Discrepancies between biomarkers of primary breast cancer and subsequent brain metastases: an international multicenter study.

PURPOSE: Discordances between the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), expression between primary breast tumors and their subsequent brain metastases (BM) were investigated in breast cancer patients. METHODS: We collected retrospective data from 11 institutions in 8 countries in a predefined-standardized format. Receptor status (positive or negative) was determined according to institutional guidelines (immunohistochemically and/or fluorescence in situ hybridization). The study was subject to each institution's ethical research committee. RESULTS: A total of 167 breast cancer patients with BM were included. 25 patients out of 129 with a complete receptor information from both primary tumor and BM (ER, PR, HER2) available, had a change in receptor status: 7 of 26 (27%) ER/PR-positive/HER2-negative primaries (3 gained HER2; 4 lost expression of ER/PR); 10 of 31 (32%) ER/PR-positive/HER2-positive primaries (4 lost ER/PR only; 3 lost HER2 only; 3 lost both ER/PR and HER2); one of 33 (3%) ER/PR-negative receptor/HER2-positive primaries (gained ER); and 7 of 39 (18%) triple-negative primaries (5 gained ER/PR and 2 gained HER2). CONCLUSIONS: The majority of breast cancer patients with BM in this series had primary HER2-enriched tumors, followed by those with a triple-negative profile. One out of 5 patients had a receptor discrepancy between the primary tumor and subsequent BM. Therefore, we advise receptor status assessment of BM in all breast cancer patients with available histology as it may have significant implications for therapy.

Multi-institutional competing risks analysis of distant brain failure and salvage patterns after upfront radiosurgery without whole brain radiotherapy for brain metastasis.

Background: In this study, we use a competing risks analysis to assess factors predictive of early-salvage whole brain radiotherapy (WBRT) and early death after upfront stereotactic radiosurgery (SRS) alone for brain metastases in an attempt to identify populations that benefit less from upfront SRS. Patients and methods: Patients from eight academic centers were treated with SRS for brain metastasis. Competing risks analysis was carried out for distant brain failure (DBF) versus death prior to DBF as well as for salvage SRS versus salvage WBRT versus death prior to salvage. Linear regression was used to determine predictors of the number of brain metastases at initial DBF (nDBF). Results: A total of 2657 patients were treated with upfront SRS alone. Multivariate analysis (MVA) identified an increased hazard of DBF associated with increasing number of brain metastases (P < 0.001), lowest SRS dose received (P < 0.001), and melanoma histology (P < 0.001), while there was a decreased hazard of DBF associated with increasing age (P < 0.001), KPS < 70 (P < 0.001), and progressive systemic disease (P = 0.004). MVA for first salvage SRS versus WBRT versus death prior to salvage revealed an increased hazard of first salvage WBRT seen with increasing number of brain metastases (P < 0.001) and a decreased hazard with widespread systemic disease (P = 0.002) and increasing age (P < 0.001). Variables associated with nDBF included age (P = 0.02), systemic disease status (P = 0.03), melanoma histology (P = 0.05), and initial number of brain metastases (P < 0.001). Conclusions: Patients with a higher initial number of brain metastases were more likely to experience DBF, have a higher nDBF, and receive early-salvage WBRT, while patients who were older, had lower KPS, or had more systemic disease were more likely to experience death prior to DBF or salvage WBRT.

Couples at risk for spinocerebellar ataxia type 2: the Cuban prenatal diagnosis experience

Cuba reports the highest worldwide prevalence of spinocerebellar ataxia type 2 (SCA2) and the greatest number of descendants at risk. A protocol for genetic counseling, presymptomatic testing, and prenatal diagnosis of hereditary ataxias has been under development since 2001. Considering that the revision of the experience with prenatal diagnosis for SCA2 in Cuba would enable comparison of ours with international findings, we designed a descriptive study, based on the retrospective revision of the medical records belonging to the 58 couples that requested their inclusion in the program, during an 11-year period (2001-2011). Most of the participants in the prenatal diagnosis program were known presymptomatic carriers, diagnosed through the presymptomatic testing in the same period of study, for an uptake among them of 22.87 percent (51 out of 223). In 28 cases, the fetuses were carriers, 20 of these couples (71.43 percent) decided to terminate the pregnancy; the rest continued the pregnancy to term, this resulting in a predictive test for their unborn children. A predominance of females as the at-risk progenitor was observed. Except for a slightly lower average age, the results attained in the Cuban SCA2 prenatal diagnosis program resulted similar to the ones reported for Huntington disease in other countries. It is necessary to have easy access to the Cuban program through its expansion to other genetic centers along the island. Future research is needed to evaluate the long-term impact of both the predictive testing in unborn children and the selection of other reproductive options by the at-risk couples (AU)

Assessment of rainwater harvesting systems at a university in Taipei.

