Concordance between estimated glomerular filtration rate using equations and that measured using an imaging method.

BACKGROUND: Guidelines recommend estimating glomerular filtration rate (GFR) using creatinine-based equations (CBE). AIM: To evaluate the agreement between GFR measured using radionuclide imaging and estimated using creatinine-based equations. MATERIAL AND METHODS: In 421 patients aged 54 ± 17 years (47% women) GFR was estimated using the MDRD-4, CKD-EPI and the body surface adjusted Cockroft Gault equation. GFR was also measured using a radionuclide imaging method with 99mTc-DTPA. The concordance between estimated and measured GFR was calculated using Lin's concordance coefficient and Bland and Altman plots. RESULTS: Average GFR values obtained with CKD-EPI, MDRD-4, body surface adjusted Cockroft Gault equation and 99mTc-DTPA imaging were 75.9 ± 26.6, 76.3 ± 28.8, 77.1 ± 31.6 and 77.9 ± 28.4 ml/min/1.73 m2, respectively. There was no significant difference in means and 29% of participants had a GFR < 60 ml/min/1.73 m2 by CKD-EPI. The correlation was good between equations, but acceptable when compared with the 99mTc-DTPA imaging. The weighted kappa between CBEs was good, but low when comparing CBEs with measured GFR. The Lin's concordance coefficient between estimated and measured GFR was low. CONCLUSIONS: GFR measured by 99mTc-DTPA radionuclide imaging has a low correlation and poor concordance with estimations using CBE.

MLL-rearranged acute myeloid leukemia: Influence of the genetic partner in allo-HSCT response and prognostic factor of MLL 3' region mRNA expression.

OBJECTIVE: MLL gene is involved in more than 80 known genetic fusions in acute leukemia. To study the relevance of MLL partner gene and selected gene's expression, in this work, we have studied a cohort of 20 MLL-rearranged acute myeloid leukemia (AML). METHODS: Twenty MLL-rearranged AML patients along with a control cohort of 138 AML patients are included in this work. By RT-PCR and sequencing, MLL genetic fusion was characterized, and relative gene expression quantification was carried out for EVI1, MEIS1, MLL-3', RUNX1, SETBP1, HOXA5, and FLT3 genes. Risk stratification and association of MLL genetic partner and gene expression to overall survival, in the context of received therapy, were performed. RESULTS: MLLr cohort showed to have an OS more similar to intermediate-risk AML. Type of MLL genetic partner showed to be relevant in allo-HSCT response; having MLLT1 and MLLT3, a better benefit from it. Expression of MLL-3' region, EVI1 and FLT3, showed association with OS in patients undergoing allo-HSCT. CONCLUSION: We show that the MLL genetic partner could have implications in allo-HSCT response, and we propose three genes whose expression could be useful for the prognosis of this leukemia in patients undergoing allo-HSCT: 3' region of MLL, EVI1, and FLT3.

Histopathology of murine toxoplasmosis under treatment with dialyzable leukocyte extract.

BACKGROUND: Dialyzable leukocyte extracts (DLEs) contain molecules smaller than 10 kDa with biological activity in receptor organisms. Primarily, they participate in the regulation of the Th1 immune response, which is essential for the control of several intracellular infections, such as toxoplasmosis. This disease is associated with congenital infection, encephalitis or systemic infections in immunocompromised individuals. The clinical course of this infection fundamentally depends on a well-regulated immune response and timely treatment with the appropriate drugs. OBJECTIVE: The aim of this study was to evaluate the effect of treatment with a leukocyte extract, derived from crocodile lymphoid tissue, on the histopathology and brain parasite load in NIH mice that had been infected with cysts of Toxoplasma gondii (ME-49 strain). METHODS: The treatment was applied during the acute and chronic stages of the infection. Histopathological changes were evaluated in the ileum, liver and spleen at one, four and eight weeks after infection and in the brain at week 8. The parasite load was evaluated by counting the cysts of T. gondii found in the brain. FINDINGS: Compared to the control mouse group, the mice infected with T. gondii and under treatment with DLE showed less tissue damage, mainly at the intestinal, splenic and hepatic levels. In addition, a greater percentage of survival was observed, and there was a considerable reduction in the parasite load in the brain. CONCLUSIONS: The results suggest that DLE derived from crocodile is a potential adjunctive therapy in the conventional treatment of toxoplasmosis.

