Prediction of intensive care admission and hospital mortality in COVID-19 patients using demographics and baseline laboratory data

Abstract Introduction: Optimized allocation of medical resources to patients with COVID-19 has been a critical concern since the onset of the pandemic. Methods: In this retrospective cohort study, the authors used data from a Brazilian tertiary university hospital to explore predictors of Intensive Care Unit (ICU) admission and hospital mortality in patients admitted for COVID-19. Our primary aim was to create and validate prediction scores for use in hospitals and emergency departments to aid clinical decisions and resource allocation. Results: The study cohort included 3,022 participants, of whom 2,485 were admitted to the ICU; 1968 survived, and 1054 died in the hospital. From the complete cohort, 1,496 patients were randomly assigned to the derivation sample and 1,526 to the validation sample. The final scores included age, comorbidities, and baseline laboratory data. The areas under the receiver operating characteristic curves were very similar for the derivation and validation samples. Scores for ICU admission had a 75% accuracy in the validation sample, whereas scores for death had a 77% accuracy in the validation sample. The authors found that including baseline flu-like symptoms in the scores added no significant benefit to their accuracy. Furthermore, our scores were more accurate than the previously published NEWS-2 and 4C Mortality Scores. Discussion and conclusions: The authors developed and validated prognostic scores that use readily available clinical and laboratory information to predict ICU admission and mortality in COVID-19. These scores can become valuable tools to support clinical decisions and improve the allocation of limited health resources.

Effect of a single high-dose vitamin d3 on the length of hospital stay of severely 25-hydroxyvitamin d-deficient patients with COVID-19

OBJECTIVES: In this ancillary analysis of a multicenter, double-blinded, randomized, placebo-controlled trial, we investigated the effect of a single high dose of vitamin D3 on the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19. METHODS: The primary outcome was length of hospital stay, defined as the total number of days that patients remained hospitalized from the date of randomization until the date of hospital discharge. Secondary outcomes included serum levels of 25-hydroxyvitamin D, mortality during hospitalization, number of patients admitted to the intensive care unit, and number of patients who required mechanical ventilation. ClinicalTrials.gov: NCT04449718. RESULTS: Thirty-two patients were included in the study. The mean (SD) age was 58.5 (15.6) years, body mass index was 30.8 (8.6) kg/m2, and 25-hydroxyvitamin D level was 7.8 (1.6) ng/mL. No significant difference was observed in the median interquartile range of length of hospital stay between the vitamin D3 group (6.0 [4.0-18.0] days) versus placebo (9.5 [6.3-15.5] days) (log-rank p=0.74; hazard ratio, 1.13 [95% confidence interval (CI), 0.53-2.40]; p=0.76). Vitamin D3 significantly increased serum 25-hydroxyvitamin D levels in the vitamin D3 group compared with that in the placebo group (between-group difference, 23.9 ng/mL [95% CI, 17.7-30.1]; p<0.001). CONCLUSIONS: A dose of 200.000 IU of vitamin D3 did not significantly reduce the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19.

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital

OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

Evaluation of relationship between hematocrit and lipid profile in adults / Avaliação da correlação entre o hematócrito e o perfil lipídico em adultos

ABSTRACT Introduction and objective: This study was carried out to analyze the relationship between hematocrit and lipid profile in adults. Material and method: A sample composed of complete blood counts and lipid profiles from the database of Hospital das Clínicas da Universidade de São Paulo (HCUSP), São Paulo, Brazil, was used in the analysis. Hematocrit was organized in five groups that were compared with total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), non-high-density-lipoprotein cholesterol (NHDL-C) and high-density-lipoprotein cholesterol (HDL-C) by means of chi-squared and Kruskal-Wallis tests. Results: Both tests showed a relevant correlation between hematocrit and lipid profile, considering a p-value < 0.05. Moreover, descriptive statistics revealed that the higher the hematocrit, the higher the proportion of people without recommended levels of each type of cholesterol, such TC, LDL-C, and NHDL-C. Just HDL-C showed an inverse association compared to the other variables, with an increased proportion of recommended levels along with rising of hematocrit. Conclusion: The relationship between hematocrit and lipid profile in all aspects of this study was more evident in women; nevertheless, the higher proportion of not recommended levels of HDL-C was shown in men. The reverse cholesterol transport probably plays an important role in the increase of cholesterol levels in blood in the presence of high hematocrit, by interaction of HDL-C and erythrocytes. Thus, further studies are necessary to elucidate these findings and to describe more aspects of the reverse cholesterol transport and its relationship with hematocrit and lipid profile.

