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Worldwide, the coronavirus 19 disease pandemic caused a worse chance of a timely diagnosis for cancer patients. We conducted a retrospective analysis of new diagnoses registered in the national pediatric oncology database, comparing the first lockdown period (March-May 2020) with the same period of 2015-2019. The total number of cases (0-19 years) dropped by 20.8% (from 441 between 2015 and 2019 to 349 in 2020). A major reduction was observed for adolescents (15-19 years) (-32.9%) and for adolescents with solid tumors (-56.4%, p = 0.03). Our data suggest that the enforced lockdown reduced the possibility for these already vulnerable patients to access the referral centers.

The aim of this study was to identify specific unusual prenatal ultrasound (US) patterns of the adrenal gland and to propose a systematic approach for diagnosis. Six fetuses with unusual aspects of one or both adrenal glands, detected during routine prenatal US screening, were evaluated. Prenatal and postnatal management are described. A checklist of US features was created to perform a detailed analysis of adrenal lesions and guide prenatal management; this includes the time of appearance, location, growth, vascularization, structure, and presence of findings suggestive of malignancy.

T-cell replete hematopoietic stem cell transplantation (HSCT) from a haploidentical donor followed by high doses of cyclophosphamide has been demonstrated to provide the best chances of a cure for many children in need of an allograft but who lack both a sibling and an unrelated donor. In this study we retrospectively compared the outcome of pediatric patients undergoing T-replete haploidentical HSCT (Haplo) for acute leukemia with those undergoing transplantation from unrelated HLA-matched donor (MUD) and HLA mismatched unrelated donor (MMUD) from 2012 to 2017 at our Center. Both univariable and multivariable analyses showed similar 5-year overall survival rates for MUD, MMUD, and Haplo patients: 71% (95% CI 56-86), 72% (95% CI 55-90), and 75% (95% CI 54-94), respectively (p = 0.97). Haplo patients showed reduced event-free survival rates compared to MUD and MMUD patients: 30% (95% CI 12-49) versus 70% (95% CI 55-84) versus 53% (95% CI 35-73), respectively (p = 0.007), but these data were not confirmed by a multivariable analysis. Non-relapse mortality (NRM) and relapse incidence (RI) were similar for the three groups. Therefore, our data confirm that Haplo is a suitable clinical option for pediatric patients needing HSCT when lacking both an MUD and an MMUD donor.

Purpose: To describe how the provision of services for adolescents with cancer has evolved in Italy, the study evaluated access to pediatric oncology centers affiliated to the national cooperative ...

Purpose: Adolescents (15–19 years) with soft tissue sarcomas (STS) have worse survival than children. One reason is the former's limited access to expert centers. We investigated where adolescents ...

Adolescents and young adults with cancer have substantially different clinical and psychological needs compared to those of pediatric patients and of older adult patients. We describe the development of an Italian national project dedicated to adolescents and young adults with cancer.

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This article reviews the primary goals and achievements of the Italian Association for Pediatric Hematology-Oncology (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP]), a national cooperative group that has been working for children and adolescents with cancer in Italy since 1975.

Acute myeloid leukemia (AML) is a rare disorder of childhood. It could arise as primary tumor or secondary transformation from a myelodysplastic syndrome (MDS). While some cases are likely acquired...

Background: The detection rate of congenital heart defects is barely acceptable. Since 2016, the French National Conference on Obstetrical and Foetal Ultrasound updated its recommendations by the inclusion of an examination of the left ventricular outflow tract (LVOT) in the second and third trimester of pregnancy. Objectives: This study aimed on the one hand to evaluate the practices related to the realization of the LVOT in the setting of fetal echocardiography in low-risk populations, and on the other hand to study the possible modifications of the practices secondary to the introduction of quality criteria. Study Design: We conducted a multicentric, retrospective and prospective, descriptive, longitudinal study divided into three distinct periods: before 2016, in 2017, and in 2020. Seven quality criteria were investigated and rated from 0 to 1 for LVOT screening. Files were randomly selected from three centers, then average total and specific scores were calculated. Results: LVOT images were present in ultrasound reports in more than 93% of cases. Before 2016, the average quality score was 5.49/7 (95% CI: 5.36-5.62), in 2017 5.91/7 (95% CI: 5.80-6.03), and in 2020 5.70/7 (95% CI: 5.58-5.82) for the three centers. There was no significant difference following the introduction of the quality criteria; 2017 vs. 2020, p = 0.054. Kappa coefficients of the inter- and intra-operator variables were all within 0.601 and 1. Conclusion: Left ventricular outflow tract images were present in most of ultrasound reports. The introduction of the proposed quality criteria is not associated with a significant change in practice.