Tumor microRNA expression profiling identifies circulating microRNAs for early breast cancer detection.

BACKGROUND: The identification of novel biomarkers for early breast cancer detection would be a great advance. Because of their role in tumorigenesis and stability in body fluids, microRNAs (miRNAs) are emerging as a promising diagnostic tool. Our aim was to identify miRNAs deregulated in breast tumors and evaluate the potential of circulating miRNAs in breast cancer detection. METHODS: We conducted miRNA expression profiling of 1919 human miRNAs in paraffin-embedded tissue from 122 breast tumors and 11 healthy breast tissue samples. Differential expression analysis was performed, and a microarray classifier was generated. The most relevant miRNAs were analyzed in plasma from 26 healthy individuals and 83 patients with breast cancer (36 before and 47 after treatment) and validated in 116 healthy individuals and 114 patients before treatment. RESULTS: We identified a large number of miRNAs deregulated in breast cancer and generated a 25-miRNA microarray classifier that discriminated breast tumors with high diagnostic sensitivity and specificity. Ten miRNAs were selected for further investigation, of which 4 (miR-505-5p, miR-125b-5p, miR-21-5p, and miR-96-5p) were significantly overexpressed in pretreated patients with breast cancer compared with healthy individuals in 2 different series of plasma. MiR-505-5p and miR-96-5p were the most valuable biomarkers (area under the curve 0.72). Moreover, the expression levels of miR-3656, miR-505-5p, and miR-21-5p were decreased in a group of treated patients. CONCLUSIONS: Circulating miRNAs reflect the presence of breast tumors. The identification of deregulated miRNAs in plasma of patients with breast cancer supports the use of circulating miRNAs as a method for early breast cancer detection.

Correction: SARS-CoV-2 in the Amazon region: A harbinger of doom for Amerindians.

[This corrects the article DOI: 10.1371/journal.pntd.0008686.].

SARS-CoV-2 in the Amazon region: A harbinger of doom for Amerindians.

As the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic continues to expand, healthcare resources globally have been spread thin. Now, the disease is rapidly spreading across South America, with deadly consequences in areas with already weakened public health systems. The Amazon region is particularly susceptible to the widespread devastation from Coronavirus disease 2019 (COVID-19) because of its immunologically fragile native Amerindian inhabitants and epidemiologic vulnerabilities. Herein, we discuss the current situation and potential impact of COVID-19 in the Amazon region and how further spread of the epidemic wave could prove devastating for many Amerindian people living in the Amazon rainforest.

Characterizing patients with multiple chromosomal aberrations detected by FISH in chronic lymphocytic leukemia.

We analyzed the features of chronic lymphocytic leukemia (CLL) with multiple abnormalities (MA) detected by FISH. A local database including 2095 CLL cases was used and 323 with MA (15.4%) were selected. MA was defined by the presence of two or more alterations (deletions of 13q14 (13q-), 11q22 (11q-), 17p13 (17p-) or trisomy 12 (+12)). The combination of 13q- with 11q- and 13q- with 17p-, accounted for 58.2% of the series, in contrast to 11q- with 17p- (3.7%). Patients carrying MA since diagnosis presented a short time to first therapy(TTFT) (27 months) and overall survival (OS) (76 months). The combinations including 17p- had a shorter OS (58 months) than the ones without 17p- (not reached, p = .002). Patients with a complex-FISH were the ones with worse OS (34 months). MA imply poor prognosis when they emerge at diagnosis, probably due to the high incidence of bad prognosis markers, which may be a reflection of a more complex karyotype.

