The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

Circular RNA (circRNA) is a novel class of single-stranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.

Hipervitaminosis B12: Nuestra experiencia y una revisión / Hypervitaminosis B12. Our experience and a review

Los altos niveles de vitamina B12 o cobalamina, también denominado hipervitaminosis B12 es una anormalidad analítica frecuentemente subestimada. De acuerdo con la literatura algunas de las entidades relacionadas con este hallazgo son las neoplasias sólidas (primarias o metastásicas) y las enfermedades hematológicas agudas o crónicas. Otras causas incluyen la afección hepática, la gammapatía monoclonal de significación indeterminada, la insuficiencia renal y, con menor frecuencia, un exceso de consumo de vitamina B12, enfermedades inflamatorias o autoinmunes y los trastornos hematológicos transitorios (neutrofilia y eosinofilia secundaria). Este artículo informa sobre causas de hipervitaminosis B12, nuestra experiencia y hace una revisión de la literatura.

High serum levels of vitamin B12 or cobalamin, also called hypervitaminemia B12, is a frequently underestimated biological abnormality. According to the literature, some of the entities related to this finding are solid neoplasia (primary or metastatic) and acute or chronic hematological diseases. Other causes include liver disorders, monoclonal gammapathy of undetermined significance, renal failure and, less frequently, excess of vitamin B12 intake, inflammatory or autoimmune diseases, and transient hematological disorders (neutrophilia and secondary eosinophilia). This article reports on causes of hypervitaminosis B12, our experience and a review of the literature.

Low Levels of High-density Lipoprotein in Patients with Pediatric Cancer at Diagnosis / Baixos Níveis de Lipoproteínas de Alta Densidade em Pacientes com Câncer Infantojuvenil ao Diagnóstico / Bajos Niveles de Lipoproteínas de Alta Densidade en Pacientes con Cáncer Juvenil en el Momento del Diagnóstico

Introduction: Cancer patients have metabolic imbalances due to the disease, treatment and their complications. Increases in triglycerides and glucose profile and catabolism of protein have been described and are associated with inflammatory response as result of the tumor activity or necrosis. Objective: To evaluate the blood lipid, lipoproteins, glucose and albumin levels in pediatric cancer patients at diagnosis. Method: Observational cross-sectional study. The inclusion criteria were children and adolescents with newly diagnosed malignancies and blood analysis results. The exclusion criteria were: previous anticancer therapy or surgical treatment, blood sample not collected and patients who refused to participate in the study. Results: It were evaluated 81 children and adolescents with newly diagnosed malignancies. There was decrease of 56% and 41% of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), 14% and 10% of albumin and glucose, and 10% and 7.6% of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), respectively, for the patients. HDL-C showed statistical differences between solid and hematological cancer patients (p < 0.05). The means and medians of albumin, glucose, HDL-C and TG demonstrated that hematological patients are more prone to metabolic disturbances. HDL-C in this group was 24 ± 12 versus 40 ± 15mg/dl in other cancers. Conclusion: The primary result found in the present study was in HDL-C, mainly in patients with hematological and metastatic cancer. These disturbances could be associated with cancer-related acute inflammatory response.

Introdução: Pacientes com câncer apresentam desequilíbrios metabólicos em virtude da doença, do tratamento e de suas complicações. Alterações nos triglicerídeos, perfil de glicose e catabolismo de proteínas foram descritas e estão associadas à resposta inflamatória por conta da atividade tumoral ou necrose. Objetivo: Avaliar os níveis de lipídios no sangue, lipoproteínas, glicose e albumina em pacientes com câncer infantojuvenil no momento do diagnóstico. Método: Estudo observacional transversal. Os critérios de inclusão foram crianças e adolescentes com neoplasias recém-diagnosticadas e resultados de exame de sangue; e os critérios de exclusão, terapia anticâncer ou tratamento cirúrgico prévio, amostra de sangue não coletada e pacientes que se recusaram a participar do estudo. Resultados: Foram avaliadas 81 crianças e adolescentes com neoplasias recém-diagnosticadas. Houve decréscimo de 56% e 41% para lipoproteína de alta densidade-colesterol (HDL-C) e triglicerídeos (TG), 14% e 10% para albumina e glicose e 10% e 7,6% para colesterol total (CT) e colesterol de lipoproteína de baixa densidade (LDL-C), respectivamente. O HDL-C mostrou diferenças estatísticas entre pacientes com câncer sólido e hematológico (p <0,05). As médias e medianas de albumina, glicose, HDL-C e TG demonstraram que pacientes com tumores hematológicos são mais propensos a distúrbios metabólicos. O HDL-C neste grupo foi de 24 ± 12 versus 40 ± 15 mg /dl em outros cânceres. Conclusão: A principal alteração encontrada no presente estudo foi no HDL-C, principalmente em pacientes com câncer hematológico e metastático. Essas alterações podem estar associadas à resposta inflamatória aguda relacionada ao câncer.

