Plasma levels of angiopoietin-2, VEGF-A,and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance)

Hypertension is a common toxicity induced by bevacizumab and other antiangiogenic drugs. There are no biomarkers to predict the risk of bevacizumab-induced hypertension. This study aimed to identify plasma proteins related to the function of the vasculature to predict the risk of severe bevacizumab-induced hypertension. Using pretreated plasma samples from 398 bevacizumab-treated patients in two clinical trials (CALGB 80303 and 90401), the levels of 17 proteins were measured via ELISA. The association between proteins and grade 3 bevacizumab-induced hypertension was performed by calculating the odds ratio (OR) from logistic regression adjusting for age, sex, and clinical trial. Using the optimal cut-point of each protein, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for hypertension were estimated. Five proteins showed no difference in levels between clinical trials and were used for analyses. Lower levels of angiopoietin-2 (p?=?0.0013, OR 3.41, 95% CI 1.67–7.55), VEGF-A (p?=?0.0008, OR 4.25, 95% CI 1.93–10.72), and VCAM-1 (p?=?0.0067, OR 2.68, 95% CI 1.34–5.63) were associated with an increased risk of grade 3 hypertension. The multivariable model suggests independent effects of angiopoietin-2 (p?=?0.0111, OR 2.71, 95% CI 1.29–6.10), VEGF-A (p?=?0.0051, OR 3.66, 95% CI 1.54–9.73), and VCAM-1 (p?=?0.0308, OR 2.27, 95% CI 1.10–4.92). The presence of low levels of 2–3 proteins had an OR of 10.06 (95% CI 3.92–34.18, p?=?1.80?×?10^–5) for the risk of hypertension, with sensitivity of 89.7%, specificity of 53.5%, PPV of 17.3%, and NPV of 97.9%. This is the first study providing evidence of plasma proteins with potential value to predict patients at risk of developing bevacizumab-induced hypertension.

Clinical trial registration: ClinicalTrials.gov Identifier: NCT00088894 (CALGB 80303); and NCT00110214 (CALGB 90401).

     

Comparison of conventional phototherapy and phototherapy along with Kangaroo mother care on cutaneous bilirubin of neonates with physiological jaundice

Background: One of the adjuvant and desirable therapies is skin contact between mother and baby or Kangaroo mother care (KMC) that is a cheap, accessible, relaxing, noninvasive and easy method. This study aimed to compare the effect of conventional phototherapy method and phototherapy along with KMC on cutaneous bilirubin in neonates with physiological jaundice.

Materials and methods: In this randomized clinical trial, all infants with physiological jaundice who referred for phototherapy to Mofid Hospital of Shahid Beheshti University of Medical Sciences, Tehran, Iran were selected by convenience sampling based on inclusion criteria and were randomly assigned into two groups of conventional phototherapy (n?=?35) and phototherapy along with KMC (n?=?35).

Results: The results showed that there was a significant difference in the average volume of skin bilirubin before treatment with cutaneous bilirubin every 24?h after treatment (p?p?=?.236). Mean duration of hospitalization of infants in the intervention group was significantly lower than the control group (2.09 versus 3.03 d, p?Conclusion: Although KMC along with phototherapy has a favorable effect on the reduction of cutaneous bilirubin in neonates with physiological jaundice, there are not significant differences in routine care. This may need to do KMC for a longer time (more than 1?h) which must be surveyed in the future studies. KMC was effective in reduction of the duration of hospitalization in jaundiced infants.     

Turning behavior in healthy older adults: Is there a preference for step versus spin turns?

This research examined the prevalence of step turns and spin turns during turning while walking in healthy older adults. The potential effect of magnitude of the turn and walking velocity on the prevalence of the step and spin turns were also investigated by examining the participants’ performance as they made 45° and 90° turns while walking at three different velocities. Results showed that healthy older adults in our study preferred spin turns while walking either slower or faster than their natural walking speed. Only during 90° turns while walking fast the participants showed a preference for step turns over spin turns. Spin turns are less stable and have a greater biomechanical cost than step turns. The high incidence of spin turns in older adults may contribute to the higher risk of falling in this population.     

