Antimicrobial Resistance, Genetic Lineages, and Biofilm Formation in Pseudomonas aeruginosa Isolated from Human Infections: An Emerging One Health Concern.

Pseudomonas aeruginosa (PA) is a leading nosocomial pathogen and has great versatility due to a complex interplay between antimicrobial resistance and virulence factors. PA has also turned into one the most relevant model organisms for the study of biofilm-associated infections. The objective of the study focused on analyzing the antimicrobial susceptibility, resistance genes, virulence factors, and biofilm formation ability of thirty-two isolates of PA. PA isolates were characterized by the following analyses: susceptibility to 12 antimicrobial agents, the presence of resistance genes and virulence factors in PCR assays, and the quantification of biofilm production as evaluated by two distinct assays. Selected PA isolates were analyzed through multilocus sequence typing (MLST). Thirty PA isolates have a multi-resistant phenotype, and most of the isolates showed high levels of resistance to the tested antibiotics. Carbapenems showed the highest prevalence of resistance. Various virulence factors were detected and, for the quantification of biofilm production, the effectiveness of different methods was assessed. The microtiter plate method showed the highest accuracy and reproducibility for detecting biofilm-producing bacteria. MLST revealed four distinct sequence types (STs) in clinical PA, with three of them considered high-risk clones of PA, namely ST175, ST235, and ST244. These clones are associated with multidrug resistance and are prevalent in hospitals worldwide. Overall, the study highlights the high prevalence of antibiotic resistance, the presence of carbapenemase genes, the diversity of virulence factors, and the importance of biofilm formation in PA clinical isolates. Understanding these factors is crucial for effective infection control measures and the development of targeted treatment strategies.

HCV Core-antigen Assay as an Effective Alternative to HCV RNA Quantification in Patients With Hepatitis C.

BACKGROUND/AIM: Hepatitis C virus (HCV) core antigen (Ag) test has been increasingly applied as an effective alternative to conventional molecular tests allowing rapid and affordable diagnosis, which is of paramount relevance to achieve global elimination of HCV infection. MATERIALS AND METHODS: ARCHITECT® HCV Ag test was evaluated in comparison with HCV RNA quantification test (CAP/CTM) to calculate its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and to determine their correlation level. Its performance, according to low and high viral load values and in different treatment stages [during treatment (T), at the end of the therapeutic protocol (EOT) and when sustained virological response (SVR) was evaluated]. RESULTS: In total, 145 samples were included. Considering CAP/CTM, the sensitivity, specificity, PPV and NPV of the HCV-Ag test were 88.9%, 99.1%, 97.0% and 96.4%, respectively, and the correlation among tests was high (r=0.890), with only five discordant results. A decrease in sensitivity was found for low viral load values (<1,000 IU/ml), but the opposite was verified for high viral concentrations (≥1,000 IU/ml). A good agreement was verified for the T and EOT groups (k=0.789 and k=0.638) and an excellent agreement in the SVR group (k=1.000). CONCLUSION: HCV-Ag seems to be an effective alternative that can be routinely combined with other faster and more accessible tests (e.g., HCV antibody tests) for the identification of new HCV infections in suspected patients, eventually reserving the molecular techniques for samples with discordant results.

Hematological ratios in coronavirus disease 2019 patients with and without invasive mechanical ventilation.

Patients with the most severe form of coronavirus disease 2019 (COVID-19) often require invasive ventilation. Determining the best moment to intubate a COVID-19 patient is complex decision and can result in important consequences for the patient. Therefore, markers that could aid in clinical decision-making such as hematological indices are highly useful. These markers are easy to calculate, do not generate extra costs for the laboratory, and are readily implemented in routine practice. Thus, this study aimed to investigate differences in the ratios calculated from the hemogram between patients with and without the need for invasive mechanical ventilation (IMV) and a control group. This was an observational retrospective analysis of 212 patients with COVID-19 that were hospitalized between April 1, 2020 and March 31, 2021 who were stratified as IMV (n = 129) or did not require invasive mechanical ventilation (NIMV) (n = 83). A control group of 198 healthy individuals was also included. From the first hemogram of each patient performed after admission, the neutrophil-to-lymphocyte ratio (NLR), the derived NLR (d-NLR), the lymphocyte-to-monocyte ratio, the platelet-to-lymphocyte ratio, the neutrophil-to-platelet ratio (NPR), and the systemic immune-inflammation index (SII) were calculated. All hematological ratios exhibited significant differences between the control group and COVID-19 patients. NLR, d-NLR, SII, and NPR were higher in the IMV group than they were in the NIMV group. The hematological indices addressed in this study demonstrated high potential for use as auxiliaries in clinical decision-making regarding the need for IMV.

