IMPACT de la déprivation sociale sur les difficultés psychosociales au décours d’un cancer pédiatrique:uneétude prospective IMPACT of the Social Deprivation on Psychosocial Difficulties of Pediatric Cancer Survivors:A Prospective Study

The posttreatment period is a key part of the management of pediatric cancer.During this time,school and psychological difficulties have been described in childhood cancer survivors(CCS)and can be prognostic for the success of social reintegration.This study estimated the influence of the household’s socioeconomic status(SES)on these psychosocial difficulties.This study is based on a prospective multicentric database and focused on children who received a psychosocial evaluation during their follow-up from 2013 to 2020.We retrieved data on school and psychological difficulties.Household SES was estimated by a social deprivation score.Data from1003 patients were analyzed.School difficulties were noted in 22%of CCS.A greater social deprivation was significantly associated with school difficulty.Tumor relapse,treatment with hematopoietic stem cell transplantation,and central nervous system(CNS)tumors remained significant risk factors.In the subgroup of CNS tumors,school difficulties were increased and associated with greater social deprivation.Psychological difficulties were not associated with the deprivation score.There is a link between SES and school difficulties in CCS.Further investigations should be carried out for children with CNS tumors,which is the population of the greatest concern.

Clinical and genetic characteristics of retinoblastoma patients in a single center with four novel RB1 variants

AIM:To assess the clinical and genetic characteristics of children diagnosed with retinoblastoma(RB)at Gazi University Faculty of Medicine’s Department of Pediatric Oncology.METHODS:All cases diagnosed with RB and received treatment and follow-up in the Ophthalmology and Pediatric Oncology Department,October 2016 to May 2021 were evaluated retrospectively.The RB1 gene was analyzed by next-generation sequencing(NGS)technique in DNAs obtained from peripheral blood samples of the patients.RESULTS:This study included 53 cases with 67 RBaffected eyes during the study period.The mean age was 24.6(median:18.5,range:3–151)mo.There were 15(22.3%)Group D eyes and 39(58.2%)Group E eyes.The RB1 gene was sequenced by the NGS method in 19 patients.Heterozygous RB1:NM_000321.3:c.54_76del(p.Glu19AlafsTer4)variant was detected in a 15-month-old female with bilateral RB.Heterozygous RB1:NM_000321.3:c.1814+3A>T variant was detected in a 5.5-month-old male with bilateral RB.The intronic RB1:NM_000321.3:c.1332+4A>G variant was detected in patient 14,a 13-month-old male with unilateral RB.The RB1:NM_000321.3:c.575_576del(p.Lys192SerfsTer10)variant was found in an 18-month-old female with an allele frequency of 37%.These variants have not been reported in the literature and mutation databases.CONCLUSION:Four novel variants are described and one of them is found in two different patients.This data is crucial for assessing prognosis.It serves as a guide for estimating the long-term risk of secondary malignancy as well as the short-term risk of developing additional malignancies in the same eye and the other eye.

Mechanism of Niacin Induced Hot Flushes and Suppression of Cholesterol

Niacin or nicotinic acid is a form of B3 vitamin prescribed at higher concentrations for the suppression of cholesterol levels. Supplemental doses may cause very little or no side effects. However, higher concentrations of niacin cause hot flushes for most people. Here we propose a biochemical mechanism of niacin induced hot flushes. Orally taken prescription doses of niacin are converted to NAD with the liberation of excess pyrophosphate which in turn releases energy in the form of heat (hot flushes through capsaicin receptor) by the action of pyrophosphatases. The excess pyrophosphate may suppress cholesterol biosynthesis through feedback mechanism. The pathways of NAD and cholesterol biosynthesis were discussed with refence to the production and function of pyrophosphate.

