Oxygen therapy in preterm infants with pulmonary hypertension

Premature neonates <34 weeks gestation can present with early-onset, late-onset and bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PHT), with clinical, echocardiographic, and histological features similar to term infants with PHT. Changes in pulmonary vascular resistance (PVR) in response to oxygen are diminished in preterm infants compared to term. Studies from preterm lambs and human infants with BPD have shown that PaO₂ > 30–55 mm Hg promotes pulmonary vasodilation. Targeting saturations of 80–85% by 5 min, 85–95% by 10 min during resuscitation and 90–95% during the postnatal course are appropriate targets for routine management of preterm infants. Among preterm infants with PHT, avoiding hypoxia/hyperoxia by titrating supplemental oxygen to maintain saturations in low to mid 90s with alarm limits at 90 and 97% seems to be a reasonable approach pending further studies. Further high-quality evidence generated from randomized trials is required to guide oxygen therapy in preterm PHT.     

Pediatric respiratory tract diseases: Chronological trends and perspectives

Background

The aim of this study was to describe the epidemiological profile of childhood respiratory tract diseases (RTD) in the region of Sfax, Tunisia, and to evaluate their trends over a 13 year period.

Methods

We conducted a retrospective study of all children hospitalized with RTD aged under 14 years. We collected data from the regional morbidity register of the university hospital of Sfax from 2003 to 2015.

Results

A total of 10 797 RTD patients were enrolled from 49 880 pediatric hospitalizations (21.7%). A male predominance was noted (60%). The median age was 8 months (IQR, 2–36 months). Acute bronchitis (AB) accounted for 53.8%, followed by asthma (15%), pneumonia (14%) and acute upper respiratory infection (AURI; 7.2%). The hospital incidence rate (HIR) of RTD was 34/10 000 inhabitants/year. It was 18.2; 5.07; 4.7 and 2.4/10 000 inhabitants for AB, asthma, pneumonia and AURI, respectively. We noted a significant increase in the HIR of RTD with an annual percentage change (APC) of 10.94% (P < 0.001); in the HIR of AB (APC, 5.27%; P < 0.001); and in asthma HIR (APC, 11.2%; P < 0.001). Otherwise, a significant decrease in AURI HIR was observed (APC, –8.8%; P < 0.001). AB lethality rate increased significantly, with an APC of 7.4% (P < 0.001). Projected trends analysis up to 2024 showed a significant rise in AB and in asthma, while AURI would significantly decrease.

Conclusions

RTD continues to be a serious health problem over time in terms of morbidity and mortality. Preventive and curative strategies are needed urgently.     

A pooled subgroup analysis of glucarpidase treatment in 86 pediatric,adolescent, and young adult patients receiving high-dose methotrexate therapy in open-label trials

Background

Delayed methotrexate elimination can occur in patients undergoing high-dose methotrexate cancer treatment. Effectiveness of glucarpidase for rapidly reducing methotrexate concentrations was shown in compassionate-use trials in patients aged 0–84 years.

Methods

We performed post hoc analyses of infants (≥28 days to <2 years), children (≥2 to <12 years), adolescents (≥12 to <15 years), and young adults (≥15 to <25 years) from four multicenter, open-label, single-arm, glucarpidase compassionate-use trials. Patients had toxic methotrexate levels due to delayed methotrexate elimination and/or renal dysfunction, and received glucarpidase (50 U/kg). The primary endpoint was clinically important reduction (CIR) in plasma methotrexate (methotrexate ≤1 μmol/L at all post-glucarpidase measurements) based on high-performance liquid chromatography.

Results

Among 86 patients included in efficacy analyses, CIR was achieved by zero of one infant (0.0%), five of 16 children (31.3%), seven of 24 adolescents (29.2%), and 26/45 young adults (57.8%). Median methotrexate reduction was 98.7% or higher in each group 15 minutes post-glucarpidase. Patients with pre-glucarpidase methotrexate less than 50 μmol/L (35/42, 83.3%) were more likely to achieve CIR than those with methotrexate 50 μmol/L or higher (1/37, 2.7%). The most common treatment-related adverse event was paresthesia, occurring in three adolescents (4.5%) and six young adults (5.2%). No other treatment-related adverse event occurred in 5% or higher of any age group.