RESUMO Introdução e objetivo: Este estudo foi escrito com o objetivo de analisar a relação entre o hematócrito e o perfil lipídico em adultos. Material e método: Utilizou-se uma amostra composta por hemogramas e perfis lipídicos do banco de dados do Hospital das Clínicas da Universidade de São Paulo (HCUSP), São Paulo, Brasil. O hematócrito foi organizado em cinco grupos, sendo eles comparados com o colesterol total, o colesterol da lipoproteína de baixa densidade (LDL-C), o colesterol da lipoproteína de alta densidade (HDL-C) e o colesterol total não HDL (NHDL-C), por meio de análise estatística com os testes de qui-quadrado e Kruskal-Wallis. Resultados: Ambos os testes mostraram correlação relevante entre o hematócrito e o perfil lipídico, considerando um valor de p < 0,05. Além disso, a estatística descritiva forneceu uma visão de que, quanto maior o hematócrito, maior a proporção de indivíduos sem níveis recomendados de cada tipo de colesterol, como colesterol total, LDL-C e NHDL-C. Excepcionalmente, o HDL-C mostrou uma associação inversa em comparação com outras variáveis, com um aumento na proporção dos níveis recomendados juntamente com o aumento do hematócrito. Conclusão: A relação entre o hematócrito e o perfil lipídico em todos os aspectos deste estudo foi mais evidente nas mulheres; no entanto, a maior proporção de níveis não recomendados de HDL-C foi demonstrada nos homens. O transporte reverso de colesterol provavelmente tem um papel importante no aumento dos níveis de colesterol no sangue na presença de hematócrito alto, pela interação do HDL-C e dos eritrócitos. Assim, outros estudos são necessários para elucidar esses achados e descrever mais aspectos sobre o transporte reverso do colesterol e sua relação com o hematócrito e o perfil lipídico.

Preanalytical conditions can interfere with M. tuberculosis detection by PCR in respiratory samples

OBJECTIVES: Tuberculosis is one of the most prevalent infections in humans. Although culture is the reference for diagnosis, its sensitivity is compromised, especially in paucibacillary samples. Because polymerase chain reaction (PCR) amplifies mycobacterial DNA, it is more sensitive than culture for the diagnosis of Mycobacterium tuberculosis (Mtb). However, its performance can be affected by intrinsic sample inhibitors and by the extraction/detection techniques used. METHODS: We evaluated the influence of preanalytical conditions on Mtb detection in samples of sputum (SPU), bronchoalveolar lavage (BAL), and pleural fluid (PF) using combinations of extraction/detection methods. Respiratory samples were prepared to contain different concentrations of red blood cells and nucleated cells to which increasing amounts of Mtb colonies were inoculated and submitted to PCR. RESULTS: Up to 102 CFU/ml of Mtb were detected in the SPU in all methods, except for the Roche extraction/detection method, regardless of the preanalytical sample condition. In BAL samples, medium and high concentrations of cells and high concentrations of red blood cells contributed to a lower Mtb detection, regardless of the extraction method used. In PF, red blood cells were the variable that most interfered with Mtb detection, with better recovery (102 CFU/ml) observed with the Qiagen/Nanogen combination. CONCLUSION: The choice of Mtb extraction and detection method is of fundamental importance for PCR analytical sensitivity, especially when paucibacillary samples and/or samples containing potential PCR inhibitors are analyzed.

Serum concentration of vascular endothelial growth factor and depth of trophoblastic invasion in ampullary ectopic pregnancy

OBJECTIVE: To evaluate the association between the depth of trophoblastic infiltration and serum vascular endothelial growth factorconcentration in patients with an ampullary pregnancy. METHODS: This prospective cross-sectionalstudy involved 34 patients with an ampullary ectopic pregnancy who underwent salpingectomy between 2012 and 2013. Maternal serum vascular endothelial growth factor concentrations were measured using Luminex technology. Trophoblastic invasion was classified histologically as follows: stage I, limited to the tubal mucosa; stage II, reaching the muscle layer; and stage III,involving the full thickness. The qualitative data were compared using Fisher's exact test. The nonparametric Kruskal-Wallis and Mann-Whitney tests were used to evaluate differences in serum vascular endothelial growth factor among the degrees of trophoblastic invasion. ROC curves were constructed to determine vascular endothelial growth factor cut-off values that predict the degree of tubal invasion based on the best sensitivity and specificity. RESULTS: Eight patients had stage I trophoblastic invasion, seven had stage II, and 19 had stage III. The median serum vascular endothelial growth factorconcentration was 69.88 pg/mL for stage I, 14.53 pg/mL for stage II and 9.08 pg/mL for stage III, with a significant difference between stages I and III. Based on the ROC curve, a serum vascular endothelial growth factor concentration of 25.9 pg/mL best differentiated stage I from stages II and III with asensitivity of 75.0%, specificity of 76.9%, and area under the curve of 0.798. CONCLUSIONS: The depth of trophoblastic penetration into the tubal wall isassociated with serum vascular endothelial growth factor concentration in ampullary pregnancies.

