Body fat predicts urinary tract infection in kidney transplant recipients: a prospective cohort study.

BACKGROUND: The association between obesity and infectious diseases is increasingly reported in the literature. There are scarce studies on the association between obesity and urinary tract infection after kidney transplantation (KTx). These studies defined obesity based on body mass index, and their results were conflicting. The present study aimed to evaluate this association using bioelectrical impedance analysis for body composition evaluation, and obesity definition. METHODS: A single-center cohort study was conducted. Demographic, clinical, anthropometric, and laboratory data were collected at KTx admission, and bioelectrical impedance analysis was performed to measure the visceral fat area, waist circumference, and total fat mass. The occurrence of urinary tract infection (symptomatic bacteriuria and/or histological evidence of pyelonephritis) was evaluated within three months after KTx. RESULTS: Seventy-seven patients were included in the cohort, and 67 were included in the final analysis. Urinary tract infection was diagnosed in 23.9% of the transplanted patients. Waist circumference (HR: 1.053; 95% CI 1.005-1.104; p = 0.032), visceral fat area (HR: 1.015; 95% CI 1.003-1.027; p = 0.014), and total fat mass (HR: 1.075; 95% CI 1.008-1.146; p = 0.028) were associated with urinary tract infection occurrence after KTx, using Cox regression models. Patients with high waist circumference (above 102 cm for men and above 88 cm for women) had a 4.7 times higher risk of a urinary tract infection than those with normal waist circumference (HR: 4.726; 95% CI 1.267-17.630; p = 0.021). Kaplan-Meier curves showed that patients with high waist circumference, high visceral fat area, and high total fat mass had more urinary tract infections (Log-rank test p = 0.014, p = 0.020, and p = 0.018, respectively). Body mass index was not able to predict urinary tract infection in the study sample. CONCLUSIONS: Waist circumference, visceral fat area, and total fat mass, assessed by bioelectrical impedance analysis, were predictors of urinary tract infection risk within the first three months after KTx.

Detection of Autoantibodies Against the Acetylcholine Receptor, Evaluation of Commercially Available Methodologies: Fixed Cell-Based Assay, Radioimmunoprecipitation Assay and Enzyme-Linked Immunosorbent Assay1.

Background/Objective: Myasthenia Gravis (MG) is an autoimmune disorder characterized by pathogenic autoantibodies (AAbs) targeting nicotinic acetylcholine receptors (AChR), disrupting neuromuscular communication. RadioImmunoPrecipitation Assay (RIPA) is recommended to detect AChR AAbs, but its complexity and radioactive requirements limit widespread use. We compare non-RIPA anti-AChR immunoassays, including Cell-Based Assay (CBA) and two ELISA kits, against the gold standard RIPA. Methods/Results: 145 samples were included with medical indication for anti-AChR testing. By the RIPA method, 63 were negative (RIPA-Neg < 0.02 nmol/L), 18 were classified as Borderline (≥0.02 -1 nmol/L), and 64 were positive (RIPA-Pos > 1 nmol/L). The competitive ELISA showed poor agreement with RIPA (Kappa = 0.216). The indirect ELISA demonstrated substantial agreement with RIPA (Kappa = 0.652), with ∼76% sensitivity and ∼94% specificity for MG diagnostic. The CBA, where fixed cells expressing clustered AChR were used as substrate, exhibited almost perfect agreement with RIPA (Kappa = 0.984), yielding ∼98% sensitivity and 96% specificity for MG. In addition, a semiquantitative analysis showed a strong correlation between CBA titration, indirect ELISA, and RIPA levels (r = 0.793 and r = 0.789, respectively). Conclusions: The CBA displayed excellent analytical performance for MG diagnostic when compared to RIPA, making it a potential replacement for RIPA in clinical laboratories. Some solid-phase assays (such as the indirect ELISA applied here), as well as CBA titration, offer reliable options to estimate anti-AChR AAb levels after confirming positivity by the CBA.∥.

Effectiveness of atopic dermatitis patient education programs - a systematic review and meta-analysis.

