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.     

Ifosfamide,gemcitabine, and vinorelbine is an effective salvage regimen with excellent stem cell mobilization in relapsed or refractory pediatric Hodgkin lymphoma

We describe 12 pediatric patients (8‐16 years) with primary refractory (N = 6) or first relapse (N = 6) Hodgkin lymphoma (HL) treated with ifosfamide, gemcitabine, and vinorelbine (IGEV). The overall response rate to IGEV was 100%, with seven (58%) complete responses (CR) and five (42%) partial responses. Successful CD34⁺ stem cell mobilization was achieved in all patients. Following subsequent autologous stem cell transplantation, 10 patients (83%) achieved CR. At a median follow‐up of 71 months, 11 patients had no evidence of disease. Five‐year second event‐free survival and overall survival were 83% ± 11.0% and 90.0% ± 9.5%, respectively. IGEV is an effective salvage regimen for children with relapsed/refractory HL.     

Intravenous nicardipine in hypertensive preterm infants

Eight preterm infants were given intravenous nicardipine, a calcium channel blocker, to treat systemic hypertension (renal artery thrombosis (n=3); dexamethasone for management of bronchopulmonary dysplasia (n=2); unexplained (n=3)). Nicardipine doses ranged from 0.5 to 2.0 µg/kg/min and were given for three to 36 days (mean (SD) 15.9 (10.3) days). Systolic blood pressure had significantly decreased after 12 and 24 hours of nicardipine treatment (-17 (17)% and -21 (10) %, respectively). Diastolic blood pressure significantly decreased after 24 hours of treatment (-22 ± 16%). The decrease in blood pressure remained significant over the subsequent days of treatment. No hypotension or other clinical side effects were observed.  It is concluded that intravenous nicardipine could be a first line treatment for hypertension in preterm infants.     

Comparative pharmacokinetics of tacrolimus in stable pediatric allograft recipients converted from immediate‐release tacrolimus to prolonged‐release tacrolimus formulation

This study was a Phase II, open‐label, multicenter, single‐arm, cross‐over study comparing the pharmacokinetics (PK) of tacrolimus in stable pediatric kidney, liver, or heart allograft recipients converted from immediate‐release tacrolimus (IR‐T) to prolonged‐release tacrolimus (PR‐T). In Days ?30 to ?1 of screening period, patients received their IR‐T‐based regimen; during Days 1‐7, patients received study IR‐T (same dose as screening). On Day 7, the first 24‐hours PK profile was taken; patients were then converted to PR‐T (1 mg:1 mg), with a second 24‐hours PK profile taken on Day 14. The primary end‐point was tacrolimus area under the blood concentration–time curve over 24 hours (AUC₂₄); secondary end‐points were maximum concentration C_maxand concentration at 24 hours C₂₄. The predefined similarity interval for confidence intervals (CIs) of least squares mean (LSM) ratios was 80%‐125%. The PK analysis set comprised 74 pediatric transplant recipients (kidney, n = 45; liver, n = 28; heart, n = 1). PR‐T:IR‐T LSM ratio (90% CI) was similar overall for AUC₂₄, _max, and C₂₄, and for kidney and liver recipients for AUC₂₄ (LSM ratio, kidney 91.8%; liver 104.1%) and C₂₄ (kidney 90.5%; liver 89.9%). Linear relationship was similar between AUC₂₄ and C₂₄, and between PR‐T and IR‐T (rho 0.89 and 0.84, respectively), suggesting that stable pediatric transplant recipients can be converted from IR‐T to PR‐T at the same total daily dose, using the same therapeutic drug monitoring method.     