Hidrocortisona reduz as concentrações séricas dos biomarcadores inflamatórios séricos em pacientes submetidos a endarterectomia de carótida / Hydrocortisone reduces serum concentrations of inflammatory biomarkers in patients subjected to carotid endarterectomy

A hidrocortisona pode reduzir a concentração dos biomarcadores inflamatórios séricos e teciduais.ObjetivoAnalisar a atividade inflamatória da proteína C-reativa ultrassensível (PCR-US), do fator de necrose tumoral (FNT)-alfa e do fator de crescimento do endotélio vascular (FCEV) séricos e teciduais, mediante administração intraoperatória de hidrocortisona, após endarterectomia de artéria carótida (EAC).MétodoVinte e dois pacientes foram divididos em Grupo Controle (5 assintomáticos e 6 sintomáticos) – não foi administrada hidrocortisona – e Grupo 1 (4 assintomáticos e 7 sintomáticos) – foram administrados 500 mg intravenoso de hidrocortisona. O PCR-US, o FNT-alfa e o FCEV séricos foram dosados no pré-operatório e em 1 hora, 6 horas e 24 horas após a EAC. Na placa carotídea, mensuramos os níveis de FNT-alfa e FCEV.ResultadosO grupo 1 exibiu menor concentração sérica de FNT-alfa em 1 hora (p=0,031), 6 horas (p=0,015) e 24 horas (p=0,017) após a EAC, e menor concentração de FCEV em 1 hora (p=0,006) e 6 horas (p=0,005) após a EAC, em relação ao grupo controle. Os pacientes sintomáticos do grupo 1 exibiram menor concentração de FNT-alfa em 1 hora e 6 horas após a EAC, e menor concentração de FCEV em 1 hora após a EAC, em relação ao grupo controle. Não houve diferença estatística entre as concentrações teciduais de FNT-alfa e FCEV entre o grupo controle e o grupo 1.ConclusãoA hidrocortisona reduz as concentrações séricas pós-operatórias de FNT-alfa e FCEV, em especial nos sintomáticos; porém, não reduz os níveis teciduais destes biomarcadores.

Hydrocortisone may reduce serum and tissue concentrations of inflammatory biomarkers.ObjectiveTo analyze the inflammatory activity of serum and tissue high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-á and vascular endothelial growth factor (VEGF) after intraoperative administration of hydrocortisone, after carotid endarterectomy (CEA).MethodTwenty-two patients were allocated to a Control Group (5 asymptomatic and 6 symptomatic patients) and were not administered hydrocortisone or to Group 1 (4 asymptomatic and 7 symptomatic patients) and were administered 500 mg intravenous hydrocortisone. Serum levels of hsCRP, TNF-á and VEGF were tested for the preoperative period and at 1 hour, 6 hours and 24 hours after CEA. Levels of TNF-á and VEGF were also measured in carotid plaques.ResultsGroup 1 exhibited lower concentrations of serum TNF-á at 1 hour (p=0.031), 6 hours (p=0.015) and 24 hours (p=0.017) after CEA and lower concentrations of serum VEGF at 1 hour (p=0.006) and 6 hours (p=0.005) after CEA, relative to controls. Symptomatic patients in group 1 exhibited lower concentrations than controls for serum TNF-á at 1 hour and 6 hours after CEA and lower concentrations than controls for serum VEGF at 1 hour after CEA. There were no statistical differences in tissue concentrations of TNF-á or VEGF between the control group and group 1.ConclusionHydrocortisone reduces postoperative concentrations of serum TNF-á and VEGF, especially in symptomatic patients; but does not reduce tissue levels of these biomarkers.

Hydrocortisone supresses inflammatory activity of metalloproteinase - 8 in carotid plaque / Hidrocortisona suprime a atividade inflamatória da metaloproteinase - 8 presente na placa carotídea

AbstractObjective:Matrix metalloproteinases are inflammatory biomarkers involved in carotid plaque instability. Our objective was to analyze the inflammatory activity of plasma and carotid plaque MMP-8 and MMP-9 after intravenous administration of hydrocortisone.Methods:The study included 22 patients with stenosis ≥ 70% in the carotid artery (11 symptomatic and 11 asymptomatic) who underwent carotid endarterectomy. The patients were divided into two groups: Control Group - hydrocortisone was not administered, and Group 1 - 500 mg intravenous hydrocortisone was administered during anesthetic induction. Plasma levels of MMP-8 and MMP-9 were measured preoperatively (24 hours before carotid endarterectomy) and at 1 hour, 6 hours and 24 hours after carotid endarterectomy. In carotid plaque, tissue levels of MMP-8 and MMP-9 were measured.Results:Group 1 showed increased serum levels of MMP- 8 (994.28 pg/ml and 408.54 pg/ml, respectively; P=0.045) and MMP-9 (106,656.34 and 42,807.69 respectively; P=0.014) at 1 hour after carotid endarterectomy compared to the control group. Symptomatic patients in Group 1 exhibited lower tissue concentration of MMP-8 in comparison to the control group (143.89 pg/ml and 1317.36 respectively; P=0.003). There was a correlation between preoperative MMP-9 levels and tissue concentrations of MMP-8 (P=0.042) and MMP-9 (P=0.019) between symptomatic patients in the control group.Conclusion:Hydrocortisone reduces the concentration of MMP- 8 in carotid plaque, especially in symptomatic patients. There was an association between systemic and tissue inflammation.

