Effector CD4+ T-cell subsets in Takayasu arteritis-differences between the peripheral blood and the aorta.

Takayasu arteritis (TAK) is a granulomatous vasculitis that affects large arteries. T cells are important in TAK pathophysiology as these cells orchestrate granulomatous infiltration in arteries. This study aims to evaluate effector CD4+ T cells in the peripheral blood and the aortic wall of TAK patients and to analyze associations with disease activity and therapy. We performed a longitudinal study including 30 TAK patients and 30 controls. CD3+ T cells, CD3+CD4- T cells, CD4+ T cells, and Th1, Th2, and Th17 cells were evaluated in peripheral blood by flow cytometry, and the expression of CD4, CD8, Tbet, GATA-3, and RORγT was analyzed in the aorta of six patients by immunohistochemistry. TAK patients presented lower CD3+ T cells and CD4+ T cells (P = 0.031 and P = 0.039, respectively) than controls. Patients with active disease and those in remission had higher proportions of Th17 cells than controls (P = 0.016 and P = 0.004, respectively). Therapy for TAK did not result in significant differences concerning CD4+ effector T-cell subpopulations. Disease duration correlated with the number and percentage of Th2 cells (rho = -0.610 and rho = -0.463, respectively) and with Th17 cells (rho = -0.365 and rho = -0.568). In the aorta, the expression of CD8 was higher than CD4, whereas GATA-3, Tbet, and RORγT were expressed in this order of frequency. In conclusion, TAK patients present an increased Th17 response in the peripheral blood regardless of disease activity, whereas in the aortic tissue CD8 cells and the Th2 response were predominant.

Immunoexpression of HER2 pathway related markers in HER2 invasive breast carcinomas treated with trastuzumab.

PURPOSE: We evaluated the immunoexpression of potential markers involved in the HER2 pathway in invasive breast carcinoma with HER2 amplification treated with trastuzumab. METHODS: Samples of ninety patients diagnosed and treated at two public Brazilian hospitals with overexpressed invasive carcinoma between 2009 and 2018 were included. Several markers (Bcl-2, CDK4, cyclin D1, EGFR, IGF1, IGF-1R, MDM2, MUC4, p16, p21, p27, p53, PTEN, RA, TNFα, and VEGF) were immune analyzed in the tumor by immunohistochemistry and then correlated with clinicopathological variables. RESULTS: Tumor sample expression results determined potential markers of good prognosis with statistically significant values: cyclin D1 with a nuclear grade, and recurrence; IGF-1 with tumor size, and death; p16 with a response after treatment; PTEN with a response after treatment, and death. Markers of poor prognosis: p53 with histological, and nuclear grade; IGF-1R with a compromised lymph node. The treatment resistance rate after trastuzumab was 40%; the overall survival was 4.13 years (95% CI 5.1-12.5) and the disease-free survival was 3.6 years (95% CI 5.1-13.1). CONCLUSIONS: The tumor samples profile demonstrated that cyclin D1, IGF-1, p16, and PTEN presented the potential for a good prognosis and p53 and IGF-1R for worse.

Carbapenem-Resistant Pseudomonas aeruginosa Spondylodiscitis Treated with Ceftazidime-Avibactam: A Case Report with Literature Review.

Pyogenic spondylodiscitis (PS) is a highly morbid and potentially fatal bacterial infection with an increasing incidence in recent decades. Its diagnosis and treatment are challenging, especially with the expansion of multidrug- or extensively drug-resistant bacteria. We report a rare case of PS caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) that was treated with ceftazidime-avibactam (C/A). The choice of C/A therapy was based on the patient's bacterial sensitivity profile and intolerance to the initial therapeutic regimen (polymyxin B and meropenem). The total antimicrobial treatment time was seven weeks. The evolution of the clinical course met the cure criteria, which was characterized by remission of signs and symptoms, normalization of inflammatory markers, and radiological improvement over 18 months of clinical follow-up. This is a rare case of CRPA spondylodiscitis that responded to C/A treatment.

Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series.

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified. (Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br]).

Breast microcalcifications: Past, present and future (Review).