Persistent thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT). While the use of thrombopoietin receptor agonists was retrospectively investigated in adults, data in pediatric posttransplant thrombocytopenia are lacking. We evaluated the safety and efficacy of eltrombopag in nine children with platelet transfusion-dependent persistent thrombocytopenia after HSCT. Eltrombopag was started at a median of 147 days after allo-SCT and continued for a median period of 64 days, the starting dose being 50mg per day. The therapy was well tolerated. After a median time of treatment of 36 days, eight patients (88%) reached sustained platelets count>50000/μL.

Patients given allogeneic hematopoietic stem cell transplantation (alloHSCT) present an increased incidence of long-term toxicities that can be attributed to the preparative regimen. We retrospectively analyzed in a population of 670 children receiving allo-HSCT for acute leukemia the occurrence of different late effects in function of the choice made between total body irradiation (TBI) and busulfan, as part of the preparative regimen. In univariable analysis, we found that patients treated with TBI developed cataract in 24% of the cases compared with 4% in patients treated with BU (p = 0.0001) and that the incidence of secondary malignant neoplasia (SMN) was higher in patients treated with TBI (18%) as compared with those prepared to the allograft with a Bu-based regimen (0%) (p = 0.019). Conditioning regimen did not show a statistically significant correlation with the occurrence of all the other investigated late effects. In multivariable analysis, TBI remained associated with the occurrence of cataracts (Relative Risk: 0.33 p = 0.012) and secondary malignancies (Relative Risk 3.96 × 10e−6 p < 0.001); however, other variables, as GvHD and disease type, were also correlated with these long-term sequels, indicating that in our study population the preparative regimen is not the only factor influencing the incidence of these complications.

ObjectiveScreening for genital infection (GI), bacterial vaginosis (BV), sexually transmitted infection (STI) and asymptomatic carriage of group B streptococcus (GBS) in pregnant women is a common reason for medical appointments. Objectives were first to determine the non-inferiority of vaginal self-sampling compared with vaginal/cervical classical sampling to screen for GIs, bacterial vaginosis (BV), STIs, and GBS asymptomatic carriage in pregnant women; second to determine the feasibility of vaginal self-sampling.MethodsVaginal self-sampling (VSS) and vaginal/cervical classical sampling (VCS) of 1027 women were collected by health care professionals and simultaneously carried out on each patient. Bacterial infection, yeast infection, Chlamydia trachomatis, Neisseria gonorrhoea, Mycoplasma genitalium, Trichomonas vaginalis and Herpes simplex virus types were systematically screened in both paired VSS and VCS samples.ResultsStatistical tests supported the non-inferiority of VSS compared with VCS. Agreements between VCS and VSS remained high regardless of the type of studied infection. VSS had successful diagnostic performances, especially for Predictive negative value (PNV) (over 90%) for all studied infections. Most participants (84%) recommended the use of VSS.ConclusionsThis study remains the most exhaustive in screening for GI, BV, STI agents and asymptomatic GBS carriage. Given its efficacy and acceptability, VSS seems to be a viable alternative to classic physician sampling among women in the general population. This study provides evidence that vaginal self-sampling can be used as a universal specimen for detection of lower genital tract infections in women.Study Identification numberID-RCB 2014-A01250-4