ResumoObjetivo:As metaloproteinases são biomarcadores inflamatórios envolvidos na instabilidade da placa carotídea. O objetivo deste estudo foi analisar a atividade inflamatória da MMP-8 e MMP-9 plasmática e presente na placa carotídea, após administração intravenosa de hidrocortisona.Métodos:Participaram do estudo 22 pacientes portadores de estenose ≥ 70% em artéria carótida (11 sintomáticos e 11 assintomáticos), submetidos à endarterectomia de artéria carótida. Os pacientes foram divididos em dois grupos: Grupo Controle - não foi administrado hidrocortisona e Grupo 1 - foi administrado 500 mg intravenoso de hidrocortisona durante a indução anestésica. As dosagens plasmáticas de MMP-8 e MMP-9 foram efetuadas no pré-operatório (24 horas antes da endarterectomia de artéria carótida) e em 1 hora, 6 horas e 24 horas após endarterectomia de artéria carótida. Na placa carotídea foram mensurados os níveis teciduais de MMP-8 e MMP-9.Resultados:O grupo 1 exibiu elevação dos níveis séricos da MMP-8 (994,28 pg/ml e 408,54 pg/ml, respectivamente; P=0.045) e MMP-9 (106.656,34 e 42.807,69, respectivamente; P=0.014) em 1 hora após a endarterectomia de artéria carótida, em relação ao grupo controle. Os pacientes sintomáticos do grupo 1 exibiram menor concentração tecidual de MMP-8, em relação ao grupo controle (143,89 pg/ml e 1317,36, respectivamente; P=0.003). Houve correlação entre os níveis pré-operatórios de MMP-9 e as concentrações teciduais de MMP-8 (P=0.042) e MMP-9 (P=0.019) entre os pacientes sintomáticos do grupo controle.Conclusão:A hidrocortisona reduz a concentração de MMP-8 na placa carotídea, em especial nos pacientes sintomáticos. Houve associação entre a inflamação sistêmica e a tecidual.

Effectiveness and safety of iodopovidone in an experimental pleurodesis model

OBJECTIVES: Chemical pleurodesis is an important therapeutic tool to control recurrent malignant pleural effusion. Among the various sclerosing agents, iodopovidone is considered effective and safe. However, in a recent study, ocular changes were described after iodopovidone was used in recurrent pneumothorax. The aim of the study was to evaluate the efficacy and morbidity of iodopovidone pleurodesis in an experimental model. METHODS: New Zealand rabbits were submitted to intrapleural injection of iodopovidone at concentrations of 2%, 4% and 10%. Biochemical (lactic dehydrogenase, proteins, triiodothyronine, free thyroxine, urea and creatinine) and immunological (Interleukin-8 [IL-8], VEGF and TGFβ) parameters were measured in the pleural fluid and blood. After 1, 3, 7, 14 and 28 days, groups of animals were euthanized, and macro- (pleura) and microscopic (pleura and retina) analyses were performed. RESULTS: An early pleural inflammatory response with low systemic repercussion was observed without corresponding changes in thyroid or renal function. The higher concentrations (4% and 10%) correlated with greater initial exudation, and maximum pleural thickening was observed after 28 days. No changes were observed in the retinal pigment epithelium of the rabbits. CONCLUSION: Iodopovidone is considered to be an effective and safe sclerosing agent in this animal model. However, its efficacy, tolerance and safety in humans should be further evaluated. .

Pleural tuberculosis: is radiological evidence of pulmonary-associated disease related to the exacerbation of the inflammatory response?

OBJECTIVE: Pleural tuberculosis is the most frequently occurring form of extra pulmonary disease in adults. In up to 40% of cases, the lung parenchyma is concomitantly involved, which can have an epidemiological impact. This study aims to evaluate the pleural and systemic inflammatory response of patients with pleural or pleuropulmonary tuberculosis. METHODS: A prospective study of 39 patients with confirmed pleural tuberculosis. After thoracentesis, a high resolution chest tomography was performed to evaluate the pulmonary involvement. Of the 39 patients, 20 exhibited only pleural effusion, and high resolution chest tomography revealed active associated-pulmonary disease in 19 patients. The total protein, lactic dehydrogenase, adenosine deaminase, vascular endothelial growth factor, interleukin-8, tumor necrosis factor-α, and transforming growth factor-β1 levels were quantified in the patient serum and pleural fluid. RESULTS: All of the effusions were exudates with high levels of adenosine deaminase. The levels of vascular endothelial growth factor and transforming growth factor-β1 were increased in the blood and pleural fluid of all of the patients with pleural tuberculosis, with no differences between the two forms of tuberculosis. The tumor necrosis factor-α levels were significantly higher in the pleural fluid of the patients with the pleuropulmonary form of tuberculosis. The interleukin-8 levels were high in the pleural fluid of all of the patients, without any differences between the forms of tuberculosis. CONCLUSION: Tumor necrosis factor-α was the single cytokine that significantly increased in the pleural fluid of the patients with pulmonary involvement. However, an overlap in the results does not permit us to suggest that cytokine is a biological marker of concomitant parenchymal involvement. Although high resolution chest tomography can be useful in identifying these patients, the investigation of fast acid bacilli and cultures for M. tuberculosis in the sputum is recommended for all patients who are diagnosed with pleural tuberculosis.