Hearing screening practices among a national sample of primary care pediatricians

The objective of this study was to describe variations in hearing screening using a survey mailed to a national sample of primary care pediatricians prior to the 2003 American Academy of Pediatrics (AAP) hearing screening guidelines. Of the 390 primary care respondents, only 303 (78%) performed audiometry, routinely beginning at age 3 (32%), 4 (44%), or 5 (17%); 81% defined abnormal audiometry primarily as failure to hear at a specified decibel level: 15 dB hearing level (HL) (<1%), 16 to 20 dB HL (10%), 21 to 25 dB HL (23%), 26 to 30 dB HL (44%), 31 to 40 dB HL (16%), and more than 40 dB HL (6%). This study serves as a baseline for comparison with postguideline practices.     

脐血25羟基维生素D3对早期婴儿特应性皮炎的预测作用

目的 探讨脐血25羟基维生素D3[25（OH）D3]对婴儿特应性皮炎的预测价值，为婴儿早期特应性皮炎的一级预防提供参考指征。方法 选择2015年7~9月期间出生的新生儿，于生后立即采集脐血并检测脐血25（OH）D3水平。所有婴儿分别于生后6周、3个月、6个月时进行门诊随访，记录特应性皮炎的发生情况。结果 最终有67例婴儿全部完成了为期6个月的随访过程，纳入本研究。有23例（34%）出现特应性皮炎，其中91%（21/23）的婴儿特应性皮炎出现在生后的第1个月。根据特应性皮炎的发生情况将婴儿分为特应性皮炎组（n=23）和健康对照组（n=44），特应性皮炎组脐血25（OH）D3水平低于正常组（P < 0.05）。根据脐血25（OH）D3水平分为 < 30 nmol/L（n=21）和 ≥ 30 nmol/L组（n=46），<30 nmol/L组婴儿特应性皮炎发病率高于 ≥ 30 nmol/L组（P < 0.05）。ROC分析结果显示：曲线下面积（AUC）为0.648，标准误为0.075，95%CI为0.502~0.795，灵敏度为52.2%，特异度为79.5%，阳性预测值为57.1%，阴性预测值为76.1%，故脐血25（OH）D3对AD的诊断价值较低。Logistic回归分析结果显示：低脐血25（OH）D3水平、母孕期喜食海鲜、特应性家族史阳性、混合喂养4个因素是影响特应性皮炎发生的危险因素（P < 0.05）。结论 脐血25（OH）D3水平与特应性皮炎的发病风险呈现负性相关关系，但是对特应性皮炎的诊断价值较低。     

High frequency oscillatory ventilation in infants with increased intra-abdominal pressure

AIMS—To describe the short term effect of high frequency oscillatory ventilation on infants with severe abdominal distension who could not be conventionally ventilated.METHODS—Eight infants (25 to 38 gestational weeks, birthweight 600-3200 g, postnatal age 1 to 190 days) with a variety of intra-abdominal pathologies, resulting in severe abdominal distension and failure of conventional ventilation, were studied.RESULTS—The oxygenation status of all infants significantly improved within an hour of changing from conventional to high frequency oscillatory ventilation. Infants who were hypercapneic on conventional ventilation also showed a reduction in PaCO₂. As a group, the mean (SD) PaO₂/FIO₂ improved from 4.99 (0.98) kpa to 11.55 (3.8) kpa (P = 0.002), and the PaCO₂ from 6.48 (2.12) kpa to 4.89 (1.22) kpa (P= 0.028). These improvements were sustained throughout the next 48 hours.CONCLUSION—High frequency oscillatory ventilation seems to be an effective rescue measure for infants with respiratory failure secondary to increased intra-abdominal pressure.     