Characterization of ESBL-Producing Escherichia coli and Klebsiella pneumoniae Isolated from Clinical Samples in a Northern Portuguese Hospital: Predominance of CTX-M-15 and High Genetic Diversity.

BACKGROUND: Enterobacteriaceae are major players in the spread of resistance to ß-lactam antibiotics through the action of CTX-M ß-lactamases. We aimed to analyze the diversity and genetic characteristics of ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates from patients in a Northern Portuguese hospital. METHODS: A total of 62 cefotaxime/ceftazidime-resistant E. coli (n = 38) and K. pneumoniae (n = 24) clinical isolates were studied. Identification was performed by MALDI-TOF MS. Antimicrobial susceptibility testing against 13 antibiotics was performed. Detection of ESBL-encoding genes and other resistance genes, phylogenetic grouping, and molecular typing (for selected isolates) was carried out by PCR/sequencing. RESULTS: ESBL activity was detected in all 62 E. coli and K. pneumoniae isolates. Most of the ESBL-producing E. coli isolates carried a blaCTX-M gene (37/38 isolates), being blaCTX-M-15 predominant (n = 32), although blaCTX-M-27 (n = 1) and blaCTX-M-1 (n = 1) were also detected. Two E. coli isolates carried the blaKPC2/3 gene. The lineages ST131-B2 and ST410-A were detected among the ESBL-producing blood E. coli isolates. Regarding the 24 ESBL-producing K. pneumoniae isolates, 18 carried a blaCTX-M gene (blaCTX-M-15, 16 isolates; blaCTX-M-55, 2 isolates). All K. pneumoniae isolates carried blaSHV genes, including ESBL-variants (blaSHV-12 and blaSHV-27, 14 isolates) or non-ESBL-variants (blaSHV-11 and blaSHV-28, 10 isolates); ten K. pneumoniae isolates also carried the blaKPC2/3 gene and showed imipenem-resistance. ESBL-positive E. coli isolates were ascribed to the B2 phylogenetic group (82%), mostly associated with ST131 lineage and, at a lower rate, to ST410/A. Regarding K. pneumoniae, the three international lineages ST15, ST147, and ST280 were detected among selected isolates. CONCLUSIONS: Different ESBL variants of CTX-M (especially CTX-M-15) and SHV-type (specially SHV-12) were detected among CTX/CAZRE. coli and K. pneumoniae isolates, in occasions associated with carbapenemase genes (blaKPC2/3 gene).

Multidrug-resistant Klebsiella pneumoniae harboring extended spectrum ß-lactamase encoding genes isolated from human septicemias.