Concordance between estimated glomerular filtration rate using equations and that measured using an imaging method / Concordancia entre la tasa de filtración glomerular estimada con ecuaciones y aquella medida mediante imágenes

ABSTRACT Background: Guidelines recommend estimating glomerular filtration rate (GFR) using creatinine-based equations (CBE). AIM: To evaluate the agreement between GFR measured using radionuclide imaging and estimated using creatinine-based equations. MATERIAL AND METHODS: In 421 patients aged 54 ± 17 years (47% women) GFR was estimated using the MDRD-4, CKD-EPI and the body surface adjusted Cockroft Gault equation. GFR was also measured using a radionuclide imaging method with 99mTc-DTPA. The concordance between estimated and measured GFR was calculated using Lin's concordance coefficient and Bland and Altman plots. RESULTS: Average GFR values obtained with CKD-EPI, MDRD-4, body surface adjusted Cockroft Gault equation and 99mTc-DTPA imaging were 75.9 ± 26.6, 76.3 ± 28.8, 77.1 ± 31.6 and 77.9 ± 28.4 ml/min/1.73 m2, respectively. There was no significant difference in means and 29% of participants had a GFR < 60 ml/min/1.73 m2 by CKD-EPI. The correlation was good between equations, but acceptable when compared with the 99mTc-DTPA imaging. The weighted kappa between CBEs was good, but low when comparing CBEs with measured GFR. The Lin's concordance coefficient between estimated and measured GFR was low. Conclusions: GFR measured by 99mTc-DTPA radionuclide imaging has a low correlation and poor concordance with estimations using CBE.

ANTECEDENTES: Las guías clínicas recomiendan estimar la tasa de filtración glomerular (TFG) usando ecuaciones basadas en la creatinina sérica. Objetivo: Estudiar la concordancia entre la TFG medida usando un método de imágenes usando radioisótopos y aquella estimada con ecuaciones. MATERIAL Y MÉTODOS: En 421 pacientes de 54 ± 17 años (47% mujeres), la TFG se estimó utilizando las ecuaciones MDRD-4, CKD-EPI y Cockroft Gault ajustada para superficie corporal. La TFG se midió también con una técnica de imágenes usando 99mTc-DTPA. La concordancia entre la estimación y medición se calculó usando el coeficiente de concordancia de Lin y gráficos de Bland y Altman. RESULTADOS: Los promedios de TFG obtenidos con CKD-EPI, MDRD-4, ecuación de Cockroft Gault e imágenes con 99mTc-DTPA fueron 75,9 ± 26,6, 76,3 ± 28,8, 77,1 ± 31,6 y 77,9 ± 28,4 ml/min/1,73 m2, respectivamente. No hubo diferencias significativas en los promedios y el 29% de los participantes tuvo una TFG < 60 ml/min/1,73 m2. La correlación entre las ecuaciones fue buena, pero sólo aceptable cuando se comparó con la medición por imágenes. El kappa ajustado entre las ecuaciones fue adecuado, pero malo cuando se comparó las ecuaciones con la medición por imágenes. El coeficiente de Lin mostró una baja concordancia entre la estimación y medición de TFG. Conclusiones: La concordancia entre la estimación de TFG usando ecuaciones y su medición directa mediante imágenes es baja.

MicroRNA deregulation in triple negative breast cancer reveals a role of miR-498 in regulating BRCA1 expression.

Emerging evidence suggests that BRCA1 pathway contributes to the behavior of sporadic triple negative breast cancer (TNBC), but little is known about the mechanisms underlying this association. Considering the central role that microRNAs (miRNAs) play in gene expression regulation, the aim of this study was to identify miRNAs specifically deregulated in TNBC and investigate their involvement in BRCA1 regulation. Using locked nucleic acid (LNA)-based microarrays, expression levels of 1919 miRNAs were measured in paraffin-embedded tissues from 122 breast tumors and 11 healthy breast tissue samples. Differential miRNA expression was explored among the main subtypes of breast cancer, and 105 miRNAs were identified as specific for triple negative tumors. In silico prediction revealed that miR-498 and miR-187-5p target BRCA1, and these results were confirmed by luciferase reporter assay. While miR-187-5p was found overexpressed in a luminal B cell line, miR-498 was highly expressed in a triple negative cell line, Hs578T, and its expression was negatively correlated with the levels of BRCA1. We functionally demonstrated that miR-498 inhibits BRCA1 in breast cancer cell lines, and showed that inhibition of miR-498 led to reduced proliferation in the triple negative cell line Hs578T. Our results indicate that miR-498 regulates BRCA1 expression in breast cancer and its overexpression could contribute to the pathogenesis of sporadic TNBC via BRCA1 downregulation.