Value of diagnosis imaging in the evaluation of the severity of histological lesions in duplex systems

ObjectiveIn order to determine the effectiveness of imagery in the assessment of the severity of histological lesions in duplex systems in children we compared histology results from heminephrectomies with diagnosis imaging findings [renal ultrasound (US), scintigraphy, unenhanced and contrast-enhanced magnetic resonance imagery (MRI)].Materials and methodsBetween 2007 and 2013, 34 children with duplex system underwent surgery. The results from US (n = 34), dimer captosuccinic acid scintigraphy (n = 23) and MRI (n = 16) were compared with histological data. Five histological lesions were found (chronic interstitial inflammation, interstitial fibrosis, tubular atrophy, glomerulosclerosis and dysplasia) and categorized as severe (>25%) or moderate (≤25%).ResultsSevere histological lesions were found in 76.5% and moderate lesions in 23.5%.Radiological features were compared with histological results. In US, severe parenchymal thinning was associated with chronic interstitial inflammatory. The absence of parenchymal enhancement and/or severe cortical thinning in MR urography (MRU) was significantly associated with interstitial fibrosis. All poorly functioning poles were associated with severe histological lesions (p = 0.091), but not to a specific category of lesions.ConclusionsMRI sensibility was excellent (90%) in the diagnosis of poorly functioning pole. Severe thinning on US and minimal pole function on MRU can be used to predict the severity of histological lesions.     

Effect of onabotulinumtoxinA treatment on symptoms and urodynamic findings in pediatric neurogenic bladder

ObjectiveTo evaluate clinical and urodynamic efficiency of onabotulinumtoxinA (Botox) treatment in pediatric patients with urinary incontinence due to neurogenic overactive bladder.Patients and methodsSeventeen patients aged from 6 to 17 years (median 11 years) were treated with Botox injections. Clinical response to incontinence, duration of the response, and urodynamic results before and 1–3 months after treatment were evaluated.ResultsMean incontinence frequency decreased significantly (p = 0.036); six of 17 patients had >90% reduction, and a further three patients had a 50–90% reduction in incontinence episodes. Median duration of the response was 15 months (range 3–42 months). Mean bladder volume changed from 380 ± 148 ml to 453 ± 147 (p = 0.078), maximal detrusor pressure decreased from 45 ± 31 cmH₂O to 32 ± 21 cmH₂O (p = 0.030), and the number of patients with detrusor contractions during filling decreased from 12 to three (p = 0.005) after the treatment. The patients with poor bladder compliance had either no response or a short duration of response. At follow-up eight patients had undergone bladder augmentation because of persistent incontinence.ConclusionsAbout one third of pediatric patients with neurogenic bladder had a good response to Botox treatment. In many patients, the clinical response was longer than expected. The patients who initially had poor bladder compliance had a poor response to the treatment.     

Management of pulmonary hypertension in congenital diaphragmatic hernia: nitric oxide with prostaglandin-E1 versus nitric oxide alone

Aim  Prostaglandin-E1 (PGE₁) is used at most centers for treating pulmonary hypertension (PH) in congenital diaphragmatic hernia (CDH) because it has been regarded as effective. The aim of this study was to investigate the role of PGE1 for treating PH in CDH. Methods  We reviewed 49 CDH cases with echocardiography-proven PH. PH was treated with PGE₁ and nitric oxide (NO) and high frequency oscillatory ventilation (HFOV) from 1997 to 2001 (PG + NO; n = 19) and with NO and HFOV from 2002 to 2007 (NO; n = 30). Results  Subject demographics, severity of PH, and presence of other anomalies were not significantly different between the two groups. In the PG + NO group, 12/19 (63.2%) survived (PG + NO-s) and 7/19 (36.8%) died (PG + NO-d). In the NO group, 21/30 (70.0%) survived (NO-s) and 9/30 (30.0%) died (NO-d). Survival rates were not significantly different. In the NO-s group, spontaneous closure of the ductus arteriosus (DA) was significantly earlier compared with the PG + NO-s group (P < 0.01; 4.0 ± 0.9 vs. 9.5 ± 2.2 days after birth). DA diameters were significantly larger in groups that died compared with groups that survived (P < 0.01), and PH persisted in groups that died. In the NO-s group, surgery was possible significantly earlier compared with the PG + NO-s group (P < 0.01; 3.75 ± 0.67 vs. 6.12 ± 0.78 days after birth). No NO-s case developed a PH crisis even though PGE₁ was not used. Hospital stay was significantly shorter in the NO-s group compared with the PG + NO-s group (P < 0.05; 39.9 ± 19 vs. 53.2 ± 23 days). Conclusion  Nitric oxide alone would appear to simplify the management of CDH with PH and provide better outcome.     