Platelets Play an Integral Role in Body Heat Production and Maintenance: A Newly Proposed Function

In platelets, most of the ADP is stored in dense granules and released into extracellular space through exocytosis as a signaling molecule upon platelet activation. Glycolysis and the TCA cycle consume considerable amounts of ADP;however, limiting quantities of available ADP to make ATP through OXPHOS result in failure of ATP production and release of energy as heat into the surroundings. Thus, body heat may be a potential product of circulating platelets. Furthermore, the incomplete OXPHOS process causes the production of ROS that leads to earlier platelet death resulting in shorter life span. In the future, this new function may have a wide variety of clinical applications.

Parenteral iron therapy in children with iron deficiency anemia

Iron deficiency anemia(IDA)continues to be a global public health problem.Oral iron is the universally accepted first-line therapy,and most children have a prompt and favorable response to oral formulations.In subsets of children who fail to respond due to intolerance,poor adherence,or inadequate intestinal absorption,parenteral iron is indicated.Despite numerous studies in adults with IDA of diverse etiologies,pediatric studies on parenteral iron use are very limited.Although mostly retrospective and small,these studies have documented the efficacy and safety profile of intravenous iron formulations.In this editorial the author comments on the most important published data and underscores the need to seriously consider parenteral iron use in children unresponsive to oral therapy.

Benign liver tumors in pediatric patients-Review with emphasis on imaging features

Benign hepatic tumors are commonly observed in adults,but rarely reported in children.The reasons for this remain speculative and the exact data concerning the incidence of these lesions are lacking.Benign hepatic tumors represent a diverse group of epithelial and mesenchymal tumors.In pediatric patients,most benign focal liver lesions are inborn and may grow like the rest of the body.Knowledge of pediatric liver diseases and their imaging appearances is essential in order to make an appropriate differential diagnosis.Selection of the appropriate imaging test is challenging,since it depends on a number of age-related factors.This paper will discuss the most frequently encountered benign liver tumors in children(infantile hepatic hemangioendothelioma,mesenchymal hamartoma,focal nodular hyperplasia,nodular regenerative hyperplasia,and hepatocellular adenoma),as well as a comparison to the current knowledge regarding such tumors in adult patients.The current emphasis is on imaging features,which are helpful not only for the initial diagnosis,but also for pre- and posttreatment evaluation and follow-up.In addition,future perspectives of contrast-enhanced ultrasound(CEUS) in pediatric patients are highlighted,with descriptions of enhancement patterns for each lesion being discussed.The role of advanced imaging tests such as CEUS and magnetic resonance imaging,which allow for non-invasive assessment of liver tumors,is of utmost importance in pediatric patients,especially when repeated imaging tests are needed and radiation exposure should be avoided.

Pediatric Non-Hodgkin Lymphoma: A Retrospective 7-Year Experience in Children &Adolescents with Non-Hodgkin Lymphoma Treated in King Fahad Medical City (KFMC)

Background: Non-Hodgkin’s lymphoma is an aggressive malignant disease in children and adolescents. Although it is the fourth most common malignancy in Saudi children as reported in Saudi cancer registry, less information is available about pediatric Non-Hodgkin lymphoma and its outcome in Saudi Arabia. Study Objectives: To provide demographic data, disease characteristics, treatment protocol, toxicity and outcome of treatment in children & adolescents with Non-Hodgkin’s lymphoma treated at KFMC. This study will form base line for future studies about pediatric Non-Hodgkin’s lymphoma in KFMC, which may help to improve outcome for children with cancer in Saudi Arabia. Study Patients and Method: We retrospectively analyzed 28 children and adolescents diagnosed to have Non-Hodgkin’s lymphoma at KFMC between December 2006 and December 2013, followed-up through June 2014. Results: Of the 28 patients, 10 (35.7%) girls and 18 (64.3%) boys, the male-to-female ratio was 1.8;1. The median age at time of diagnosis was 6.4 years old (range 2.0 to 13.0 years old). The majority of patients (64.3%) were aged between 5 and 12 years old. Burkitt’s lymphoma BL/BLL was the most common pathological subtype (60.7%), and DLBCL was the second most common subtype (21.4%). Abdominal and Retroperitoneal involvement was the most common primary site (78.6%) including the ileocaecal region. Most of the children presented with advanced Stage III and IV (75%), Cytogenetic study which screens specifically for the t (8;14) (q24;q32) a characteristic genetic feature of Burkitt’s Lymphoma was obtained from 21 patients, variant rearrangement was observed in 3/21 samples and complex chromosomes karyotype in addition to IGH/MYC rearrangement was observed in 2/21 samples. Those patients presented with very aggressive lymphoma and combined BM and CNS involvement. We use the French-American-British Mature B-Cell Lymphoma 96 Protocol (FAB LMB 96) for treatment fornewly diagnosed Mature B-Cell type NHL and high risk ALL CCG 1961 Protocol for lymphoblastic lymphoma and international Anaplastic Large Cell Lymphoma 99 Study Protocol for ALCL. The median follow-up in patients not experiencing an adverse event was 53.1 months. The estimated 3-year EFE and OS rates in the entire cohort of patients with newly diagnosed NHL treated in the KFMC were 85.2% and 89.2% respectively;Overall survival (OS) rate of patients with mature B-cell-NHL was 88.9%. Conclusion: The outcomes and survival in our small series appeared to be excellent compared with those reported in other international trials even though most of our patients presented in advanced stage of the disease. We feel that the importance of the current study is to document the relative distribution of various types of pediatric non-Hodgkin’s lymphomas and age-specific distribution in different Histological subtypes.