Patient education in atopic dermatitis (AD) has worked in parallel to the gold standard of pharmacological treatment as a foundational component of therapeutic regimens. In addition to improving patient education, past investigations of educational interventions have demonstrated profound reductions in disease severity for patients living with AD. However, prior meta-analytical work has focused mostly on comparing in-person interventions, and thus the need to determine the effectiveness of virtual methodologies in the current post-COVID era remains. In this study, we conducted a systematic review of the literature to determine the effectiveness of online programming in AD education compared to in-person interventions. A comprehensive search was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions 2019. Studies were retrieved based on articles published up to 04 April 2023. Adherence to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement guided the reportage process for this systematic review and meta-analysis. The primary outcome of our meta-analysis was the effect of various educational modalities on atopic dermatitis severity as measured by multiple scales across the studies, the most common including SCORAD, Dermatology Life Quality Index (DLQI), Patient Oriented Eczema Measure (POEM), and Eczema Area and Severity Index (EASI). Most studies were randomized controlled trials, primarily from North America and Western Europe and focused on patient and/or caregiver education about disease management, self-care techniques, avoidance of triggers, and comprehensive understanding of the disease process. Our pooled analyses showed that targeted educational programs in understudied adult populations can be as impactful as those in pediatric groups. Moreover, virtual interventions can be employed as constructive tools for reducing barriers of access to patient education. Future research on educational interventions should utilize various methodologies to encourage individual learning preferences with a focus on adult cohorts.

Application of natural language processing to predict final recommendation of Brazilian health technology assessment reports.

INTRODUCTION: Health technology assessment (HTA) plays a vital role in healthcare decision-making globally, necessitating the identification of key factors impacting evaluation outcomes due to the significant workload faced by HTA agencies. OBJECTIVES: The aim of this study was to predict the approval status of evaluations conducted by the Brazilian Committee for Health Technology Incorporation (CONITEC) using natural language processing (NLP). METHODS: Data encompassing CONITEC's official report summaries from 2012 to 2022. Textual data was tokenized for NLP analysis. Least Absolute Shrinkage and Selection Operator, logistic regression, support vector machine, random forest, neural network, and extreme gradient boosting (XGBoost), were evaluated for accuracy, area under the receiver operating characteristic curve (ROC AUC) score, precision, and recall. Cluster analysis using the k-modes algorithm categorized entries into two clusters (approved, rejected). RESULTS: The neural network model exhibited the highest accuracy metrics (precision at 0.815, accuracy at 0.769, ROC AUC at 0.871, and recall at 0.746), followed by XGBoost model. The lexical analysis uncovered linguistic markers, like references to international HTA agencies' experiences and government as demandant, potentially influencing CONITEC's decisions. Cluster and XGBoost analyses emphasized that approved evaluations mainly concerned drug assessments, often government-initiated, while non-approved ones frequently evaluated drugs, with the industry as the requester. CONCLUSIONS: NLP model can predict health technology incorporation outcomes, opening avenues for future research using HTA reports from other agencies. This model has the potential to enhance HTA system efficiency by offering initial insights and decision-making criteria, thereby benefiting healthcare experts.

Brain insulin resistance and Alzheimer's disease: a systematic review.

The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been well-researched in organs such as adipose tissue, muscle, and liver, has been linked to neurodegenerative diseases like Alzheimer's disease (AD) when it occurs in the brain. Objective: The authors aimed to gather data from the current literature on brain insulin resistance (BIR) and its likely repercussions on neurodegenerative disorders, more specifically AD, through a systematic review. Methods: A comprehensive search was conducted in multiple medical databases, including the Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline), and PubMed®, employing the descriptors: "insulin resistance", "brain insulin resistance", "Alzheimer's disease", "neurodegeneration", and "cognition". The authors focused their search on English-language studies published between 2000 and 2023 that investigated the influence of BIR on neurodegenerative disorders or offered insights into BIR's underlying mechanisms. Seventeen studies that met the inclusion criteria were selected. Results: The results indicate that BIR is a phenomenon observed in a variety of neurodegenerative disorders, including AD. Studies suggest that impaired glucose utilization and uptake, reduced adenosine triphosphate (ATP) production, and synaptic plasticity changes caused by BIR are linked to cognitive problems. However, conflicting results were observed regarding the association between AD and BIR, with some studies suggesting no association. Conclusion: Based on the evaluated studies, it can be concluded that the association between AD and BIR remains inconclusive, and additional research is needed to elucidate this relationship.

A incapacidade das células de reagir à insulina, ocasionando intolerância à glicose e hiperglicemia, é chamada de resistência à insulina. Essa condição clínica, que tem sido bem pesquisada em órgãos como tecido adiposo, músculo e fígado, tem sido associada às doenças neurodegenerativas como a doença de Alzheimer (DA) quando ocorre no cérebro. Objetivo: O objetivo dos autores foi reunir os dados da literatura atual sobre a resistência insulínica cerebral (RIC) e sua provável repercussão em doenças neurodegenerativas, mais especificamente na DA, por meio de uma revisão sistemática da literatura. Métodos: Foi realizada uma pesquisa abrangente em vários bancos de dados médicos, incluindo o Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline) e PubMed, empregando os descritores: "resistência à insulina", "resistência insulínica cerebral", "doença de Alzheimer", "neurodegeneração" e "cognição". Os autores concentraram sua busca em estudos no idioma inglês publicados entre 2000 e 2023 que investigaram a influência da RIC em distúrbios neurodegenerativos ou ofereceram insights sobre os mecanismos subjacentes da RIC. Dezessete estudos que atenderam aos critérios de inclusão foram selecionados. Resultados: Os resultados demonstram que a RIC é um fenômeno observado em uma variedade de doenças neurodegenerativas, incluindo a DA. Estudos sugerem que a utilização e captação prejudicadas de glicose, a produção reduzida de trifosfato de adenosina (ATP) e as alterações na plasticidade sinápticas causadas pela RIC estão ligadas a problemas cognitivos. No entanto, foram observados resultados conflitantes com relação à associação entre DA e RIC, com alguns estudos sugerindo nenhuma associação. Conclusão: Com base nos estudos avaliados, pode-se concluir que a associação entre DA e RIC ainda é inconclusiva, e pesquisas adicionais são necessárias para elucidar essa relação.

