field. Objective: To identify the impact of CKD on the occupational performance of children and adolescents on hemodialysis. Method: Twenty-one children and adolescents with CKD undergoing hemodialysis treatment participated in the study. The tools applied were the profile identification questionnaire and the semi-structured interview Canadian Measurement of Occupational Performance (COPM). Numerical variables were described as measures of central tendency and dispersion, and for categorical variables were calculated the frequencies. Results: 13 impacted occupations were identified, in which 9 are related to play/leisure , 1 to productivity/ school, 3 to self-care. In addition, 57% of the sample dropped out of school and 23% repeated one school year or more. Conclusion: Impacts on different areas of occupational performance, mainly related to play and leisure, have been identified. Children and adolescents present specific demands related to their age ranges. Therefore, the occupational therapist, considering this specificity, can enable these clients to improve their performance in occupations and resume significant roles in their lives.

Background One of the roles of the clinical pharmacist is to review medical prescriptions and suggest therapeutic interventions to avoid potential adverse events in hospitalised patients. Purpose To analyse the pharmaceutical interventions (PI) during electronic prescription validation and the degree of acceptance. Material and methods Retrospective study in a four-week period, using the electronic prescription order entry to quantify and classify PI, and the acceptance rate by the prescribers. The PI was classified as Informative: pharmaceutical compounding (PC), therapeutic equivalent (TE) and drug availability (DA), and Safety: dose modification (DM), posology adjustment (PA), pharmacokinetics monitoring (PM), drug combination (DC), dose duplicity (DD), incorrect dosage (ID), renal dose adjustment (RDA), therapeutic recomendation (TR) and administration (A). Results During this period there were a total of 143 PI in 95 patients, 60% Informative (DA 33.6%, TE 17.5% and PC 11.9%) and 40% Safety-related (PA 15.4%, PM 9.8%, TR 2.8%, DD 2.8%, DM 2.1%, RDA 1.4%, A 1.4%, DC 0.7% and ID 0.7%). The rate of acceptance was 84.6%. The PI made by phone, email or handwritten were not accounted for in this analysis but are undoubtedly an important part of the pharmacist interventions since this type of electronic advice is only available on the prescription menu. Conclusion The acceptance rate of PIs was highly significant, which demonstrates that physicians take into account these recomendations. PI registration is essential in emphasising the role of the pharmacist in preventing medication errors and improving patient safety. References and/or acknowledgements Romero G. Intervenciones farmaceuticas, errores de medicación y su gravdad en el área de observación de un hospital de tercer nível. Rev Ofil Ila Phar 2018;28:115–21. Sartore M. The significance of pharmacy interventions: and updated review in the presence of electronic order entry. AM J Pharm Ben 2014;6:e24–e30. Available at Internet https://www.ajmc.com/journals/issue/2014/ajpb_marapr2014/the-significance-of-pharmacy-interventions-an-updated-review-in-the-presence-of-electronic-order-entry No conflict of interest.

Background Rheumatoid arthritis (RA) patients have loss of muscle mass. The balance between muscle protein synthesis and degradation is regulated by cytokines and growth factors, named myokines, such as irisin and myostatin. Myokines are mainly expressed by skeletal muscle and exert systemic effects promoting crosstalk among different tissues. Irisin increases cortical bone mass and its low levels are related to muscle atrophy and obesity[,1, 2 while myostatin is a negative regulator of muscle growth and regeneration and has a direct role in osteoclastogenesis of inflammatory bone destruction[.3, 4 Objectives To evaluate serum levels of irisin and myostatin and body composition of RA patients and controls. Methods 122 female patients with RA, mean age 53 years, mean disease activity score (DAS28) 4.09, mean disease duration 11.2 years and mean body mass index 27.33 kg/m2 were included. 69 age and sex-matched healthy subjects were enrolled as control group. Irisin (Phoenix Pharmaceuticals) and myostatin (R and D Systems) serum levels were evaluated by ELISA. Fat mass index (FMI;Kg/m2) and appendicular lean mass index (ALMI;Kg/m2) were assessed by total body dual-energy x-ray absorptiometry. Student’s t test and Spearman correlation were performed. Significance was set at p<0.05. Results RA patients had decreased serum levels of irisin (25,61±8,25 vs 30,36±10,95 ng/ml; p<0.05) and myostatin (3011,28±1271,11 vs 4049,08±1610,01 pg/ml; p<0.05), decreased ALMI (6,09±0,88 vs 6,50±1,10; p<0.05) and increased FMI (11,26±3,30 vs 9,44±2,65; p<0.05), compared to controls. No correlations were observed among irisin and myostatin levels and ALMI and FMI. Of the 122 RA patients, 40 were analysed for the use of biologic medication. Serum levels of irisin and myostatin were different between RA patients treated and non-treated with biologics (table 1). Conclusions RA patients presented loss of lean mass and gain of fat mass, as well as lower irisin and myostatin serum levels, in comparison with controls. Additionally, the use of biologic medication by patients impacted on myokines serum levels. Further analyses are needed for a better comprehension of irisin and myostatin roles in RA, and to verify their correlation to other RA features. References [1] Colaianni G, et al. Proc Natl Acad Sci2015;112(39):12157–62. [2] Chang J, et al. Geriatr Gerontol Int. 2017;17(11):2266–2273. [3] Huang Z, et al. Cell Signal2011;23(9):1441–6. [4] Dankbar B, et al. Nat Med2015;21(9):1085–90. Disclosure of Interest None declared