Introducciòn: Los pacientes con cáncer tienen desequilibrios metabólicos debido a la enfermedad, el tratamiento y sus complicaciones. Los cambios en los triglicéridos y el perfil de glucosa y el catabolismo de las proteínas se han descrito y están asociados con la respuesta inflamatoria debido a la actividad tumoral o la necrosis. Objetivo: Evaluar los niveles de lípidos, lipoproteínas, glucosa y albúmina en sangre en pacientes con cáncer juvenil en el diagnóstico. Método: Estudio transversal observacional. El criterio de inclusión fue niños y adolescentes con neoplasias recién diagnosticadas con análisis de sangre realizado. Criterios de exclusión: terapia anticancerígena previa o tratamiento quirúrgico, muestra de sangre no realizada y pacientes que se negaron a participar en el estudio del protocolo. Resultados: Se evaluaron 81 niños y adolescentes con neoplasias recién diagnosticadas. Se observó un cambio en 56% y 41% para el colesterol de lipoproteínas de alta densidad (HDL-C) y triglicéridos (TG), 14% y 10% para albúmina y glucosa, y 10% y 7,6% para colesterol total (TC) y colesterol de lipoproteínas de baja densidad (LDL-C), respectivamente. HDL-C mostró diferencias entre pacientes con cáncer sólido y hematológico (p <0.05). Las medias y medianas de albúmina, glucosa, HDL-C y TG demostraron que el grupo hematológico tienden a alteraciones metabólicas más importantes. El HDL-C en este grupo fue de 24 ± 12 versus 40 ± 15 mg / dl en otros tipos de cáncer. Conclusión: El cambio primario encontrado en el presente estudio fue en HDL-C, principalmente en pacientes con cáncer hematológico y metastásico. Estos cambios podrían estar asociados con la respuesta inflamatoria aguda relacionada con el cáncer.

Mutaciones en JAK2, MPL y CALR en neoplasias mieloproliferativas: análisis de disociación de alta resolución / Mutations in JAK2, MPL and CALR in myeloproliferative neoplasms: High Resolution Melting analysis / Mutações em JAK2, MPL e CALR em neoplasias mieloproliferativas: análise de dissociação em alta resolução

La policitemia vera (PV), la trombocitemia esencial (TE) y la mielofibrosis idiopática (MI) constituyen las Neoplasias Mieloproliferativas cromosoma Filadelfia negativas (NMP Ph-neg). La mutación V617F en el exón 14 del gen JAK2 ha sido descripta en un 90% de los casos de PV y en un 50% de TE y MI. Recientemente, se identificaron mutaciones en el exón 10 del gen MPL y en el exón 9 del gen CALR, presentes en un 5 y 73% de pacientes con TE y MI sin mutaciones en JAK2, respectivamente. En el presente trabajo se estudió la detección de dichas mutaciones en 52 pacientes con NMP, mediante amplificaciones por PCR en Tiempo Real con posterior análisis por High Resolution Melting (HRM) y secuenciación. La mutación V617F en JAK2 fue registrada en un 83,3% de pacientes con PV y 42,8% con TE y MI. Un 6,25% y 56,25% de pacientes con TE y MI JAK2 negativos resultaron positivos para mutaciones en el exón 10 de gen del receptor de la trombopoyetina (MPL) y el exón 9 de gen de la calreticulina (CALR). El análisis por HRM puede ser considerado como herramienta diagnóstica eficaz para las NMP debido a su alta sensibilidad, bajo costo y tiempo de procesado, teniendo en cuenta el impacto clínico que podría tener en los pacientes la detección temprana de dichas mutaciones.

Polycythemia vera (PV), essential thrombocythemia (TE) and idiopathic myelofibrosis (MI) are Philadelphia chromosome-negative myeloproliferative neoplasms (MPN-Ph. Neg). The presence of the V617F mutation in exon 14 of the JAK2 gene has been described in 90% of cases of PV and 50% of MI and TE. Recently, mutations in exon 10 of the MPL gene and exon 9 of CALR gene have been identified, which are present in 5 to 73% of patients with TE and MI without mutations in JAK2, respectively. In this work, the detection of these mutations was studied in 52 patients with NMP, using real time PCR amplifications with subsequent High Resolution Melting (HRM) analysis and sequencing. A total of 83.3% of patients with PV and 42.8% with MI and TE were recorded as positive for the V617F mutation in JAK2. A total of 6.25% and 56.25% of the patients with MI and TE with non-mutated JAK2 were positive for mutations in MPL exon 10 and CALR exon 9. HRM analysis could be considered an effective diagnostic tool for NMP due to its high sensitivity, low cost and processing time, taking into account the clinical impact that early detection of such mutations could have on patients.