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.     

Medication adherence in pediatric renal transplant patients: The role of family functioning and parent health locus of control

Children and adolescents with renal disease experience daily social, emotional, and medical challenges. Renal transplantation can help to improve quality of life but requires a lifelong regimen of immunosuppressant medication to maintain health. Adherence to a daily complex regimen can be difficult, particularly for adolescents who are beginning to develop autonomy from caregivers and are faced with a unique set of socio‐emotional challenges. This study examines two factors that have shown to influence adherence in other pediatric populations, namely family functioning and parent health locus of control, from mothers’ perspectives, in predicting medication non‐adherence for adolescents (ages 12‐19 years) 1 year post‐transplant. Non‐adherence was defined as the percentage of missed doses and late doses of the weekly immunosuppressant doses prescribed. Regression results demonstrated that mothers’ perceptions of poorer overall family functioning predicted missed medication doses (ΔR² = 0.383, F(7, 21) = 2.570, P = 0.044) with significant contributions in the domains of problem‐solving (β = ?0.795, t(21) = ?2.927, P = 0.008) and affective involvement (β = 0.872, t(21) = 3.370, P = 0.003). Moreover, mothers who perceived that their adolescent had control over his/her health also predicted more missed medication doses (ΔR² = 0.133, F(1, 27) = 5.155, P = 0.031). Important implications for these findings include implementation of family‐based interventions that promote developmentally appropriate skills for adolescents and cultivate emotional involvement within the family.     

Cisapride reduces neonatal postoperative ileus: randomised placebo controlled trial

AIM—To assess the efficacy of cisapride in reducing ileus persisting to the tenth postoperative day after neonatal abdominal surgery.METHODS—A prospective, randomised, double blind trial comparing rectal cisapride (l.4-2.3 mg/kg/day) with placebo over seven days was undertaken in 33 neonates.RESULTS—Seven of 12 (58%) patients receiving placebo and eight of 11 (73%) receiving cisapride achieved a first sustained feed during treatment. Of those receiving cisapride, the first sustained feed occurred at 2.3 days (SEM 0.6) compared with 4.7 days (SEM 0.8) with placebo. By the seventh day the mean daily net enteral balance was 69 (SEM 18) ml/kg in the cisapride subgroup and 17 (SEM 8) ml/kg for those receiving placebo. Stool was passed on 6.3 (SEM 0.4) treatment days in the cisapride subgroup compared with 4.1 (SEM 1.0) treatment days in the placebo subgroup.CONCLUSION—Cisapride is effective in neonates with a prolonged ileus after abdominal surgery.     

Clinical Course and Interstage Monitoring After the Norwood and Hybrid Procedures for Hypoplastic Left Heart Syndrome