Mammary microcalcifications (MCs) are calcium deposits that are considered as robust markers of breast cancer when identified on mammography. MCs are frequently associated with premalignant and malignant lesions. The aim of the present review was to describe the MC types and associated radiological and pathological aspects in detail, provide insights and approaches to the topic, and describe specific clinical scenarios. The primary MC types are composed of calcium oxalate, hydroxyapatite and hydroxyapatite associated with magnesium. The first type is usually associated with benign conditions, while the others remain primarily associated with malignancy. Radiologically, MCs are classified as benign or suspicious. MCs may represent an active pathological mineralization process rather than a passive process, such as degeneration or necrosis. Practical management of breast specimens requires finely calibrated radiological pathological procedures. Understanding the molecular and structural development of MCs may contribute to breast lesion detection and treatment.

Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series / Achados clínicos, radiológicos e de biópsia transbrônquica em pacientes com COVID-19 prolongada: série de casos

ABSTRACT This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified. (Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br])

RESUMO Esta comunicação breve demonstra a correlação de sintomas respiratórios persistentes com achados funcionais, tomográficos e de biópsia pulmonar transbrônquica em pacientes com COVID-19 que tiveram um longo período de acompanhamento. Relatamos uma série de seis pacientes com COVID-19 com acometimento pulmonar que apresentavam dispneia persistente após 4-15 meses da alta. Realizamos biópsias transbrônquicas, e o padrão histopatológico consistentemente demonstrou remodelação peribrônquica com fibrose pulmonar intersticial. Portanto, a biópsia pulmonar pode ser útil na abordagem de pacientes com COVID-19 prolongada, embora o tipo de procedimento, suas indicações precisas e o momento de sua realização ainda não estejam esclarecidos. (Registro Brasileiro de Ensaios Clínicos - ReBEC; número de identificação: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br])

Increase in antimicrobial resistance and emergence of major international high-risk clonal lineages in dogs and cats with urinary tract infection: 16 year retrospective study.

Objectives: To evaluate temporal trends in antimicrobial resistance, over 16 years, in bacteria isolated from dogs and cats with urinary tract infection (UTI) and the clonal lineages of bacteria harbouring critical antimicrobial resistance mechanisms. Methods: Antimicrobial susceptibility testing was conducted for 948 bacteria isolated from dogs and cats with UTI (1999-2014). Resistance mechanisms were detected by PCR, namely ESBL/AmpC in third-generation cephalosporin (3GC)-resistant Escherichia coli and Proteus mirabilis, mecA in methicillin-resistant staphylococci, and aac(6')-Ieaph(2″)-Ia and aph(2″)-1d in high-level gentamicin-resistant (HLGR) enterococci. Resistant bacteria were typed by MLST, and temporal trends in E. coli and Enterobacteriaceae antimicrobial resistance were determined by logistic regression. Results: Enterobacteriaceae had a significant temporal increase in resistance to amoxicillin/clavulanate, 3GCs, trimethoprim/sulfamethoxazole, fluoroquinolones, gentamicin and tetracycline (P < 0.001). An increase in MDR was also detected (P < 0.0001). 3GC resistance was mainly caused by the presence of blaCTX-M-15 and blaCMY-2 in E. coli and the presence of blaCMY-2 in P. mirabilis. Two major 3GC-resistant E. coli clonal lineages were detected: O25b:H4-B2-ST131 and ST648. The mecA gene was detected in 9.2% (n = 11/119) of Staphylococcus spp., including MRSA clonal complex (CC) 5 (n = 2) and methicillin-resistant Staphylococcus epidermidis CC5 (n = 4). A temporal increase in MDR methicillin-resistant Staphylococcus pseudintermedius was detected (P = 0.0069). Some ampicillin-resistant and/or HLGR Enterococcus spp. were found to belong to hospital-adapted CCs, namely Enterococcus faecalis ST6-CC6 (n = 1) and Enterococcus faecium CC17 (n = 8). Conclusions: The temporal increase in antimicrobial resistance and in MDR bacteria causing UTI in dogs and cats creates important therapeutic limitations in veterinary medicine. Furthermore, the detection of MDR high-risk clonal lineages raises public health concerns since companion animals with UTI may contribute to the spread of such bacteria.