Klebsiella pneumoniae is a major pathogen implicated in nosocomial infections. Extended-spectrum ß-lactamase (ESBL)-producing K. pneumoniae isolates are a public health concern. We aim to characterize the type of ß-lactamases and the associated resistance mechanisms in ESBL-producing K. pneumoniae isolates obtained from blood cultures in a Portuguese hospital, as well as to determine the circulating clones. Twenty-two cefotaxime/ceftazidime-resistant (CTX/CAZR) K. pneumoniae isolates were included in the study. Identification was performed by MALDI-TOF MS and the antimicrobial susceptibility testing by disk-diffusion. The screening test for ESBL-production was performed and ESBL-producer isolates were further characterized. The presence of different beta-lactamase genes (blaCTX-M, blaSHV, blaTEM, blaKPC, blaNDM, blaVIM, blaOXA-48, blaCMY-2, blaDHA-1, blaFOX, blaMOX, and blaACC) was analyzed by PCR/sequencing in ESBL-producer isolates, as well as the presence of other resistance genes (aac(6')-Ib-cr, tetA/B, dfrA, qnrA/B/S, sul1/2/3) or integron-related genes (int1/2/3). Multilocus-sequence-typing (MLST) was performed for selected isolates. ESBL activity was detected in 12 of the 22 CTX/CAZR K. pneumoniae isolates and 11 of them carried the blaCTX-M-15 gene (together with blaTEM), and the remaining isolate carried the blaSHV-106 gene. All the blaCTX-M-15 harboring isolates also contained a blaSHV gene (blaSHV-1, blaSHV-11 or blaSHV-27 variants). Both blaSHV-27 and blaSHV-106 genes correspond to ESBL-variants. Two of the CTX-M-15 producing isolates carried a carbapenemase gene (blaKPC2/3 and blaOXA-48) and showed imipenem resistance. The majority of the ESBL-producing isolates carried the int1 gene, as well as sulphonamide-resistance genes (sul2 and/or sul3); the tetA gene was detected in all eight tetracycline-resistant isolates. Three different genetic lineages were found in selected isolates: ST348 (one CTX-M-15/TEM/SHV-27/KPC-2/3-producer isolate), ST11 (two CTX-M-15/TEM/SHV-1- and CTX-M-15-TEM-SHV-11-OXA-48-producer isolates) and ST15 (one SHV-106/TEM-producer isolate). ESBL enzymes of CTX-M-15 or SHV-type are detected among blood K. pneumoniae isolates, in some cases in association with carbapenemases of KPC or OXA-48 type.

Diagnostic characteristics of immature platelet fraction for the assessment of immune thrombocytopenia.

The diagnosis of immune thrombocytopenia (ITP) remains an exclusion, as a specific biomarker is missing. We aimed to investigate the diagnostic characteristics, establish a cut-off point for reticulated platelets, and compare it with the clinical exclusion diagnosis used in the assessment of ITP. Forty-one patients with ITP and 187 healthy individuals were enrolled in Santa Maria, Brazil. Sysmex XE-5000 was used to measure IPF. We obtained an IPF cut-off point of 6.3% with a sensitivity of 92.7% (95% CI: 80.1-98.5) and a specificity of 92.5% (95% CI: 87.8-95.8). The area under the curve was 0.97. The kappa coefficient was 0.85 (95% CI: 0.75-0.95), which shows high agreement between methods. The positive (PPV) and negative predictive values (NPV) were 81.25% and 96.42%, respectively. From the cut-off point, kappa index, PPV, and NPV obtained, it is possible to conclude that IPF can be an efficient laboratory marker for diagnosing ITP.

Translation and cultural adaptation into Brazilian Portuguese of the Finnish Diabetes Risk Score (FINDRISC) and reliability assessment.

INTRODUCTION: The Finnish Diabetes Risk Score (FINDRISC) is a tool that was initially developed to predict the risk of developing type 2 diabetes mellitus in adults. This tool is simple, quick to apply, non-invasive, and low-cost. The aims of this study were to perform a translation and cultural adaptation of the original version of FINDRISC into Brazilian Portuguese and to assess test-retest reliability. METHODOLOGY: This work was done following the ISPOR Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes Measures. Once the final Brazilian Portuguese version (FINDRISC-Br) was developed, the reliability assessment was performed using a non-random sample of 83 individuals attending a primary care health center. Each participant was interviewed by trained registered dieticians on two occasions with a mean interval of 14 days. The reliability assessment was performed by analyzing the level of agreement between the test-retest responses of FINDRISC-Br using Cohen's kappa coefficient and the intraclass correlation coefficient (ICC). RESULTS: The steps of ISPOR guidelines were consecutively followed without major problems. Regarding the reliability assessment, the questionnaire as a whole presented adequate reliability (Cohen's kappa = 0.82, 95%CI 0.72 - 0.92 and ICC = 0.94, 95%CI 0.91 - 0.96). CONCLUSION: FINDRISC was translated into Brazilian Portuguese and culturally adapted following standard procedures. FINDRISC-Br has thus become available for use and has potential as a screening tool in different Brazilian settings and applications.

Emergence of community-acquired methicillin-resistant Staphylococcus aureus EMRSA-15 clone as the predominant cause of diabetic foot ulcer infections in Portugal.

