Thermal Index for early non-invasive assessment of brain injury in newborns treated with therapeutic hypothermia: preliminary report.

Perinatal asphyxia (PA) is the 3rd most common cause of neonatal death and one of the most common causes of severe neurological impairments in children. Current tools and measurements mainly based on the analysis of clinical evaluation and laboratory and electrophysiological tests do not give consistent data allowing to predict the severity of hypoxic-ischemic encephalopathy (HIE) until a magnetic resonance imaging (MRI) score is performed. The aim of this work is to evaluate the usefulness of the new index, called Thermal Index (TI) in the assessment of the degree of brain damage in newborns in the course of therapeutic hypothermia (TH) due to PA. This was a prospective, observational, pilot study which did not require any changes in the applicable procedures. Analysis has been applied to six newborn babies treated with TH in Neonatal/Paediatric ICU in University Hospital in Opole in 2018 due to PA. They all met criteria for TH according to the current recommendations. Brain MRI was performed after the end of TH when the children were brought back to normal temperature, with the use of a 1.5 T scanner, using T1-, T2-weighted images, fluid-attenuated inversion recovery (FLAIR), inversion recovery (IR), susceptibility-weighted imaging (SWI), and diffusion-weighted imaging (DWI). The images were assessed using MRI score according to the scoring system proposed by Weeke et al. The Thermal Index assessing endogenous heat production was calculated according to the formula proposed in this paper. A high, statistically significant positive correlation was found between MRI scores and TI values (0.98; p = 0.0003) in the 1st hour of therapy. High correlation with MRI assessment, the non-invasiveness of measurements and the availability of results within the first few hours of treatment, allow authors to propose the Thermal Index as a tool for early evaluating of the brain injury in newborns treated with TH. Further research is required to confirm the usefulness of the proposed method.

Bone status in adolescents with type 1 diabetes.

AIMS: The aim of the study was to investigate the potential negative impact of type 1 diabetes on bone status of adolescents. Bone status in adolescents with type 1 diabetes was assessed by means of quantitative ultrasound (QUS) and the influence of metabolic control and other disease-related and growth variables was analysed. METHODS: Group I consisted of 99 pubertal (Tanner > or = 2) adolescents (49 female), aged 14.3 +/- 2.5 years, diabetes duration 4.6 +/- 2.3 years. Controls (group II) were 297 children, matched by sex and age, from a healthy population. The influence of glycated haemoglobin (current: HbA(1c)D; last year's mean: HbA(1c)Y; whole duration mean: HbA(1c)T), diabetes duration, percentage of life with disease and daily insulin requirement (DIR) on amplitude dependent speed of sound (Ad-SoS) at distal phalanges was studied. RESULTS: In comparison to the control group, adolescents with type 1 diabetes presented significantly higher BMI SDS (0.82 [95% CI 0.54, 1.10] vs -0.06 [95% CI -0.16, 0.04] p < 0.001) and lower Ad-SoS SDS (-0.34 [95% CI -0.57, -0.11] vs -0.03 [95% CI -0.15, 0.08], p < 0.05). No correlation between Ad-SoS SDS and sex, DIR or diabetes duration was observed. The lower Ad-SoS SDS reflects reduced bone status, and the reduction was significantly more marked in those patients whose HbA(1c)T was higher than 7.0% when compared with those whose HbA(1c)T was lower. CONCLUSIONS: Bone status of adolescents with type 1 diabetes mellitus assessed with QUS differs from that of healthy peers and is dependent on long-term metabolic control.

Phalangeal quantitative ultrasound measurements in former pre-term children aged 9-11 years.

The objective of this study was to compare phalangeal ultrasound values in 38 former pre-term children, aged 9-11 years, with 50 age-matched term controls. Skeletal status was evaluated using phalangeal quantitative ultrasound measurements (QUS) by DBM Sonic 1200 (IGEA, Carpi, Italy) which measures the amplitude dependent speed of sound (Ad-SoS, m s(-1)). There were no significant differences in values of Ad-SoS, weight and height between patients and controls irrespective of birth weight or prematurity. In conclusion, phalangeal ultrasound measurements performed in prematurely born infants show that at the age of 9-11 years their bone status does not differ from children born at term.

