Utilidad de la relación aclaramiento de creatinina - índice de resistencia de la ecografía Doppler renal como predictor de rechazo agudo en riñones trasplantados

ResumenObjetivoAnalizar la utilidad de la asociación del índice de resistencia (IR) en las arterias arcuatas renales con el aclaramiento de creatinina (Cl Cr) para predecir el rechazo agudo del riñón trasplantado.Materiales y métodosSe realizó un estudio prospectivo de una cohorte de 87 pacientes que fueron sometidos a una biopsia renal por alteraciones clínicas de la función renal. Se les midió el IR junto con el Cl Cr mediante el método de modificación de la dieta en la enfermedad renal.ResultadosLa sensibilidad de la asociación IR mayor de 0,7 y Cl Cr 0-30 fue del 53,3% (intervalo de confianza [IC] de 95%: 34,3-71,7%) y la especificidad del 98,2% (95% IC: 90,4-100%). El área bajo la curva fue de 0,758 (95% IC: 0,665-0,85), el likelihood ratio positivo de 22,9 (95% IC: 4,16-214), el likelihood ratio negativo de 0,475 (95% IC: 0,324- 0,685), el odds ratio de 62,9, el valor predictivo positivo de 94,1% (95% IC: 71,3- 99,9%) y el valor predictivo negativo de 79,1% (95% IC: 68,3-88,4%).ConclusiónLa asociación IR mayor de 0,7 y Cl Cr 0-30 demostró ser útil para confirmar la posibilidad de rechazo renal agudo, al tener una buena especificidad (98,2%) a pesar de su baja sensibilidad (53%).AbstractObjectiveTo determine the usefulness of the association between the resistance index (RI) values in renal arcuate arteries and creatinine clearance (Cr Cl) levels in order to predict or detect acute rejection in a kidney transplant patient.Materials and methodsA prospective study was conducted on a cohort of 87 patients who were subjected to a kidney biopsy due to clinical changes in renal function. The RI was measured, and Cr Cl levels determined using the modification of diet in renal disease formula.ResultsThe sensitivity of an RI association higher than 0.7 and a Cr Cl 0-30 was 53.3% (95% confidence interval [CI]: 34.3-71.7%), with a specificity of 98.2% (95% CI: 90.4-100%). The area under the curve was 0.758 (95% CI: 0.665-0.85), the positive and negative likelihood ratio was 22.9 (95% CI: 4.16-214) and 0.475 (95% CI: 0.324-0.685), respectively. The odds ratio was 62.9, and the positive and negative predicted value was 94.1% (95% CI: 71.3-99.9%) and 79.1% (95% CI: 68.3-88.4%), respectively.ConclusionThe RI association higher than 0.7- Cr Cl 0-30 showed to be useful to detect the possibility of acute renal rejection, with its good specificity (98.2%), although with a low sensitivity (53%)

Colour-emotion associations in individuals with red-green colour blindness

Colours and emotions are associated in languages and traditions. Some of us may convey sadness by saying feeling blue or by wearing black clothes at funerals. The first example is a conceptual experience of colour and the second example is an immediate perceptual experience of colour. To investigate whether one or the other type of experience more strongly drives colour-emotion associations, we tested 64 congenitally red-green colour-blind men and 66 non-colour-blind men. All participants associated 12 colours, presented as terms or patches, with 20 emotion concepts, and rated intensities of the associated emotions. We found that colour-blind and non-colour-blind men associated similar emotions with colours, irrespective of whether colours were conveyed via terms (r = .82) or patches (r = .80). The colour-emotion associations and the emotion intensities were not modulated by participants’ severity of colour blindness. Hinting at some additional, although minor, role of actual colour perception, the consistencies in associations for colour terms and patches were higher in non-colour-blind than colour-blind men. Together, these results suggest that colour-emotion associations in adults do not require immediate perceptual colour experiences, as conceptual experiences are sufficient

miR451 and AMPK Mutual Antagonism in Glioma Cell Migration and Proliferation: A Mathematical Model

Glioblastoma multiforme (GBM) is the most common and the most aggressive type of brain cancer; the median survival time from the time of diagnosis is approximately one year. GBM is characterized by the hallmarks of rapid proliferation and aggressive invasion. miR-451 is known to play a key role in glioblastoma by modulating the balance of active proliferation and invasion in response to metabolic stress in the microenvironment. The present paper develops a mathematical model of GBM evolution which focuses on the relative balance of growth and invasion. In the present work we represent the miR-451/AMPK pathway by a simple model and show how the effects of glucose on cells need to be “refined” by taking into account the recent history of glucose variations. The simulations show how variations in glucose significantly affect the level of miR-451 and, in turn, cell migration. The model predicts that oscillations in the levels of glucose increase the growth of the primary tumor. The model also suggests that drugs which upregulate miR-451, or block other components of the CAB39/AMPK pathway, will slow down glioma cell migration. The model provides an explanation for the growth-invasion cycling patterns of glioma cells in response to high/low glucose uptake in microenvironment in vitro, and suggests new targets for drugs, associated with miR-451 upregulation

HER2 status of bone marrow micrometastasis and their corresponding primary tumours in a pilot study of 27 cases: a possible tool for anti-HER2 therapy management?