Methicillin-resistant Staphylococcus aureus (MRSA) are often found in infected diabetic foot ulcers, in which the prevalence may reach 40%. These complications are one of the main causes of morbidity in diabetic patients. The objectives of this study were to investigate the prevalence and antimicrobial resistance of MRSA strains in infected diabetic foot ulcers and to characterize their genetic lineages. Samples collected from 42 type 2 diabetic patients, presenting infected foot ulcers, were seeded onto ORSAB plates with 2 mg/L of oxacillin for MRSA isolation. Susceptibility to 14 antimicrobial agents was tested by the Kirby-Bauer disk diffusion method. The presence of resistance genes, virulence factors, and the immune evasion cluster system was studied by PCR. All isolates were characterized by MLST, accessory gene regulator (agr), spa, and staphylococcal chromosomal cassette mec (SCCmec) typing. Twenty-five MRSA strains were isolated. All isolates showed resistance to penicillin and cefoxitin. Sixteen isolates showed phenotypic resistance to erythromycin being 7 co-resistant to clindamycin. Resistance to trimethoprim-sulfamethoxazole was found in 2 isolates harboring the dfrA and dfrG genes. The IEC genes were detected in 80% of isolates, 16 of which were ascribed to IEC-type B. Isolates were assigned to 12 different spa types. The MLST analysis grouped the isolates into 7 sequence types being the majority (68%) ascribed to SCCmec type IV. In this study, there was a high prevalence of the EMRSA-15 clone presenting multiple resistances in diabetic foot ulcers making these infections complicated to treat leading to a higher morbidity and mortality in diabetic patients.

Translation and cultural adaptation into Brazilian Portuguese of the Finnish Diabetes Risk Score (FINDRISC) and reliability assessment / Tradução e adaptação transcultural para o português brasileiro do Escore Finlandês de Risco de Diabetes (FINDRISC) e avaliação da confiabilidade

ABSTRACT: Introduction: The Finnish Diabetes Risk Score (FINDRISC) is a tool that was initially developed to predict the risk of developing type 2 diabetes mellitus in adults. This tool is simple, quick to apply, non-invasive, and low-cost. The aims of this study were to perform a translation and cultural adaptation of the original version of FINDRISC into Brazilian Portuguese and to assess test-retest reliability. Methodology: This work was done following the ISPOR Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes Measures. Once the final Brazilian Portuguese version (FINDRISC-Br) was developed, the reliability assessment was performed using a non-random sample of 83 individuals attending a primary care health center. Each participant was interviewed by trained registered dieticians on two occasions with a mean interval of 14 days. The reliability assessment was performed by analyzing the level of agreement between the test-retest responses of FINDRISC-Br using Cohen's kappa coefficient and the intraclass correlation coefficient (ICC). Results: The steps of ISPOR guidelines were consecutively followed without major problems. Regarding the reliability assessment, the questionnaire as a whole presented adequate reliability (Cohen's kappa = 0.82, 95%CI 0.72 - 0.92 and ICC = 0.94, 95%CI 0.91 - 0.96). Conclusion: FINDRISC was translated into Brazilian Portuguese and culturally adapted following standard procedures. FINDRISC-Br has thus become available for use and has potential as a screening tool in different Brazilian settings and applications.

RESUMO: Introdução: O Escore Finlandês de Risco de Diabetes (FINDRISC) é um instrumento que inicialmente foi desenvolvido para predizer o risco de desenvolver diabetes mellitus tipo 2 em adultos. Esse instrumento é simples, rápido de aplicar, não invasivo e de baixo custo. Os objetivos deste estudo foram descrever o processo de tradução e adaptação transcultural do FINDRISC para o português do Brasil e avaliar a sua confiabilidade teste-reteste. Metodologia: O projeto foi conduzido de acordo com as recomendações dos Princípios de Boas Práticas para o Processo de Tradução e Adaptação Transcultural de Medidas de Resultados Relatados pelo Paciente desenvolvidas pela ISPOR. Uma vez desenvolvida a versão final em português brasileiro (FINDRISC-Br), realizou-se a avaliação da confiabilidade usando uma amostra não aleatória de 83 indivíduos atendidos em uma unidade de atenção básica. Cada participante foi entrevistado por nutricionistas registradas treinadas em duas ocasiões com intervalo médio de 14 dias. A avaliação da confiabilidade foi realizada por meio da análise do nível de concordância entre as respostas do teste-reteste, utilizando-se o coeficiente kappa de Cohen e o coeficiente de correlação intraclasse (CCI). Resultados: As etapas das diretrizes da ISPOR foram seguidas consecutivamente sem maiores problemas. Em relação à avaliação da confiabilidade do teste-reteste, o questionário como um todo apresentou confiabilidade adequada (kappa de Cohen = 0,82; IC95% 0,72 - 0,92 e CCI = 0,94; IC95% 0,91 - 0,96). Conclusão: O FINDRISC foi traduzido e adaptado transculturalmente para o português do Brasil seguindo procedimentos padronizados. O FINDRISC-Br já está disponível para uso e tem potencial para ser usado como ferramenta de rastreamento em diferentes cenários brasileiros.