Quantitative ultrasound at the hand phalanges in 2850 females aged 7 to 77 yr: a cross-sectional study.

In the study, skeletal status was evaluated in 2850 females aged 7 to 77 yr using quantitative ultrasound (QUS amplitude-dependent speed of sound [Ad-SoS]). Ad-SoS ranged from 1923 +/- 30 to 1876 +/- 81 m/s, and the peak value (2121 m/s) was achieved in 19-yr-old females. Ad-SoS increased significantly between subgroups aged 11 and 12 yr, 12 and 13 yr, 13 and 14 yr, 14 and 15 yr, and 15 and 16 yr. After the age of 19 yr the only significant drop was noted between age groups 47 and 48 yr. Ad-SoS was regressed on age, weight, and height for age ranges 7 to 11 yr.(before an increase in Ad-SoS), 12 to 19 yr (from the onset of the increase to the peak value), and older than 19 yr to menopause. In females after menopause, years since menopause (YSM) were taken into consideration. In the two youngest groups Ad-SoS was affected positively by age, and in the two next groups, age had a negative influence on Ad-SoS, whereas weight had a negative and height a positive influence in all groups. YSM did not influence the Ad-SoS value. It was concluded that QUS measurements at the hand phalanges are a useful tool in assessment of skeletal status in the female population.

Skeletal status in survivors of acute lymphoblastic leukemia assessed by quantitative ultrasound at the hand phalanges: a longitudinal study.

The skeletal growth in a course of acute lymphoblastic leukemia (ALL) may be affected, and the aim of the longitudinal study was to assess the skeletal status in survivors of (ALL). The studied population consisted of 38 subjects (17 female and 21 male) measured at the age of 13.9 +/- 3.8 years (5.7 +/- 2.9 years after completion of the therapy, 11.0 +/- 14.4 years after diagnosis) and 2 years earlier; compared with 1402 controls (628 female and 774 male). Patients and controls did not differ significantly in regard to age, height or weight. Skeletal status was assessed by quantitative ultrasound (US) measurements at the hand phalanges using the DBM Sonic 1200, which measures amplitude-dependent speed-of-sound, Ad-SoS (m/s). rms CV% was 0.43%. Mean baseline Ad-SoS value in patients was 1990 +/- 76 m/s and, at second measurement, 2045 +/- 86 m/s (p < 0.000001). In 31 patients, Ad-SoS increased and, in one patient, decreased more than the value of the least significant change. In controls, mean Ad-SoS values were 1973 +/- 64 m/s (baseline) and 2016 +/- 86 m/s (follow-up) and did not differ significantly vs. baseline values in patients. At second measurement, Ad-SoS in controls was significantly lower than in patients (p < 0.05). In five patients with low baseline Ad-SoS values, bone mineral density (BMD) at the spine using DPX-L was estimated; baseline mean BMD was 0.95 +/- 0.11 g/cm2, Z-score was 1.25 +/- 0.97 and, at second measurement, 1.16 +/- 0.07 g/cm2, Z-score was 0.23 +/- 0.43. A significant increase in BMD (p < 0.01) and Z-score (p < 0.05) was noted. In patients, Ad-SoS correlated significantly with age, period after completion of the therapy, body size and Tanner stages (r ranged from 0.43 to 0.83, p ranged from 0.0001 to 0.05). It can be concluded that skeletal status assessed by quantitative US at the hand phalanges in survivors of ALL improved significantly over the period of observation.

Quantitative ultrasound of the hand phalanges in patients with genetic disorders: a pilot case-control study.