Discrepancies have been reported between HER2 status in primary breast cancer and micrometastatic cells in bone marrow. The aim of this study was to assess HER2 gene status in micrometastatic cells in bone marrow and corresponding primary tumour. Micrometastatic cells were detected in bone marrow aspirations in a prospective series of 27 breast cancer patients by immunocytochemistry (pancytokeratin antibody). HER2 status of micrometastatic cells was assessed by fluorescence in situ hybridisation (FISH), respectively in 24 out of 27. Primary tumour HER2 status was assessed by immunohistochemistry (CB11 antibody) and by FISH in 20 out of 27 of the cases. HER2 was amplified or overexpressed in five out of 27 (18.5%) primary tumours and in four out of 27 (15%) micrometastatic cells. In two cases, HER2 was overexpressed and amplified in primary tumour, but not in micrometastatic cells, whereas, in one case, HER2 presented a low amplification rate (six copies) in micrometastatic cells not found in the primary tumour. We demonstrated that negative and positive HER2 status remained, in the majority of the cases, stable between the bone marrow micrometastasis and the primary tumour. Therefore, the efficiency of anti-HER2 adjuvant therapy could be evaluated, in a clinical trial, by sequential detection of HER2-positive micrometastatic cells within the bone marrow, before and after treatment

Strategies of Eradicating Glioma Cells: A Multi-Scale Mathematical Model with MiR-451-AMPK-mTOR Control

The cellular dispersion and therapeutic control of glioblastoma, the most aggressive type of primary brain cancer, depends critically on the migration patterns after surgery and intracellular responses of the individual cancer cells in response to external biochemical and biomechanical cues in the microenvironment. Recent studies have shown that a particular microRNA, miR-451, regulates downstream molecules including AMPK and mTOR to determine the balance between rapid proliferation and invasion in response to metabolic stress in the harsh tumor microenvironment. Surgical removal of main tumor is inevitably followed by recurrence of the tumor due to inaccessibility of dispersed tumor cells in normal brain tissue. In order to address this multi-scale nature of glioblastoma proliferation and invasion and its response to conventional treatment, we propose a hybrid model of glioblastoma that analyses spatio-temporal dynamics at the cellular level, linking individual tumor cells with the macroscopic behaviour of cell organization and the microenvironment, and with the intracellular dynamics of miR-451-AMPK-mTOR signaling within a tumour cell. The model identifies a key mechanism underlying the molecular switches between proliferative phase and migratory phase in response to metabolic stress and biophysical interaction between cells in response to fluctuating glucose levels in the presence of blood vessels (BVs). The model predicts that cell migration, therefore efficacy of the treatment, not only depends on oxygen and glucose availability but also on the relative balance between random motility and strength of chemoattractants. Effective control of growing cells near BV sites in addition to relocalization of invisible migratory cells back to the resection site was suggested as a way of eradicating these migratory cells.Publisher PDFPeer reviewe

Portadores asintomáticos de hidatidosis: epidemiología, diagnóstico y tratamiento Asymptomatic carriers of hydatidosis: epidemiology, diagnosis, and treatment

Hasta hace poco tiempo, la hidatidosis se consideraba un estado patológico de resolución exclusivamente quirúrgica. Sin embargo, en los últimos años se ha avanzado en los campos de la epidemiología, el diagnóstico y el tratamiento de la enfermedad y la nueva información aportada sobre la historia natural de la hidatidosis ha permitido definir nuevos criterios de atención. Ahora se sabe que hasta 67% de los portadores no sintomáticos de quistes hepáticos mantienen esa condición durante toda la vida. Esta situación genera resultados especiales en el inmunodiagnóstico. Así, la inmunoadsorción enzimática (ELISA) rinde una sensibilidad de 63% y una especificidad de 97% en portadores asintomáticos, mientras que la doble difusión cinco (DD5) tiene una sensibilidad de solo 31% en esos portadores. Por otra parte, los estudios por imágenes basados en la ecografía se han transformado en el método de elección para detectar a los portadores no sintomáticos. Son de 49 a 73% más sensibles que la serología e incluso pueden utilizarse como parte del sistema de vigilancia epidemiológica y del monitoreo de programas de control. También se han modernizado los esquemas de intervención. El tratamiento quimioterápico de portadores asintomáticos con albendazol produce hasta 69% de respuestas favorables, mientras que los tratamientos quirúrgicos mínimamente invasores como la punción-aspiración- inyección-reaspiración (PAIR) producen una reducción del volumen medio del quiste de hasta 66%. Estos factores han permitido instaurar un protocolo de tratamiento para portadores asintomáticos en los servicios hospitalarios de la Provincia de Río Negro, Argentina. Este se basa en el seguimiento de los quistes pequeños (tipo Ia de la escala de Gharbi modificada), tratamiento inicial con albendazol y con PAIR si no hay respuesta, en los quistes de mayor tamaño o complejidad (tipos Ib, II y III), y seguimiento de los quistes no vitales o muertos (tipos IV y V).<br>Until a short time ago, hydatidosis was considered a pathology that could only be resolved surgically. However, in recent years progress has been made with the epidemiology, diagnosis, and treatment of the disease, and new information on the natural history of hydatidosis has helped define new criteria for its treatment. It is now known that as many as 67% of the carriers of liver cysts who are asymptomatic remain so throughout their lives. This situation produces special results in immunologic testing. Enzyme-linked immunosorbent assay (ELISA) has a sensitivity of 63% and a specificity of 97% with asymptomatic carriers, while the double diffusion arc 5 test (DD5) achieves a sensitivity of only 31% with the same population. On the other hand, imaging studies based on ultrasonography have become the method of choice to detect asymptomatic carriers. Ultrasonography studies are 49% to 73% more sensitive than serological tests, and they can even be used as a part of epidemiological surveillance systems and to monitor control programs. Treatment schemes have also been modernized. Treating asymptomatic carriers chemotherapeutically with albendazole produces favorable results in as many as 69% of cases, while such minimally invasive surgical treatments as puncture-aspiration-injection-reaspiration (PAIR) reduce average cyst volume by as much as 66%. These factors have made it possible for hospital services in the province of Río Negro, Argentina, to establish a treatment scheme for asymptomatic carriers. It is based on the monitoring of small cysts (type Ia on the modified Gharbi scale); initial treatment with albendazole, followed by PAIR if there is no response, in larger or more complex cysts (types Ib, II, and III); and follow-up of inviable or dead cysts (types IV and V)