É possível diferenciar derrames pleurais linfocíticos secundários a tuberculose ou linfoma através de variáveis clínicas e laboratoriais? / Differentiating between tuberculosis-related and lymphoma-related lymphocytic pleural effusions by measuring clinical and laboratory variables: Is it possible?

OBJETIVO: Descrever características clínicas e laboratoriais em pacientes com derrames pleurais linfocíticos secundários a tuberculose ou linfoma, a fim de identificar as variáveis que possam contribuir no diagnóstico diferencial dessas doenças. MÉTODOS: Estudo retrospectivo com 159 pacientes adultos HIV negativos com derrame pleural linfocítico secundário a tuberculose ou linfoma (130 e 29 pacientes, respectivamente) tratados no Ambulatório da Pleura, Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo (SP), entre outubro de 2008 e março de 2010. RESULTADOS: A média de idade e de duração dos sintomas foi menor no grupo tuberculose que no grupo linfoma. Os níveis pleurais de proteínas, albumina, colesterol, amilase e adenosina desaminase (ADA), assim como os níveis séricos de proteínas, albumina e amilase, foram maiores no grupo tuberculose, enquanto os níveis séricos de colesterol e triglicérides foram maiores no grupo linfoma. As contagens de leucócitos e linfócitos no líquido pleural foram maiores no grupo tuberculose. Células malignas estavam ausentes no grupo tuberculose, entretanto, linfócitos atípicos foram observados em 4 desses pacientes. No grupo linfoma, a citologia para células neoplásicas foi positiva, suspeita e negativa em 51,8%, 24,1% e 24,1% dos pacientes, respectivamente. A imunofenotipagem do líquido pleural foi conclusiva na maioria dos pacientes com linfoma. CONCLUSÕES: Nossos resultados demonstram semelhanças clínicas e laboratoriais entre os pacientes com tuberculose ou linfoma. Embora os níveis de proteínas e ADA no líquido pleural tendam a ser mais elevados no grupo tuberculose que no grupo linfoma, mesmo essas variáveis mostraram uma sobreposição. Entretanto, nenhum paciente com tuberculose apresentou níveis de ADA no líquido pleural inferiores ao ponto de corte (40 U/L).

OBJECTIVE: To describe clinical and laboratory characteristics in patients with tuberculosis-related or lymphoma-related lymphocytic pleural effusions, in order to identify the variables that might contribute to differentiating between these diseases. METHODS: This was a retrospective study involving 159 adult HIV-negative patients with tuberculosis-related or lymphoma-related lymphocytic effusions (130 and 29 patients, respectively), treated between October of 2008 and March of 2010 at the Pleural Diseases Outpatient Clinic of the University of São Paulo School of Medicine Hospital das Clínicas Heart Institute, in the city of São Paulo, Brazil. RESULTS: Mean age and the mean duration of symptoms were lower in the tuberculosis group than in the lymphoma group. The levels of proteins, albumin, cholesterol, amylase, and adenosine deaminase (ADA) in pleural fluid, as well as the serum levels of proteins, albumin, and amylase, were higher in the tuberculosis group, whereas serum cholesterol and triglycerides were higher in the lymphoma group. Pleural fluid leukocyte and lymphocyte counts were higher in the tuberculosis group. Of the tuberculosis group patients, none showed malignant cells; however, 4 showed atypical lymphocytes. Among the lymphoma group patients, cytology for neoplastic cells was positive, suspicious, and negative in 51.8%, 24.1%, and 24.1%, respectively. Immunophenotyping of pleural fluid was conclusive in most of the lymphoma patients. CONCLUSIONS: Our results demonstrate clinical and laboratory similarities among the patients with tuberculosis or lymphoma. Although protein and ADA levels in pleural fluid tended to be higher in the tuberculosis group than in the lymphoma group, even these variables showed an overlap. However, none of the tuberculosis group patients had pleural fluid ADA levels below the 40-U/L cut-off point.

Characteristics of ascitic fluid from patients with suspected spontaneous bacterial peritonitis in emergency units at a tertiary hospital / Características do líquido ascítico de pacientes com suspeita de peritonite bacteriana espontânea nas unidades de emergência de um hospital terciário