Skeletal status in subjects with genetic disorders rarely has been a matter of interest, and the risk for osteoporotic fracture in this population is not known. The aim of this study was to estimate ultrasound values in subjects with genetic disorders. In the study 50 patients (36 boys and 14 girls, mean age 11.8 +/- 2.9 years) and 528 healthy controls matched for age and body size (380 boys and 148 girls, mean age 11.9 +/- 2.5 years) were evaluated. Patients with the following disorders were included: Down syndrome, Martin-Bell syndrome, Marfan-Mass phenotype and others. Bone status was assessed by quantitative ultrasound (QUS) of hand phalanges using DBM Sonic 1200 (IGEA, Carpi, Italy), which measures amplitude-dependent speed of sound (Ad-SoS, m/s). Ad-SoS was significantly lower in patients than in controls (in the whole group 1,915 +/- 69 m/s vs. 1,970 +/- 62.0 m/s, P<0.0000001; in males 1,917 +/- 73 m/s vs. 1,972 +/- 63 m/s, P<0.000001; in females 1,910 +/- 58 m/s vs. 1,963 +/- 58 m/s, P<0.01). Ad-SoS correlated significantly with age and body size (except for Ad-SoS with age in female patients). In all subgroups of patients (except for the subjects with Marfan-Mass syndrome) Ad-SoS values were significantly lower than in controls. In a multiple, stepwise regression analysis of Ad-SoS on age and body size, in the whole group of patients age and height had significant influence on Ad-SoS, and in controls age, height and weight. In conclusion, the study shows significantly lower phalangeal ultrasound values in subjects with different genetic disorders compared to normal healthy persons.

Skeletal status in children and adolescents with chronic renal failure before onset of dialysis or on dialysis.

Bone status was assessed in 15 children and adolescents with predialysis chronic renal failure (CRF) and in 25 subjects with end-stage renal failure (ESRF). The mean age in the whole group was 14.6+/-3.2 years and CRF had been recognized 5.8+/-4.0 years earlier. The mean age, body size, duration of the disease and Tanner stages did not differ significantly between patients with predialysis CRF and ESRF. The control group consisted of 890 healthy subjects matched with patients for age. Bone mineral density (BMD) was measured by DPX-L (Lunar, Madison, WI) at the spine (s-BMD) and total body (TB-BMD); quantitative ultrasound (QUS) was performed by DBM 1200 (IGEA, Italy) at the hand phalanges (Ad-SoS). Laboratory investigations included the evaluation of intact parathyroid hormone (i-PTH), total and ionized serum calcium, and serum phosphate. In the whole group of patients the following mean values were obtained: Ad-SoS 1952+/-79 m/s (significantly lower than in controls, who had Ad-SoS 2022+/-85 m/s, p<0.05; the difference remained significant after adjusting for body mass index), s-BMD 0.87+/-0.22 g/cm2 ( Z-score -1.6), TB-BMD 0.92+/-0.12 g/cm2 ( Z-score -1.44), i-PTH 276+/-300 pg/ml, total calcium 2.46+/-0.19 mmol/l, ionized calcium 1.14+/-0.08 mmol/l, phosphate 1.68+/-0.61 mmol/l. Skeletal measurements correlated significantly with age, body size and Tanner stages (also after adjusting for age), while significant correlations of these parameters with the duration of CRF and laboratory investigations (except of correlations of i-PTH with Ad-SoS and with TB-BMD in predialysis patients) were not observed. None of the studied variables differed significantly between predialysis and dialysis patients. In conclusion, both predialysis and dialysis children and adolescents showed a decrease in BMD and quantitative ultrasound measurements. The severity of skeletal alterations was similar in the early phase (predialysis patients) and end stage (dialysis patients) of the disease and did not show a tendency to progress with CRF duration.

Skeletal status in survivors of childhood acute lymphoblastic leukemia assessed by quantitative ultrasound: a pilot cross-sectional study.