[Frequency of allergy to cow's milk proteins and its association to other allergic diseases in patients of Hospital Infantil de Mexico Federico Gomez]. / Frecuencia de alergia a las proteínas de la leche de vaca y su asociación con otras enfermedades alérgicas en pacientes del Hospital Infantil de México Federico Gómez.

BACKGROUND: The cow's milk protein allergy is the most common food allergy among children under two years and is associated with other atopic diseases. OBJECTIVES: To evaluate cow's milk protein allergy frequency in patients sensitized to them, attended at the consultation of Immunology and Allergy in the Hospital Infantil de México Federico Gómez, and its association with other atopic diseases. MATERIAL AND METHOD: A cross-sectional, analytical and descriptive study that reviewed medical records of patients aged 0-19 years, attended at the consultation of Immunology and Allergy in the Hospital Infantil de México Federico Gómez, from January 2010 to January 2013, sensitized to the cow's milk protein by in vitro or in vivo studies, mediated or not by IgE, to determine its association with other atopic diseases during the course of their clinical evolution. RESULTS: We included 252 patients with symptoms suggestive of cow's milk protein allergy, which was diagnosed only in 15.1% by oral challenge. In relation to respiratory symptoms, about two-thirds of patients had rhinorrhea, nasal obstruction and nasal itching. Regarding gastrointestinal symptoms, about a third had abdominal pain, diarrhea and abdominal distension, being statistically significant. The most common dermatologic symptom, statistically significant, was xerosis. The most frequently associated atopic diseases were food allergy (76.3%), allergic rhinitis (65.8%), asthma (47.4%) and atopic dermatitis (23%). CONCLUSIONS: The cow's milk protein allergy can be associated with other atopic diseases, such as allergy to other foods, allergic rhinitis, asthma and atopic dermatitis.

Antecedentes: la alergia a las proteínas de la leche de vaca es la alergia alimentaria más común entre los niños menores de dos años y se asocia con otras enfermedades atópicas. Objetivo: evaluar la frecuencia de alergia a las proteínas de la leche de vaca en pacientes sensibilizados a las mismas, que acuden a la consulta de Inmunología y Alergia del Hospital Infantil de México Federico Gómez, así como su asociación con otras enfermedades atópicas. Material y método: estudio retrolectivo, analítico y descriptivo en el que se revisaron los expedientes clínicos de pacientes de 0 a 19 años de edad, atendidos en la consulta de Inmunología y Alergia del Hospital Infantil de México Federico Gómez, de enero de 2010 a enero de 2013, sensibilizados a las proteínas de leche de vaca por estudios in vitro o in vivo, mediada o no mediada por IgE, para determinar su asociación con otras enfermedades atópicas durante el curso de su evolución clínica. Resultados: se incluyeron 252 pacientes con síntomas sugerentes de alergia a las proteínas de la leche de vaca, de los que sólo en 15.1% se diagnosticó por reto oral. Con respecto a los síntomas respiratorios, alrededor de 66% de los pacientes manifestó rinorrea, obstrucción y prurito nasales. En cuanto a los síntomas gastrointestinales, cerca de 30% tuvo diarrea y dolor y distensión abdominales, lo que fue estadísticamente significativo. El síntoma dermatológico más frecuente y estadísticamente significativo fue la xerosis. Las enfermedades atópicas asociadas con más frecuencia fueron: alergia alimentaria (76.3%), rinitis alérgica (65.8%), asma (47.4%) y dermatitis atópica (23%). Conclusiones: la alergia a las proteínas de la leche de vaca puede asociarse con otras enfermedades atópicas, como alergia a otros alimentos, rinitis alérgica, asma y dermatitis atópica.