Hematological profile of COVID-19 infected children before and after the spread of the Omicron variant in Istanbul

Objective:To examine the effect of the COVID-19 virus,especially the Omicron variant,on hematological parameters of hospitalized pediatric patients during the COVID-19 pandemic.Methods:Medical records of pediatric COVID-19 patients hospitalized at Kartal Dr.Lütfi K?rdar City Hospital in Istanbul,Turkey,between March 2020 and May 2022 were retrospectively reviewed to analyze data regarding demographics,SARS-Co V-2 infection polymerase chain reaction(PCR)test results,reversetranscriptase(RT)-PCR for other respiratory agents,duration of hospital stay,and hematological and biochemical laboratory findings.Results:Out of 467 children with a confirmed diagnosis of SARSCo V-2 infection,94(20.1%)had Omicron infection and 373(79.9%)were infected with other variants;the Omicron group had younger patients than the remaining samples(P<0.001).The most frequent clinical symptoms in all children were cough(53.5%)and fever(32.3%),followed by vomiting(20.8%).Lung involvement in the Omicron group(10.6%)was significantly lower than in the remaining samples(29.8%)(P<0.001).Hemoglobin and lymphocyte levels were lower in the Omicron-infected group(both P<0.001),while prothrombin time,activated partial thromboplastin time,international normalized ratio,and D-dimer levels were significantly higher in this group(P<0.001,P<0.001,P<0.001,and P=0.023,respectively).In terms of lung involvement,those with lung involvement were significantly older(P<0.001).Conclusions:Although lung involvement was less common with Omicron infection,this group had greater hematological system involvement,such as anemia,lymphopenia,D-dimer elevation,and coagulation disorders.

Asparaginase-associated pancreatitis in chemotherapytreated pediatric patients:a five-year retrospective study

Asparaginase(Asp)represents a key agent in induction remission for acute lymphoblastic leukemia(ALL)and certain subtypes of non-Hodgkin lymphoma(NHL).By catalyzing the hydrolysis of extracellular asparagine,thus depleting the level of plasma asparagine necessary for the growth of leukemic lymphoblasts,Asp can inhibit leukemic lymphoblast protein synthesis and lead to subsequent apoptosis with little myelosuppression.[1]This will achieve anti-leukemia efficacy,and promote the remission of leukemia.[2]A previous study showed that an Asp-containing regimen could significantly increase the event-free survival rate(71%vs.31%).[3]A previous study showed that those who completed the Asp regimen had a higher 5-year event-free survival rate(90%)than those who were unable to tolerate toxicity and quitted the treatment(73%).[4]