Conclusion

After accounting for pre-glucarpidase methotrexate levels, glucarpidase efficacy at inducing CIR in pediatric/young adult patients was consistent, with efficacy observed in the overall study population (i.e., patients aged 0–84), and no unexpected safety findings were observed. These findings demonstrate glucarpidase (50 U/kg) is an effective and well-tolerated dose for pediatric, adolescent, and young adult patients.     

Duration of anaemia during the first week of life is an independent risk factor for retinopathy of prematurity

Aim

This study evaluated the correlation between retinopathy of prematurity (ROP), anaemia and blood transfusions in extremely preterm infants.

Methods

We included 227 infants born below 28 weeks of gestation at King Edward Memorial Hospital, Perth, Australia, from 2014–2016. Birth characteristics and risk factors for ROP were retrieved, and anaemia and severe anaemia were defined as a haemoglobins of <110 g/L and <80 g/L, respectively. Logistic regression was used for the analysis.

Results

Retinopathy of prematurity treatment was needed in 11% of cases and the mean number of blood transfusions (p < 0.01), and mean number of weeks of anaemia (p < 0.001) and of severe anaemia (p < 0.05), had positive associations with ROP cases warranting treatment. In the multivariate logistic regression analysis, the best‐fit model of risk factors included anaemic days during first week of life, with an odds ratio (OR) of 1.46% and 95% confidence interval (CI) of 1.16–1.83 (p < 0.05), sepsis during the first 4 weeks of life (OR 3.14, 95% CI 1.10–9.00, p < 0.05) and days of ventilation (OR 1.03, 95% CI 1.01–1.06, p < 0.05).

Conclusion

The duration of anaemia during the first week of life was an independent risk factor for ROP warranting treatment and preventing early anaemia may decrease this risk.     

Neonatal outcomes of very preterm infants from a neonatal intensive care center

Background

Information about clinical outcomes of very preterm (VPT) infants in tertiary neonatal intensive care unit (NICU) setting is scant in China. This study aimed to investigate the mortality and morbidity of VPT infants admitted to BaYi Children’s Hospital, which serves as a NICU referral center for the city of Beijing, China.

Methods

Retrospectively collected perinatal/neonatal data on all admissions of infants born at <32 weeks of gestational age and subsequently admitted to the VPTNICU from clinical records between October 2010 and September 2011.

Results

Totally 729 infants were identified. 90% of VPT infants were outborn. The overall survival of the infants to discharge was 92%, which increased with increasing gestational age (range from 69% at <28 weeks to 99% at 31 weeks). The incidence of bronchopulmonary dysplasia was 4%, retinopathy of prematurity requiring treatment 2%, intraventricular hemorrhage III-IV 6%, and periventricular leukomalacia 2%. 10% of the VPT infants had a major morbidity at discharge.

Conclusions

The outcomes of the VTP infants at this referral NICU were comparable to those in tertiary centers in developed countries. The most common complications were lower than those in other cohorts. Accordingly, high-volume NICU may minimize the adverse effects of VPT infants’ transport.     

