The identification of KRAS mutations at codon 12 in plasma DNA is not a prognostic factor in advanced non-small cell lung cancer patients

Background

Qualitative analysis of circulating DNA in the blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the presence of KRAS mutations at codon 12 and several clinical variables in advanced non-small cell lung cancer (NSCLC) patients.

Methods

We examined 308 stage IIIB and IV NSCLC patients who were treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the plasma using commercial adsorption columns. The KRAS mutational status was determined by an RT-PCR method that is based on allelic discrimination.

Results

The median age of the patients was 60 years [31-80], 84% were male, 98% had a performance status of 0-1 and 84% of the patients were in stage IV. The histological subtypes were as follows: 30% squamous cell carcinoma (SCC), 51% adenocarcinoma (ADC) and 19% others. Of the 277 response-evaluated patients, 1% achieved a complete response (CR), 26% achieved a partial response (PR), 34% had stable disease (SD) and 39% had progressive disease (PD). Additionally, 27 (8.8%) patients had KRAS mutations; 26 had a KRAS codon 12 TGT mutation, and 1 had a codon 12 GTT mutation. Plasmatic KRAS mutations were found in patients presenting SCC or ADC. Patients with KRAS mutations in plasma DNA had a median progression free survival (PFS) of 5.77 months [3.39-8.14], whereas for patients with wild-type (wt) KRAS, the PFS was 5.43 months [4.65-6.22] (p = 0.277). The median overall survival (OS) in KRAS-mutated patients was 9.07 months [4.43-13.70] vs 10.03 months [8.80-11.26] in wt patients (p = 0.514).

Conclusions

In advanced NSCLC patients, there were no significant differences between patients with or without KRAS mutations in plasma-free DNA with respect to the baseline characteristics, response rates, PFS or OS.     

Decreased high-density lipoprotein cholesterol levels in polyarticular juvenile idiopathic arthritis

OBJECTIVES:

To investigate the prevalence of dyslipoproteinemia in a homogeneous cohort of polyarticular juvenile idiopathic arthritis patients.

METHODS:

Based on the National Cholesterol Education Program, fasting lipoprotein levels and risk levels for coronary artery disease were determined in 28 patients with polyarticular juvenile idiopathic arthritis. The exclusion criteria included diabetes, thyroid dysfunction, smoking, proteinuria, lipid-lowering drugs, and hormone/diuretic therapy. Disease activity, disease duration, and therapy with corticosteroids and/or chloroquine were defined at the time of lipid measurements.

RESULTS:

Dyslipoproteinemia was identified in 20 of the 28 (71%) patients with polyarticular juvenile idiopathic arthritis. The primary lipoprotein risk factor was decreased high-density lipoprotein cholesterol (57%), followed by elevated levels of low-density lipoprotein cholesterol (18%), triglycerides (14%), and total cholesterol (7%). The male patients had decreased high-density lipoprotein cholesterol levels than the female patients (p<0.05). The incidence of decreased high-density lipoprotein cholesterol levels did not seem to be affected by disease activity or therapy because the incidence was similar in patients with active or inactive disease, with or without corticosteroid use and with or without chloroquine use. In addition, the frequency of decreased high-density lipoprotein cholesterol levels was similar in patients with short (≤5 years) vs. long (>5 years) disease duration.

CONCLUSIONS:

Dyslipoproteinemia is highly prevalent in patients with polyarticular juvenile idiopathic arthritis and is primarily related to decreased high-density lipoprotein cholesterol levels; therefore, early intervention is essential.     

Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial

Creatine supplementation may have a therapeutic role in diabetes, but it is uncertain whether this supplement is safe for kidney function. The aim of this study was to investigate the effects of creatine supplementation on kidney function in type 2 diabetic patients. A randomized, double-blind, placebo-controlled trial was performed. The patients were randomly allocated to receive either creatine or placebo for 12?weeks. All the patients underwent exercise training throughout the trial. Subjects were assessed at baseline and after the intervention. Blood samples and 24-h urine samples were obtained for kidney function assessments. Additionally, (51)Cr-EDTA clearance was performed. To ensure the compliance with creatine intake, we also assessed muscle phosphorylcreatine content. The creatine group presented higher muscle phosphorylcreatine content when compared to placebo group (CR Pre 44?±?10, Post 70?±?18?mmol/kg/wt; PL Pre 52?±?13, Post 46?±?13?mmol/kg/wt; p?=?0.03; estimated difference between means 23.6; 95% confidence interval 1.42-45.8). No significant differences were observed for (51)Cr-EDTA clearance (CR Pre 90.4?±?16.9, Post 96.1?±?15.0?mL/min/1.73?m(2); PL Pre 97.9?±?21.6, Post 96.4?±?26.8?mL/min/1.73?m(2); p?=?0.58; estimated difference between means -0.3; 95% confidence interval -24.9 to 24.2). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria were unchanged. CR supplementation does not affect kidney function in type 2 diabetic patients, opening a window of opportunities to explore its promising therapeutic role in this population. ClinicalTrials.gov registration number: NCT00992043.     