Drugging SUMOylation for neuroprotection and oncotherapy

Recently there have been exciting research advances in neuroprotective therapies for ischemic stroke. In the past, the search for neu- roprotective agents has been fraught with failure at the clinical trials stage due to numerous factors, including subject heterogeneity and improper therapeutic windows （Tymianski, 2017）. Moreover, it is becoming clearer that the complex and evolving pathobiology of stroke requires multimodal therapeutic approaches capable of modulating the numerous axes that contribute to ischemia/reperfusion damage, rather than targeting a single axis （Bernstock et al., 2018a）. With the success of recent endovascular thrombectomy （EVT） trials, it has been suggested that clinical trials of EVT with adjunct neuroprotection can overcome past difficulties and maximize the effect size by using imaging to reduce patient heterogeneity （i. e., selecting those with large vessel occlusions, small ischemic cores, and good collateral circulation）, restoring perfusion using better EVT devices, and enrolling patients in the correct therapeutic window （i.e., when they still have salvageable brain tissue） （Tymianski, 2017）. Considering the opportunity that this represents for new, better clinical trials of neuroprotective agents, the search is on for high-potential compounds that may be investigated in these future studies.

Dexamethasone versus Prednisone in Childhood Acute Lymphoblastic Leukemia Treatment: Results of the Indonesian Randomized Trial

Background: Randomized trials report that, compared to prednisone, dexamethasone has reduced CNS relapse and improved event-free survival (EFS), despite a trend toward a higher risk for induction death. Because toxic death is a specific problem in the Indonesian setting, this study compares the outcome of dexamethasone versus prednisone. Methods: In the period 2006 - 2011, 196 patients with childhood acute lymphoblastic leukemia (ALL) treated on the Indonesia-ALL-2006 protocol [first standard risk (SR) and later high risk (HR) patients] were randomized to receive dexamethasone or prednisone as steroid. Patients in the dexamethasone arm (n = 102: 68 SR, 34 HR) received dexamethasone 4 mg/m2/day (SR) or 6 mg/m2/day (HR), while the prednisone arm (n = 94: 66 SR, 28 HR) received prednisone 40 mg/m2/day (SR and HR). Results: Patients in the dexamethasone arm showed no significant difference compared to the prednisone arm in abandonment rate (24.5% vs. 25.5%, P = 0.91), death rate (17.7% vs. 14.9%, P = 0.54), or leukemic events (13.7 vs. 11.7%, P = 0.59). After stratification for risk group, a trend towards a higher death rate was found in the dexamethasone arm of SR patients (16.2 vs. 6.1%, P = 0.06). The 3-year survival for EFS in SR and HR patients for dexamethasone versus prednisone was 31.5% ± 6.6% vs. 41.5% ± 5.9% (P = 0.51), for leukemia-free survival (LFS) it was 63.7% ± 9.3% vs. 74.5% ± 7.6% (P = 0.47), and for overall survival (OS) it was 49.5% ± 7.7% vs. 69.3% ± 6.1% (P = 0.09). Conclusions: In our setting, a trend toward higher induction deaths was observed in the dexamethasone arm of SR patients and the 3-year EFS;LFS and OS rates were lower in the dexamethasone group;however, these differences were not significant.

Risk and benefit from clinical trials in minors:Making the case for transparent and consistent publications

Rationale, aim and objectives: The European (EU) regulation on medicinal products for pediatric use (EC 1901/2006), which became effective in 2007, aimed to stimulate the clinical testing of medications in minors in order to reduce off-label use. In consequence, the number of minors taking part in randomized controlled clinical trials (RCTs) is likely to increase. Clinical trials in minors require a complex methodological design, a careful consideration of risks and benefits and a high level of ethical reflection. Unfortunately, as to the quality of clinical trials and their publications in minors little is known. Therefore, we assessed published reports of randomized, controlled clinical trials in minors, focusing on a common disease (asthma) and a defined spectrum of lifethreatening diseases (malignant diseases). Method: In an exploratory design, we scanned the publications for methodological aspects as well as indicators of ethical soundness, e.g., statements that informed consent had been obtained before the start of the trial or that a Data and Safety Monitoring Board ensured the patients’ safety during the trial. We also looked for passages reflecting the debate on equipoise or other forms of weighing risks and benefits. Results: We found that many of these aspects, which according to the scientific literature and generally acknowledged guidelines are essential to ensure good-quality trials and trial reports, were not considered in the publications analyzed. Conclusion: Therefore, we call for a more transparent and consistent presentation of the trials, especially of safety aspects, relying on a more critical and transparent ethical reflection.

