VIncristine,irinotecan, and temozolomide in children and adolescents with relapsed rhabdomyosarcoma

1 Background

The combination of vincristine, irinotecan, and temozolomide (VIT) is often used to treat children and adolescents with relapsed rhabdomyosarcoma (RMS); however, the outcome of these patients has not been previously described.

2 Procedures

We sought to determine the response rate (RR) and progression‐free survival (PFS) for patients with relapsed RMS treated with VIT by retrospective review of patients treated at five tertiary care hospitals. Prior treatment with irinotecan was permitted.

3 Results

Among 19 patients with a median age of 8 years (range 2–17 years), 12 (63%) were males and 12 (63%) had embryonal histology. Median time to relapse from initial diagnosis was 16 months (range 2.8‐45 months). VIT was used as first, second, third, or fourth line of therapy in four (21%), seven (37%), six (32%), and two (10%) patients, respectively. Four patients received VIT as adjuvant therapy following radiation and/or surgery. Therefore, among 15 evaluable patients, the best response to VIT was 0 (complete response, CR), 0 (partial response, PR), 4 (stable disease, SD), and 11 (progressive disease, PD) for an overall clinical benefit rate (CR + PR + SD) of 26.7% (95% CI: 7.8–55.1%). After a median follow‐up of 8 months, 2 (10%) patients were alive without disease, 3 (16%) were alive with disease, and 14 (74%) patients died of PD. PFS at 3 months was 23% (95% CI: 5.7–46.7%).

4 Conclusions

VIT therapy in combination with adequate local control is associated with some disease control in patients with first relapse RMS and may be another reasonable option to offer patients as salvage therapy.     

Diagnostic performance of fluorine-18-dihydroxyphenylalanine positron emission tomography in diagnosing and localizing the focal form of congenital hyperinsulinism: a meta-analysis

Introduction

We performed a meta-analysis on published data on the diagnostic performance of fluorine-18 dihydroxyphenylalanine (¹⁸F-DOPA) positron emission tomography (PET) in diagnosing and localizing focal congenital hyperinsulinism (CHI).

Materials and methods

A comprehensive computer literature search of studies published up to 31 January 2012 regarding ¹⁸F-DOPA PET or PET/CT in patients with CHI was performed. Pooled sensitivity and specificity, area under the ROC curve and diagnostic odds ratio (DOR) of ¹⁸F-DOPA PET or PET/CT in diagnosing focal CHI were calculated. The localization accuracy of focal CHI was also estimated. Seven studies comprising 195 CHI patients were included.

Results

The pooled sensitivity and specificity of ¹⁸F-DOPA PET or PET/CT in differentiating between focal and diffuse CHI were 89% (95% confidence interval [CI]:81–95%) and 98% (95% CI:89–100%), respectively. The DOR was 74.5 (95% CI:18–307). The area under the ROC curve was 0.95. The pooled accuracy of these functional imaging methods in localizing focal CHI was 80% (95% CI:71–88%).

Discussion

In CHI patients, ¹⁸F-DOPA PET or PET/CT demonstrated high sensitivity and specificity in differentiating between focal and diffuse CHI. ¹⁸F-DOPA PET or PET/CT are accurate methods of localizing focal CHI. Nevertheless, possible sources of false-negative results for focal CHI should be kept in mind.     

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.     

Utility of PET scans to predict disease relapse in pediatric patients with Hodgkin lymphoma

BACKGROUND: Positron emission tomography (PET) differentiates normal from abnormal cells based on metabolic activity. Numerous studies report that PET scan offers increased sensitivity, specificity and predictive values as compared to computed tomography (CT) in adult lymphoma patients. PROCEDURE: Twenty-three consecutive pediatric Hodgkin lymphoma (HL) patients were evaluated with PET scan either at diagnosis or during treatment, then at therapy completion and in follow-up. RESULTS: Twenty two of the 23 patients had a negative PET scan at the end of therapy; however, ten later developed a positive scan for a total of 11 (47.8%) patients with a positive post treatment PET scan. Six tissue biopsies were performed in five patients; four specimens were negative for disease and two confirmed HL relapse. Six patients were monitored clinically and remained asymptomatic; four had resolution of abnormalities on repeat PET while two had persistently positive, but stable PET scan findings and continue to be in remission at 11 and 40 months following treatment. Twelve (52.2%) patients of the original cohort have had consistently negative PET scans and have not relapsed. CONCLUSIONS: PET is a sensitive (100%), but not a specific (57.1%) method for evaluating post-treatment pediatric HL patients with a strong negative predictive value (NPV; 100%), but poor positive predictive value (PPV; 18.2%). We do not recommend treatment decisions be based solely on PET scan results.     