Utilização de escore e dosagem de lactato no líquor para diagnóstico diferencial entre meningite bacteriana e meningite asséptica / Use of score and cerebrospinal fluid lactate dosage in differential diagnosis of bacterial and aseptic meningitis

RESUMO Objetivo: Avaliar o Escore para Meningite Bacteriana (EMB) isolado e associado ao valor do lactato no líquor para diferenciar meningite bacteriana (MB) e meningite asséptica (MA). Métodos: Foram selecionadas crianças com meningite atendidas em hospital terciário privado entre janeiro de 2011 e dezembro de 2014. Os dados foram obtidos na admissão. Utilizou-se o EMB com: coloração de Gram no líquor (2 pontos); neutrófilos no líquor ≥1.000 células/mm3 (1 ponto); proteína no líquor ≥80 mg/dL (1 ponto); neutrófilos no sangue periférico ≥10.000 células/mm3 (1 ponto); e convulsão durante/antes da chegada (1 ponto). Analisou-se também o lactato no líquor (elevado: ≥30 mg/dL). Avaliaram-se sensibilidade, especificidade e valor preditivo negativo de diversos valores de corte do EMB e do EMB associado ao lactato elevado para prever MB. Resultados: Dos 439 pacientes elegíveis, 94 não tinham todos os dados necessários para o escore, sendo 345 pacientes selecionados: 7 no grupo de MB e 338 no de MA. Como preditivos de MB, o EMB ≥1 mostrou sensibilidade de 100% (intervalo de confiança de 95% - IC95% 47,3-100), especificidade de 64,2% (58,8-100) e valor preditivo negativo de 100% (97,5-100), enquanto o EMB ≥2 ou EMB ≥1 associado a lactato liquórico ≥30 mg/dL mostrou sensibilidade de 100% (47,3-100), especificidade de 98,5% (96,6-99,5) e valor preditivo negativo de 100% (98,3-100). Conclusões: O EMB com 2 pontos associado à dosagem de lactato no líquor manteve a sensibilidade e o valor preditivo negativo, ao passo que aumentou a especificidade para identificar meningites bacterianas em relação à utilização do EMB com 1 ponto.

ABSTRACT Objective: To evaluate Bacterial Meningitis Score (BMS) on its own and in association with Cerebrospinal Fluid (CSF) lactate dosage in order to distinguish bacterial from aseptic meningitis. Methods: Children diagnosed with meningitis at a tertiary hospital between January/2011 and December/2014 were selected. All data were obtained upon admission. BMS was applied and included: CSF Gram staining (2 points); CSF neutrophil count ≥1,000 cells/mm3 (1 point); CSF protein ≥80 mg/dL (1 point); peripheral blood neutrophil count ≥10,000 cells/mm3 (1 point) and seizures upon/before arrival (1 point). Cutoff value for CSF lactate was ≥30 mg/dL. Sensitivity, specificity and negative predictive value of several BMS cutoffs and BMS associated with high CSF lactate were evaluated for prediction of bacterial meningitis. Results: Among 439 eligible patients, 94 did not have all data available to complete the score, and 345 patients were included: 7 in bacterial meningitis group and 338 in aseptic meningitis group. As predictive factors of bacterial meningitis, BMS ≥1 had 100% sensitivity (95%CI 47.3-100), 64.2% specificity (58.8-100) and 100% negative predictive value (97.5-100); BMS ≥2 or BMS ≥1 associated with high CSF lactate also showed 100% sensitivity (47.3-100); but 98.5% specificity (96.6-99.5) and 100% negative predictive value (98.3-100). Conclusions: 2 point BMS in association with CSF lactate dosage had the same sensitivity and negative predictive value, with increased specificity for diagnosis of bacterial meningitis when compared with 1-point BMS.

USE OF SCORE AND CEREBROSPINAL FLUID LACTATE DOSAGE IN DIFFERENTIAL DIAGNOSIS OF BACTERIAL AND ASEPTIC MENINGITIS. / UTILIZAÇÃO DE ESCORE E DOSAGEM DE LACTATO NO LÍQUOR PARA DIAGNÓSTICO DIFERENCIAL ENTRE MENINGITE BACTERIANA E MENINGITE ASSÉPTICA.