Rainwater harvesting systems (RWHSs), a pilot-scale one (PSR) and a full-scale one (FSR), at a university campus in Taipei were assessed. Characteristics of harvested rainwater were analyzed, including pH, electrical conductivity (EC), turbidity, alkalinity, dissolved organic carbon (DOC), total coliform (TC), concentration of 14 metals (Al, Ca, K, Mg, Na, Cu, Fe, Mn, V, Zn, Cd, Cr, Pb and Ni) and concentration of 3 anions (Cl(-), SO(4)(2-) and NO(3)(-)). Rainwater in the FSR had pH in the neutral range and high alkalinity, whereas those of the PSR were acidic and with low buffer ability because of different catchment materials. Median concentrations of 14 metals from two RWHSs were low, except for Na, Ca, K and Mg. Anions, including Cl(-), NO(3)(-), and SO(4)(2-) showed much higher concentration in winter, indicating the influences of marine source and northeast monsoon. Effects of 14-day storage were examined and it was found that pH did not change, while EC, turbidity and DOC slightly decreased. Concentrations of anions and metals were stable, and TC counts of harvested rainwater increased in the beginning, and then declined with storage time. During antecedent dry days, total suspended particulates (TSPs) were collected and their dissolution was examined. Preliminary correlation of wet and dry depositions with rainwater quality was explored.

A comprehensive review of MR imaging changes following radiosurgery to 500 brain metastases.

BACKGROUND AND PURPOSE: Stereotactic radiosurgery is known to control 85%-95% of intracranial metastatic lesions during a median survival of 6-8 months. However, with the advent of newer systemic cancer therapies, survival is improving; this change mandates a longitudinal quantitative analysis of the radiographic response of brain metastases to radiosurgery. MATERIALS AND METHODS: MR imaging of 516 metastases in 120 patients treated with GK-SRS from June 2006 to December 2009 was retrospectively reviewed. Lesion volume at initial treatment and each follow-up was calculated by using the following formula: length × width × height / 2. Volume changes were correlated with patient demographics, histopathology, and radiation treatment variables. RESULTS: Thirty-two percent of lesions increased in volume following radiosurgery. Clinically, this translated into 54% of patients having ≥1 of their lesions increase in size. This increase begins at 6 weeks and can last beyond 15 months' post-SRS. Male sex (P = .002), mean voxel dose <37 Gy (P = .009), and initial treatment volume >500 mm(3) (P < .001) are associated with posttreatment increases in tumor size. Median survival following radiosurgery was 9.5 months for patients with all lesions exhibiting stable/decreased volumes, >18.4 months for patients with all lesions exhibiting increased volumes, and 16.4 months for patients with mixed lesional responses. CONCLUSIONS: Most metastatic lesions are stable or smaller in size during the first 36 months post-SRS. However, a transient increase in volume is seen in approximately one-third of lesions. Sex, treatment dose, initial lesion size, and histopathology all correlate with variations in lesion volume post-SRS. The longer the patient survives, the more likely an increase in lesion size will be seen on follow-up imaging.

Label-free in situ imaging of lignification in the cell wall of low lignin transgenic Populus trichocarpa.

Chemical imaging by confocal Raman microscopy has been used for the visualization of the cellulose and lignin distribution in wood cell walls. Lignin reduction in wood can be achieved by, for example, transgenic suppression of a monolignol biosynthesis gene encoding 4-coumarate-CoA ligase (4CL). Here, we use confocal Raman microscopy to compare lignification in wild type and lignin-reduced 4CL transgenic Populus trichocarpa stem wood with spatial resolution that is sub-microm. Analyzing the lignin Raman bands in the spectral region between 1,600 and 1,700 cm(-1), differences in lignin signal intensity and localization are mapped in situ. Transgenic reduction of lignin is particularly pronounced in the S2 wall layer of fibers, suggesting that such transgenic approach may help overcome cell wall recalcitrance to wood saccharification. Spatial heterogeneity in the lignin composition, in particular with regard to ethylenic residues, is observed in both samples.