Treatment‐related mortality in relapsed childhood acute lymphoblastic leukemia

1 Background

Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment‐related toxicity impacts survival.

2 Procedure

In this retrospective population‐based study, we described the causes of death and estimated the risk for treatment‐related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL‐92 and ALL‐2000 trials.

3 Results

Among the 483 patients who received relapse treatment with curative intent, we identified 52 patients (10.8%) who died of treatment‐related causes. Twelve of these died before achieving second remission and 40 died in second remission. Infections were the cause of death in 38 patients (73.1%), predominantly bacterial infections during the chemotherapy phases of the relapse treatment. Viral infections were more common following hematopoietic stem cell transplantation (HSCT) in second remission. Independent risk factors for treatment‐related mortality were as follows: high‐risk stratification at relapse (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.3–3.9; P < 0.01), unfavorable cytogenetic aberrations (HR 3.4; 95% CI 1.3–9.2; P = 0.01), and HSCT (HR 4.64; 95% CI 2.17–9.92; P < 0.001). In contrast to previous findings, we did not observe any statistically significant sex or age differences. Interestingly, none of the 17 patients with Down syndrome died of treatment‐related causes.

4 Conclusions

Fatal treatment complications contribute significantly to the poor overall survival after relapse. Implementation of novel therapies with reduced toxicity and aggressive supportive care management are important to improve survival in relapsed childhood ALL.     

Early differential diagnosis methods of biliary atresia: a meta-analysis

Purpose

To evaluate the accuracy of early differential diagnosis methods of biliary atresia in patients with infantile cholestasis.

Methods

We searched PubMed, EMBASE and the Web of Science databases for articles evaluated the early differential diagnosis methods of biliary atresia. The methodological quality of each study was assessed with version 2 of the Quality Assessment of Diagnostic Accuracy Studies tool. Two reviewers extracted data independently. Pooled sensitivity, specificity, positive likelihood ratio (LR?+), negative likelihood ratio (LR??), diagnostic odds ratio (DOR) with 95% CIs were calculated to assess each diagnosis method.

Results

A total of 38 articles were included. Summary sensitivity and specificity were 77% (95% CI 74–80%) and 93% (95% CI 91–94%), respectively, for B-US in 23 studies; 96% (95% CI 92–98%) and 58% (95% CI 51–65%), respectively, for MRCP in five studies; 87% (95% CI 82–91%) and 78% (95% CI 74–82%), respectively, for acholic stool in seven studies; 84% (95% CI 78–89%) and 97% (95% CI 97–98%), respectively, for serum liver function test in seven studies; 96% (95% CI 94–97%) and 73% (95% CI 70–76%), respectively, for hepatobiliary scintigraphy in 18 studies; 98% (95% CI 96–99%) and 93% (95% CI 89–95%), respectively, for percutaneous liver biopsy in 11 studies.

Conclusion

The accuracy rate of percutaneous liver biopsy is better than all of the noninvasive methods. Take into consideration the advantages and disadvantages of the six methods, combination of multidisciplinary noninvasive diagnosis methods is the first choice for differential diagnosis of BA from other causes of neonatal cholestasis.

     

Phase II study of 131I-metaiodobenzylguanidine with 5 days of topotecan for refractory or relapsed neuroblastoma: Results of the French study MIITOP

Purpose

We report the results of the French multicentric phase II study MIITOP (NCT00960739), which evaluated tandem infusions of ¹³¹I-metaiodobenzylguanidine (mIBG) and topotecan in children with relapsed/refractory metastatic neuroblastoma (NBL).

Methods

Patients received ¹³¹I-mIBG on day 1, with intravenous topotecan daily on days 1–5. A second activity of ¹³¹I-mIBG was given on day 21 to deliver a whole-body radiation dose of 4 Gy, combined with a second course of topotecan on days 21–25. Peripheral blood stem cells were infused on day 31.