intermediate fibrotic stages.The serum levels of ACE might represent an accurate, non-invasive, widely available, and easy method to evaluate fibrosis related to CHB.Moreover, therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.

"Transthyretin (ATTR) amyloidosis nephropathy: lessons from a TTR stabilizer molecule." Amyloid, 24(sup1), pp. 81–82

INTRODUCTION:Chronic kidney disease (CKD) has been considered an important public health issue in all countries. Experimental and clinical studies support the general idea that the pathophysiology of CKD is associated with the interaction of several endogenous mediators, including components of the renin-angiotensin system (RAS) and cytokines.OBJECTIVE:This review aims to report available evidence on the interaction of RAS molecules and cytokines in CKD.RESULTS:Therapeutic administration of angiotensin converting enzyme (ACE) inhibitors and/or angiotensin type 1 (AT1) receptor antagonists can slow down the deterioration of renal function. These medications reduce the formation (ACE inhibitor) or the receptor-mediated effects of Angiotensin II (AT1 antagonist) and by so doing inhibit cytokine-mediated kidney tissue inflammation. In sharp contrast, the activation of ACE2, the stimulation of Angiotensin-(1-7) synthesis and/or the effects mediated by its G-protein coupled receptor, named Mas receptor, ameliorates experimental renal injury by reducing renal tissue inflammation and fibrosis in many experimental models of renal diseases.CONCLUSION:Novel compounds that activate and/or stimulate ACE2-Angiontensin-(1-7)-Mas receptor axis may also play a role in the treatment of CKD, mainly by controlling inflammatory response and pathways of fibrosis at kidney tissue. Clinical trials with these new pharmacological compounds will, in due course, determine whether this promise will become a helpful treatment.

INTRODUCTION:It is still unknown how the pharmacological inhibition of the Renin Angiotensin System (RAS) impacts the levels of inflammation and fibrosis biomarkers.OBJECTIVE:This study sought to evaluate the effect of enalapril, candesartan and aliskiren on urinary levels of cytokines in a model of chronic kidney disease (CKD).METHODS:Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy), or subjected to sham surgery (control). Animals were then randomized into five groups: Sham surgery receiving vehicle; ¾ Nephrectomy receiving vehicle; ¾ Nephrectomy receiving enalapril (10 mg/kg); ¾ Nephrectomy receiving candesartan (10 mg/kg) and ¾ Nephrectomy receiving aliskiren (10 mg/kg). Urine output, water intake, mean arterial pressure (MAP) and urinary concentrations of creatinine, urea, albuminuria, Na+, K+, interleukin (IL) -1β, IL-6, IL-10 and transforming growth factor beta (TGF-β) were measured.RESULTS:Nephrectomy significantly impaired renal function, increased MAP and altered the levels of all evaluated cytokines in urine. Enalapril, candesartan and aliskiren improved renal function and decreased MAP and IL-6 when compared to vehicle-treated nephrectomized group. Candesartan and aliskiren decreased IL-1β, while only candesartan reduced TGF-β and only aliskiren increased IL-10.CONCLUSION:Enalapril, candesartan and aliskiren presented similar effects on improving renal function and reducing MAP and urinary levels of IL-6 in rats with CKD. On the other hand, cytokine profile differed according to the treatment, suggesting that differential mechanisms were triggered in response to the site of RAS blockade.