Effect of macrophage migration inhibitory factor (MIF) in human placental explants infected with Toxoplasma gondii depends on gestational age

Because macrophage migration inhibitory factor (MIF) is a key cytokine in pregnancy and has a role in inflammatory response and pathogen defense, the objective of the present study was to investigate the effects of MIF in first- and third-trimester human placental explants infected with Toxoplasma gondii. Explants were treated with recombinant MIF, IL-12, interferon-γ, transforming growth factor-β1, or IL-10, followed by infection with T. gondii RH strain tachyzoites. Supernatants of cultured explants were assessed for MIF production. Explants were processed for morphologic analysis, immunohistochemistry, and real-time PCR analysis. Comparison of infected and stimulated explants versus noninfected control explants demonstrated a significant increase in MIF release in first-trimester but not third-trimester explants. Tissue parasitism was higher in third- than in first-trimester explants. Moreover, T. gondii DNA content was lower in first-trimester explants treated with MIF compared with untreated explants. However, in third-trimester explants, MIF stimulus decreased T. gondii DNA content only at the highest concentration of the cytokine. In addition, high expression of MIF receptor was observed in first-trimester placental explants, whereas MIF receptor expression was low in third-trimester explants. In conclusion, MIF was up-regulated and demonstrated to be important for control of T. gondii infection in first-trimester explants, whereas lack of MIF up-regulation in third-trimester placentas may be involved in higher susceptibility to infection at this gestational age.     

Description of the motor development of 3-12 month old infants with Down syndrome: the influence of the postural body position

The purpose of the present study was to describe the rate of motor development in infants with Down syndrome in the age range of 3-12 months and identify the difficulties both in performance and acquiring motor skills in prone, supine, sitting and standing positions. Nineteen infants with Down syndrome and 25 healthy full term typical infants were assessed using the Alberta Infant Motor Scale (AIMS) monthly from 3 to 12 months of age. The infants with Down syndrome achieved significant later the level of motor performance of the typical infants. In the supine posture, the performance was significantly lesser for the Down syndrome infants in comparison to the typical infants from the 3rd to 6th month and in the 8th month. In the prone, sitting and standing postures this difference is found for all the months. In conclusion, the sequence of motor development of the Down syndrome is the same as the typical infants. However infants with Down syndrome need more time to acquire skills, mainly antigravitational ones, among them the standing position.     

Prenatal MR imaging of dural sinus malformation: a case report

OBJECTIVE: To describe prenatal magnetic resonance imaging (MRI) findings of dural sinus malformation (DSM), a very rare, congenital form of dural arteriovenous shunt (DAVS), typically affecting newborns. METHODS: Ultrasound (US) and MRI were performed at 34 weeks' gestation, and the findings of these examinations were compared with postnatal MRI studies performed at 2 days and 1 month. RESULTS: US showed an anechoic, midline posterior fossa collection with irregular internal echodensities. Color Doppler showed prominent arterial vascularity at the lesion margins. The prenatal MRI showed a large, profoundly hypointense, midline retrocerebellar mass. Postnatal MRI, complemented with magnetic resonance (MR) angiography, showed the lesion to be a giant dural venous pouch fed by multiple mural arteriovenous shunts. Follow-up MRI at 1 month suggested latent venous hypertension and prompted endovascular treatment. CONCLUSION: Prenatal MR imaging is useful to establish the diagnosis, to assess complications such as hydrocephalus and tonsillar prolapse, and to help plan perinatal management, postnatal follow-up, and treatment decision-making.     

Reference values for Doppler velocimetry of the ophthalmic and central retinal arteries in low-risk pregnancy

ObjectiveTo establish reference values for Doppler velocimetry of the ophthalmic artery (OA) and the central retinal artery (CRA) in low-risk pregnancy.MethodBetween January 2008 and March 2009, 63 low-risk pregnant women underwent an ultrasound scan every 2 weeks at the Women's Hospital, Campinas, Brazil, to determine the resistance index (RI), pulsatility index (PI), and peak systolic velocity of both arteries, in addition to the flow velocity of the second peak and peak ratio (PR) of the OA. For analysis, linear regression was used with mixed models for longitudinal data, coefficient of determination, and estimates of the 5th and 95th percentiles for each parameter at each gestational age. Intra- and inter-observer variability was evaluated via the intraclass correlation coefficient.ResultsThere was a trend of a reduction with gestational age in PI and RI of the OA, and PI of the CRA, but not in PR of the OA; and the respective reference values were established. Intra- and inter-observer variability was considered satisfactory.ConclusionUnilateral assessment of the orbital Doppler velocimetry is feasible. Establishment of reference values showed a negative correlation between gestational age and PI and RI of the OA, and PI of the CRA. The method demonstrated satisfactory reproducibility.     

Correlation of obesity with elevated blood pressure among racial/ethnic minority children in two Los Angeles middle schools

Introduction

To identify anthropometric and fitness correlates of elevated blood pressure, serum cholesterol, and glycated hemoglobin, we examined anthropometric and physiologic biomarkers among racial/ethnic minority children aged 11 to 13 years in two urban Los Angeles middle schools. We explored the potential for using obesity or fitness level as screening variables for cardiovascular disease risk factors in these students.

Methods

During regularly scheduled physical education classes, we collected data on demographic characteristics, height, weight, blood pressure, nonfasting total serum cholesterol, glycated hemoglobin, time to run/walk 1 mile, and a range of self-reported behaviors. A total of 199 sixth-graders (121 Latinos, 78 African Americans) participated in the study.

Results

Bivariate analyses indicated that 48.6% of sixth-graders were of desirable weight, 17.5% were overweight, 29.9% were at risk for overweight, and 4.0% were underweight. Higher weight was associated with higher levels of serum cholesterol, systolic blood pressure, and diastolic blood pressure (P values for all associations <.02) but not with glycated hemoglobin. Multivariate analyses maintained the findings with regard to blood pressure but not serum cholesterol.

Conclusion

Overweight status could be a screening variable for identifying youth at risk for high blood pressure. Obesity prevention and intervention programs and policies need to target low-income racial/ethnic minority children. Assessment of hypertension status also seems warranted in low-income racial/ethnic minority sixth-graders, as does early intervention for children at high risk.