Prostaglandin E2 After Septostomy for Simple Transposition

In simple transposition of the great arteries (sTGA), balloon atrial septostomy is performed prior to arterial switch to improve mixing of systemic and pulmonary circulations. Following septostomy, some patients are also given prostaglandin E2 (PGE2) until surgical repair. The aims of our study were to identify how often PGE2 is given after septostomy, the indications for starting PGE2, and the effect this has on postoperative outcome. The study was a retrospective review of infants born with sTGA between 2000 and 2005, who underwent arterial switch at Yorkhill Children’s Hospital, Glasgow. Over a 5-year period, 26 infants (16 male) with sTGA underwent septostomy. There was a significant rise in mean oxygen saturation following septostomy (mean, 61.4 ± 11.5% before, 81.5 ± 9.4% after; p < 0.05). Four of 26 (15%) did not receive PGE2 at all (group 1) and 8 of 26 (30%) received PGE2 before but not after septostomy (group 2). A total of 14 of 26 infants (54%) were given PGE2 following septostomy. This comprised 11 who received PGE2 before and after septostomy (group 3) and 3 who did not receive PGE2 prior to septostomy but did after (group 4). Groups 2 and 3 were compared directly, as they both received PGE2 before septostomy. In group 3, oxygen saturations were lower when PGE2 was started compared with saturations immediately after septostomy (45 ± 23.6% vs. 80 ± 10.3%; p < 0.05). Groups 2 and 3 showed no difference in atrial gap after septostomy (9.4 ± 3 vs. 8 ± 1 mm; p > 0.05). Fifty percent of infants in group 3 underwent echocardiography prior to restarting PGE2, which revealed a patent arterial duct in all but one patient. Despite PGE2, Group 3 had lower saturations at arterial switch compared with Group 2 (71 ± 14% vs. 82 ± 8%; p < 0.05). No difference was observed between group 2 and group 3 with regard to length of cardiopulmonary bypass (group 2, 173 ± 101.4 min, vs. group 3, 157.9 ± 42.1 min; p > 0.05). However, the Intensive Care Unit stay was longer for patients who received PGE2 following septostomy (8.5 ± 10.3 vs. 5 ± 0.93 days; p < 0.05). Total postoperative stay was also longer for infants who received PGE2 after septostomy (26.8 ± 14.3 vs. 16.8 ± 6.3 days; p < 0.05). In conclusion, the use of pulse oximetry has led to an increase in the administration of PGE2 after septostomy. PGE2 administration was associated with a longer ICU stay. The association between administration of PGE2 and longer postoperative stay supports the approach of early surgical repair with minimal preoperative medical intervention. This article is submitted with the full approval of both authors. Beattie LM, McLeod K. Neonatal transposition: atrial gap and post-septostomy prostaglandin E2. Presented at the British Paediatric Cardiac Association, Royal College of Paediatrics and Child Health Annual Spring Meeting, York, UK, April 5, 2006.     

Value of surgical resection in children with high‐risk neuroblastoma

Background

The value of gross total resection (GTR) for children with high‐risk neuroblastoma (NB) is controversial. We hypothesized that patients undergoing GTR would demonstrate improved overall survival (OS) compared those having <GTR.

Methods

Using a single institutional database, we reviewed the medical records of all children with high‐risk NB undergoing hematopoietic stem cell transplantation (HSCT) as part of multimodality therapy from 1990 to 2012. Children had received surgical care at multiple institutions (n = 14) prior to HSCT and were divided into two groups based on extent of surgical resection: GTR (no visible or palpable disease at end of operation) and <GTR (no surgery, biopsy only, or subtotal resection). Kaplan–Meier curves and Cox hazards models evaluated differences in overall survival (OS).

Results

One hundred four children underwent HSCT, and 87 (83.6%) had adequate data for analysis. Thirty eight percent had GTR while 62% had <GTR prior to HSCT. There was no significant difference in OS in patients undergoing GTR compared to <GTR (Log rank test: P = 0.49). Post‐hoc analysis demonstrated a survival advantage for patients undergoing >90% resection compared to <90% resection (P = 0.008). Multivariable Cox models confirmed these findings with improved survival in children undergoing >90% vs. <90% resection but no difference in GTR vs. <GTR.

Conclusion

Gross total resection prior to HSCT in high‐risk NB patients is not associated with improved OS compared to <GTR; however, these results suggest that >90% resection is associated with improved OS compared to less than 90% resection. Pediatr Blood Cancer 2015;62:1529–1535. © 2015 Wiley Periodicals, Inc.     

Oxygen Saturation Immediately after Birth in Infants Delivered in Tertiary Care Hospital in India

Objective

To study the sequential changes in SpO₂ values in newborns delivered in a teaching hospital in India.

Methods

Full-term infants born by normal vaginal delivery to registered mothers at KLE University Hospital, Belgaum with birth weight more than 2,500 g, no congenital anomalies and who had received only routine care at birth were included in the study. After delivery, newborn infants were placed on a resuscitation trolley under a radiant warmer; the oxygen saturation sensor was attached (Nellcor DURA-Y multisite oxygen sensor) and then connected to the monitor (Planet 55 multiparameter recorder).

Results

The mean (SD) gestational age of infants included in the study was 38.8 (1.1) wk and birth weight was 2,800 (300) g. The median (IQR) oxygen saturation level (SpO₂) at 2 min of age was 69 % (68 %–79 %). The median level of SpO₂ at 90 % and 95 % saturation was attained at 6.5 min and at 11 min of life, respectively.