CONTEXT AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is a complication of ascites, especially in cirrhosis. Ascitic fluid with 250 or more neutrophils/mm³ is an acceptable criterion for diagnosis, even when bacterial fluid cultures are negative. The aims here were to estimate SBP frequency among emergency room patients based on cellular criteria and evaluate the biochemical profile of these fluids. DESIGN AND SETTING: Retrospective study at a public tertiary hospital. METHODS: Laboratory records of patients with ascites attended in emergency rooms between November 2001 and November 2006, from whom ascitic fluid samples were sent to the laboratory due to suspected SBP, were evaluated. The 691 samples included were divided into group A (presumed SBP: > 250 neutrophils/mm³; n = 219; 31.7 percent) and group B (no presumed SBP: < 250 neutrophils/mm3; n = 472; 68.3 percent). Patients' sex and age; ascitic fluid characteristics (numbers of neutrophils, leukocytes and nucleated cells); bacteriological characteristics; and protein, lactate dehydrogenase, adenosine deaminase and glucose concentrations were evaluated. RESULTS: Among group A cultured samples, 63 (33.8 percent) had positive bacterial cultures with growth of pathogens commonly associated with SBP. In total, the group A samples showed higher lactate dehydrogenase levels than seen in the group B samples. The latter presented predominance of lymphocytes and macrophages. CONCLUSION: Among the ascitic fluid samples with clinically suspected SBP, 31.7 percent fulfilled the cellular diagnostic criteria. Positive bacterial isolation was found in 33.8 percent of the cultured samples from the presumed SBP group.

CONTEXTO E OBJETIVO: Peritonite bacteriana espontânea (PBE) é uma complicação da ascite, especialmente na cirrose. Líquido ascítico com 250 ou mais neutrófilos/mm³ é um critério aceitável para o diagnóstico, mesmo com cultura bacteriana negativa. Os objetivos foram estimar a frequência de PBE em pacientes atendidos na sala de emergência, baseando-se no critério celular e avaliar o perfil bioquímico desses líquidos peritoneais. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo em hospital público terciário. MÉTODOS: Foram avaliados registros laboratoriais de pacientes com ascite atendidos no setor de emergência entre novembro de 2001 e novembro de 2006, cujas amostras de líquido ascítico foram encaminhadas ao laboratório por suspeita de PBE. As 691 amostras incluídas foram divididas em grupo A (PBE presumida: > 250 neutrófilos/mm³; n = 219; 31.7 por cento) e grupo B (Ausência de PBE presumida: < 250 neutrófilos/mm3; n = 472; 68.3 por cento). Também foram avaliados sexo e idade dos pacientes além de características dos líquidos ascíticos: número de neutrófilos, leucócitos e células nucleadas; bacteriologia; e concentrações de proteínas, desidrogenase láctica, adenosina deaminase e glicose. RESULTADOS: Das amostras cultivadas do grupo A, 63 (33,8 por cento) tiveram cultura bacteriana positiva com crescimento de patógenos comumente associados à PBE. O total de amostras do grupo A exibiu maiores níveis de desidrogenase lática que as do grupo B. Este último demonstrou predomínio de linfócitos e macrófagos. CONCLUSÃO: Dos líquidos ascíticos com suspeita clínica de PBE, 31.7 por cento preencheram o critério diagnóstico celular. O isolamento bacteriano foi positivo em 33.8 por cento das amostras cultivadas no grupo PBE presumida.

Derrame pleural incomum: metástase pleuropulmonar de tumor neuroectodérmico primitivo / Uncommon pleural effusion: pleuropulmonary metastasis from primitive neuroectodermal tumor

O tumor neuroectodérmico primitivo é uma neoplasia com diferenciação neural de comportamento invasivo que origina metástases para diversos órgãos. Relatamos um caso de tumor neuroectodérmico primitivo primário em axila com metástases para pulmão, pleura, osso, músculo ilíaco e medula óssea. Enfatizamos o achado incomum da análise citológica do líquido pleural.

Primitive neuroectodermal tumor is an invasive neoplasm with neuronal differentiation, which frequently results in metastasis in various organs. We report the case of a patient with primitive neuroectodermal tumor whose primary site was the axilla. The patient presented with metastases in the lung, pleura, bone, iliac muscle and bone marrow. We highlight the uncommon finding in the pleural fluid cytology.

Malignant and tuberculous pleural effusions: immunophenotypic cellular characterization

INTRODUCTION AND OBJECTIVES: Tuberculosis and cancer are the main causes of pleural effusion. Pleural involvement is associated with migration of immune cells to the pleural cavity. We sought to characterize the immunophenotype of leukocytes in the pleural effusion and peripheral blood of patients with tuberculosis or malignancy. METHODS: Thirty patients with tuberculosis (14) or malignancy (16) were studied. A control group included 20 healthy blood donors. RESULTS: Malignant phycoerythrin pleural effusions showed higher percentages of CD3, CD4, CD3CD45RO, and CD20CD25 lymphocytes and lower percentages of CD3CD25 and CD20HLA-DR when compared to PB lymphocytes. Compared to PB, tuberculous effusions had a higher percentage of lymphocytes that co-expressed CD3, CD4, CD3CD45RO, CD3TCRáâ, CD3CD28, and CD20 and a lower percentage of CD14, CD8 and CD3TCRãä-positive lymphocytes. Malignant effusions presented higher expression of CD14 whereas tuberculous effusions had higher expression of CD3 and CD3CD95L. Peripheral blood cells from tuberculosis patients showed higher expression of CD14, CD20CD25 and CD3CD95L. Compared with the control cells, tuberculosis and cancer peripheral blood cells presented a lower percentage of CD3CD4 and CD3CD28-positive cells as well as a higher percentage of CD3CD8, CD3CD25 and CD3CD80-positive cells. CONCLUSIONS: Tuberculous and malignant peripheral blood is enriched with lymphocytes with a helper/inducer T cell phenotype, which are mainly of memory cells. CD14-positive cells were more frequently found in malignant effusions, while CD3-positive cells expressing Fas ligand were more frequently found in tuberculous effusions.