组织因子表达下调影响阿霉素诱导人胶质母细胞瘤细胞凋亡的研究

目的研究组织因子(TF)对阿霉素诱导人胶质母细胞瘤细胞凋亡的影响。方法以免疫印迹法检测TF表达。分子生物学方法构建TFsiRNA-pSUPER表达载体,以脂质体介导进行基因转染。以水溶性四唑盐法检测阿霉素的细胞毒性。以印迹法检测阿霉素诱导的Caspase-3、PARP的裂解。以Hochest33342染色荧光显微镜检测凋亡细胞。结果人胶质母细胞瘤细胞系U373MG高表达TF。转染TFsiRNA-pSUPER表达载体的U373MG细胞及对照细胞分别以阿霉素处理,可见转染细胞较对照细胞Caspase-3、PARP的裂解增强。以不同浓度阿霉素处理48h后,可见转染后的U373MG细胞的存活数较对照细胞明显减少(P<0.05)。以Hochest33342染色检测到转染后的U373MG细胞经阿霉素处理后的凋亡细胞数显著增多(P<0.05)。结论人胶质母细胞瘤U373MG中TF异常高表达的下调,可增强阿霉素诱导的细胞凋亡。肿瘤细胞中TF的异常高表达可能影响肿瘤细胞对化疗药物的耐受性。

Hepatitis B virus infection in Latin America:A genomic medicine approach

Hepatitis B virus(HBV)infection is the leading cause of severe chronic liver disease.This article provides a critical view of the importance of genomic medicine for the study of HBV infection and its clinical outcomes in Latin America.Three levels of evolutionary adaptation may correlate with the clinical outcomes of HBV infection.Infections in Latin America are predominantly of genotype H in Mexico and genotype F in Central and South America;these strains have historically circulated among the indigenous population.Both genotypes appear to be linked to a benign course of disease among the native and mestizo Mexicans and native South Americans.In contrast,genotypes F,A and D are common in acute and chronic infections among mestizos with Caucasian ancestry.Hepatocellular carcinoma is rare in Mexicans,but it has been associated with genotype F1b among Argentineans.This observation illustrates the significance of ascertaining the genetic and environmental factors involved in the development of HBV-related liver disease in Latin America,which contrast with those reported in other regions of the world.

Recurrent lymphoma presenting as painless, chronic intussusception: A case report

BACKGROUND The clinical presentation of acute lymphoblastic lymphoma is highly varied.While prognosis is good, recurrence of disease can occur. Gastrointestinal relapse, including intussusception, is well-described but the absence of abdominal pain in this setting is rare.CASE SUMMARY We report a 13-year-old male with B-cell precursor acute lymphoblastic leukemia in remission presenting with anemia and weight loss. Examination was significant for absence of abdominal pain, but a stool sample was positive for occult blood. Pan-endoscopy was performed with colonoscopy revealing a mass filling the colonic lumen. Biopsy of the mass confirmed recurrence of recurrent Bcell lymphoma. Computed tomography scan revealed ileocolic intussusception resulting from the tumor. This case is unusual in that the patient had no abdominal pain despite the presence of intussusception.CONCLUSION While intestinal involvement with lymphoma has been well described in the literature, presentation as painless intussusception has not been reported. This case report highlights the wide spectrum of clinical manifestations of recurrent Bcell lymphoma involving the gastrointestinal tract, in particular the near absence of symptoms despite the finding of intussusception.