Objective: The Oxford Classification for Immunoglobulin A nephropathy (IgAN) identifies pathological variables that may predict the decline of renal function. This study aimed to evaluate the Oxford Classification variables as predictors of renal dysfunction in a cohort of Brazilian children and adolescents with IgAN.Methods: A total of 54 patients with IgAN biopsied from 1982 to 2010 were assessed. Biopsies were re-evaluated and classified according to the Oxford Classification. Multivariate analysis of laboratory and pathological data was performed. The primary outcomes were decline of baseline estimated glomerular filtration rate (eGFR) greater than or equal to 50%.Results: Mean follow-up was 7.6 +/- 5.0 years. Mean renal survival was 13.5 +/- 0.8 years and probability of decline >= 50% in baseline eGFR was 8% at five years of follow-up and 15% at ten years. Ten children (18.5%) had a decline of baseline eGFR >= 50% and five (9.3%) evolved to end-stage renal disease. Kaplan-Meier analysis showed that baseline proteinuria, proteinuria during follow-up, endocapillary proliferation, and tubular atrophy/interstitial fibrosis were associated with the primary outcome. Multivariate Cox analysis showed that only baseline proteinuria (HR, 1.73; 95% CI, 1.20-2.50, p = 0.003) and endocapillary hypercellularity (HR, 37.18; 95% CI, 3.85-358.94, p = 0.002) were independent predictors of renal dysfunction. No other pathological variable was associated with eGFR decline in the multivariate analysis.Conclusion: This is the first cohort study that evaluated the predictive role of the Oxford Classification in pediatric patients with IgAN from South America. Endocapillary proliferation was the unique pathological feature that independently predicted renal outcome. (C) 2017 Published by Elsevier Editora Ltda. on behalf of Sociedade Brasileira de Pediatria.

This paper aims to review the diagnosis, epidemiological data, etiology, pathophysiology and progression of Chronic Kidney Disease (CKD), with emphasis on pediatric patients. CKD is defined as a group of structural and functional kidney abnormalities observed for more than three months, which affects patient's health. CKD prevalence in children is lower than in adults, but is associated to cardiovascular diseases and has high mortality and morbidity rates. CKD-affected children have alterations in physical and psychological development, growth retardation and muscle weakness, among other complications which decrease patients’ quality of life. The main causes of CKD in children are congenital anomalies of the kidney and urinary tract, and primary glomerulopathy, especially focal segmental glomerulosclerosis. Some conditions contribute to CKD progression, such as responsiveness to treatment. The knowledge of the pathophysiology of CKD and disease progression mechanisms is important for the early treatment and to predict the clinical evolution, aiming to provide counseling to families and to slow the progression of kidney disease to an end stage.

The Renin Angiotensin System (RAS) is a pivotal physiological regulator of heart and kidney homeo-stasis, but also plays an important role in the pathophysiology of heart and kidney diseases. Recently, new components of the RAS have been discovered, including angiotensin converting enzyme 2 (ACE2), Angiotensin(Ang)-(1-7), Mas receptor, Ang-(1-9) and Alamandine. These new components of RAS are formed by the hydrolysis of Ang I and Ang II and, in general, counteract the effects of Ang II. In experimental models of heart and renal diseases, Ang-(1-7), Ang-(1-9) and Alamandine produced vasodilation, inhibition of cell growth, anti-thrombotic, anti-inflammatory and anti-fibrotic effects. Recent pharmacological strategies have been proposed to potentiate the effects or to enhance the formation of Ang-(1-7) and Ang-(1-9), including ACE2 activators, Ang-(1-7) in hydroxypropyl beta-cyclodextrin, cyclized form of Ang-(1-7) and nonpeptide synthetic Mas receptor agonists. Here, we review the role and effects of ACE2, ACE2 activators, Ang-(1-7) and synthetic Mas receptor agonists in the control of inflammation and fibrosis in cardiovascular and renal diseases and as counter-regulators of the ACE-Ang II-AT(1) axis. We briefly comment on the therapeutic potential of the novel members of RAS, Ang-(1-9) and alamandine, and the interactions between classical RAS inhibitors and new players in heart and kidney diseases. (C) 2016 Elsevier Ltd. All rights reserved.