Luminescent Properties of ß-(hydroxyaryl)-butenolides and Fluorescence Quenching in Water.

This work describes the luminescent properties of the new compound ß-(hydroxyaryl)-butenolides recently discovered. The compounds were subjected to UV-Vis absorption and fluorescence analyzes when diluted in different solvents. Through the results, it was possible to observe that the ß-hydroxyarylutenolides have two absorption bands, one at 289-291 nm and the other with higher intensity at 328-354 nm. The emission band between 385-422 nm is observed under excitation at 324-327 nm. The compounds showed solvatochromism as a function of the analyzed solvent. In water, fluorescence quenching of all compounds occurs. Therefore, studies with compound containing the methylenedioxy group attached in phenyl ring were carried at different concentrations of water in DMSO. The decrease in the fluorescence intensity of this compound is linearly proportional to the increase in the amount of water in the DMSO, with a minimum detection volume of 0.028%. Quantum yields of three compounds were evaluated in different solvents, showing that the relationship between the structure of the compound and the solvent is essential for a high value. The fluorescence quantum yield was also measured by Thermal Lens Spectroscopy (TLS) using DMSO as the solvent, confirming the high value for the analyzed samples. Despite being preliminary, the studies revealed that these compounds have luminescent properties that could be applied in the development of chemical sensors for detecting water in DMSO.

Comparing Survival Outcomes between Hemodialysis and Hemodiafiltration Using Real-World Data from Brazil.

The CONVINCE trial demonstrates that high-dose hemodiafiltration offers a survival advantage for patients in the high-flux hemodiafiltration group compared to hemodialysis. We compared the outcomes of hemodialysis and hemodiafiltration using real-world data. We conducted an analysis on a cohort of patients who underwent hemodiafiltration therapy (HDF) at a single center, NefroStar Clinics. The results obtained were then compared with data from patients receiving hemodialysis (HD) therapy within the Brazilian Public Health System (SUS). The primary outcome was mortality from any cause. Results: A total of 85 patients undergoing hemodiafiltration were compared with 149,372 patients receiving hemodialysis through the Brazilian Public Health System (SUS). Using a 2:1 propensity score, we compared the 170 best-match HD patients with 85 HDF patients. In the Cox analysis, HDF therapy showed a reduced risk of mortality with an HR of 0.29 [0.11-0.77]. The propensity score analysis showed a HR of 0.32 [95% CI: 0.11-0.91]. This analysis was adjusted for age, type of access, KT/v, hemoglobin, and phosphorus. The Kaplan-Meier analysis showed respective survival rates for HDF and HD at the end of one year, 92.1% and 79.9%, p < 0.001. These results suggest high-flux hemodiafiltration has survival advantages over hemodialysis in a real-world scenario.

New anti-SARS-CoV-2 aminoadamantane compounds as antiviral candidates for the treatment of COVID-19.

Here, the antiviral activity of aminoadamantane derivatives were evaluated against SARS-CoV-2. The compounds exhibited low cytotoxicity to Vero, HEK293 and CALU-3 cells up to a concentration of 1,000 µM. The inhibitory concentration (IC50) of aminoadamantane was 39.71 µM in Vero CCL-81 cells and the derivatives showed significantly lower IC50 values, especially for compounds 3F4 (0.32 µM), 3F5 (0.44 µM) and 3E10 (1.28 µM). Additionally, derivatives 3F5 and 3E10 statistically reduced the fluorescence intensity of SARS-CoV-2 protein S from Vero cells at 10 µM. Transmission microscopy confirmed the antiviral activity of the compounds, which reduced cytopathic effects induced by the virus, such as vacuolization, cytoplasmic projections, and the presence of myelin figures derived from cellular activation in the face of infection. Additionally, it was possible to observe a reduction of viral particles adhered to the cell membrane and inside several viral factories, especially after treatment with 3F4. Moreover, although docking analysis showed favorable interactions in the catalytic site of Cathepsin L, the enzymatic activity of this enzyme was not inhibited significantly in vitro. The new derivatives displayed lower predicted toxicities than aminoadamantane, which was observed for either rat or mouse models. Lastly, in vivo antiviral assays of aminoadamantane derivatives in BALB/cJ mice after challenge with the mouse-adapted strain of SARS-CoV-2, corroborated the robust antiviral activity of 3F4 derivative, which was higher than aminoadamantane and its other derivatives. Therefore, aminoadamantane derivatives show potential broad-spectrum antiviral activity, which may contribute to COVID-19 treatment in the face of emerging and re-emerging SARS-CoV-2 variants of concern.