OBJECTIVE: To evaluate Bacterial Meningitis Score (BMS) on its own and in association with Cerebrospinal Fluid (CSF) lactate dosage in order to distinguish bacterial from aseptic meningitis. METHODS: Children diagnosed with meningitis at a tertiary hospital between January/2011 and December/2014 were selected. All data were obtained upon admission. BMS was applied and included: CSF Gram staining (2 points); CSF neutrophil count ≥1,000 cells/mm3 (1 point); CSF protein ≥80 mg/dL (1 point); peripheral blood neutrophil count ≥10,000 cells/mm3 (1 point) and seizures upon/before arrival (1 point). Cutoff value for CSF lactate was ≥30 mg/dL. Sensitivity, specificity and negative predictive value of several BMS cutoffs and BMS associated with high CSF lactate were evaluated for prediction of bacterial meningitis. RESULTS: Among 439 eligible patients, 94 did not have all data available to complete the score, and 345 patients were included: 7 in bacterial meningitis group and 338 in aseptic meningitis group. As predictive factors of bacterial meningitis, BMS ≥1 had 100% sensitivity (95%CI 47.3-100), 64.2% specificity (58.8-100) and 100% negative predictive value (97.5-100); BMS ≥2 or BMS ≥1 associated with high CSF lactate also showed 100% sensitivity (47.3-100); but 98.5% specificity (96.6-99.5) and 100% negative predictive value (98.3-100). CONCLUSIONS: 2 point BMS in association with CSF lactate dosage had the same sensitivity and negative predictive value, with increased specificity for diagnosis of bacterial meningitis when compared with 1-point BMS.

OBJETIVO: Avaliar o Escore para Meningite Bacteriana (EMB) isolado e associado ao valor do lactato no líquor para diferenciar meningite bacteriana (MB) e meningite asséptica (MA). MÉTODOS: Foram selecionadas crianças com meningite atendidas em hospital terciário privado entre janeiro de 2011 e dezembro de 2014. Os dados foram obtidos na admissão. Utilizou-se o EMB com: coloração de Gram no líquor (2 pontos); neutrófilos no líquor ≥1.000 células/mm3 (1 ponto); proteína no líquor ≥80 mg/dL (1 ponto); neutrófilos no sangue periférico ≥10.000 células/mm3 (1 ponto); e convulsão durante/antes da chegada (1 ponto). Analisou-se também o lactato no líquor (elevado: ≥30 mg/dL). Avaliaram-se sensibilidade, especificidade e valor preditivo negativo de diversos valores de corte do EMB e do EMB associado ao lactato elevado para prever MB. RESULTADOS: Dos 439 pacientes elegíveis, 94 não tinham todos os dados necessários para o escore, sendo 345 pacientes selecionados: 7 no grupo de MB e 338 no de MA. Como preditivos de MB, o EMB ≥1 mostrou sensibilidade de 100% (intervalo de confiança de 95% - IC95% 47,3-100), especificidade de 64,2% (58,8-100) e valor preditivo negativo de 100% (97,5-100), enquanto o EMB ≥2 ou EMB ≥1 associado a lactato liquórico ≥30 mg/dL mostrou sensibilidade de 100% (47,3-100), especificidade de 98,5% (96,6-99,5) e valor preditivo negativo de 100% (98,3-100). CONCLUSÕES: O EMB com 2 pontos associado à dosagem de lactato no líquor manteve a sensibilidade e o valor preditivo negativo, ao passo que aumentou a especificidade para identificar meningites bacterianas em relação à utilização do EMB com 1 ponto.

Comparison of enterovirus detection in cerebrospinal fluid with Bacterial Meningitis Score in children.