Uso do Cilostazol na adolescência para pacientes com bradicardia relacionada à vagotonia: descrição de uma série de casos / Cilostazol use in adolescence for bradycardia patients related to vagotonia: description of a case series

INTRODUÇÃO: As bradicardias em adolescentes podem ser geradas por doenças próprias no tecido de condução ou por influência externa (tônus vagal por exemplo). A vagotonia sintomática leva profissionais de saúde a precocemente indicar o implante de dispositivos de estimulação cardíaca artificial. Entretanto a exiguidade de próteses em nosso meio, relacionado à grande demanda e o caráter transitório da vagotonia na população hebiatrica leva ao receio da superindicação. Os inibidores de fosfodieterase como o cilostazol podem auxiliar na disfunção transitória por aumentar a condução dos canais de sódio na fase de despolarização espontânea (canais funny) das células automáticas. OBJETIVO: Descrever 4 casos de adolescentes com bradicardia de causa extrínseca em avaliação para implante de marca-passo definitivo submetidos à terapia oral com cilostazol. RESULTADOS: Foram avaliados 4 adolescentes (12,15,16 e 18 anos), sendo 3 masculinos, com bradicardia de origem externa (responsivas à ergometria ou atropina) foram submetidos à terapia medicamentosa com cilostazol após descartar-se arritmias ventriculares originadas por atividade deflagrada. Uma paciente possuia cardiopatia congênita (cavopulmonar total - ventrículo único tipo esquerdo sem isomerismo atrial). Os demais possuíam coração estruturalmente normal. A função ventricular estava preservada em todos. Todos apresentavam pausas sinusais superiores a 2,5s e ou bloqueios atrioventriculares paroxísticos. A dose inicial de 50 mg/dia foi introduzida com progressão da dose até 100 mg a cada 12 horas como objetivo terapêutico. Apenas a portadora de cardiopatia congênita foi mantida com a dose inicial devido boa resposta do Holter e na saturação. Em todos houve redução de mais de 90% das pausas com elevação da FC média sem exacerbação dos períodos de taquicardia ao Holter (periodicidade quinzenal). A variabilidade da frequência cardíaca no domínio do tempo e da frequência após o uso do fármaco apresentou melhora da relação LF/HF em todos os casos e redução do pNN50 em 75% dos pacientes. Não houve alteração hepática ou renal durante o uso de medicação. Todos estiveram assintomáticos durante o seguimento de 3 meses a 4 anos. CONCLUSÃO: 1) O uso de cilostazol diminui o desbalanço simpático parassimpático reduzindo episódios de pausas e bradicardias; 2) O tratamento do desequilíbrio autonômico com cilostazol em adolescentes púberes sintomáticos pode evitar o implante de dispositivo anti bradicardia. (AU)

High Serum Uric Acid Is Associated with Tubular Damage and Kidney Inflammation in Patients with Type 2 Diabetes.