Results

Thirty patients were enrolled from November 2008 to June 2015. Median age at diagnosis was 5.5 years (2–20). Twenty-one had very high-risk NBL (VHR-NBL), that is, stage 4 NBL at diagnosis or at relapse, with insufficient response (i.e., less than a partial response of metastases and more than three mIBG spots) after induction chemotherapy; nine had progressive metastatic relapse. Median Curie score at inclusion was 6 (1–26). Median number of prior lines of treatment was 3 (1–7). Objective response rate was 13% (95% confidence interval [CI]: 4–31) for the whole population, 19% for VHR-NBL, and 0% for progressive relapses. Immediate tolerance was good, with nonhematologic toxicity limited to grade-2 nausea/vomiting in eight patients. Two-year event-free survival was 17% (95% CI: 6–32). Among the 16 patients with VHR-NBL who had not received prior myeloablative busulfan-melphalan consolidation, 13 had at least stable disease after MIITOP; 11 subsequently received busulfan-melphalan; four of them were alive (median follow-up: 7 years).

Conclusion

MIITOP showed acceptable tolerability in this heavily pretreated population and encouraging survival rates in VHR-NBL when followed by busulfan-melphalan.     

Pediatric Hodgkin lymphoma: are we over-scanning our patients?

Despite the favorable outcome of most pediatric patients with Hodgkin lymphoma (HL), there is rising concern about risks of carcinogenesis from both diagnostic and therapeutic radiation exposure for patients treated on study protocols. Although previous studies have investigated radiation exposure during treatment, radiation from post-treatment surveillance imaging may also increase the likelihood of secondary malignancies. All diagnostic imaging examinations involving ionizing radiation exposure performed for surveillance following completion of therapy were recorded for 99 consecutive pediatric patients diagnosed with HL from 2000 to 2010. Cumulative radiation dosage from these examinations and the frequency of relapse detection by these examinations were recorded. In the first 2 years following completion of therapy, patients in remission received a median of 11 examinations (range 0-26). Only 13 of 99 patients relapsed, 11 within 5 months of treatment completion. No relapse was detected by 1- or 2-view chest radiographs (n = 38 and 296, respectively), abdomen/pelvis computed tomography (CT) scans (n = 211), or positron emission tomography (PET) scans alone (n = 11). However, 10/391 (2.6%) of chest CT scans, 4/364 (1.1%) of neck CT scans, and 3/47 (6.4%) of PET/CT scans detected relapsed disease. Thus, only 17 scans (1.3%) detected relapse in a total of 1358 scans. Mean radiation dosages were 31.97 mSv for Stage 1, 37.76 mSv for Stage 2, 48.08 mSv for Stage 3, and 51.35 mSv for Stage 4 HL. Approximately 1% of surveillance imaging examinations identified relapsed disease. Given the very low rate of relapse detection by surveillance imaging stipulated by current protocols for pediatric HL patients, the financial burden of the tests themselves, the high cure rate, and risks of second malignancy from ionizing radiation exposure, modification of the surveillance strategy is recommended.     

Outcomes in childhood AML in the absence of transplantation in first remission--Children's Cancer Group (CCG) studies 2891 and CCG 213

Background

The majority of childhood acute myeloid leukemia (AML) patients lack a matched‐related bone marrow transplant (BMT) donor in first remission.

Procedure

Disease‐free survival (DFS), overall survival (OS), relapse‐free survival (RFS), and post‐relapse outcome were evaluated for children with de novo AML on CCG 213 and the standard timing (ST) and intensive timing (IT) induction arms of CCG 2891 who were randomized to (intent‐to‐treat, ITT) or who received (as‐treated, AT) only chemotherapy intensification.

Results

Outcomes at 8 years post‐induction in ITT analysis of chemotherapy intensification were as follows: 31% DFS, 43% OS on CCG 213; 34% DFS, 51% OS on CCG 2891 ST; 48% DFS, 56% OS on CCG 2891 IT. All toxic deaths during and following Capizzi II chemotherapy intensification on both protocols were in patients >3 years of age (P ≤ 0.001). Black race was a significant poor prognostic factor for OS (P = 0.008, hazard ratio: 1.74, 95% CI: 1.15–2.61). Overall 48% of patients on both trials relapsed and 19.1% of patients who relapsed on these trials survived. CR1 >12 months portends a much better OS for patients who relapse. Post‐relapse treatment included BMT in 47% of patients.