OBJECTIVE: To measure the role of enterovirus detection in cerebrospinal fluid compared with the Bacterial Meningitis Score in children with meningitis. METHODS: A retrospective cohort based on analysis of medical records of pediatric patients diagnosed as meningitis, seen at a private and tertiary hospital in São Paulo, Brazil, between 2011 and 2014. Excluded were patients with critical illness, purpura, ventricular shunt or recent neurosurgery, immunosuppression, concomitant bacterial infection requiring parenteral antibiotic therapy, and those who received antibiotics 72 hours before lumbar puncture. RESULTS: The study included 503 patients. Sixty-four patients were excluded and 94 were not submitted to all tests for analysis. Of the remaining 345 patients, 7 were in the Bacterial Meningitis Group and 338 in the Aseptic Meningitis Group. There was no statistical difference between the groups. In the Bacterial Meningitis Score analysis, of the 338 patients with possible aseptic meningitis (negative cultures), 121 of them had one or more points in the Bacterial Meningitis Score, with sensitivity of 100%, specificity of 64.2%, and negative predictive value of 100%. Of the 121 patients with positive Bacterial Meningitis Score, 71% (86 patients) had a positive enterovirus detection in cerebrospinal fluid. CONCLUSION: Enterovirus detection in cerebrospinal fluid was effective to differentiate bacterial from viral meningitis. When the test was analyzed together with the Bacterial Meningitis Score, specificity was higher when compared to Bacterial Meningitis Score alone. OBJETIVO: Avaliar o papel da pesquisa de enterovírus no líquido cefalorraquidiano em comparação com o Escore de Meningite Bacteriana em crianças com meningite. MÉTODOS: Coorte retrospectiva, realizada pela análise de prontuários, incluindo pacientes pediátricos, com diagnóstico de meningite e atendidos em um hospital privado e terciário, localizado em São Paulo, entre 2011 e 2014. Foram excluídos os pacientes com doença crítica, púrpura, derivação ventricular ou neurocirurgia recente, imunossupressão, outra infecção bacteriana concomitante que necessitasse de antibioticoterapia parenteral e aqueles que receberam antibiótico 72 horas antes da punção lombar. RESULTADOS: Foram incluídos no estudo 503 pacientes. Destes, 64 foram excluídos e 94 não realizaram todos os exames para análise. Dos 345 pacientes restantes, 7 ficaram no Grupo de Meningite Bacteriana e 338 no Grupo de Meningite Asséptica. Não houve diferença estatística entre os grupos. Na análise do Escore de Meningite Bacteriana, dos 338 pacientes com possível meningite asséptica (culturas negativas), 121 deles tiveram um ou mais pontos para o Escore de Meningite Bacteriana, com valor de sensibilidade de 100%, especificidade de 64,2% e valor preditivo negativo de 100%. Dos 121 pacientes com Escore de Meningite Bacteriana positivo, 71% (86 pacientes) tiveram a pesquisa de enterovírus positiva no líquido cefalorraquidiano. CONCLUSÃO: A pesquisa de enterovírus no líquido cefalorraquidiano mostrou-se eficaz em diferenciar a meningite bacteriana da viral. Analisada junto com o Escore de Meningite Bacteriana, a especificidade foi maior em comparação ao Escore de Meningite Bacteriana isolado.

Comparison of enterovirus detection in cerebrospinal fluid with Bacterial Meningitis Score in children / Comparação da pesquisa de enterovírus no liquor com Escore de Meningite Bacteriana em crianças

ABSTRACT Objective To measure the role of enterovirus detection in cerebrospinal fluid compared with the Bacterial Meningitis Score in children with meningitis. Methods A retrospective cohort based on analysis of medical records of pediatric patients diagnosed as meningitis, seen at a private and tertiary hospital in São Paulo, Brazil, between 2011 and 2014. Excluded were patients with critical illness, purpura, ventricular shunt or recent neurosurgery, immunosuppression, concomitant bacterial infection requiring parenteral antibiotic therapy, and those who received antibiotics 72 hours before lumbar puncture. Results The study included 503 patients. Sixty-four patients were excluded and 94 were not submitted to all tests for analysis. Of the remaining 345 patients, 7 were in the Bacterial Meningitis Group and 338 in the Aseptic Meningitis Group. There was no statistical difference between the groups. In the Bacterial Meningitis Score analysis, of the 338 patients with possible aseptic meningitis (negative cultures), 121 of them had one or more points in the Bacterial Meningitis Score, with sensitivity of 100%, specificity of 64.2%, and negative predictive value of 100%. Of the 121 patients with positive Bacterial Meningitis Score, 71% (86 patients) had a positive enterovirus detection in cerebrospinal fluid. Conclusion Enterovirus detection in cerebrospinal fluid was effective to differentiate bacterial from viral meningitis. When the test was analyzed together with the Bacterial Meningitis Score, specificity was higher when compared to Bacterial Meningitis Score alone.