BACKGROUND: Uric acid presents different roles in an organism. High serum uric acid concentrations may induce inflammatory pathways and promote kidney damage through different mechanisms. Therefore, this study investigated the association among high serum uric acid concentrations, renal tubular damage, and renal inflammation assessed via estimation of urinary kidney injury molecule-1 (KIM-1) and inflammatory cytokines in patients with type 2 diabetes (T2D). METHODS: Urinary concentrations of KIM-1, IL-1, IL-6, IL-10, and TNF-alpha, as well as other biochemical parameters, were assessed in 125 patients with T2D who were grouped into two groups based on the serum uric acid levels (<6.0 mg/dL and ≥6.0 mg/dL). Patients were also stratified according to the tertiles of serum uric acid concentrations. RESULTS: Urinary KIM-1, IL-1, IL-6, and TNF-alpha were higher in patients with serum uric acid concentrations ≥ 6.0 mg/dL. However, the differences between the groups were not statistically significant when the urinary values of KIM-1 and cytokines were normalized by the urinary creatinine concentration. Serum uric acid concentrations were significantly associated with urinary KIM-1 (values normalized by urinary creatinine concentration) and urinary TNF-alpha (absolute values and values normalized by urinary creatinine concentration), independent of the body mass index (BMI) and estimated glomerular filtration rate (eGFR). CONCLUSIONS: High serum uric acid concentrations were associated with high urinary KIM-1 levels accompanied by the increase of urinary proinflammatory cytokines in patients with T2D. However, normalization of urinary markers by urine creatinine concentration seems to influence the profile of the results.

Impaired chair-to-bed transfer ability leads to longer hospital stays among elderly patients.

BACKGROUND: The study objectives were to identify the main predictive factors for long hospital stays and to propose new and improved methods of risk assessment. METHODS: This prospective cohort study was conducted in the clinics and surgical wards of a tertiary hospital and involved 523 elderly patients over 60 years of age. Demographic, clinical, functional, and cognitive characteristics assessed between 48 and 72 h after admission were analyzed to investigate correlations with lengths of stay greater than 10 days. Univariate and multivariate analyses were performed, and in the final model, long-term probability scores were estimated for each variable. RESULTS: Of the 523 patients studied, 33 (6.3%) remained hospitalized for more than 10 days. Multiple regression analysis revealed that both the presence of diabetes and the inability to perform chair-to-bed transfers (Barthel Index) remained significant risk predictors. Diabetes doubled the risk of prolonged hospital stays, while a chair-to-bed transfer score of 0 or 5 led to an eight-fold increase in risk. CONCLUSIONS: In this study, we propose an easy method that can be used, after external validation, to screen for long-term risk (using diabetes and bed/chair transfer) as a first step in identifying hospitalized elderly patients who will require comprehensive assessment to guide prevention plans and rehabilitation programs.

Impact on the physical activity level of adults at high and very high risk of developing type 2 diabetes mellitus: email follow-up intervention

Aims: The present study aimed to assess the effect of a 24-week intervention on the physical activity level among adults at risk of developing type 2 diabetes mellitus (DM2). Methods: It was included 129 individuals of both sexes who underwent the Preventive Health Check-up at the Albert Einstein Israelita Hospital between January and August 2010 and who were at high and very high risk of developing DM2. The risk of developing DM2 was assessed according to the FINDRISC criteria. All participants were evaluated by the International Physical Activity Questioner (IPAQ). Subjects were followed-up for 24 weeks by a physical education professional through emails during a 6 month period. The IPAQ was sent by email after 3 and 6 months of follow-up. Statistical analysis was performed using the chi-square test with p<0.05 and the Yule Coefficient test. Results: At baseline of the follow-up period, 80.3% of individuals failed to comply with the recommended weekly physical activity. In the end, motivational intervention by e-mail encouraged 74.2% of individuals to comply with the weekly-recommended physical activity and only 1.5% were classified as sedentary. Conclusion: Therefore, the follow-up protocol conducted by periodic and personalized e-mails proved to be effective in promoting physical activity among people at risk of developing metabolic diseases.(AU)

Uso do Cilostazol na adolescência para pacientes com bradicardia relacionada à vagotonia: descrição de uma série de casos / Cilostazol use in adolescence for patients with vagotonia-related bradycardia: case report