Conclusions

Infants delivered in resource poor facilities of developing countries take 11 min to reach 95 % saturations after birth but they are within the reference range values of Neonatal Resuscitation Program 2010 guidelines.     

Early school-based learning difficulties in children born very preterm

Background

Educational underachievement is a major morbidity associated with very preterm (VPT) birth. However, few studies have examined early school outcomes with most employing global, clinic based measures.

Objective

To examine the early school achievement in a cohort of children born VPT and studied to age 6 years.

Methods

A regional cohort of 102 VPT children (≤ 33 weeks GA) were followed prospectively alongside a comparison group of 108 full term (FT) children born during the same period (1998-2000). At 6 years corrected age, all children underwent a comprehensive neurodevelopmental evaluation that included the Woodcock-Johnson Tests of Achievement (WJ-III), teacher report and national numeracy and literacy test results. Rates of specific learning disabilities (LD) were also examined.

Results

VPT children performed less well than FT children on WJ-III subtests (ps < .05), national tests (ps < .01), and in all curricular areas rated by teachers (ps < .01) except expressive language. Even VPT children without severe neurodevelopmental impairment scored lower on the WJ-III math, national tests (ps < .05) and were 2-3 times more likely to show delays (ps < .02) in math (43% vs. 19%), written language (36% vs. 22%), language comprehension (26% vs. 14%), handwriting (36% vs. 17%), spelling (38% vs. 30%) and physical education (33% vs. 11%). They were also twice as likely as FT children to have math LD (47% vs. 21%).

Conclusions

By age 6, a substantial proportion of VPT children are lagging behind their FT peers across multiple curriculum areas, with difficulties being most prominent in math. Findings highlight the need for early identification and educational supports to help maximise VPT children's learning opportunities during the transition to school.     

Healthcare utilization and cost barriers among U.S. childhood cancer survivors

Background

To evaluate healthcare utilization and cost barrier patterns among childhood cancer survivors (CCS) compared with noncancer controls.

Procedure

Using the 2014-2019 Behavioral Risk Factor Surveillance System, we identified CCS < 50 years and matched controls. We used chi-squared tests to compare characteristics between the two groups. Logistic regression analyses were used to assess the likelihood of having a checkup, receiving influenza vaccine, and experiencing healthcare cost barriers (being unable to see the doctor due to cost) during the past 12 months. Conditional models accounted for the matching.

Results

We included 231 CCS and 692 controls. CCS had lower household income (p < 0.001), lower educational attainment (p = 0.021), more chronic health conditions (p < 0.001), and a higher proportion of being current smokers (p = 0.005) than controls. Both groups had similar rates of having a checkup and influenza vaccine; however, a quarter of CCS experienced healthcare cost barriers compared with 13.9% in controls (p = 0.001; regression findings: adjusted odds ratio (aOR) = 1.72, 95% confidence interval (CI): 1.11-2.65). Compared with the youngest CCS group (18-24 years), CCS ages 25-29 years were five times more likely to experience healthcare cost barriers (aOR = 4.79; 95% CI, 1.39-16.54). Among CCS, current smokers were less likely to have a checkup (aOR = 0.46; 95% CI, 0.23-0.94). Uninsured CCS were less likely to have a checkup (aOR = 0.33; 95% CI, 0.14-0.75) and ∼8 times more likely to experience healthcare cost barriers (aOR = 8.28; 95% CI, 3.45-19.88).

Conclusion

CCS being 25-29 years, uninsured, or current smokers encounter inferior outcomes in healthcare utilization and cost barriers. We suggest emphasis on programs on care transition and smoking cessation for CCS.     

Predictors of mortality and major morbidities in extremely low birth weight neonates

Objectives

To determine predictors of mortality and morbidity in extremely low birth weight neonates (ELBW) from a developing country

Study design

Prospective observational study.

Setting

Level III neonatal unit in Northern India.

Subjects

Neonates <1000g born and admitted to intensive care during study period were enrolled. They were analyzed based on survival and development of major morbidity. Multivariable logistic regression model was used to determine independent risk factors.