The usefulness of adenosine deaminase in the diagnosis of tuberculous pericarditis

The objective of this study was to evaluate the adenosine deaminase (ADA) activity usefulness in the diagnosis of tuberculous pericarditis (TP), comparing its value with pericardial effusions (PE) caused by other pericardial diseases. A retrospective case-control study was conducted with nine cases of TP and 39 other than TP diseases (12 neoplastic, 11 septic and 16 unknown origin). Every patient included in this study had PE samples submitted to ADA activity measures and microbiological analysis, and then had pericardial tissue samples submitted to microbiological and histopathological examination. Considering the value of 40 U/L as the cut-off for the diagnosis of TP, the specificity and sensitivity were respectively of 72 percent and 89 percent. The specificity of ADA activity for the TP was best applied in the differential diagnosis from PE of unknown origin. The present study demonstrates the clinical value of the measurement of ADA activity in PE in the diagnosis of TP.

O objetivo deste estudo foi avaliar a atividade da adenosina deaminase (ADA) como auxiliar no diagnóstico da tuberculose pericárdica (TP), comparando o seu valor no derrame pericárdico com outras doenças pericárdicas. Um estudo retrospectivo tipo caso-controle foi conduzido com nove casos de TP e 39 pacientes com outras doenças pericárdicas (12 neoplasias, 11 pericardites bacterianas e 16 pericardites de etiologia indeterminada). Cada paciente incluído no estudo teve sua amostra de tecido pericárdico encaminhada para estudo microbiológico e histopatológico. Considerando o valor de 40 U/L como corte para o diagnóstico de TP, a especificidade e sensibilidade foram respectivamente 72 e 89 por cento. A especificidade da atividade de ADA para a TP foi melhor aplicada no diagnóstico diferencial entre derrame pericárdico de origem indeterminada. O presente estudo demonstrou o valor clínico da mensuração da atividade de ADA no diagnóstico de TP.

Clinical and laboratory parameters in the differential diagnosis of pleural effusion secondary to tuberculosis or cancer

PURPOSE: To evaluate the clinical and laboratory characteristics of pleural effusions secondary to tuberculosis (TB) or cancer (CA). METHODS: A total of 326 patients with pleural effusion due to TB (n=182) or CA (n=144) were studied. The following parameters were analyzed: patient gender, age and pleural effusion characteristics (size, location, macroscopic fluid aspect, protein concentration, lactate dehydrogenase (DHL) and adenosine deaminase activity (ADA) and nucleated cell counts). RESULTS: Young male patients predominated in the tuberculosis group. The effusions were generally moderate in size and unilateral in both groups. Yellow-citrine fluid with higher protein (p < 0.001) levels predominated in effusions from the tuberculosis group (5.3 + 0.8 g/dL) when compared to the CA group (4.2 ± 1.0 g/dL), whereas DHL levels were more elevated in CA (1,177 ± 675 x 1,030 ± 788 IU; p = 0.003) than in TB. As expected, ADA activity was higher in the TB group (107.6 ± 44.2 x 30.6 ± 57.5 U/L; p < 0.001). Both types of effusions presented with high nucleated cell counts, which were more pronounced in the malignant group (p < 0.001). TB effusion was characterized by a larger percentage of leukocytes and lymphocytes (p < 0.001) and a smaller number of mesothelial cells (p = 0.005). Lymphocytes and macrophages were the predominant nucleated cell in neoplastic effusions. CONCLUSION: Our results demonstrate that in lymphocytic pleural exudate obtained from patients with clinical and radiological evidence of tuberculosis, protein and ADA were the parameters that better characterize these effusions. In the same way, when the clinical suspicion is malignancy, serous-hemorrhagic lymphocytic fluid should be submitted to oncotic cytology once this easy and inexpensive exam reaches a high diagnostic performance (approximately 80 percent). In this context, we suggest thoracocentesis with fluid biochemical...