Brain insulin resistance and Alzheimer's disease: a systematic review / Resistência insulínica cerebral e a doença de Alzheimer: uma revisão sistemática

ABSTRACT. The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been well-researched in organs such as adipose tissue, muscle, and liver, has been linked to neurodegenerative diseases like Alzheimer's disease (AD) when it occurs in the brain. Objective: The authors aimed to gather data from the current literature on brain insulin resistance (BIR) and its likely repercussions on neurodegenerative disorders, more specifically AD, through a systematic review. Methods: A comprehensive search was conducted in multiple medical databases, including the Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline), and PubMed®, employing the descriptors: "insulin resistance", "brain insulin resistance", "Alzheimer's disease", "neurodegeneration", and "cognition". The authors focused their search on English-language studies published between 2000 and 2023 that investigated the influence of BIR on neurodegenerative disorders or offered insights into BIR's underlying mechanisms. Seventeen studies that met the inclusion criteria were selected. Results: The results indicate that BIR is a phenomenon observed in a variety of neurodegenerative disorders, including AD. Studies suggest that impaired glucose utilization and uptake, reduced adenosine triphosphate (ATP) production, and synaptic plasticity changes caused by BIR are linked to cognitive problems. However, conflicting results were observed regarding the association between AD and BIR, with some studies suggesting no association. Conclusion: Based on the evaluated studies, it can be concluded that the association between AD and BIR remains inconclusive, and additional research is needed to elucidate this relationship.

RESUMO. A incapacidade das células de reagir à insulina, ocasionando intolerância à glicose e hiperglicemia, é chamada de resistência à insulina. Essa condição clínica, que tem sido bem pesquisada em órgãos como tecido adiposo, músculo e fígado, tem sido associada às doenças neurodegenerativas como a doença de Alzheimer (DA) quando ocorre no cérebro. Objetivo: O objetivo dos autores foi reunir os dados da literatura atual sobre a resistência insulínica cerebral (RIC) e sua provável repercussão em doenças neurodegenerativas, mais especificamente na DA, por meio de uma revisão sistemática da literatura. Métodos: Foi realizada uma pesquisa abrangente em vários bancos de dados médicos, incluindo o Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline) e PubMed, empregando os descritores: "resistência à insulina", "resistência insulínica cerebral", "doença de Alzheimer", "neurodegeneração" e "cognição". Os autores concentraram sua busca em estudos no idioma inglês publicados entre 2000 e 2023 que investigaram a influência da RIC em distúrbios neurodegenerativos ou ofereceram insights sobre os mecanismos subjacentes da RIC. Dezessete estudos que atenderam aos critérios de inclusão foram selecionados. Resultados: Os resultados demonstram que a RIC é um fenômeno observado em uma variedade de doenças neurodegenerativas, incluindo a DA. Estudos sugerem que a utilização e captação prejudicadas de glicose, a produção reduzida de trifosfato de adenosina (ATP) e as alterações na plasticidade sinápticas causadas pela RIC estão ligadas a problemas cognitivos. No entanto, foram observados resultados conflitantes com relação à associação entre DA e RIC, com alguns estudos sugerindo nenhuma associação. Conclusão: Com base nos estudos avaliados, pode-se concluir que a associação entre DA e RIC ainda é inconclusiva, e pesquisas adicionais são necessárias para elucidar essa relação.