Outcome

Mortality and major morbidity (one or more of the following: Bronchopulmonary dysplasia (BPD), Retinopathy of Prematurity (ROP) requiring laser, grade III or IV intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL) and necrotizing enterocolitis (NEC) stage III) during hospital stay.

Results

Of 255 ELBW neonates born, 149 received optimal care, of which 78 (52%) survived and 57 (39%) developed morbidities. Mean birth weight and gestational age were 29.1±2.6 weeks and 843±108g. Major causes of mortality were sepsis (46%), birth asphyxia (20%) and pulmonary hemorrhage (19%). Birth weight ≤800g [OR (95% CI)-3.51 (1.39–8.89), P=0.008], mechanical ventilation [4.10 (1.64–10.28), P=0.003] and hypotensive shock [10.75 (4.00–28.89), P<0.001] predicted mortality while birth weight ≤800g [3.75 (1.47–9.50), P=0.006], lack of antenatal steroids [2.62 (1.00–6.69), P=0.048), asphyxia [4.11 (1.45–11.69), P=0.008], ventilation [4.38 (1.29–14.79), P=0.017] and duration of oxygen therapy [0.004 (1.001–1.006), P=0.002] were the predictors of major morbidities.

Conclusions

Low birth weight, mechanical ventilation and hypotensive shock predicted mortality in ELBW neonates while low birth weight, lack of antenatal steroids, birth asphyxia, ventilation and duration of oxygen therapy were predictors for major morbidity.     

High‐dose treatment for malignant rhabdoid tumor of the kidney: No evidence for improved survival—The Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) experience

1 Background

Malignant rhabdoid tumor of the kidney (MRTK) is the most aggressive childhood renal tumor with overall survival (OS) rates ranging from 22% to 42%. Whether high‐dose chemotherapy with autologous stem‐cell transplantation (HDSCT) in an intensive first‐line treatment offers additional benefit is an ongoing discussion.

2 Methods

A retrospective analysis of all 58 patients with MRTK from Austria, Switzerland, and Germany treated in the framework of consecutive, prospective renal/rhabdoid tumor studies SIOP9/GPO, SIOP93‐01/GPOH (where SIOP is International Society of Pediatric Oncology and GPOH is German Society of Pediatric Oncology and Hematology), SIOP2001/GPOH, and European Rhabdoid Tumor Registry from 1991 to 2014.

3 Results

Median age at diagnosis was 11 months. Fifty percent of patients had metastases or multifocal disease at diagnosis (Stage IV). Local stage distribution was as follows: not done/I/II/III—1/6/11/40. Fifteen (26%) patients underwent upfront surgery. Thirty‐seven (64%) patients achieved a complete remission, 17 (29%) relapsed, 34 (59%) died of disease progression, and two (3%) died of treatment‐related complication. Mean time to the first event was 3.5 months. Two‐year EFS/OS (where EFS is event‐free survival) for the whole group was 37 ± 6%/38 ± 6%. Metastases/multifocal disease, younger age, and local stage III were associated with significantly inferior survival. Eleven (19%) patients underwent HDSCT (carboplatin + thiotepa, n = 6; carboplatin + etoposide + melphalan, n = 4; others, n = 1); 2‐year OS in this group was 60 ± 15% compared to 34 ± 8% in the non‐HDSCT group (P = 0.064). However, the time needed from radiologic to histologic diagnosis, stem‐cell harvest, and HDSCT must also be taken into account to avoid selection bias by excluding the highest risk group with early progression (<90 days). Thus, 2‐year EFS only for patients without progression until day 90 was 60 ± 16% consolidated by HDSCT compared to 62 ± 11% without (P = 0.8).

4 Conclusion

Our retrospective analysis suggests comparable outcomes for patients with and without HDSCT, if adjusted for early disease progression.     

Sputum TWEAK expression correlates with severity and degree of control in non‐eosinophilic childhood asthma

Background

Tumor necrosis factor‐like weak inducer of apoptosis (TWEAK) is known to play a role in the pathogenesis of various inflammatory diseases. However, no study has been performed on childhood asthma.