Infants with hypoplastic left heart syndrome (HLHS) are at risk for interstage morbidity and mortality, especially between the first and second surgical stages after the Norwood and hybrid procedures. This study compared the morbidity and mortality of patients treated by either the Norwood or the hybrid procedure for HLHS between the first and second stages who were undergoing interstage monitoring. Between October 2008 and December 2011, 26 infants (14 boys) with HLHS (n = 16) and other univentricular heart malformations with aortic arch anomaly (n = 10) were scheduled for interstage monitoring after Norwood I (n = 12) and hybrid (n = 14) procedures. Three infants (11.5 %) died after first-stage palliation (one hybrid patient and two Norwood patients), and three infants (11.5 %) died after second-stage palliation (two hybrid patients and one Norwood patient) (p = 0.83), all after early second-stage surgery (<90 days). The Norwood I and hybrid procedures did not differ in terms of overall mortality (23 %) (three hybrid and three Norwood patients; p = 1.00). Seven infants (26.9 %) could not be discharged from the hospital due to hemodynamic instability and were referred for early second-stage surgery (<90 days). After the first stage, the invasive reevaluation rate before discharge was high (53.8 %), with cardiac catheterizations for 8 of 14 patients after the hybrid procedure and for 6 of 12 patients after the Norwood procedure (p = 0.69). A total of 11 reinterventions were performed (eight by catheter and three by surgery). Of the eight catheter reinterventions, five were performed for hybrid patients (p = 0.22). For 14 infants, 89 days (range 10–177 days) of interstage monitoring were scheduled. One infant (3.9 %) died during the interstage monitoring. The findings showed a breach of the physiologic criteria for interstage monitoring in seven infants (50 %) after 10 days (range 4–68 days) (five hybrid and two Norwood patients), leading to rehospitalization and catheterization for six patients (four hybrid and two Norwood patients), requiring interventions for two patients (patent arterial duct stent dilation, and atrial septal defect stenting, all for hybrid patients). Overall, three of the seven patients with red flag events of interstage monitoring were candidates for early second-stage surgery. In conclusion, morbidity among infants treated for HLHS remains high, either before or after hospital discharge, emphasizing the need of interstage monitoring programs. Despite retrograde aortic flow in infants with HLHS after the hybrid procedure, the mortality rate was comparable between the two groups. Mortality occurs after early second-stage surgery (<90 days).     

Assessment of pulmonary function in resolving chronic lung disease of prematurity

AIM—To investigate the longitudinal changes of interstitial and airways disease in resolving chronic lung disease of prematurity (CLD).METHODS—Thirty three infants were studied between 35 and 40 weeks of postconceptional age, and then at three monthly intervals throughout their first year. Measurements of mean arterial oxygen saturation (MSaO₂) and its variability (δMSaO₂) were recorded. PaCO₂ and PaO₂ were determined while the infants breathed steady state 50% oxygen via a hood. From these, the alveolar arterial difference (A-a) Do₂⁵⁰ was calculated. Airway disease was assessed by the measurement of partial forced expiratory flow volume curves (PEFC) to give V?_max Frc.RESULTS—The cohort mean +/- 95% confidence intervals measured between 35 and 40 weeks were for MSaO₂ (89·25 +/- 1·87%, range 75-96·5%) and δMSaO₂ (4·79 +/- 0·8%, range 0·16-9·64%), PaCO₂ (5·89 +/- 0·56 kpa, range 4·2-10·11 kpa), (A-a) Do₂⁵⁰ (22·7 +/- 2·56 kpa, range 6·67-31·4 kpa) and V?_maxFrc (41·5 +/- 8·65 mls/second, range 8·5-103·7 ml/second). The most significant improvement in all measurements occurred within the first three months (P = 0·05). An MSaO₂ of less than 90% in room air at 1 year of age was predicted between 35 and 40 weeks postconceptional age by an (A-a) Do₂⁵⁰ of greater than 29 kpa, with a sensitivity of 0·85 and a specificity of 0·88, and a PaCO₂ greater than 7 kpa predicted a specificity of 0·78 and a sensitivity of 0·88. Predictions were strengthened by combining the above criteria and these then gave a sensitivity and specificity of 1.CONCLUSION—Measurements of (A-a) Do₂⁵⁰ and PaCO₂ taken between 35 and 40 weeks can be used to assess the degree of pulmonary dysfunction at 1 year. Quantification of the severity of CLD could be used as a measurable end point for early neonatal intervention studies.     