Policitemia vera (PV), trombocitemia essencial (TE) e mielofibrose idiopática (MI) constituem as Neoplasias Mieloproliferativas cromossomo Filadélfia negativas (NMP Ph-neg). A mutação V617F no exon 14 do gene JAK2 foi descrita em 90% dos casos de PV e em 50% de TE e MI. Recentemente, foram identificadas mutações no exon 10 do gene MPL e no exon 9 do gene CALR, presentes em 5 a 73% de pacientes com TE e MI sem mutações em JAK2, respectivamente. Neste trabalho foi estudada a detecção de tais mutações em 52 pacientes com NMP, usando amplificações por PCR em Tempo Real, com posterior análise por High Resolution Melting (HRM) e sequenciamento. 83,3% dos pacientes com PV e 42,8% com TE e MI foram positivos para a mutação V617F em JAK2. 6,25% e 56,25% de pacientes com TE e MI JAK2 negativo foram positivos para mutações no exon 10 de gene do receptor da trombopoietina (MPL) e o exon 9 de gene da calreticulina (CALR). A análise por HRM pode ser considerada como ferramenta de diagnóstico eficaz para as NMP, devido à sua alta sensibilidade, baixo custo e tempo de processamento, tendo em conta o impacto clínico que poderia ter a detecção precoce de tais mutações nos pacientes.

Biomarkers as predictors of mortality in critically ill patients with solid tumors

ABSTRACT Biochemical markers produced by the affected organ or body in response to disease have gained high clinical value due to assess disease development and being excellent predictors of morbidity and mortality. The aim of this study is to analyze different biochemical markers in critically cancer patients and to determine which of them can be used as predictors of mortality. This is a prospective, cross-sectional study conducted at a University Hospital in Porto Alegre - RS. Screening was done to include patients in the study. Serum biochemical markers obtained in the first 24 hours of Intensive Care Unit hospitalization were analyzed. A second review of medical records occurred after three months objected to identify death or Unit discharged. A sample of 130 individuals was obtained (control group n = 65, study group n = 65). In the multivariate model, serum magnesium values ​​OR = 3.97 (1.17; 13.5), presence of neoplasia OR = 2.68 (95% CI 1.13; 6.37) and absence of sepsis OR = 0.31 (95% CI 0.12; 0.79) were robust predictors of mortality. The association of solid tumors, sepsis presence and alteration in serum magnesium levels resulted in an increased chance of mortality in critically ill patients.

Eritrosedimentación extremadamente elevada en una población de adultos en la ciudad de Buenos Aires / Extremely elevated erythrosedimentation in an adult population in the City of Buenos Aires

Resumen Introducción: Una velocidad de eritrosedimentación (VHS) extremadamente elevada, definida como mayor o igual a 100 mm/h, se ha asociado a condiciones graves subyacentes como enfermedades infecciosas, enfermedades del colágeno u oncológicas. Objetivo: Analizar un grupo de pacientes para determinar los diagnósticos de base y las características que se asocian con valores de VHS mayores a 100 mm/h en nuestro medio. Pacientes y Métodos: Estudio tipo observacional de corte transversal, con recolección retrospectiva de datos de pacientes adultos con al menos un valor de VHS mayor o igual a 100 mm/h, registrado en el laboratorio entre enero de 2002 y agosto de 2014 en el Hospital Italiano de Buenos Aires. Resultados: Durante el período evaluado se analizaron 879 pacientes mayores de 18 años. La mediana de los valores de VHS fue 111 mm/h (Rango intercuartil 105-120). La etiología prevalente de VHS elevada fueron las enfermedades infecciosas (41,6%), seguida de malignidad (21,6%) y de autoinmune/inflamatoria (12,9%). El diagnóstico individual más frecuente fue el de neumonía (11,4%), seguido por causa indeterminada (5,9%). Conclusión: En pacientes internados, la causa más frecuente de VHS ≥ 100 mm/h fue las enfermedades infecciosas, mientras que en pacientes ambulatorios la causa más frecuente fue la malignidad.