Medicina e espiritualidade: o perfil de estudantes e médicos de uma escola médica brasileira / Medicine and spirituality: the profile of students and physicians at a Brazilian medical school

Resumo Introdução: Pesquisas científicas indicam que a espiritualidade desempenha um papel importante na vida da maioria dos pacientes. Além disso, atividades e crenças religiosas podem, de acordo com algumas pesquisa, estar relacionadas à melhor saúde e qualidade de vida1. Objetivo: Este estudo teve como objetivos avaliar o nível de espiritualidade de estudantes de Medicina e de médicos já formados, e analisar o ensino da interface "medicina e espiritualidade" na escola médica. Método: Realizamos um estudo transversal descritivo por meio da aplicação de questionários a estudantes de Medicina e médicos de uma escola médica pública brasileira. Resultado: Avaliaram-se 234 participantes. A maioria acredita em uma força superior. A espiritualidade foi maior entre médicos já formados e entre pessoas do sexo feminino. A maioria acredita que a formação universitária não prepara o médico para abordar o tema com os pacientes. Apesar dessa limitação, a maioria já abordou a espiritualidade com seus pacientes. Conclusão: Médicos e estudantes de Medicina consideram importante contemplar, de maneira ecumênica e respeitosa, aspectos espirituais dos pacientes. Apesar disso, consideram que não receberam preparo suficiente na escola médica para essa abordagem.

Abstract Introduction: Scientific research indicates that spirituality plays an important role in the daily life of most patients. Moreover, there are studies indicating that religious activities and beliefs may be related to better health and quality of life1. Objective: to evaluate the level of spirituality of medical students and graduated physicians, in addition to analyzing the teaching of the "Medicine and Spirituality" interface in medical school. Methodology: A descriptive cross-sectional study was carried out by applying questionnaires to medical students and doctors at a Brazilian public medical school. Results: a total of 234 participants were evaluated. Most believe in a higher power. Spirituality was higher among doctors who had already graduated and among females. Most believe that university education does not prepare doctors to address the topic with the patients. Despite this limitation, most have already discussed spirituality with their patients. Conclusion: Doctors and medical students consider it important to contemplate spiritual aspects of patients using an ecumenical and respectful approach. Nevertheless, they consider they were not sufficiently prepared in medical school for this approach.

Treatment of post-burn pruritus - A systematic review and meta-analysis.

BACKGROUND: Post-burn pruritus is one of the most common complaints reported by patients with limited evidence for a gold-standard treatment. OBJECTIVE: To review the literature and assess the efficacy of various interventions in treating post-burn pruritus. METHODS: PubMed, MEDLINE, CINAHL, Web of Sciences, Ovid Databases, and ClinicalTrials.Gov were searched. The articles were scored by two assessors for inclusion with a third independent assessor resolving conflicting scores. RESULTS: The present systematic review and meta-analysis synthesised findings from a total of nine studies, representing a pool of 323 patients. The standardized mean effect size for the various categories of interventions was: naltrexone at 1.47 (95 % CI of 0.75-2.20, p < 0.0000), coverings at 0.94 (95 % CI of 0.40-1.48, p = 0.006), topical ozonated oil at 2.64 (95 % CI of 1.94-3.34, p < 0.00001), lasers at 2.34 (95 % CI of 1.60-3.09, p < 0.00001), current stimulation at 1.03 (95 % CI of -0.04 to 2.10, p = 0.06), and lemon balm tea at 0.54 (95% CI of 0.12-0.96, p = 0.01). CONCLUSIONS: Current evidence suggests that current modalities have a statistically significant, but not clinically significant, reduction in pruritus. This review highlights the limited quality of evidence in the literature and the poor quality of reporting among excluded studies.

Factors associated with the evolution of COVID-19 in pregnant women: a Brazilian population-based study.

OBJECTIVE: To assess the evolution of COVID-19 among Brazilian pregnant women, identifying sociodemographic and clinical predictors related to admission to ICU - Intensive Care Unit and death. METHOD: Cross-sectional, population-based study, carried out with a secondary database, based on data from the Influenza Epidemiological Surveillance Information System. Descriptive analysis was performed, followed by multiple linear regression with Poisson response, adopting critical p < 0.05. RESULTS: Intensive care admission rates of 28.2% and death rates of 9.5% were identified. Region of residence, gestational trimester, number of comorbidities and respiratory signs and symptoms were associated with the risk of admission to intensive care. Age over 34 years, comorbidities, oxygen saturation equal to or less than 95%, admission to intensive care and ventilatory support, invasive or not, increased the risk of death. CONCLUSION: Sociodemographic and clinical predictors showed an association with hospitalization in intensive care and death of pregnant women with COVID-19.

Genetic and phenotypic profile of Fabry disease in the population of Vale do Paraiba and Eastern São Paulo / Perfil genético e fenotípico da doença de Fabry na população do Vale do Paraíba e Zona Leste de São Paulo

ABSTRACT Introduction: Fabry disease (FD) is an inborn error of metabolism characterized by α-galactosidase A deficiency. The primary objective was to evaluate the genetic and phenotypic profile of Fabry disease in hemodialysis. Methods: Observational cohort study to determine the incidence of genetic variations and phenotypic changes for FD in hemodialysis patients in the Paraiba Valley and Eastern São Paulo. Genetic testing for the GLA gene was performed for men and women over 12 years of age at the hemodialysis clinics between January 2016 and December 2019 as a screening protocol. Results: The cases came from screening exams of the index case among patients with chronic kidney disease, resulting in 17 families and totaling 82 patients under study. The classification of the most prevalent variant was that of uncertain significance (54%), followed by the pathogenic variant (46%). Five patients in two families were described with two types of variants not previously described in the literature, with pathogenic behavior. Comparing the types of variants, the presence of a pathogenic variant was associated with higher levels of lysoGB3, lower values for alpha-GAL activity and higher frequency of symptoms related to FD. Conclusion: We characterized an extensive population of patients with FD variants with rich genetic, clinical and biomarker details. We believe that this study can help to better characterize the Brazilian population with FD and the most frequent types of variants.