OBJETIVO: Avaliar as características clínicas e laboratoriais de derrames pleurais secundários à tuberculose ou câncer. MÉTODOS: Um total de 326 pacientes com derrame pleural por tuberculose (n=182) ou câncer (n=144) foi avaliado. Os seguintes parâmetros foram analisados: sexo e idade dos pacientes e características do líquido pleural (tamanho, localização, aspecto macroscópico, concentração de proteínas, atividade da desidrogenase lática (DHL) e da adenosina deaminase (ADA) e contagem de células nucleadas). RESULTADOS: A tuberculose pleural predominou nos pacientes mais jovens e do sexo masculino. Em ambos os grupos, os derrames pleurais foram de tamanho moderado e unilaterais. Derrames com aspecto amarelo-citrino com níveis mais elevados de proteínas predominaram na tuberculose (5,3 ± 0,8 g/dL), quando comparados aos neoplásicos (4,2 ± 1,0 g/dL), enquanto que níveis mais elevados de DHL foram observados nos derrames neoplásicos (1.177 ± 675 x 1.030 ± 788 UI; p = 0,003). Conforme esperado, a atividade da ADA foi maior na tuberculose que no câncer (107,6 ± 44,2 x 30,6 ± 57,5 U/L; p < 0,001). Ambos os derrames apresentaram alta celularidade, embora mais pronunciada no grupo neoplásico (p < 0,001). Os derrames de etiologia tuberculosa se caracterizaram por apresentar uma maior percentagem de leucócitos e de linfócitos (p < 0,001) e um pequeno número de células mesoteliais (p = 0,005). Linfócitos e macrófagos foram as células nucleadas que predominaram nos derrames pleurais malignos. CONCLUSÃO: Nossos resultados demonstram que em exsudatos pleurais linfocíticos de pacientes com evidências clínicas e radiológicas de tuberculose, os níveis de proteína e de ADA foram os parâmetros que melhor caracterizaram esses derrames. Da mesma maneira, quando a suspeita clínica é câncer, um líquido serohemorrágico e linfocítico deve ser submetido à citologia oncótica, uma vez que este exame laboratorial de fácil...

Morphometric evaluation of NB84, synaptophysin and AgNOR is useful for the histological diagnosis and prognosis in peripheral neuroblastic tumors (pNTs)

OBJECTIVE: To study the importance of NB84, synaptophysin and AgNOR and explore the quantitative association of these factors with diagnosis and outcome as well as the association between NB84 and AgNOR and other tumor and stromal factors in twenty-eight peripheral neuroblastic tumors. METHODS: We assessed AgNORs, NB84, synaptophysin and several other markers in tumor tissues from 28 patients with primary neuroblastic tumors. The treatment included: surgery for stage 1, chemotherapy and bone marrow transplantation for most of stages 3 and 4. Histochemistry, immunohistochemistry and morphometry were used to evaluate the amount of tumor staining for AgNOR, NB84 and synaptophysin; the outcome for our study was survival time until death due to recurrent neuroblastic tumors. RESULTS: Only stage (p<0.01), AgNOR (p<0.01), NB84 (p<0.01) and synaptophysin (p=0.01) reached statistical significance as prognostic indicators. CONCLUSIONS: Determination of NB84 and synaptophysin are useful tools for the diagnosis of peripheral neuroblastic tumors The association of the evaluation of AgNOR expression by the tumor cells may provide an important contribution to the prognostic evaluation and management approach of the patients.

OBJETIVO: Estudar a importância dos marcadores NB84 e AgNOR e explorar as relações quantitativas entre esses marcadores com o diagnóstico e prognóstico assim como as relações entre NB84 e AgNOR e outros marcadores tumorais e estromais em 28 tumores neuroblásticos periféricos. MÉTODOS: Examinamos AgNOR, NB84 e sinaptofisina e vários outros marcadores em tecidos tumorais de vinte e oito pacientes com tumors neuroblásticos primários. Tratamento dos pacientes incluiu: cirurgia para o estágio 1, quimioterapia e transplante de medula óssea para a maioria dos pacientes nos estágios 3 e 4. Utilizamos histoquímica, imunohistoquímica e morfometria para avaliar a intensidade e extensão de expressão do AgNOR, NB84 e sinaptofisina, tendo o prognóstico dos pacientes incluído o tempo de sobrevida até a morte por recurrência dos tumores neuroblásticos. RESULTADOS: Estadiamento (p<0.01), AgNOR (p<0.01), NB84 (p<0.01) e sinaptofisina (p=0.01) foram marcadores independents de sobrevida. CONCLUSÕES: A determinação dos marcadores NB84 e sinaptofisina mostrou-se como uma ferramenta útil no diagnóstico dos tumors neuroblásticos periféricos; a associação desses marcadores à expressão de AgNOR pelas células tumorais contribuiu à determinação do prognóstico e estabelecimento do protocolo terapêutico para os pacientes.

Coleta e preservação do líquido pleural e biópsia pleural / Collection and preservation of the pleural fluid and pleural biopsy

As amostras de líquido pleural obtidas por toracocentese para o diagnóstico de transudatos e exsudatos devem obedecer a uma rotina de coleta e preservação para a realização de uma análise laboratorial adequada. Igualmente, fragmentos de biópsia de pleura obtidos para o diagnóstico diferencial dos exsudatos devem ser coletados de forma sistemática com o objetivo de otimizar o diagnóstico e facilitar a instituição da terapêutica adequada.

The samples of pleural fluid obtained by thoracentesis for the diagnosis of transudates and exudates shall follow a routine of collection and preservation for an appropriate laboratorial analysis. Equally, fragments of pleura biopsy obtained for the differential diagnosis of the exudates should be collected in a systematic way in order to optimize the diagnosis and facilitate the institution of appropriate therapeutics actions.