Background: An extremely elevated erythrosedimentation rate (ESR), defined as equal or higher than 100 mm/h, has been linked to serious underlying conditions, such as infections, connective tissue and oncologic disease. Aim: To analyze a group of patients in order to determine the underlying diagnosis and the characteristics associated with extremely elevated ESR in our environment. Methods: Cross-sectional study of adult patients, who presented with at least one ESR equal or higher than 100 mm/h at Hospital Italiano, in Buenos Aires (Buenos Aires, Argentina) between January 2002 and August 2014. Results: During the previously stated period of time, we analyzed the results of 879 patients. All patients were over 18 years of age. The median for the ESR results was 111 mm/h (interquartile range 105-120). The most prevalent etiology of an elevated ESR was infectious (41.64%), followed by malignancies (21.62%) and autoimmune / inflammatory diseases (12.97%). The most frequent individual diagnosis found was pneumonia (11.49%), followed by undetermined causes (5.92%). Conclusion: When comparing inpatient versus outpatient populations, the most frequent cause was infectious in the former group, while malignancies were the most frequent diagnosis in the latter.

Hemangioma: descrição de um caso clínico e sua importância no diagnóstico diferencial / Hemangioma: description of a clinical case and the importance in the differential diagnosis

O hemangioma infantil é um tumor vascular benigno que ocorre devido a uma proliferação anormal dos vasos sanguíneos. O quadro clínico apresenta três fases bem definidas: proliferativa, involutiva e involuída. O diagnóstico é realizado basicamente por meio da anamnese e do exame físico, e quando necessário preconiza-se avaliação histopatológica. O presente trabalho, descreve um caso clínico de um hemangioma presente em um bebê de 3 meses de idade que foi, de principio, diagnosticado como mucocele ou fibroma. A cirurgia excisional foi realizada eo material encaminhado para análise histopatológica, confirmando o diagnóstico de hemangioma. Nessas situações, vale ressaltar a importância do diagnostico diferencial, manobra cirúrgica adequada e a avaliação das características clínicas da lesão para evitar possíveis complicações cirurgicas.

The infantile hemangioma is a benign vascular tumor which occurs due to an abnormal proliferation of blood vessels. The clinical features three well-defined phases: proliferative, involution,and involuted. The diagnosis is made primarily by clinical history and physical examination, but when necessary, help to close the histopathological diagnosis. This paper describes a clinical case of a gift hemangioma in a baby three months old who was, in principle, diagnosed as mucocele or fibroma. The excisional surgery was performed and material sent for histopathological confirmation hemangioma. It is worth emphasizing the importance of differential diagnosis, appropriate surgical maneuver, assessment of clinical characteristics of the lesion to prevent potential surgical complications possible.

Association of serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-α) with diagnosis of delirium in oncology inpatients

Objective:To evaluate brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) blood levels as disease biomarkers of delirium in oncology inpatients.Methods:Seventeen oncology inpatients with delirium, 28 oncology inpatients without delirium, and 25 non-oncology controls (caregivers) were consecutively recruited from a Brazilian cancer center. This sample was matched by age, sex, and education level. The Confusion Assessment Method, the Mini-Mental State Examination, and the Digit Span Test were administered to ascertain delirium diagnosis. BDNF and TNF-α levels were measured by the Sandwich-ELISA method and flow cytometry, respectively. Blood samples were collected immediately after clinical evaluation.Results:Oncology inpatients (with and without delirium) showed significantly lower BDNF levels compared with non-oncology controls (F = 13.830; p = 0.001). TNF-α levels did not differ between the three groups.Conclusion:A cross-sectional relationship of BDNF and TNF-α blood levels with delirium in oncology inpatients was not demonstrated. The association between cancer and reduced serum BDNF levels may be mediated by confounding factors.

Self-rated health in Brazilian adults and elderly: Data from the National Household Sample Survey 2008 / Percepción de la salud en adultos y ancianos brasileños: datos de la Encuesta Nacional de Hogares 2008

Objective. To investigate prevalence of poor self-rated health and its association with individual and household-level characteristics among adults and elderly in Brazil. Materials and methods. Cross-sectional study with Brazilian National Household Sample Survey 2008 (n=257 816). Crude and multilevel-adjusted Poisson regression models were fitted. Results. After adjusted analysis, poor self-rated health was significantly associated with higher household income, living alone, not having piped water nor garbage collection, lower education, not having health insurance, female sex, higher age, being a current or previous smoker, physical inactivity, having chronic diseases, having physical impairment. Subjects living in rural areas also had higher prevalence of poor self-rated health. The factors most strongly associated with the outcome were physical impairment and reporting three or more chronic diseases. Conclusions. Socioeconomic, health related behaviors, and physical health were associated with poor self-rated health.