Nefroma mesoblástico infantil: informe de un caso clínico y revisión bibliográfica / Mesoblastic nephroma in children: report of a clinic case and bibliographic revision

En una paciente pediátrica de 2 meses y medio se detecta por ecografía un tumor en el polo superior del riñón derecho, que debutó clínicamente por hematuria. Los exámenes de ingreso demostraron buen estado general, ausencia de masa abdominal palpable, y exámenes de laboratorio normales. La TAC abdominal confirma una masa de 3,1x 2,5cm., sin invasión aparente de la grasa perirrenal.Se somete a laparotomía exploradora que demuestra un tumor renal derecho que ocupa un 80 por ciento de éste órgano, sin compromiso ganglionar hiliar ni paraaórtico, en tanto que el riñon izquierdo está indemne.El estudio histológico concluyó que se trata de un nefroma mesoblástico, tumor infrecuente y que debe diferenciarse rigurosamente del tumor de Wilms, pues su pronóstico casi siempre es muy bueno sólo con cirugía. Se describe la lesión y los métodos aplicados para el diagnóstico diferencial. Los autores revisan la literatura disponible de estas lesiones, raras en la práctica clínica habitual

Ventriculopleural shunt obstruction and positive-pressure ventilation. Case report.

The authors report an unusual case of a patient with low-pressure hydrocephalus and a ventriculopleural shunt, in whom routine respiratory management performed using positive-pressure ventilation caused shunt obstruction and coma. While the patient received positive-pressure ventilation with external cerebrospinal fluid (CSF) drainage at subatmospheric pressure, the ventricles returned to normal size and the coma rapidly reversed. After the authors' recognition of the effect of positive-pressure ventilation on intrapleural pressure and ventriculopleural shunt function, and the subsequent removal of positive-pressure ventilation, CSF flow through the shunt resumed and the patient's coma resolved.

The last step of syringyl monolignol biosynthesis in angiosperms is regulated by a novel gene encoding sinapyl alcohol dehydrogenase.

Cinnamyl alcohol dehydrogenase (CAD; EC 1.1.1.195) has been thought to mediate the reduction of both coniferaldehyde and sinapaldehyde into guaiacyl and syringyl monolignols in angiosperms. Here, we report the isolation of a novel aspen gene (PtSAD) encoding sinapyl alcohol dehydrogenase (SAD), which is phylogenetically distinct from aspen CAD (PtCAD). Liquid chromatography-mass spectrometry-based enzyme functional analysis and substrate level-controlled enzyme kinetics consistently demonstrated that PtSAD is sinapaldehyde specific and that PtCAD is coniferaldehyde specific. The enzymatic efficiency of PtSAD for sinapaldehyde was approximately 60 times greater than that of PtCAD. These data suggest that in addition to CAD, discrete SAD function is essential to the biosynthesis of syringyl monolignol in angiosperms. In aspen stem primary tissues, PtCAD was immunolocalized exclusively to xylem elements in which only guaiacyl lignin was deposited, whereas PtSAD was abundant in syringyl lignin-enriched phloem fiber cells. In the developing secondary stem xylem, PtCAD was most conspicuous in guaiacyl lignin-enriched vessels, but PtSAD was nearly absent from these elements and was conspicuous in fiber cells. In the context of additional protein immunolocalization and lignin histochemistry, these results suggest that the distinct CAD and SAD functions are linked spatiotemporally to the differential biosynthesis of guaiacyl and syringyl lignins in different cell types. SAD is required for the biosynthesis of syringyl lignin in angiosperms.

Rate and prediction of infection in children with diabetic ketoacidosis.

The purpose of this retrospective cohort study was to determine the rate and prediction of infection in children, < or = 21 years, with diabetic ketoacidosis (DKA). Over a 6-year period, 247 admissions were identified. There were 171 (69%) with no infection, 44 (17.8%) with presumed viral infection, and 32 (12.9%) with bacterial infection. The mean WBC for all patients was 17,519 ( +/- 9,582). 118 (50%) had leukocytosis as defined by a WBC > or = 15,000/mm3. WBC, differential, leukocytosis, as well as sex, temperature and new onset diabetes, were not significant predictors (P > .05) of bacterial infection. Bacterial infections were more common in children < or = 3 years of age (P = .03). There was a significant correlation of WBC with both pH (r = -0.59, P < .001) and bicarbonate (r = -0.43, P < .001). In conclusion, most children in DKA have no evidence of infection. Leukocytosis is common but most likely reflects the severity of DKA rather than the presence of infection.