RESUMO Objetivo Avaliar o papel da pesquisa de enterovírus no líquido cefalorraquidiano em comparação com o Escore de Meningite Bacteriana em crianças com meningite. Métodos Coorte retrospectiva, realizada pela análise de prontuários, incluindo pacientes pediátricos, com diagnóstico de meningite e atendidos em um hospital privado e terciário, localizado em São Paulo, entre 2011 e 2014. Foram excluídos os pacientes com doença crítica, púrpura, derivação ventricular ou neurocirurgia recente, imunossupressão, outra infecção bacteriana concomitante que necessitasse de antibioticoterapia parenteral e aqueles que receberam antibiótico 72 horas antes da punção lombar. Resultados Foram incluídos no estudo 503 pacientes. Destes, 64 foram excluídos e 94 não realizaram todos os exames para análise. Dos 345 pacientes restantes, 7 ficaram no Grupo de Meningite Bacteriana e 338 no Grupo de Meningite Asséptica. Não houve diferença estatística entre os grupos. Na análise do Escore de Meningite Bacteriana, dos 338 pacientes com possível meningite asséptica (culturas negativas), 121 deles tiveram um ou mais pontos para o Escore de Meningite Bacteriana, com valor de sensibilidade de 100%, especificidade de 64,2% e valor preditivo negativo de 100%. Dos 121 pacientes com Escore de Meningite Bacteriana positivo, 71% (86 pacientes) tiveram a pesquisa de enterovírus positiva no líquido cefalorraquidiano. Conclusão A pesquisa de enterovírus no líquido cefalorraquidiano mostrou-se eficaz em diferenciar a meningite bacteriana da viral. Analisada junto com o Escore de Meningite Bacteriana, a especificidade foi maior em comparação ao Escore de Meningite Bacteriana isolado.

O uso adjuvante da imunoglobulina endovenosa no tratamento da sepse neonatal: uma revisão sistemática com metanálise / Adjuvant use of intravenous immunoglobulin in the treatment of neonatal sepsis: a systematic review with a meta-analysis

OBJETIVO: Avaliar se a imunoglobulina endovenosa reduz a mortalidade e o tempo de internação no tratamento da sepse neonatal. FONTES DOS DADOS: A base de dados utilizada foi a MEDLINE. Os descritores, procurados por meio da ferramenta Medical Subject Headings, foram combinados na seguinte estratégia de busca: [(sepsis OR shock, septic OR infection) AND immunoglobulins, intravenous] AND infant, newborn. Apenas ensaios clínicos randomizados de boa qualidade e que avaliaram o efeito da imunoglobulina endovenosa adjuvante no tratamento da sepse neonatal foram selecionados. SÍNTESE DOS DADOS: Foram selecionados sete estudos para análise. Todos os estudos avaliaram a taxa de mortalidade, totalizando 3.756 pacientes. O efeito global desse desfecho revela que não há diferenças significativas entre os grupos avaliados. Apenas cinco estudos avaliaram o tempo médio de internação, contabilizando 3.672 pacientes. Embora o resultado final apresente uma redução estatisticamente significativa de 1,24 dias no tempo de internação no grupo da imunoglobulina endovenosa, essa diferença é clinicamente desprezível, e o alto custo não justifica o seu uso rotineiro na prática médica. Esses dados contradizem a revisão de Ohlsson et al., atualizada em 2010, que demonstrou diferença estatisticamente significativa entre os grupos, tanto no desfecho de mortalidade quanto no tempo médio de internação. CONCLUSÕES: Este estudo conclui que não há diferença significativa na taxa de mortalidade no uso adjuvante da imunoglobulina endovenosa no tratamento da sepse neonatal e que a diferença no tempo de internação é clinicamente desprezível.