Objetivo. Investigar la prevalencia de la percepción negativa de salud y su asociación con características individuales a nivel de los hogares en adultos y adultos mayores de Brasil. Material y métodos. Estudio transversal con datos de la Encuesta Nacional de Hogares de 2008 (n=257 816). Se estimaron modelos de regresión de Poisson multinivel crudos y ajustados. Resultados. Después del análisis ajustado, la autopercepción negativa de salud se asoció significativamente con mayor ingreso, vivir solo, no tener agua corriente ni recolección de basura, baja educación, carecer de seguro de salud, sexo femenino, mayor edad, tabaquismo, inactividad física, enfermedades crónicas y deterioro físico. Los habitantes de zonas rurales también tuvieron mayor prevalencia de percepción negativa. Los factores más fuertemente asociados fueron impedimento físico y presentación de tres o más enfermedades crónicas. Conclusiones. Factores socioeconómicos, comportamientos relacionados con la salud y salud física se asociaron con la percepción negativa.

Effect of socioeconomic status on the association between air pollution and mortality in Bogota, Colombia / Efecto del nivel socioeconómico sobre la asociación entre contaminantes atmosféricos y mortalidad en Bogotá, Colombia

Objective. To evaluate the modification effect of socioeconomic status (SES) on the association between acute exposure to particulate matter less than 10 microns in aerodynamic diameter (PM10) and mortality in Bogota, Colombia. Materials and methods. A time-series ecological study was conducted (1998-2006). The localities of the cities were stratified using principal components analysis, creating three levels of aggregation that allowed for the evaluation of the impact of SES on the relationship between mortality and air pollution. Results. For all ages, the change in the mortality risk for all causes was 0.76% (95%CI 0.27-1.26) for SES I (low), 0.58% (95%CI 0.16-1.00) for SES II (mid) and -0.29% (95%CI -1.16-0.57) for SES III (high) per 10µg/m³ increment in the daily average of PM10 on day of death. Conclusions. The results suggest that SES significantly modifies the effect of environmental exposure to PM10 on mortality from all causes and respiratory causes.

Objetivo. Evaluar el efecto modificador del nivel socioeconómico (NSE) sobre la asociación entre la exposición aguda a partículas menores de 10 micras de diámetro aerodinámico (PM10) y la mortalidad en Bogotá, Colombia. Material y métodos. Se realizó un estudio ecológico de series de tiempo (1998-2006). Mediante análisis de componentes principales se estableció una estratificación de las localidades de la ciudad, de lo que se generaron tres niveles de agregación que permitieron evaluar el impacto de la variable NSE en la relación mortalidad-contaminación atmosférica. Resultados. En todas las edades, para la mortalidad por todas las causas, el porcentaje de cambio en el riesgo fue 0.76% (IC95% 0.27-1.26) en el NSE I (bajo), 0.58% (IC95% 0.16-1.00) en el NSE II (medio) y -0.29% (IC95% -1.16-0.57) en el NSE III (alto), por incremento de 10µg/m³ en el promedio diario de PM10 en el día del deceso. Conclusiones. Los resultados sugieren que el NSE modifica de manera significativa el efecto de la exposición ambiental a PM10 sobre la mortalidad por todas las causas y causas respiratorias.

Efficacy of Ferric Carboxymaltose in Anaemia of Malignancy - A Pilot Study.

Anaemia is an important problem in malignancy. It may be due to chronic causes like malnutrition, marrow infiltration, associated renal or endocrine disorders and it may be complicated with blood loss. Measures like blood transfusion, erythropoietin injections often pose a logistical problem. Parenteral iron injections have proved to be useful in fighting anaemia in some chronic conditions e.g. patients on hemodialysis. Aims and Objectives: Primarily to see the observable change in hemoglobin (Hb) level with ferric carboxymaltose (FCM) in treating patients of malignancy on anti-cancer treatment. Materials and Methods: Twenty seven patients were enrolled for this study who were suffering from various malignancies. The baseline Hb level was estimated and FCM injection was administered as per the schedule of 500 mg intravenously (IV) weekly once. The overall results of increase in Hb level was noted during the middle of the treatment (chemotherapy or radiotherapy) and later 3-4 weeks after treatment completion. The results were analysed using SPSS and the mean values of initial Hb and after treatment were analysed. Level of significance (p value) was noted using t test. Results: In 27 patients the mean initial Hb level was 8.09 g/dl before treatment which increased to 10.28 g/dl after FCM treatment (p <0.0001). Conclusion: Treatment with FCM definitely led to a significant increase in Hb level in patients of malignancy undergoing treatment. However, further detailed study is needed to establish its definite role in improving the body iron parameters.