Intensive treatment in acute lymphoblastic leukemia (ALL) with the use of multimodality therapies, including radiotherapy, corticosteroids and cytotoxic agents, may lead to disturbances in bone metabolism. The aim of this study was to determine the degree of possible changes in bone status in survivors of ALL. The studied population consisted of 54 subjects aged 13.0 +/- 3.3 years (31 girls and 23 boys). The mean age at diagnosis was 5.5 +/- 3.5 years, age at the completion of therapy was 8.4 +/- 3.5 years, and the period of follow-up was 4.6 +/- 3.4 years. Patients were divided into three subgroups (low-, moderate- and high-risk) according to the presence of risk factors of ALL and compared with 1020 healthy subjects (508 girls and 512 boys). Patients and controls did not differ significantly in regard to age, height, or weight. Bone status was assessed by quantitative ultrasound (US) at right (dominant) hand phalanges using DBM Sonic 1200 (IGEA, Carpi, Italy) that measures amplitude-dependent speed of sound (Ad-SoS, m/s). Root mean square (RMS)_CV% was 0.43%. Mean Ad-SoS values were 2018 +/- 73 m/s in patients and 2003 +/- 80 m/s in controls and did not differ significantly. Ad-SoS tended to be lower in moderate- and high-risk patients, but differences were not significant. Ad-SoS correlated significantly with age in patients (r value ranged from 0.63 to 0.77, p < 0.01) and controls (r value ranged from 0.79 to 0.84, p < 0.0001). In multiple forward regression analysis, the following equation was obtained: Ad-SoS (m/s) = 1878 (m/s) + 11.4 x age at the study (y) + 4.0 x period after therapy completion (y) - 9.5 x duration of the therapy (y). It can be concluded that bone status assessed by quantitative US at the hand phalanges in survivors of acute lymphoblastic leukemia 4.6 years after completion of the therapy is not affected in comparison to healthy controls.

Skeletal status in children, adolescents and young adults with end-stage renal failure treated with hemo- or peritoneal dialysis.

The skeletal status in 30 children, adolescents and young adults (18 females, 12 males) with end-stage renal failure (ESRF) aged 9-23 years (mean 15.8 +/- 3.6 years) was evaluated using measurements of bone mineral density (BMD, g/cm2) at the spine and total body (TB) (Lunar DPX-L, USA), quantitative ultrasound (QUS) of the hand phalanges (DBM Sonic 1200, IGEA, Italy) and laboratory investigations (parathyroid hormone, serum total and ionized calcium, serum phosphate). Eleven subjects were treated with hemodialysis and 19 with peritoneal dialysis. The mean value of the amplitude-dependent speed of sound (Ad-SoS, m/s) measured by QUS was significantly decreased in comparison with the value obtained in a group of 686 age-matched controls (1942 +/- 74 m/s vs 2050 +/- 77 m/s, p<0.0001). BMD measurements were also decreased in comparison with mean values for the healthy population (Z-scores for spine -1.47, and for TB -1.53). Duration of dialysis correlated significantly with spine-BMD, TB-BMD and Ad-SoS (r = -0.37, r = -0.45, r = -0.55, respectively, p<0.05), while duration of ESRF did not have such an influence. Laboratory investigations did not correlate with skeletal parameters. Ad-SoS correlated significantly with spine-BMD (r = 0.45, p<0.05) and TB-BMD (r = 0.56, p<0.01). Both QUS and BMD values correlated significantly with Tanner stages (r ranged from 0.59 to 0.69, p<0.001) and did not increase with age except for correlation between age and TB-BMD. In conclusion, skeletal status in the population studied is strongly affected by ESRF. Both QUS and BMD measurements show an ability to express skeletal changes in a similar manner, though the QUS parameter seems to be more sensitive at revealing changes due to renal failure.

The assessment of development of bone mass in children by quantitative ultrasound through the proximal phalanxes of the hand.

The purpose of this study was to determine the relationship between quantitative ultrasound and age and body size, and to establish reference ranges for speed of sound (Ad-SoS) in the phalanxes of children. Healthy children (433), aged from 9 to 15 y were studied (226 girls and 207 boys). Ultrasound device (DBM Sonic 1200, IGEA, Italy) measuring the Ad-SoS through the phalanxes was used. Up to 11 y, the mean values for boys and girls were not significantly different. The increase of values was observed in the girls at 11 y, in the boys 2 y later. Stepwise multiple linear-regression analysis has shown that, in girls, the main factor influencing Ad-SoS was age and, in boys, height and weight. In the study, the ability of measurements of proximal phalanxes to reveal skeletal changes in healthy Polish children was shown. The study enabled us to establish the reference curves for healthy Polish children.