Conclusions

OS on CCG 2891 was superior to CCG 213 but equivalent between ST and IT arms due to better salvage rates post‐relapse in ST patients. Overall survival for childhood AML in the absence of BMT in CR1 is influenced by duration of CR1 and by race. Pediatr Blood Cancer 2008;50:9–16. © 2007 Wiley‐Liss, Inc.     

Diagnostic performance of contrast-enhanced MR for acute appendicitis and alternative causes of abdominal pain in children

Objective

Unenhanced MRI has emerged as a useful tool for diagnosing pediatric acute appendicitis. The use of contrast-enhanced MRI for diagnosing pediatric appendicitis has not been documented. The purpose of this study is to examine the diagnostic performance of contrast-enhanced MRI for acute appendicitis and alternative entities in the pediatric population presenting with acute abdominal pain.

Materials and methods

A retrospective review was conducted of 364 consecutive pediatric patients undergoing contrast-enhanced MRI for the evaluation of possible appendicitis at a single institution between November 2012 and September 2013.

Results

There were 132 cases of pathologically confirmed appendicitis out of 364 pediatric patients (36.3%) included in the study. Overall sensitivity and specificity were 96.2% (95% CI [91.4–98.4%]) and 95.7% (95% CI [92.3–97.6%]), respectively. Positive predictive value and negative predictive value were 92.7% (95% CI [86.6–96.3%]) and 97.8% (95% CI [94.7–99.1%]), respectively. The appendix was visualized in 243 cases (66.8%). Imaging confirmed alternative diagnoses in 75 patients, including most commonly colitis, enteritis or terminal ileitis (n?=?25, 6.9%), adnexal cysts (n?=?25, 6.9%) and mesenteric adenitis (n?=?7, 1.9%).

Conclusion

Contrast-enhanced MRI is capable of accurately diagnosing acute appendicitis while detecting many alternative entities of abdominal pain, and it allows good visualization of the appendix. Further evaluation is needed to determine whether contrast-enhanced MRI provides an advantage over non-enhanced MRI for imaging evaluation of acute abdominal pain in the pediatric population.     

Laparoscopic-assisted pull-through operation for Hirschsprung’s disease: a systematic review and meta-analysis

Purpose

In the last two decades, laparoscopic-assisted pull-through (LAPT) has gained much popularity in the treatment of Hirschsprung’s disease. The aim of this meta-analysis was to determine the long-term outcome of patients treated laparoscopically.

Methods

A systematic literature-based search for relevant cohorts was performed using the terms “Hirschsprung’s disease and Laparoscopy”, “Laparoscopic-assisted pull-through outcome”, “Laparoscopic-assisted Soave pull-through” “Laparoscopic-assisted Swenson pull-through” and Laparoscopic-assisted Duhamel pull-through. The relevant cohorts of laparoscopic operated HD were systematically searched for outcome regarding continence, constipation, secondary surgery related to the laparoscopic approach and enterocolitis. Pooled incidence rates and odds ratios (ORs) with 95 % confidence intervals (CI) were calculated using standardized statistical methodology.

Results

Sixteen studies met defined inclusion criteria, reporting a total of 820 patients. All studies were retrospective case series, with variability in outcome assessment quality and length of follow-up. The median cohort size consisted of 28 patients (range 15–218). In the long-term follow-up, 97 patients (11.14 %) experienced constipation (OR 0.06, 95 % CI 0.05–0.08, p < 0.00001), 53 (6.46 %) incontinence/soiling (OR 0.01 95 % CI 0.01–0.01, p < 0.00001), 75 (9.14 %) recurrent enterocolitis (OR 0.02 95 % CI 0.01–0.02, p < 0.00001) and 69 (8.4 %) developed complications requiring secondary surgery (OR 0.01 95 % CI 0.01–0.02, p < 0.00001). Overall events in long-term follow-up occurred in 225 (27.5 %) patients (OR 0.24 95 % CI 0.20–0.30, p < 0.00001).

Conclusions

This meta-analysis shows that nearly one-third of the patients continue to have long-term bowel problems, such as constipation, soiling and recurrent enterocolitis following LAPT. Many patients treated by LAPT require secondary surgery. Large randomized studies with long-term follow-up are necessary to determine the difference in outcome between LAPT and completely transanal pull-through operation.