INTRODUÇÃO: As bradicardias em adolescentes podem ser geradas por doenças próprias no tecido de condução ou por influência externa(tônus vagal por exemplo). A vagotonia sintomática leva profissionais de saúde a precocemente indicar o implante de dispositivos de estimulação cardíaca artificial. Entretanto a exiguidade de próteses em nosso meio, relacionado à grande demanda e o caráter transitório da vagotonia na população hebiatrica leva ao receio da superindicação. Os inibidores de fosfodieterase como o cilostazol podem auxiliar na disfunção transitória por aumentar a condução dos canais de sódio na fase de despolarização espontânea (canais funny) das células automáticas. OBJETIVO: Descrever 4 casos de adolescentes com bradicardia de causa extrínseca em avaliação para implante de marca-passo definitivo submetidos à terapia oral com cilostazol. RESULTADOS: Foram avaliados 4 adolescentes (12,15,16 e 18 anos), sendo 3 masculinos, com bradicardia de origem externa (responsivas à ergometria ou atropina) foram submetidos à terapia medicamentosa com cilostazol após descartarse arritmias ventriculares originadas por atividade deflagrada. Uma paciente possuia cardiopatia congênita (cavopulmonar total - ventrículo único tipo esquerdo sem isomerismo atrial). Os demais possuíam coração estruturalmente normal. A função ventricular estava preservada em todos. Todos apresentavam pausas sinusais superiores a 2,5s e ou bloqueios atrioventriculares paroxísticos. A dose inicial de 50 mg/dia foi introduzida com progressão da dose até 100 mg a cada 12 horas como objetivo terapêutico. Apenas a portadora de cardiopatia congênita foi mantida com a dose inicial devido boa resposta do Holter e na saturação. Em todos houve redução de mais de 90% das pausas com elevação da FC média sem exacerbação dos períodos de taquicardia ao Holter (periodicidade quinzenal). A variabilidade da frequência cardíaca no domínio do tempo e da frequência após o uso do fármaco apresentou melhora da relação LF/HF em todos os casos e redução do pNN50 em 75% dos pacientes. Não houve alteração hepática ou renal durante o uso de medicação. Todos estiveram assintomáticos durante o seguimento de 3 meses a 4 anos. CONCLUSÃO: 1) O uso de cilostazol diminui o desbalanço simpático parassimpático reduzindo episódios de pausas e bradicardias; 2) O tratamento do desequilíbrio autonômico com cilostazol em adolescentes púberes sintomáticos pode evitar o implante de dispositivo anti bradicardia. (AU)

Reference limits of the urinary gamma-glutamyltransferase in a healthy population and effects of short-term storage on the enzyme activity.

BACKGROUND: Gamma-glutamyltransferase (GGT) is present mainly in proximal renal tubule, and urinary GGT is an indicator of tubular damage since it may show renal changes before they are identified by using conventional measurements. Therefore, it is of interest to establish the reference limits of urinary GGT for a healthy population, as well as to investigate the stability of GGT in urine samples stored at 4 °C and -20 °C. METHODS: GGT was assessed in urine samples from 127 healthy patients by use of a reference method based on the 5-Amino-2-Nitrobenzoate formation. Stability of GGT was evaluated in 10 urine samples stored at temperatures of 4 °C and -20 °C for a period up to 4 weeks. RESULTS: Urinary GGT values for healthy volunteers were 14 U/g creatinine for the lower reference limit and 79 U/g creatinine for the upper reference limit. Urinary GGT values were approximately 56% lower in samples stored at -20 °C than fresh samples, while samples stored at 4 °C presented a decrease of 11% in GGT values compared to fresh samples. CONCLUSIONS: Reference limits for urinary GGT in healthy subjects were 14 to 79 U/g creatinine, and it is recommended to measure urinary GGT in fresh specimens.

Evaluation of the adequacy of Hadlock's reference chart for identification of fetuses with growth restriction.

OBJECTIVE: This study aimed to verify whether Hadlock's reference values for fetal weight identify fetuses below the 10th percentile in our population correctly. METHODS: The fitness of the Hadlock reference range to our study population was tested by assessment of Z scores. We evaluated differences between the reference weight ranges proposed in our study and those recommended by Hadlock. RESULTS: Z scores for Hadlock reference values were non-normally distributed. The difference between the 50th percentile fetal weight proposed by our study model and that proposed by Hadlock was ≤1% at GAs ≥22 weeks and 2-3% at 19-21 weeks. For the 90th percentile level, the maximum difference at GAs ≥17 weeks was 1.5%. For the 10th percentile level, the differences were 2-4% in the third trimester, reaching 8% in week 20 and 13% at a GA of 14 weeks. CONCLUSIONS: The weight reference ranges of this study virtually overlap with the Hadlock ranges. We believe that only at lower gestational ages in the second trimester might some FGR diagnoses be missed in the population study with Hadlock's reference.