dilemma of serum tumor marker [STM] flares

Serum tumor marker [STM] estimation is often used in clinical practice in monitoring response to treatment and as a predictor of treatment failure and relapse. However, there are pitfalls in interpretation, particularly in the immediate post treatment period, when a rise in titre could be observed, the phenomenon being termed as [flare]. A literature search was done to examine this phenomenon for some of the commonly used serum tumor markers in malignancies. This phenomenon has been documented with respect to AFP, beta HCG, CEA, AC 15.3, PSA, CA 19.9 and CA 125 with or without other evidence of progression. Based on this review, a practical approach is suggested so that the clinician is not misled into changing a potentially effective treatment regime. A practical approach would be to correlate serum tumor marker values with other clinical and radiological parameters, and not to rely exclusively on serum marker values to guide therapy

Optimal Time to Start Peripheral Blood Stem Cell Collection in Children with High-Risk Solid Tumors

In order to clarify the optimal timing for peripheral blood stem cell (PBSC) collection, PBSC collection records of 323 children who were scheduled to undergo autologous stem cell transplantation from two study periods differing in the timing of PBSC collection were analyzed. In the early study period (March 1998 to August 2007, n=198), PBSC collection was initiated when the peripheral WBC count exceeded 1,000/microL during recovery from chemotherapy. Findings in this study period indicated that initiation of PBSC collection at a higher WBC count might result in a greater CD34+ cell yield. Therefore, during the late study period (September 2007 to December 2012, n=125), PBSC collection was initiated when the WBC count exceeded 4,000/microL. Results in the late study period validated our conclusion from the early study period. Collection of a higher number of CD34+ cells was associated with a faster hematologic recovery after transplant in the late study period. Initiation of PBSC collection at WBC count > 4,000/microL was an independent factor for a greater CD34+ cell yield. In conclusion, PBSC collection at a higher WBC count is associated with a greater CD34+ cell yield, and consequently a faster hematologic recovery after transplant.

Cell-free DNA concentration and integrity as a screening tool for cancer.

AIM OF THE STUDY: This study aims to evaluate cell-free DNA (CFDNA) concentration and integrity in patients with malignant and nonmalignant diseases and in controls to investigate their value as a screening test for cancer, and to correlate them with clinicopathological parameters of cancer patients. MATERIALS AND METHODS: The study included three groups; group I: 120 cancer patients, group II: 120 patients with benign diseases and group III: 120 normal healthy volunteers as control. One plasma sample was collected from each subject. CFDNA was purified from the plasma then its concentration was measured and integrity was assessed by PCR amplification of 100, 200, 400, and 800 bp bands. RESULTS: There was a highly significant difference in CFDNA levels between cancer group and each of benign and control groups. AUC of ROC curve for cancer group versus normal and benign groups were 0.962 and 0.895, which indicated the efficiency of CFDNA as a marker of cancer. As for integrity, normal and benign subjects showed only two bands at 100 and 200 bp, while all cancer patients demonstrated the 400 bp band and 78% of them had the 800 bp whose presence correlated with vascular invasion. CONCLUSION: The combined use of CFDNA concentration and integrity is a candidate for a universal screening test of cancer. Upon setting suitable boundaries for the test it might be applied to identify cancer patients, particularly among subjects with predisposing factors. Being less expensive, CFDNA concentration could be applied for mass screening and for patients with values overlapping those of normal and benign subjects, the use of the more expensive, yet more specific, integrity test is suggested.

Evaluation of blood Bisphenol A contents: a case study / Evaluación de las concentraciones de Bisfenol A en la sangre: estudio de caso

OBJECTIVE: It has been recently reported that Bisphenol A (BPA) may leach out into food, beverages and water samples from the plastic ware in which it is stored. Serious health hazards have been reported from BPA. The purpose of this study is to assess the BPA contents in blood and to assess the risk of cancer. METHOD: A total of 100 individuals were selected for study according to the following five age groups: 5-10, 11-20, 21-30, 31-40 and 41-50 years. They were then further divided into normal and diseased. Age, gender, education, source of drinking water, type of food, smoking habit, any exposure to chemicals and history of cancer were elicited during interview. Blood samples were collected and processed for analysis using reversed phase-high performance liquid chromatography (rp-HPLC) in isocratic mode. The mobile phase consisted of acetonitrile and water (1:1) at a flow-rate of 1 ml min-1. RESULTS: Bisphenol A contents found in blood samples of all age groups ranged from 1.53-3.98 (mean = 2.94, SD = 0.9). P-values, for the exposed people and those having a history of cancer, were < 0.05 showing a significant relationship between BPA and cancer. The United States Environmental Protection Agency (US EPA) has established a reference dose of 50 µg/L. Odd ratios and relative risk for smoking habit were < 1 while for all others they were > 1. CONCLUSION: It was concluded from the study that people using bottled water, packaged food, having a history ofcancer and who had been exposed to any type ofchemicals are at higher risk ofdisease.