Outcome of fetuses with heart disease diagnosed in utero

OBJECTIVE—To review the outcomes of 193 fetuses with cardiac abnormalities detected by echocardiography.METHODS—A total of 422 fetuses between 16 and 41 gestational weeks, referred to paediatric cardiologists for detailed echocardiography, were included in this study.RESULTS—Structural heart defects were found in 55 (28%), isolated arrhythmia in 105 (54%), and other non-structural abnormalities (dilated cardiomyopathy, hypertrophic cardiomyopathy, aneurysm of the foramen ovale, isolated pericardial effusion or echogenic foci) in 33 (17%) of 193 fetuses. Total mortality was 26%. The prognosis was poor in fetuses with structural heart defects; 37 of 55 cases (67%) died in utero or postnatally. Chromosomal abnormality was associated with structural heart defect in 38% of fetuses, of whom 38% died. Among fetuses with isolated arrhythmia survival was 95%. Poor outcome was associated with complete heart block (n=14) in 2 (14%) fetuses with hydrops and heart rate of less than 55 per minute, and with supraventricular tachycardia (n=21) in three (14%) neonates delivered prematurely at a mean gestational age of 33 weeks. Furthermore, nine of 12 fetuses (75%) with structural heart defects and arrhythmia died. Among fetuses with non-structural cardiac abnormalities, survival was 73%. Poor outcome was evident in fetuses with dilated cardiomyopathy in eight of 13 (62%) and with hypertrophic cardiomyopathy in one of eight (13%) of cases.CONCLUSIONS—Factors associated with a poor prognosis were: structural heart defect associated with chromosomal abnormality or arrhythmia, congestive heart failure associated with supraventricular tachycardia or complete heart block, especially if delivery occurs preterm; and fetal hydrops with congestive heart failure and atrioventricular valve regurgitation.     

Effects of red cell transfusion on pulmonary blood flow and right ventricular systolic time intervals in neonates

Blood transfusion increases blood volume and blood viscosity of the neonate. Since both volume expansion and increase in blood viscosity may be associated with increased pulmonary artery pressure, we studied effects of transfusion (10 ml of red blood cells per kilogramme of body weight) on right ventricular output and right systolic time intervals by means of pulsed-Doppler echocardiography in 38 preterm infants with a mean (SD) gestational age of 28 (5) weeks (range 25–34), birth weight 1060 (395) g (range 480–1910), actual body weight 1875 (450) g (range 820–2790) and postnatal age of 44 (23) days (range 17–105). After transfusion, packed cell volume and haemoglobin increased significantly from 0.26 (0.044) to 0.38 (0.046), and from 8.2 (1.6) g/l to 12.8 (1.9), respectively. Blood viscosity increased from 1.78 (0.3) mPa to 2.68 (0.4) by 33%. Right ventricular output decreased significantly from 320 (57) ml/kg/min to 290 (70) due to decrease in heart rate by 7%. Blood pressure and right ventricular stroke volume did not change. There was a significant increase in pulmonary red cell transport (right ventricular output times packed cell volume) of 21%. Right ventricular pre-ejection period (RPEP), right time peak velocity (RTPV), right ventricular ejection time (RVET), and ratios of RTPV/RVET_(c), RPEP:RVET did not change after transfusion. Conclusion These results suggest that neither pulmonary artery pressure nor right ventricular function changed as a result of transfusion in spite of rising blood volume and blood viscosity. Received: 19 October 1996 / Accepted: 23 December 1996     

The timing of autologous stem cell transplantation and the prognostic factors affecting the prognosis in children with relapsed hodgkin lymphoma

Although ASCT is used as a standard treatment following second remission for adults in oncology practice, data are lacking for relapsed childhood HL. Therefore, we evaluated the exact timing of the ASCT treatment, as well as factors affecting the prognosis in children with relapsed HL who underwent ASCT. Patients were divided into two groups (Group 1: ASCT after second remission [n = 6], Group 2: ASCT after >2 remissions [n = 3]). Overall, DFS rate was 64.8% at 24 months after ASCT. In Group 1, post‐transplant DFS and OS were 83.3% and 75%, respectively, and the post‐transplant response without event rate was 5/6 (83.3%). However, in Group 2 this was 1/3 (33.3%). Nonetheless, the timing of ASCT was not a significant prognostic factor for DFS and OS in univariate analyses (p = 0.21 and p = 0.73, respectively). Median follow‐up time was 21 months after transplant, and DFS and OS were 62.5% and 75% in early relapse group (n = 6) at 24 months. DFS and OS were both 66.7% in late relapse (n = 3). In addition, response rates of ASCT without event were 66.7% for both early and late relapse groups. Relapse types (early: 3–12 months, late: >12 months) was not a significant prognostic factor for DFS and OS in univariate analyses (p = 0.96 and p = 0.92). While we found ASCT to be a useful treatment following second remission, it does not demonstrate better success in early relapse cases, when compared to late relapse cases. Therefore, after second remission for relapsed HL, ASCT is advisable regardless of the time of relapse.     