RESUMO Introdução: A doença de Fabry (DF) é um erro inato do metabolismo caracterizado pela deficiência da enzima α-galactosidase A. O objetivo primário foi avaliar o perfil genético e fenotípico da doença de Fabry em hemodiálise. Métodos: Estudo de coorte observacional para determinar a incidência de variações genéticas e alterações fenotípicas para DF em pacientes em hemodiálise no Vale do Paraíba e Zona Leste de São Paulo. O teste genético para o gene GLA foi realizado para homens e mulheres em todos os pacientes das clínicas de hemodiálise maiores de 12 anos entre janeiro de 2016 a dezembro de 2019 como protocolo de rastreio. Resultados: Os casos foram provenientes de exames de triagem do caso índice entre pacientes portadores de doença renal crônica, resultando em 17 famílias e totalizando 82 pacientes em estudo. A classificação da variante mais prevalente foi a de significado incerto (54%), seguida da variante patogênica (46%). Foram descritos 5 pacientes em duas famílias com dois tipos de variantes ainda não previamente descritos na literatura com comportamento patogênico. Na comparação entre os tipos de variantes, a presença de variante patogênica foi associada a maiores níveis de lysoGB3, menores valores da atividade da alfa-GAL e maior frequência de sintomas relativos à DF. Conclusão: Caracterizamos uma extensa população de pacientes com variantes para DF com riqueza de detalhes de genética, clínica e de biomarcadores. Acreditamos que este estudo possa auxiliar na melhor caracterização da população brasileira com DF e nos tipos mais frequentes de variantes.

A comprehensive model for assessing and classifying patients with thrombotic microangiopathy: the TMA-INSIGHT score.

BACKGROUND: Thrombotic Microangiopathy (TMA) is a syndrome characterized by the presence of anemia, thrombocytopenia and organ damage and has multiple etiologies. The primary aim is to develop an algorithm to classify TMA (TMA-INSIGHT score). METHODS: This was a single-center retrospective cohort study including hospitalized patients with TMA at a single center. We included all consecutive patients diagnosed with TMA between 2012 and 2021. TMA was defined based on the presence of anemia (hemoglobin level < 10 g/dL) and thrombocytopenia (platelet count < 150,000/µL), signs of hemolysis, and organ damage. We classified patients in eight categories: infections; Malignant Hypertension; Transplant; Malignancy; Pregnancy; Thrombotic Thrombocytopenic Purpura (TTP); Shiga toxin-mediated hemolytic uremic syndrome (STEC-SHU) and Complement Mediated TMA (aHUS). We fitted a model to classify patients using clinical characteristics, biochemical exams, and mean arterial pressure at presentation. RESULTS: We retrospectively retrieved TMA phenotypes using automatic strategies in electronic health records in almost 10 years (n = 2407). Secondary TMA was found in 97.5% of the patients. Primary TMA was found in 2.47% of the patients (TTP and aHUS). The best model was LightGBM with accuracy of 0.979, and multiclass ROC-AUC of 0.966. The predictions had higher accuracy in most TMA classes, although the confidence was lower in aHUS and STEC-HUS cases. CONCLUSION: Secondary conditions were the most common etiologies of TMA. We retrieved comorbidities, associated conditions, and mean arterial pressure to fit a model to predict TMA and define TMA phenotypic characteristics. This is the first multiclass model to predict TMA including primary and secondary conditions.

THE CONNECTION BETWEEN BILE ACIDS AND TYPE 2 DIABETES MELLITUS - A REVIEW.