OBJECTIVE: To evaluate whether intravenous immunoglobulin reduces mortality and length of hospital stay in the treatment of neonatal sepsis. SOURCES: The MEDLINE database was searched. The keywords were combined using the following search strategy: [(sepsis OR shock, septic OR infection) AND immunoglobulins, intravenous] AND infant, newborn. Only randomized clinical trials (RCTs) showing good methodological quality and assessing the effect of adjuvant intravenous immunoglobulin in the treatment of neonatal sepsis were selected for inclusion and data analysis. SUMMARY OF THE FINDINGS: Seven RCTs were selected. All of them evaluated the mortality rate, including 3,756 patients. The global effect of this outcome showed no statistically significant difference between the groups. Only five studies evaluated the mean length of hospital stay, including 3,672 patients. Although there is a statistically significant reduction of 1.24 days in the length of hospital stay with the use of intravenous immunoglobulin, such difference is clinically irrelevant and its high cost does not warrant its routine use in medical practice. The data reported in the present review contradict the review by Ohlsson et al., which was updated in 2010 and showed significant benefit with the use of intravenous immunoglobulin on both outcomes. CONCLUSIONS: We concluded that the use of adjuvant intravenous immunoglobulin shows no benefit regarding mortality, whereas the reduction in the length of hospital stay is irrelevant.

Adjuvant use of intravenous immunoglobulin in the treatment of neonatal sepsis: a systematic review with a meta-analysis.

OBJECTIVE: To evaluate whether intravenous immunoglobulin reduces mortality and length of hospital stay in the treatment of neonatal sepsis. SOURCES: The MEDLINE database was searched. The keywords were combined using the following search strategy: [(sepsis OR shock, septic OR infection) AND immunoglobulins, intravenous] AND infant, newborn. Only randomized clinical trials (RCTs) showing good methodological quality and assessing the effect of adjuvant intravenous immunoglobulin in the treatment of neonatal sepsis were selected for inclusion and data analysis. SUMMARY OF THE FINDINGS: Seven RCTs were selected. All of them evaluated the mortality rate, including 3,756 patients. The global effect of this outcome showed no statistically significant difference between the groups. Only five studies evaluated the mean length of hospital stay, including 3,672 patients. Although there is a statistically significant reduction of 1.24 days in the length of hospital stay with the use of intravenous immunoglobulin, such difference is clinically irrelevant and its high cost does not warrant its routine use in medical practice. The data reported in the present review contradict the review by Ohlsson et al., which was updated in 2010 and showed significant benefit with the use of intravenous immunoglobulin on both outcomes. CONCLUSIONS: We concluded that the use of adjuvant intravenous immunoglobulin shows no benefit regarding mortality, whereas the reduction in the length of hospital stay is irrelevant.

Efeitos da suplementação aguda de aspartato de arginina na fadiga muscular em voluntários treinados / Effects of the acute arginine aspartate supplement on the muscular fatigue in trained volunteers

A atividade física influi em mecanismos específicos responsáveis pela redução da produção de força e conseqüentemente à fadiga. A preocupação em melhorar o desempenho físico tem sido propostos; observamos que estudos dão atenção para reduzir acúmulos dos metabólitos que diminuem a fadiga durante o exercício físico intenso, usando aminoácidos conhecidos por induzir mudanças metabólicas, entre eles a arginina. O presente estudo teve como objetivo estudar o efeito da suplementação aguda de aspartato de arginina em indivíduos sadios treinados submetidos a um protocolo de exaustão em um cicloergômetro. Foram utilizados 12 indivíduos treinados do sexo masculino, idade de 22,6 ± 3,5 anos. Realizaram três testes 90 minutos após a administração em dose única do aspartato de arginina ou solução placebo, em um cicloergômetro, em que incrementos de cargas foram adicionados até a exaustão. Amostras sanguíneas foram obtidas para análises bioquímicas como: creatinina, uréia, glicose e lactato. Diferenças estatísticas não foram encontradas ao comparar os valores de Freqüência Cardíaca Máxima, Tempo Máximo e Carga Máxima e também ao comparar os resultados anteriores e posteriores ao teste para uréia, creatinina e glicose. As concentrações de lactato (mmol/l) apresentaram diferença estatística ao comparar os valores pré-teste (Controle: 2,2 ± 0,14; Arginina: 2,43 ± 0,23; Placebo: 2,26 ± 0,11) com valores pós-teste (Controle 10,35 ± 0,57; Arginina: 12,07 ± 0,88; Placebo: 12,2 ± 0,96), p < 0,001. Os principais resultados deste estudo indicam que a administração aguda de aspartato de arginina não se mostrou efetiva em aumentar a tolerância à fadiga dos indivíduos avaliados e tratados no protocolo de teste incremental até a exaustão. Assim, podemos concluir que a dose utilizada não foi capaz de aumentar a tolerância à fadiga muscular.