Early spica cast for fracture shaft of femur in children: the north of Jordan experience

This is a case series study that was conducted to assess the findings and usefulness of early spica in children less than 10 years of age. Forty patients less than 10 years of age with femoral shaft fractures were treated by early hip spica between 2000 and 2005 and were followed up for 6 months. The setting was a public university hospital and a public university-affiliated hospital in the north of Jordan. Ultimate shortening of the affected limb of ≥2 cm was observed in those patients with an overlap between fragments of ≥2 cm in the first post-spica X-ray. One case of significant angulation and no cases of rotation deformities were observed. It is concluded that early spica cast in children under the age of 10 is an effective treatment modality. Only in the presence of overlap of ≥2 cm between fragments in the first post-spica X-ray, there would be a chance of ultimate shortening of the affected limb by ≥2 cm. Children aged ≥6 are more liable to develop leg shortening.     

Placental IGF-I, IGFBP-1, zinc, and iron, and maternal and infant anthropometry at birth

Aim: To correlate placental protein levels of insulin‐like growth factor (IGF)‐I and insulin‐like growth factor binding protein (IGFBP)‐1, with previously determined levels of IGF‐I and IGF‐II mRNA expression, and the micronutrients zinc and iron, and maternal and newborn anthropometry. Methods: Placental samples were collected from rural field sites in Pakistan. Samples were divided into small and large for gestational age groups (SGA and LGA, respectively). IGFBP‐1 levels were assessed using Western immunoblotting. IGF‐I protein levels were assessed using ELISA techniques. IGF mRNA expression, zinc, and iron, were quantified as previously described and were used for comparative purposes only. Results: Thirty‐three subjects were included (SGA, n = 12; LGA n = 21). Higher levels of IGFBP‐1 were seen in the SGA group (p < 0.01). IGFBP‐1 correlated positively with maternal and infant triceps skin‐fold thickness in the LGA and SGA groups, respectively (p < 0.05). Significantly lower IGF‐I protein levels were seen in the SGA group. IGF‐I levels correlated significantly with maternal and newborn anthropometry. IGFBP‐1 correlated significantly with IGF‐II mRNA expression (p < 0.05). Conclusion: Placental protein levels of IGF‐I and IGFBP‐1 appear to be associated with maternal anthropometry. Maternal anthropometry may thus influence IGFBP‐1 and IGF‐I levels and may possibly be used for screening of pregnancies, with the potential for timely identification of these high‐risk pregnancies.     

In vitro comparative study of white and dark polycaprolactone trifumarate in situ cross-linkable scaffolds seeded with rat bone marrow stromal cells

OBJECTIVE:

Dark poly(caprolactone) trifumarate is a successful candidate for use as a bone tissue engineering scaffold. Recently, a white polymeric scaffold was developed that shows a shorter synthesis time and is more convenient for tissue-staining work. This is an in vitro comparative study of both the white and dark scaffolds.

METHODS:

Both white and dark poly(caprolactone) trifumarate macromers were characterized via Fourier transform infrared spectroscopy before being chemically cross-linked and molded into disc-shaped scaffolds. Biodegradability was assessed by percentage weight loss on days 7, 14, 28, 42 and 56 (n = 5) after immersion in 10% serum-supplemented medium or distilled water. Static cell seeding was employed in which isolated and characterized rat bone marrow stromal cells were seeded directly onto the scaffold surface. Seeded scaffolds were subjected to a series of biochemical assays and scanning electron microscopy at specified time intervals for up to 28 days of incubation.

RESULTS:

The degradation of the white scaffold was significantly lower compared with the dark scaffold but was within the acceptable time range for bone-healing processes. The deoxyribonucleic acid and collagen contents increased up to day 28 with no significant difference between the two scaffolds, but the glycosaminoglycan content was slightly higher in the white scaffold throughout 14 days of incubation. Scanning electron microscopy at day 1 revealed cellular growth and attachment.

CONCLUSIONS:

There was no cell growth advantage between the two forms, but the white scaffold had a slower biodegradability rate, suggesting that the newly synthesized poly(caprolactone) trifumarate is more suitable for use as a bone tissue engineering scaffold.