Spirometry‐adjusted fraction of exhaled nitric oxide increases accuracy for assessment of asthma control in children

Spirometry and exhaled nitric oxide are two important complimentary tools to identify and assess asthma control in children. We aimed to determine the ability of a new suggested spirometry‐adjusted fraction of exhaled nitric oxide (NO) index in doing that. A random sample of 1602 schoolchildren were screened by a health questionnaire, skin prick tests, spirometry with bronchodilation and exhaled NO. A total of 662 children were included with median (IQR) exhaled NO 11(14) ppb. Receiver operating characteristic (ROC) curves using exhaled NO equations from Malmberg, Kovesi and Buchvald, and spirometry‐adjusted fraction of exhaled NO values were applied to identify asthmatic children and uncontrolled asthma. Receiver operating characteristic (ROC) curves failed to identify asthmatic children (all AUC < 0.700). Spirometry‐adjusted fraction of exhaled NO/FEV₁ (AUC = 0.712; P = .010) and NO/FEF_25%‐75% (AUC = 0.735 P = .004) had a fair and increased ability to identify uncontrolled disease compared with exhaled NO (AUC = 0.707; P = .011) or the Malmberg equation (AUC = 0.701; P = .014). Sensitivity and specificity identifying non‐controlled asthma were 59% and 81%, respectively, for the cut‐off value of 9.7 ppb/L for exhaled NO/FEV₁, and 40% and 100% for 15.7 ppb/L/s for exhaled NO/FEF_25%‐75%. Exhaled NO did not allow to identify childhood asthma. Spirometry‐adjusted fraction of exhaled NO performed better‐assessing asthma control in children. Thus, although more validation studies are needed, we suggest its use in epidemiological studies to assess asthma control.     

Pediatric urolithiasis in a non-endemic country: A single center experience from The Netherlands

ObjectiveTo provide insight in causative factors of pediatric urolithiasis in The Netherlands, a non-endemic country.Patients and methodsData from 71 children with urolithiasis and stone analyses between 1996 and 2010 in the Radboud University Nijmegen Medical Centre were studied retrospectively. Patients (48 boys, 23 girls, ratio 2.1:1) were aged 0.5–18.3 years (mean 8.8, SD 5.6). All stone analyses were performed with FTIR spectroscopy.ResultsOf the 49 patients with metabolic analysis, 78% showed one (n = 15) or more (n = 23) metabolic abnormalities. Forty-seven percent had hypercalciuria (n = 23), 31% had hyperoxaluria (n = 15), 29% hypocitraturia (n = 14), 10% hyperuricosuria (n = 5), 10% cystinuria (n = 5), and 6% had hypomagnesiuria (n = 3).Sixty-one percent of the stones were composed of calcium phosphate, calcium oxalate, or a combination of those. Twenty-six percent consisted of pure or mixed magnesium ammonium phosphate, 8.3% pure or mixed urate, and 8.3% cystine.ConclusionChildren with urolithiasis in The Netherlands show stone composition similar to other Western European countries. However, a high percentage of metabolic abnormalities (78%) was found, indicating the need for extensive evaluation of pediatric urolithiasis to find underlying causes and thereby prevent stone recurrences. A close collaboration between a pediatric nephrologist and urologist is mandatory for optimal surgical and medical treatment.