Early diagnosis, treatment and follow-up of cystic echinococcosis in remote rural areas in Patagonia: impact of ultrasound training of non-specialists.

Cystic echinococcosis (CE) is a chronic, complex and neglected disease caused by the larval stage of Echinococcus granulosus. The effects of this neglect have a stronger impact in remote rural areas whose inhabitants have no chances of being diagnosed and treated properly without leaving their jobs and travelling long distances, sometimes taking days to reach the closest referral center. BACKGROUND: In 1980 our group set up a control program in endemic regions with CE in rural sections of Rio Negro, Argentina. Since 1997, we have used abdominopelvic ultrasound (US) as a screening method of CE in school children and determined an algorithm of treatment. OBJECTIVES: To describe the training system of general practitioners in early diagnosis and treatment of CE and to evaluate the impact of the implementation of the field program. MATERIALS AND METHODS: In 2000, to overcome the shortage of radiologists in the area, we set up a short training course on Focused Assessment with Sonography for Echinococcosis (FASE) for general practitioners with no previous experience with US. After the course, the trainees were able to carry out autonomous ultrasound surveys under the supervision of the course faculty. From 2000 to 2008, trainees carried out 22,793 ultrasound scans in children from 6 to 14 years of age, and diagnosed 87 (0.4%) new cases of CE. Forty-nine (56.4%) were treated with albendazole, 29 (33.3%) were monitored expectantly and 9 (10.3%) were treated with surgery. DISCUSSION: The introduction of a FASE course for general practitioners allowed for the screening of CE in a large population of individuals in remote endemic areas with persistent levels of transmission, thus overcoming the barrier of the great distance from tertiary care facilities. The ability of local practitioners to screen for CE using US saved the local residents costly travel time and missed work and proved to be an efficacious and least expensive intervention tool for both the community and health care system

Relationship between survival and increased radiation dose to subventricular zone in glioblastoma is controversial

To test the hypothesis on prolonged survival in glioblastoma cases with increased subventricular zone (SVZ) radiation dose. Sixty glioblastoma cases were previously treated with adjuvant radiotherapy and Temozolamide. Ipsilateral, contralateral and bilateral SVZs were contoured and their doses were retrospectively evaluated. Median follow-up, progression free survival (PFS) and overall survival (OS) were 24.5, 8.5 and 19.3 months respectively. Log-rank tests showed a statistically significant correlation between contralateral SVZ (cSVZ) dose > 59.2 Gy (75th percentile) and poor median PFS (10.37 [95% CI 8.37-13.53] vs 7.1 [95% CI 3.5-8.97] months, p = 0.009). cSVZ dose > 59.2 Gy was associated with poor OS in the subgroup with subtotal resection/biopsy (HR: 4.83 [95% CI 1.71-13.97], p = 0.004). High ipsilateral SVZ dose of > 62.25 Gy (75th percentile) was associated with poor PFS in both subgroups of high performance status (HR: 2.58 [95% CI 1.03-6.05], p = 0.044) and SVZ without tumoral contact (HR: 10.57 [95% CI 2.04-49], p = 0.008). The effect of high cSVZ dose on PFS lost its statistical significance in multivariate Cox regression analysis. We report contradictory results compared to previous publications. Changing the clinical practice based on retrospective studies which even do not indicate consistent results among each other will be dangerous. We need carefully designed prospective randomized studies to evaluate any impact of radiation to SVZ in glioblastoma