The physical activity influences specific mechanisms responsible by a reduction in the power production, and consequently on the fatigue. It has been proposed premises to improve the physical performance, and we observed that some studies have been focused on the reduction of the metabolites that decrease the fatigue on intense physical exercising, using aminoacids known for their properties to induce to metabolic changes, and among these, it is the arginine. The present study had the purpose to study the effects of the acute arginine aspartate supplement in trained healthy individuals submitted to an exhaustion protocol on ergonomic bicycle. Twelve 22.6 ± 3.5 years old trained individuals were used in the research. After taking a single dose of arginine aspartate or a placebo solution, they performed three 90 minute test on an ergonomic bicycle to which load increments were added up to reaching the exhaustion. The blood samples were obtained through biochemical analysis, such as: creatinine, urea, glycosis, and lactate. It was found no statistical differences upon the comparison of the Maximal Heart Rate, Maximal Time and Load, and also comparing to the previous and later results on the urea, creatinine and glycosis tests. The lactate concentrations (mmol/l) presented statistical differences compared to the pre-test values (Control: 2.2 ± 0.14; Arginine: 2.43 ± 0.23; Placebo: 2.26 ± 0.11) to the post-test values (Control 10.35 ± 0.57; Arginine: 12.07 ± 0.88; Placebo: 12.2 ± 0.96), p < 0.001. The main results found in this study indicate that the acute administration of the arginine aspartate did not show effective to increase the fatigue tolerance in the individuals evaluated and treated in the incremental test protocol up to the exhaustion. Thus, it can be concluded that the dosage used was not able to increase the muscular fatigue tolerance.

La actividad física influencia los mecanismos específicos responsables por la reducción de la producción de fuerza y por consiguiente a la fatiga. La preocupación por mejorar la acción física se ha propuesto constantemente; nosotros hemos observamos que los estudios prestan la atención para reducir acumulaciones del metabólitos que reducen la fatiga durante el intenso ejercicio físico, mientras se usan los aminoácidos conocidos que puedan inducir cambios metabólicos, entre ellos la arginina. El estudio presente tiene como objetivo el analizar los estudios del efecto de la suplementación de aspartato del arginina en individuos saludables sometidos a un protocolo de agotamiento en un cicloergómetro. Se usaron 12 individuos especializados de sexo masculino, de edad de 22,6 ± 3,5 años. Ellos lograron tres pruebas de 90 minutos después de la administración en una sóla dosis del aspartato del arginina o de solución placebo, en un cicloergómetro dónde se incrementaron las cargas hasta el agotamiento. Se obtuvieron las muestras sanguíneas para los análisis bioquímicos como de creatinina, urea, glucosa y lactato. No se encontraron diferencias con las estadísticas al comparar los valores de frecuencia máxima del corazón FMC, Tiempo Máximo y Carga Máxima y también al comparar los resultados anteriores y subsecuentes a la prueba para el urea, creatinina y glucosa. Las concentraciones del lactato (el mmol/l) si, presentaron la diferencia estadística al comparar el pré-prueba de valores (Controles: 2,2 ± 0,14; Arginina: 2,43 ± 0,23; Placebo: 2,26 ± 0,11) con el power-proof de valores (Control 10,35 ± 0,57; Arginina: 12,07 ± 0,88; Placebo: 12,2 ± 0,96), p < 0,001. Los resultados principales de este estudio indican que la administración marcada de aspartato del arginina no fue demostrada aumentando la tolerancia a la fatiga de los individuos estimados y tratados en el protocolo de prueba incremental al agotamiento. Así, podemos concluir que la dosis...