Methods

Ninety‐five children with asthma and 78 controls aged 5‐18 years were included. Sputum induction, pulmonary function test (PFT), and methacholine challenge test were performed. The subjects were divided into the eosinophilic airway (EA) and non‐EA (NEA) groups based on sputum analysis and into the high and low TWEAK groups according to the TWEAK cutoff level (263.0 pg/mL). TWEAK in induced sputum supernatant was measured through enzyme‐linked immunosorbent assay.

Results

Children with asthma had higher TWEAK levels than healthy controls (493.0 [157.1‐904.3] vs 118.2 (67.5‐345.5) pg/mL, P < .001). Sputum TWEAK levels were significantly correlated with PFT parameters reflecting airway obstruction. This association was particularly prominent in subjects with NEA inflammation. Significant differences in FEF_25‐75 (maximum mid‐expiratory flow, % predicted; P = .017), AX (reactance area; P < .001), R5‐R20 (difference between resistance at 5 and 20 Hz; P = .025), and X5 (reactance at 5 Hz, % predicted; P < .001) were noted between the high and low TWEAK groups within the NEA group. Sputum TWEAK level also showed significant positive correlations with asthma severity (r = .358, P = .001) and control status (r = .470, P < .001), distinctively in subjects with NEA inflammation.

Conclusions

Airway TWEAK may play a role in small airway inflammation especially in children with non‐eosinophilic asthma.     

Lactate clearance as a marker of mortality in Pediatric Intensive Care Unit

Objectives

To correlate lactate clearance with Pediatric Intensive Care Unit (PICU) mortality.

Methods

45 (mean age 40.15 mo, 60% males) consecutive admissions in the PICU were enrolled between May 2012 to June 2013. Lactate clearance (Lactate level at admission — level 6 hr later × 100 / lactate level at admission) in first 6 hours of hospitalization was correlated to in-hospital mortality and PRISM score.

Results

Twelve out of 45 patients died. 90% died among those with delayed/poor clearance (clearance <30%) compared to 8.5% in those with good clearance (clearance >30%) (P<0.001). Lactate clearance <30% predicted mortality with sensitivity of 75%, specificity of 97%, positive predictive value of 90%, and negative predictive value of 91.42%. Predictability was comparable to PRISM score >30.

Conclusion

Lactate clearance at six hours correlates with mortality in the PICU.     

Anthropometric surrogates to identify low birth weight Nepalese newborns: a hospital-based study

Background  

In Nepal, more than 90% of the deliveries take place at home where birth weight is often not recorded. In developing countries, low birth weight (LBW, <2500 grams) accounts for 60–80% of neonatal deaths. Early identification and referral of LBW babies for extra essential newborn care is vital in preventing neonatal deaths. Studies carried out in different populations have suggested that the use of newborn anthropometric surrogates of birth weight may be a simple and reliable method to identify LBW babies in a home setting. However, a reliable anthropometric surrogate to identify LBW babies and its cut-off point is not known for Nepalese newborns.     

Use of near-infrared spectroscopy for estimation of renal oxygenation in children with heart disease

We evaluated whether near-infrared spectroscopy (NIRS) measurement from the flank correlates with renal vein saturation in children undergoing cardiac catheterization. Thirty-seven patients <18 years of age were studied. A NIRS sensor was placed on the flank, and venous oxygen saturations were measured from the renal vein and the inferior vena cava (IVC). There was a strong correlation between flank NIRS values (rSO₂) and renal vein saturation (r = 0.821, p = 0.002) and IVC saturation (r = 0.638, p = 0.004) in children weighing ≤ 10 kg. In children weighing > 10 kg, there was no correlation between rSO₂ and renal vein saturation (r = 0.158, p = 0.57) or IVC saturation (r = –0.107, p = 0.67). Regional tissue oxygenation as measured by flank NIRS correlates well with both renal vein and IVC oxygen saturations in children weighing <10 kg undergoing cardiac catheterization, but not in larger children.     

Inhibitory effect of drug-free hybrid liposomes on metastasis of human neuroblastoma

Purpose  

Hybrid liposomes composed of vesicular and micellar molecules have been used as drug-delivery systems. It has become clear that hybrid liposomes alone have an inhibitory effect against the growth of various tumor cells. The present study was designed to determine whether a drug-free hybrid liposome composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylenealkyl ether (EO) [90 mol% DMPC/10% C₁₂(EO)₂₁ (HL21), 90 mol% DMPC/10% C₁₂(EO)₂₃ (HL23), or 90 mol% DMPC/10% C₁₂(EO)₂₅ (HL25)], inhibit the liver metastasis of human neuroblastoma cells and thus increases survival.     