Ph^+儿童急性淋巴细胞性白血病:良好的类固醇初始反应可以早期预测较件的治疗结果

目前,世界各主要白血病研究小组均在探讨如何识别影响儿童急性淋巴细胞性白血病(Acute twn-phoblastic leukemia,ALL)成功治疗的各种特有危险因素。大约3%～5%的 ALL 患儿存在染色体 t(9;22)(q34;q11)易位,即所谓的 Ph^+染色体,这一分子标志被认为是与 ALL 治疗失败相关的特有高危因素。这种染色体易位可引起原癌基因 c-ABL 和断裂点决定簇区(Breakpoint cluster region,BCR)基因间的重排。

Pathogens causing diarrhoea among Bangladeshi children with malignancy: Results from two pilot studies

BACKGROUND Diarrhoea is a frequent symptom in children with cancer, and occurs due to a composite effect of underlying disease and immunosuppression consequent to therapy, malnutrition, and non-infective aetiologies such as mucositis. In a large proportion of cases, the aetiology of diarrhoea remains unknown but is often attributed to multiple pathogens including parasites.AIM To identify and describe the pathogens causing diarrhoea in Bangladeshi children with cancer.METHODS Two cross-sectional pilot studies were conducted involving paediatric oncology patients with diarrhoea. Stool samples were collected from children who were hospitalised with or without being treated with chemotherapy during the study period, and had diarrhoea at any stage during their admission. In the first study,stool samples were tested by conventional microbiological methods and by polymerase chain reaction for parasites, and by immunoassays for Clostridium difficile. In the second study, conventional microbiology was conducted for bacteria and parasites including an enzyme-linked immunosorbent assay for Cryptosporidium antigen, and in a subset, immunoassays for Clostridium difficile.RESULTS In the first study Giardia lamblia was detected in 68.5% of samples, Entamoeba histolytica in 13%, Cryptosporidium in 5.6%, non-toxigenic C. difficile in 22.4%, and other bacteria in 5.2%. In the second study, E. histolytica was detected in 10% of samples, Cryptosporidium in 4.3%, G. lamblia in 1.4%, C. difficile in 5.1%, and other bacteria in 5.7% of samples.CONCLUSION These pilot data suggest that parasites are important aetiologies of diarrhoea in Bangladeshi children with malignancy. While molecular diagnostic tools detect an array of stool pathogens with greater sensitivity, conventional diagnostic methods are also useful.

Current approach to relapsed acute lymphoblastic leukemia in children

Recurrent acute lymphoblastic leukaemia(ALL) is a common disease for pediatric oncologists and accounts for more deaths from cancer in children than any other malignancy. Although most patients achieve a second remission, about 50% of relapsed ALL patients do not respond to salvage therapy or suffer a second relapse and most children with relapse die. Treatment must be tailored after relapse of ALL, since outcome will be influenced by well-established prognostic features, including the timing and site of disease recurrence, the disease immunophenotype, and early response to retrieval therapy in terms of minimal residual disease(MRD). After reinduction chemotherapy, high risk(HR) patients are clear candidates for allogeneic stem cell transplantation(SCT) while standard risk patients do better with conventional chemotherapy and local therapy. Early MRD response assessment is currently applied to identify those patients within the more heterogeneous intermediate risk group who should undergo SCT as consolidation therapy. Recent evidence suggests distinct biological mechanisms for early vs late relapse and the recognition of the involvement of certain treatment resistance related genes as well cell cycle regulation and B-cell development genes at relapse, all providing the opportunity to search for novel target therapies.

Acute lymphoblastic leukemia in a β-thalassemia intermedia child: A case report

BACKGROUNDβ-thalassemia intermedia(βTI)is one of the hemoglobinopathies.It constitutes 10%ofβ-thalassemia cases yet being associated with a better quality of life thanβ-thalassemia major(βTM).CASE SUMMARY We recently reported the first case of acute lymphoblastic leukemia(ALL)from Egypt in a child withβTM,and we herein report the first case of ALL from Egypt in a child withβTI.In this report,literature was reviewed for cases of malignancies associated withβTI and the possible factors underling the relationship between the two entities.CONCLUSION We stress that physicians should have a high index of suspicion of malignancies in thalassemia patients if they present with any suggestive symptoms or signs.