OBJETIVO: Se ha reportado recientemente que el bisfenol A (BPA) puede filtrarse a alimentos, bebidas y agua, a partir de los recipientes plásticos en que aquellos se almacenan. En tal sentido, se han reportado serios casos de riesgo para la salud a causa del BPA. El propósito de este estudio es evaluar la concentración de BPA en sangre, y el consiguiente riesgo de enfermedades cancerosas. MÉTODO: Un total de 100 individuos fueron seleccionados para el estudio, de acuerdo con los siguientes cinco grupos etarios: 5-10, 11-20, 21-30, 31-40 y 41-50 años. Dichos grupos fueron divididos entonces sobre la base de sujetos normales frente a enfermos. En la entrevista se tomó nota de la edad, el género, la educación, la fuente de agua potable, el tipo de comida, el hábito de fumar, cualquier exposición a productos químicos, así como la historia de cáncer. Las muestras de sangre fueron recogidas y procesadas para realizar análisis, utilizando cromatografía líquida de alta eficacia de fase reversa (rp-HPLC) en modo isocrático. La fase móvil consistió en acetonitrilo y agua (1:1) con una tasa de flujo de 1 ml min-1. RESULTADOS: Las concentraciones de bisfenol-A halladas en las muestras de sangre de todos los grupos etarios, oscilaron de 1.53 - 3.98 (M = 2.94, SD = 0.9). Los valores P para las personas expuestas y con una historia de cáncer, fueron < 0.05, indicando una relación directa entre el BPA y el cáncer. La Agencia de Protección Ambiental de los Estados Unidos (US EPA) ha establecido una dosis de referencia de 50 µg/L. El cociente de probabilidades (odd ratios) y el riesgo relativo con respecto al hábito de fumar fueron < 1 mientras que para todos los otros casos otros fueron >1. CONCLUSIÓN: A partir del estudio se concluye que las personas que usan agua embotellada, alimentos empaquetados, así como las personas que poseen una historia de cáncer, y los individuos que habían estado expuestos a cualquier tipo de productos químicos, presentan un mayor riesgo de enfermedad.

Clinical and nutritional status of surgical patients with and without malignant diseases: cross-sectional study / Estado clínico e nutricional de pacientes cirúrgicos com e sem doenças malignas: estudo transversal

CONTEXT: Malnutrition is frequently observed in inpatients with malignant diseases and may contribute to longer hospital stays. OBJECTIVE: To compare the nutritional status, lymphocyte count, hemoglobin values and length of hospital stay of patients with and without malignant diseases. METHODS: This comparative study assessed indicators of nutritional status, namely body mass index, recent weight loss, lymphocyte count, hemoglobin and length of hospital stay, of 928 surgical patients with and without malignant diseases (50.2 percent females and 49.8 percent males). The chi-square test was used to compare proportions and the Mann-Whitney test was used to compare continuous measurements between two groups. The significance level was set at 5 percent. RESULTS: Patients with malignant diseases had longer hospital stays (P<0.0001), furthermore, a higher percentage of patients with malignant diseases had body mass index <18.5 (P<0.0001) and experienced recent weight changes (P<0.0002). Lymphocyte count also differed statistically between the groups (P = 0.0131), which lower levels were identified among patients with malignant diseases. CONCLUSION: The lymphocyte count, hemoglobin values and weight loss are important findings of nutritional depletion in patients with malignant diseases.

CONTEXTO: A desnutrição em pacientes com doenças malignas é frequentemente observada durante a hospitalização e pode acarretar num aumento do período de internação. OBJETIVO: Comparar o estado nutricional, valores de linfócitos e hemoglobina e o tempo de internação em pacientes com e sem doenças malignas. MÉTODOS: Estudo comparativo com 928 pacientes cirúrgicos com e sem doenças malignas (50,2 por cento do sexo feminino e 49,8 por cento do sexo masculino), sendo analisados os indicadores do estado nutricional como índice de massa corporal, perda de peso recente, contagem de linfócitos, hemoglobina e o tempo de internação. Foi aplicado o teste qui ao quadrado para comparação de proporções e para a comparação de medidas contínuas entre dois grupos e foi aplicado também o teste de Mann-Whitney, com nível de significância de 5 por cento. RESULTADOS: Os pacientes com doenças malignas ficaram internados por mais tempo (P<0.0001), sendo constatado ainda neste grupo, maior percentual de pacientes com índice de massa corporal <18.5 (P<0.0001) e alteração de peso (P = 0.0002). Na contagem de linfócitos, constatou-se diferença estatística entre os grupos (P = 0,0131), sendo os menores valores encontrados entre os pacientes com doenças malignas (P = 0.01). CONCLUSÃO: A contagem de linfócitos, os valores de hemoglobina e a perda ponderal são achados importantes de depleção nutricional em pacientes com doenças malignas.