Application of FISH 7q in MDS patients without monosomy 7 or 7q deletion by conventional G-banding cytogenetics: does -7/7q- detection by FISH have prognostic value?

Chromosomal abnormalities are detected in 40-60% of patients with de novo myelodysplastic syndromes (MDS). This study used the FISH technique in 773 patients with de novo MDS without evidence of monosomy 7 (-7) or 7q deletion (7q-) by conventional G-banding cytogenetics (CC) to analyze their prognostic impact by FISH alone. FISH detected -7/7q- in 5.2% of patients. Presence of -7/7q- was associated with shorter overall survival than absence of such aberrations. Our results suggest that FISH 7q could be beneficial in patients with intermediate WHO morphologic risk stratification and no evidence of -7/7q- by CC.

Síndrome de Mounier Kuhn en una paciente de 78 años con fibrosis pulmonar / Mounier Kuhn syndrome in a 78-year-old patient with pulmonary fibrosis

Resumen Se presenta el caso de una mujer de 78 años de edad con fibrosis pulmonar idiopàtica, quien consultó por exacerbación de sus síntomas respiratorios, a quien se le realizan estudios radiológicos, donde se evidencia dilatación de la vía aérea, previamente no descrita, y se realiza diagnóstico de síndrome de Mounier Kuhn. Hasta donde el conocimiento alcanza, es el primer caso reportado en Colombia y la tercera persona de mayor edad reportada en el mundo. Este es un hallazgo incidental, dado que desde el punto de vista fisiopatológico no hay ninguna relación causal entre la fibrosis pulmonar idiopática y el síndrome de Mounier Kuhn. Sin embargo, su presencia puedo afectar aún más el compromiso funcional, dado el eventual colapso de la vía aérea, lo cual puede llevar a intervenciones terapéuticas adicionales, como colocación de stent. (Acta Med Colomb 2017: 42-198-201).

Abstract The case of a 78-year-old woman with idiopathic pulmonary fibrosis who consulted for exacerbation of her respiratory symptoms is presented. Radiologic studies showed dilation of the airway that was not previously described, and for this reason the diagnosis of Mounier Kuhn Syndrome was made. To our knowledge, this is the first case reported in Colombia and the third oldest person reported in the world. This is an incidental finding, since from the pathophysiological point of view there is no causal relationship between idiopathic pulmonary fibrosis and Mounier Kuhn's syndrome. However, its presence may further affect the functional compromise, given the eventual collapse of the airway, which may lead to additional therapeutic interventions, such as stent placement. (Acta Med Colomb 2017: 42-198-201).

Histopathology of murine toxoplasmosis under treatment with dialyzable leukocyte extract

BACKGROUND Dialyzable leukocyte extracts (DLEs) contain molecules smaller than 10 kDa with biological activity in receptor organisms. Primarily, they participate in the regulation of the Th1 immune response, which is essential for the control of several intracellular infections, such as toxoplasmosis. This disease is associated with congenital infection, encephalitis or systemic infections in immunocompromised individuals. The clinical course of this infection fundamentally depends on a well-regulated immune response and timely treatment with the appropriate drugs. OBJECTIVE The aim of this study was to evaluate the effect of treatment with a leukocyte extract, derived from crocodile lymphoid tissue, on the histopathology and brain parasite load in NIH mice that had been infected with cysts of Toxoplasma gondii (ME-49 strain). METHODS The treatment was applied during the acute and chronic stages of the infection. Histopathological changes were evaluated in the ileum, liver and spleen at one, four and eight weeks after infection and in the brain at week 8. The parasite load was evaluated by counting the cysts of T. gondii found in the brain. FINDINGS Compared to the control mouse group, the mice infected with T. gondii and under treatment with DLE showed less tissue damage, mainly at the intestinal, splenic and hepatic levels. In addition, a greater percentage of survival was observed, and there was a considerable reduction in the parasite load in the brain. CONCLUSIONS The results suggest that DLE derived from crocodile is a potential adjunctive therapy in the conventional treatment of toxoplasmosis.