     

Efficacy of Preoperative Chemotherapy in Treatment of Children With Wilms’ Tumor: A Meta-Analysis

Context:

To assess the efficacy of preoperative chemotherapy in Wilms’ tumor patients and explore its true value for specific subgroups.

Objectives:

In the presence of these controversies, a meta-analysis that examines the efficacy of preoperative chemotherapy in Wilms’ tumor patients and specific subgroups is needed to clarify these issues. The objective of this meta-analysis is to assess the efficacy of preoperative chemotherapy in Wilms’ tumor patients and explore its true value for specific subgroups.

Data Sources:

Computer-based systematic search with “preoperative chemotherapy”, “Neoadjuvant Therapy” and “Wilms’ tumor” as search terms till January 2013 was performed.

Study Selection:

No language restrictions were applied. Searches were limited to randomized clinical trials (RCTs) or retrospective studies in human participants under 18 years. A manual examination of references in selected articles was also performed.

Data Extraction:

Relative Risk (RR) and their 95% Confidence Interval (CI) for Tumor Shrinkage (TS), total Tumor Resection (TR), Event-Free Survival (EFS) and details of subgroup analysis were extracted. Meta-analysis was carried out with the help of the software STATA 11.0. Finally, four original Randomized Clinical Trials (RCTs) and 28 retrospective studies with 2375 patients were included.

Results:

For preoperative chemotherapy vs. up-front surgery (PC vs. SU) group, the pooled RR was 9.109 for TS (95% CI: 5.109 - 16.241; P < 0.001), 1.291 for TR (95% CI: 1.124 - 1.483; P < 0.001) and 1.101 for EFS (95% CI: 0.980 - 1.238; P = 0.106). For subgroup short course vs. long course (SC vs. LC), the pooled RR was 1.097 for TS (95% CI: 0.784 - 1.563; P = 0.587), 1.197 for TR (95% CI: 0.960 - 1.493; P = 0.110) and 1.006 for EFS (95% CI: 0.910 - 1.250; P = 0.430).

Conclusions:

Short course preoperative chemotherapy is as effective as long course and preoperative chemotherapy only benefits Wilms’ tumor patients in tumor shrinkage and resection but not event-free survival.     

Apneas en lactantes con bronquiolitis: incidencia y factores de riesgo para un modelo de predicción

Introduction

The presence of apnoea in acute bronchiolitis (AB) varies between 1.2% and 28.8%, depending on the series, and is one of its most fearsome complications. The aim of this study is to determine the incidence of apnoea in hospitalised patients diagnosed with AB, and to define their associated risk factors in order to construct a prediction model.

Outcome of patients with undifferentiated embryonal sarcoma of the liver treated according to European soft tissue sarcoma protocols

Background

To assess the outcomes of pediatric patients with undifferentiated embryonal sarcoma of the liver (UESL) and treatment including at least surgery and systemic chemotherapy.

Methods

This study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three European trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT), and chemotherapy.

Results

Out of 65 patients with a median age at diagnosis of 8.7 years (0.6–20.8), 15 had T2 tumors, and one had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, nine IRS II, 38 IRS III, and four IRS IV. Twenty-eight upfront surgeries resulted in five operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (p = .0119) and three infiltrated margins (p = .0238). All patients received chemotherapy, including anthracyclines in 47. RT was administered in 15 patients. With a median follow-up of 78.6 months, 5-year overall and event-free survivals (EFS) were 90.1% (95% confidence interval [CI]: 79.2–95.5) and 89.1% (95% CI: 78.4–94.6), respectively. Two out four local relapses had previous infiltrated margins and two out of three patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (p = .1607), T2 stage (p = .3870), use of RT (p = .8731), and anthracycline-based chemotherapy (p = .1181) were not correlated with EFS.

Conclusions

Multimodal therapy improved the outcome of UESL. Neoadjuvant chemotherapy for pediatric patients increases the probability of complete surgical resection. The role of anthracyclines and RT for localized disease remains unclear.     

Feelings of depression in people with arm: The role of critical incidents and perceived difficulties in close and sexual relationships

Purpose

Managing a chronic disease may be a difficult task which may lead patients to experience psychological distress and depression. Some studies showed that, in ARM patients, fecal incontinence (FI) is related to symptoms of depression while others studies did not. No studies investigated this relationship in adults. Since fear of having FI episodes, negative feelings associated with these episodes, and difficulties in close and sexual relationships are often reported by patients as important consequences of ARM, we were interested in investigating whether these aspects contribute in explaining feelings of depression.