Lactate and base deficit are predictors of mortality in critically ill patients with cancer

OBJECTIVE: Cancer patients frequently require admission to intensive care unit. However, there are a few data regarding predictive factors for mortality in this group of patients. The aim of this study was to evaluate whether arterial lactate or standard base deficit on admission and after 24 hours can predict mortality for patients with cancer. METHODS: We evaluated 1,129 patients with severe sepsis, septic shock, or postoperative after high-risk surgery. Lactate and standard base deficit collected at admission and after 24 hours were compared between survivors and non-survivors. We evaluated whether these perfusion markers are independent predictors of mortality. RESULTS: There were 854 hospital survivors (76.5 percent). 24 h lactate .1.9 mmol/L and standard base deficit , -2.3 were independent predictors of intensive care unit mortality. 24 h lactate .1.9 mmol/L and 24 h standard base deficit , -2.3 mmol/Lwere independent predictors of hospital death. CONCLUSION: Our findings suggest that lactate and standard base deficit measurement should be included in the routine assessment of patients with cancer admitted to the intensive care unit with sepsis, septic shock or after highrisk surgery. These markers may be useful in the adequate allocation of resources in this population.

Inspection of the pathophysiology of anemia among children with cancer

The pathophysiologies of cancer-associated anemia has been categorized as being similar to those of anemia of chronic diseases. However, modern studies made for investigating the pathophysiology of anemia among children with cancer refer to obvious differences from that seen in adults. And as it has been confirmed that a defect in erythropoietin production is a principal cause of anemia among adults with solid tumors; it seems that anemia among children with cancer is associated with a decrease in bone marrow erythropoietic activity without a decrease in erythropoietin production. We have measured the values of haemoglobin, serum concentrations of erythropoietin and soluble transferrin receptor among groups of children with cancer undergoing chemotherapy, who have either solid tumors or haematological malignancies, to inspect the pathophysiology of cancer-associated anemia among them; by determining values of erythropoietin and bone marrow response. The study included 54 children all suffering from cancer, their ages varied between 1 and 152 months. Patients was divided into four groups: Tow of them are for patients of cancer-associated anemia [showing haemoglobin values lower than values of reference ranges according to age], one of them is for solid tumors and the other is for haematological malignancies. The other two are control groups [showing haemoglobin values within the reference ranges according to age], one of them is for solid tumers and the other is for haematological malignancies. Our results indicate that anemia among children with cancer undergoing chemotherapy is mainly caused by an intrinsic failure in bone marrow and not by a reduction in erythropoietin production, which means that there is a difference in pathophysiology of anemia among children with cancer from that seen in adults

Serum fucose level in malignant diseases.

We review the present knowledge of serum fucose with special attention to its relation with various malignant diseases. We summarize the role of serum fucose as a useful diagnostic and prognostic marker when used singly or in combination. The purpose of this review is to provide an expert opinion on the practical and applied aspect of serum fucose level in clinical practice and research settings. Our review is based on information from published research studies, library books, and electronic searches through Medline and PubMed. The available published data were used as the basis for recommendations. Each of the subsections concludes to provide information to assist the clinicians and the research scientists make informed decisions.

Possible involvement of granulocyte oxidative burst in Nrf2 signaling in cancer.

The activation process of granulocytes is accompanied by the intense production of reactive oxygen species (ROS). Overproduction of ROS is cytotoxic, damages macromolecules and can lead to the occurrence of lipid peroxidation. Cellular defense against the toxicity of ROS is enhancement of detoxifying enzymes activation. Regulation of many detoxifying enzymes is mediated by the antioxidant response element (ARE) that is located in the promoter region of related genes. In eukaryotes, there are only few transcription factors known to be activated by ROS. One of them is NF-E2-related factor 2 (Nrf2). Normally, Nrf2 is present in the cytoplasm as an inactive Keap1-Nrf2 complex. However, after direct attack by ROS, Nrf2 is released from Keap1 repression and translocated into nucleus where it binds with ARE sequence to initiate gene expression. ROS may also influence nuclear factor-κB (NF-κB) intracellular signaling repressing the Nrf2-ARE pathway at transcriptional level. Since ROS are crucial in granulocyte-mediated tumor cell lysis the induction of NF-κB signaling pathway may be an important mechanism in suppressing the tumor growth.