BACKGROUND: Bile acids (BAs) are steroid molecules synthesized exclusively in the liver, being end products of cholesterol catabolism. BAs are known to be involved in several metabolic alterations, including metabolic syndrome and type 2 diabetes mellitus (DM2). DM2 is a chronic degenerative disease characterized by insulin resistance, insulin deficiency due to insufficient production of pancreatic ß-cells, and elevated serum glucose levels leading to multiple complications. OBJECTIVE: The objective of this study is to investigate the role of BAs in the pathophysiology of DM2, highlighting the possibilities in the development of therapeutic procedures targeting BAs as an optional pathway in the treatment of DM2. METHODS: The research was carried out through narrative review and publications on the relationship between BAs and DM2. The databases used for the search include PubMed, Scopus, and Web of Science. The keywords used for the search include bile acids, type 2 diabetes mellitus, metabolic syndrome, and metabolic disorders. RESULTS: The studies have reported the involvement of BAs in the pathophysiology of DM2. BAs act as a ligand for the nuclear farnesoid X receptor, regulating glucose metabolism, lipid metabolism, and cellular energy production. Additionally, BAs modulate the production, elimination, and mobilization of BAs through the farnesoid X receptor. BAs also act as a signaling pathway through Takeda G protein-coupled receptor 5, further contributing to metabolic regulation. These findings suggest that targeting BAs may offer a novel therapeutic approach in the treatment of DM2. CONCLUSION: This study highlights the important role of BAs in DM2, specifically through their interactions with key metabolic pathways. Targeting BAs may represent an innovative and effective approach to the treatment of DM2.

A Cost-Based Analysis of Anti-aging Products Across Four Major United States Retailers.

Background In the field of aesthetic dermatology, there is currently very little data on affordability and cost analysis regarding cosmeceuticals as more demand from patients showing interest in cosmeceutical products to reduce and prevent aging continues to grow. Photoaging, a form of extrinsic aging from sun exposure, can be ameliorated by applying sunscreen and retinol products. Topical ascorbic acid and niacinamide have been shown to target the oxidative stress process that contributes to photoaging. These four products have been identified as the cosmeceutical ingredients with the most evidence-based data on photoaging prevention and treatment. Objective Given the demand for effective skin care, the paucity of data on cost differentiation, and the availability of cosmeceutical products, we analyzed the unit cost of four anti-aging products from major online and physical retailers in the United States. Such a cost comparison may facilitate more economically appropriate recommendations on skin care to consumers. Methods and materials We analyzed sunscreen, topical vitamin C (ascorbic acid), topical vitamin B3 (niacinamide), and topical vitamin A (retinol) products sold by four major United States retailers: Walmart, Ulta, Walgreens, and Amazon. The average cost in dollars per ounce (dollar/oz) was calculated for each product category at each retailer. Statistical analyses were done to determine statistical significance for each product category between retailers as well as between each category of product. Results Between the four retailers, Walmart offered the lowest cost per ounce for every product. In contrast, Amazon offered the highest cost per ounce for every product except for sunscreen. We also found that sunscreen products are less expensive per ounce as compared to retinol, ascorbic acid, and niacinamide products. Conclusion Dermatologists should be knowledgeable of product costs when providing patients with anti-aging product recommendations. Our study provides data on the financial cost by retail location of evidence-based anti-aging cosmeceuticals to better guide physicians in patient consulting and economical resource sharing.

Safety of cinacalcet in children and adolescents with chronic kidney disease-mineral bone disorder: systematic review and proportional meta-analysis of case series.

BACKGROUND: Mineral and bone disease in children with chronic kidney disease can cause abnormalities in calcium, phosphorus, parathyroid hormone, and vitamin D and when left untreated can result in impaired growth, bone deformities, fractures, and vascular calcification. Cinacalcet is a calcimimetic widely used as a therapy to reduce parathyroid hormone levels in the adult population, with hypocalcemia among its side effects. The analysis of safety in the pediatric population is questioned due to the scarcity of randomized clinical trials in this group. OBJECTIVE: To assess the onset of symptomatic hypocalcemia or other adverse events (serious or non-serious) with the use of cinacalcet in children and adolescents with mineral and bone disorder in chronic kidney disease. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: The bibliographic search identified 2699 references from 1927 to August/2023 (57 LILACS, 44 Web of Science, 686 PubMed, 131 Cochrane, 1246 Scopus, 535 Embase). Four references were added from the bibliography of articles found and 12 references from the gray literature (Clinical Trials). Of the 77 studies analyzed in full, 68 were excluded because they did not meet the following criteria: population, types of studies, medication, publication types and 1 article that did not present results (gray literature). PARTICIPANTS AND INTERVENTIONS: There were 149 patients aged 0-18 years old with Chronic Kidney Disease and mineral bone disorder who received cinacalcet. STUDY APPRAISAL AND SYNTHESIS METHODS: Nine eligible studies were examined for study type, size, intervention, and reported outcomes. RESULTS: There was an incidence of 0.2% of fatal adverse events and 16% of serious adverse events (p < 0.01 and I2 = 69%), in addition to 10.7% of hypocalcemia, totaling 45.7% of total adverse events. LIMITATIONS: There was a bias in demographic information and clinical characteristics of patients in about 50% of the studies and the majority of the studies were case series. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: If used in the pediatric population, the calcimimetic cinacalcet should be carefully monitored for serum calcium levels and attention to possible adverse events, especially in children under 50 months. SYSTEMATIC REVIEW REGISTRATION NUMBER (PROSPERO REGISTER): CRD42019132809.