Methods

Questionnaires were sent to 160 adult members of the Italian Association for Anorectal Malformation. A new scale measuring the fear of having FI episodes, negative feelings associated with these episodes and difficulties in close/sexual relationship was developed. Depressive feelings and FI were also measured.

Results

Seventy-two adults answered the questionnaires. Regression analyses showed that, in males, depressive feelings were predicted by difficulties in close and sexual relationships (B = 0.46; P < 0.01), while, in females, they were predicted by the fear of having FI episodes (B = 0.53; P < 0.05) and by negative feelings (B = 0.58; P < 0.01).

Conclusions

Interventions aimed to prevent depression in ARM patients should consider gender and should be targeted on different aspects.     

Clinical predictors of positive urine cultures in young children at risk for urinary tract infection

BACKGROUND:

Urinary tract infections (UTIs) are a common source of bacterial infection among young febrile children. The diagnosis of UTI is challenging because the clinical presentation is not specific.

OBJECTIVE:

To describe clinical predictors to identify young children needing urine culture for evaluation of UTI.

METHODS:

Retrospective cohort study of all children younger than two years of age (719 hospital visits for 545 patients) suspected of having a UTI during a 12-month period. The outcome was UTI, defined as a catheterized urine culture with pure growth of 10⁴ colonies/mL or greater, or suprapubic aspiration culture with 10³ colonies/mL or greater. Candidate predictors included demographic, historical and physical examination variables.

RESULTS:

The medical records of 545 children younger than two years of age were reviewed. Forty-six per cent were girls. Mean age was 9.1 months (SD 7 months). Four variables were found to predict UTI: absence of another source of fever on examination (odds ratio [OR]=41.6 [95% CI, 8.8 to 197.4]), foul smelling urine (OR=19.7 [95% CI, 5.7 to 68.2]), white blood cell count greater than 15,000/mm³ (OR=4.3 [95% CI, 2.0 to 9.3]), younger than six months old (OR=3.1 [95% CI, 1.3 to 7.1]). The sensitivity of an abnormal urine analysis was 0.77 (95% CI, 0.66 to 0.88) and the specificity was 0.31 (95% CI, 0.2 to 0.42).

CONCLUSION:

An incremental increase in risk for UTI is associated with younger age (younger than six months), having a white blood cell count higher than 15,000/mm³, parental report of malodorous or foul smelling urine and the absence of an alternative source of fever. In the present patient population, obtaining a urine culture from children with at least one of these clinical predictors would have resulted in missing one UTI (2%), and 111 negative cultures (20%) would have been avoided.     

贝林妥欧单抗治疗儿童复发/难治急性淋巴细胞白血病的安全性及近期疗效分析

目的 分析贝林妥欧单抗治疗儿童复发/难治急性淋巴细胞白血病的安全性及近期疗效。方法 以2021年8月—2022年8月接受贝林妥欧单抗治疗的6例复发/难治急性淋巴细胞白血病患儿作为研究对象,回顾性分析患儿临床数据。结果 6例患儿中,男女各3例,中位入组年龄为10.5 （范围：5.0～13.0）岁。1例为难治性,经多次化疗均未缓解;5例为第一次复发,从诊断至复发中位间隔时间为30 （范围：9～60）个月。治疗前骨髓微小残留病为15.50 （范围：0.08～78.30）%。治疗后3例完全缓解,其中骨髓微小残留病转阴2例。5例患儿发生细胞因子释放综合征,其中1级3例,2级2例。4例桥接了异基因造血干细胞移植,贝林妥欧单抗治疗结束至移植中位间隔时间为50 （范围：40～70） d。6例患儿中位随访时间为170 d,总生存率为41.7%(95%CI:5.6%～76.7%),中位生存时间为126 (95%CI:53～199) d。结论 贝林妥欧单抗治疗儿童复发/难治急性淋巴细胞白血病短期安全有效,长期疗效需扩大样本量进一步观察。[中国当代儿科杂志,2023,25 (4):374-380]     

Long-term mortality in pediatric solid organ recipients—A nationwide study

Background

The present study aimed at investigating long-term mortality of patients who underwent solid organ transplantation during childhood and at identifying their causes of death.