Impact of ovarian transposition before pelvic irradiation on ovarian function among long‐term survivors of childhood Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study

1 Background

We reviewed the effect of ovarian transposition (OT) on ovarian function among long‐term survivors of childhood Hodgkin lymphoma (HL) treated with pelvic radiotherapy.

2 Procedure

Female participants (age 18+ years) with HL in the St. Jude Lifetime Cohort Study (SJLIFE) were clinically evaluated for premature ovarian insufficiency (POI) 10 or more years after pelvic radiotherapy. Reproductive history including age at menopause and pregnancy/live births was available on all patients.

3 Results

Of 127 eligible females with HL, 90 (80%) participated in SJLIFE, including 49 who underwent OT before pelvic radiotherapy. Median age at STLIFE evaluation was 38 years (range 25–60). In a multiple regression adjusted for age at diagnosis, pelvic radiotherapy doses > 1,500 cGy (hazard ratio [HR] = 25.2, 95% confidence interval [CI] = 3.1–207.3; P = 0.0027) and cumulative cyclophosphamide equivalent doses of alkylating agents > 12,000 mg/m² (HR = 11.2, 95% CI = 3.4–36.8; P < 0.0001) were significantly associated with POI. There was no significant association between OT and occurrence of POI (HR = 0.6, 95% CI = 0.2–1.9; P = 0.41).

4 Conclusions

OT did not appear to modify risk of POI in this historic cohort of long‐term survivors of HL treated with gonadotoxic therapy. Modern fertility preservation modalities, such as mature oocyte cryopreservation, should be offered to at‐risk patients whenever feasible.     

Changes in physiological and behavioural pain indicators over time in preterm and term infants at risk for neurologic impairment

Background

Approximately 10% of infants admitted to a Neonatal Intensive Care Unit (NICU) are at risk for Neurological Impairment (NI). While we have limited knowledge on the influence of NI risk on pain responses, we have no knowledge of how these responses change over time.

Objective

To compare physiological and behavioural pain responses of infants at three levels of NI risk during the NICU neonatal period (Session 1) and at 6 months of age (Session 2).

Design/methods

Prospective observational design with 149 preterm and term infants at high (Cohort A, n = 54), moderate (Cohort B, n = 45) and mild (Cohort C, n = 50) risks for NI from 3 Canadian tertiary level NICUs. Infants were observed in the NICU during 3 standardized phases of a heel lance: baseline, stick and return-to-baseline. At 6 months, infants were observed during the same three phases during an intramuscular immunization injection. Physiological (heart rate, oxygen saturation) and behavioural (9 facial actions, cry) responses were continuously recorded.

Results

A significant interaction of Phase by Session was found with less total facial activity observed during Session 2 (all p values < 0.04). A significant interaction for Session by Cohort was found, showing that infants in Cohort A had significantly more change from baseline-to-stick phase for brow bulge, eye squeeze, nasolabial furrow and open lips between sessions with less facial actions demonstrated at Session 2 (all p < 0.02). There were significantly lower mean and minimum heart rate (all p < 0.02) and higher minimum and maximum oxygen saturation (p < 0.04) at Session 2. Significantly higher mean and minimum fundamental cry frequencies (pitch) in Cohort B (p < 0.04) were found in Session 1. Cohort A had significantly longer cry durations, but no significant differences in cry dysphonation.

Conclusions

Behavioural and physiological infant pain responses were generally diminished at 6 months of age compared to those in the neonatal period with some differences between NI risk groups in cry responses. Future exploration into the explanation for these differences between sessions and cohorts is warranted.     

Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study

Background

Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA.

Methods

In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO₂), anaerobic threshold, O₂ pulse, VE/VCO₂ slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO₂. Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected.

Results

Ten hemoglobin SS patients aged 12–24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P₅₀ left shift of average −11 mmHg (p < .0001) with decreased oxygen off-loading at low pO₂. The change in % predicted peak VO₂ from CPET#1 to CPET#2 ranged from −12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive.

Conclusion

In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO₂ in 9 out of 10 patients.