Brazilian autoimmune encephalitis network (BrAIN): antibody profile and clinical characteristics from a multicenter study.

Background: The frequency of antibodies in autoimmune encephalitis (AIE) may vary in different populations, however, data from developing countries are lacking. To describe the clinical profile of AIE in Brazil, and to evaluate seasonality and predictors of AIE in adult and pediatric patients. Methods: We evaluated patients with possible AIE from 17 centers of the Brazilian Autoimmune Encephalitis Network (BrAIN) between 2018 and 2022. CSF and serum were tested with TBAs and CBAs. Data on clinical presentation, complementary investigation, and treatment were compiled. Seasonality and predictors of AIE in adult and pediatric populations were analyzed. Results: Of the 564 patients, 145 (25.7%) were confirmed as seropositive, 69 (12.23%) were seronegative according to Graus, and 58% received immunotherapy. The median delay to diagnosis confirmation was 5.97 ± 10.3 months. No seasonality variation was observed after 55 months of enrolment. The following antibodies were found: anti-NMDAR (n=79, 54%), anti-MOG (n=14, 9%), anti-LGI1(n=12, 8%), anti-GAD (n=11, 7%), anti-GlyR (n=7, 4%), anti-Caspr2 (n=6, 4%), anti-AMPAR (n=4, 2%), anti-GABA-BR (n=4, 2%), anti-GABA-AR (n=2, 1%), anti-IgLON5 (n=1, 1%), and others (n=5, 3%). Predictors of seropositive AIE in the pediatric population (n=42) were decreased level of consciousness (p=0.04), and chorea (p=0.002). Among adults (n=103), predictors of seropositive AIE were movement disorders (p=0.0001), seizures (p=0.0001), autonomic instability (p=0.026), and memory impairment (p=0.001). Conclusion: Most common antibodies in Brazilian patients are anti-NMDAR, followed by anti-MOG and anti-LGI1. Only 26% of the possible AIE patients harbor antibodies, and 12% were seronegative AIE. Patients had a 6-month delay in diagnosis and no seasonality was found. Findings highlight the barriers to treating AIE in developing countries and indicate an opportunity for cost-effect analysis. In this scenario, some clinical manifestations help predict seropositive AIE such as decreased level of consciousness, chorea, and dystonia among children, and movement disorders and memory impairment among adults.

Anti-ribosomal P (anti-P) antibodies in patients with autoimmune hepatitis.

OBJECTIVE: Anti-P-ribosomal antibody is a biomarker of systemic lupus erythematosus mainly associated with renal, nervous, and hepatic involvement. Systemic lupus erythematosus may present with features similar to autoimmune hepatitis. This study aimed to investigate the association of Anti-P-ribosomal antibodies in systemic lupus erythematosus compared to autoimmune hepatitis in the general Brazilian population. Autoimmune hepatitis and systemic lupus erythematosus share several clinical features. ÛªAnti-P ribosomal antibody is a biomarker for systemic lupus erythematosus. The association between anti-P ribosomal antibody and autoimmune hepatitis has shown conflicting results. Our results showed no association between anti-P ribosomal antibody and autoimmune hepatitis. Published studies have shown associations between anti-ribosomal P (anti-P) antibody and systemic lupus erythematosus with hepatic manifestations. This has been reported also in autoimmune hepatitis. However, the consistency of the latter association remains controversial. This study aimed to evaluate the frequency of anti-P antibodies in autoimmune hepatitis using two different immunoassays. METHODS: One-hundred and seventy-seven patients with autoimmune hepatitis were screened, and 142 were analyzed for anti-P antibody positivity. The samples were first analyzed using two different immunoassays: enzyme-linked immunosorbent assay (ELISA) and chemiluminescence and then compared with a group of 60 patients with systemic lupus erythematous. The positive samples were subjected to western blot analysis. RESULTS: Anti-P was found in 5/142 autoimmune hepatitis cases (3.5%) by chemiluminescence and in none by ELISA. Among the five chemiluminescence-positive autoimmune hepatitis samples, on anti-P western blot analysis one was negative, two were weakly positive, and two were positive. In contrast, anti-P was detected in 10/60 patients with systemic lupus erythematosus (16.7%) and presented higher chemiluminescence units than the autoimmune hepatitis samples. CONCLUSION: A low frequency of anti-P antibodies was observed in autoimmune hepatitis, suggesting that this test is not useful for the diagnosis or management of this disease.