Methods

A cohort of 233 pediatric solid organ transplant recipients who had a kidney, liver, or heart transplantation between 1982 and 2015 in Finland were studied. Year of birth-, sex-, and hometown-matched controls (n = 1157) were identified using the Population Register Center registry. The Causes of Death Registry was utilized to identify the causes of death.

Results

Among the transplant recipients, there were 60 (25.8%) deaths (median follow-up 18.0 years, interquartile range of 11.0–23.0 years). Transplant recipients' risk of death was nearly 130-fold higher than that of the controls (95% CI 51.9–1784.6). The 20-year survival rates for kidney, liver, and heart recipients were 86.1% (95% CI 79.9%–92.3%), 58.5% (95% CI 46.2%–74.1%), and 61.4% (95% CI 48.1%–78.4%), respectively. The most common causes of death were cardiovascular diseases (23%), infections (22%), and malignancies (17%). There were no significant differences in survival based on sex or transplantation era.

Conclusion

The late mortality is still significantly higher among pediatric solid organ recipients in comparison with controls. Cardiovascular complications, infections, and cancers are the main causes of late mortality for all studied transplant groups. These findings emphasize the cruciality of careful monitoring of pediatric transplant recipients in order to reduce long-term mortality.     

Familial History and Recurrence of Febrile Seizures; a Systematic Review and Meta-Analysis

Objective

Febrile seizure (FS) as the most common form of seizures in childhood, affects 2-5% of all children across the world. The present study reviews available reports on FS recurrence frequency and evaluates its associated risk factors in Iran.

Methods

We searched the Persian database such as: SID, MagIran, Medlip, Irandoc, Iranmedex as well as English databases PubMed, ISI, and Scopus. Random effects models were used to calculate 95% confidence intervals. Meta regression was introduced to explore the heterogeneity between studies.

Findings

The overall FS recurrence rate was 20.9% [95% confidence interval (CI): 12.3-29.5%]. The frequency of FS simple and complex types was 69.3% (95% CI: 59.5-79.0) and 25.3% (95% CI: 19.6-31.0), respectively. A positive familial history of 28.8% (95% CI: 19.3-38.4%) was observed for childhood FS including 36.2% (95% CI: 27.3-39.6%) for the simple and 29.4% (95% CI: 23.1-33.5%) for the complex type. The heterogeneity of recurrent FS was significantly affected by sample size (P=0.026).

Conclusion

Almost one-third of FS children had a positive familial history. The increased risk of recurrence in patients with symptomatic seizures needs to be fully considered by parents, physicians, nurses and health policy makers.     

Fluid balance in pediatric postoperative liver transplant recipients

Background

Positive fluid balance (FB) is associated with poor outcomes in critically ill children but has not been studied in pediatric liver transplant (LT) recipients. Our goal is to investigate the relationship between postoperative FB and outcomes in pediatric LT recipients.

Methods

We performed a retrospective cohort study of first-time pediatric LT recipients at a quaternary care children's hospital. Patients were stratified into three groups based on their FB in the first 72 h postoperatively: <10%, 10–20%, and > 20%. Outcomes were pediatric intensive care unit (PICU) and hospital length of stay, ventilator-free days (VFD) at 28 days, day 3 severe acute kidney injury, and postoperative complications. Multivariate analyses were adjusted for age, preoperative admission status, and Pediatric Risk of Mortality (PRISM)-III score.

Results

We included 129 patients with median PRISM-III score of 9 (interquartile range, IQR 7–15) and calculated Pediatric End-stage Liver Disease score of 15 (IQR 2–23). A total of 37 patients (28.7%) had 10–20% FB, and 26 (20.2%) had >20% FB. Greater than 20% FB was associated with an increased likelihood of an additional PICU day (adjusted incident rate ratio [aIRR] 1.62, 95% CI: 1.18–2.24), an additional hospital day (aIRR 1.39, 95% CI: 1.10–1.77), and lower likelihood of a VFD at 28 days (aIRR 0.85, 95% CI: 0.74–0.97). There were no differences between groups in the likelihood of postoperative complications.

Conclusions

In pediatric LT recipients, >20% FB at 72 h postoperatively is associated with increased morbidities, independent of age and severity of illness. Additional studies are needed to explore the impact of fluid management strategies on outcomes.