Background & aim Screening for genital infection (GI) such as bacterial vaginosis (BV) and yeast infection, for sexually transmitted infection (STI), and for asymptomatic carriage of group B streptococcus (GBS) in pregnant women are common reason for medical appointments. The diagnosis and control of GIs, STIs, and GBS are major issues, for fertility and overall well-being of affected women. Conventional testing is performed using vaginal/cervical classical sampling (VCS); this procedure requires pelvic examination performed by health care professionals which raises concerns among women. Vaginal-self-sampling (VSS), as an alternative to VCS, might capture more women. The aim was first to show non-inferiority of VSS compared with VCS to screen for GIs, STIs, and GBS; second to determine the feasibility of VSS. Methods VSS and VCS from 1027 women were collected by health care professionals and simultaneously carried out on each patient. GIs, STIs, and GBS were systematically screened in both paired VSS and VCS samples. Non-inferiority of VSS compared with VCS was assessed using z statistic for binomial proportions. Results Prevalence of GIs were 39.7% using VSS and 38.1% using VCS (p = 0.0016). Prevalence of STIs was 8.5% (VSS) vs 8.1% (VCS) (p = 0.0087). Prevalence of GBS was 13.4% (VSS) and 11.5% (VCS) (p = 0.0001). Most participants (84%) recommended the use of VSS. Conclusions This study shows that VSS was not inferior to VCS for the detection of GIs, STIs, and GBS. This study provides evidence that VSS can be used as a universal specimen for detection of lower genital tract infections in women. Study identification number ID-RCB 2014-A01250-4.

International audience; Background: The significant number of qualitative and quantitative ultrasound markers described for first-trimester screening of open spina bifida (OSB) and other posterior brain defects (oPBD) has resulted in their complex implementation and interpretation for a widespread screening and in a lack of consensus regarding diagnostic accuracy.Objectives: To assess and compare the accuracy of qualitative and quantitative cranial sonographic markers at 11-14 weeks of gestation for the detection of OSB and oPBD.Search strategy: A systematic literature search was performed in MEDLINE and COCHRANE from 2009 to April 2020.Selection criteria: Studies assessing the diagnostic accuracy of quantitative and/or qualitative ultrasound signs to predict OSB and oPBD were included. Cohort studies and case-control studies were also considered.Data collection and analysis: Two reviewers independently extracted data and assessed the risk of bias. The overall pooled estimate and a summary receiver operating characteristic curve was estimated for each subgroup (qualitative and quantitative assessment).Main results: Twenty-three studies were included in our meta-analysis. The pooled sensitivity and specificity for qualitative assessment were 76.5% and 99.6%, and for quantitative assessment were 84.5% and 96.3%, respectively; specificity for the qualitative ultrasound signs was significantly higher (P = 0.001). The overall sensitivity of cranial sonographic markers for the screening of oPBD was 76.7% and specificity was 97.5%.Conclusions: The qualitative approach demonstrated greater specificity, so this would appear to be more appropriate for daily screening, as a first-line tool, whereas the quantitative approach should be reserved for expert ultrasound.Tweetable abstract: This study highlights the relevance of first-trimester qualitative ultrasound signs in the screening of open spina bifida.

Whereas 90% of patients with Wilms tumor (WT) reach cure, approximately half of patients developing a recurrent tumor die of the disease. Therefore, to disclose events leading to recurrence represents a clinical need. To study paired primary/recurrent tumor samples, being aware of the intra-tumoral heterogeneity, might help finding these answers. We previously suggested that mutations in SIX1 and DROSHA underlie WT recurrence. With the aim to better investigate this scenario, we collected 19 paired primary/recurrent tumors and 10 primary tumors from relapsing patients and searched for mutations in the SIX1/2 genes and microRNA processing genes (miRNAPGs). We found SIX1 mutation in one case, miRNAPGs mutations in seven cases, and the co-occurrence of SIX1 and miRNAPG mutations in one case. We could observe that, whereas in primary tumors the mutations could be heterogeneously present, in all cases they were positively selected and homogeneously present in the recurrent disease, as also indicated by a “moderate” and “almost perfect” agreement (according to the Landis and Koch classification criteria) between paired samples. Analysis of SIX1/2 genes and miRNAPGs in 50 non-relapsing WTs disclosed SIX2 mutation in one case and miRNAPGs mutations in seven. A borderline statistically significant association was observed between miRNAPGs mutations and the occurrence of relapse (p value: 0.05). These data suggest that SIX1 and miRNAPGs mutations may provide an advantage during tumor progression to recurrence and can represent oncogenic drivers in WT development.

Cell-free DNA (cfDNA) as a primary screening test has been available for years but few studies have addressed this option in a prospective manner. The question is of interest after reports that maternal serum screening (MSS) is less accurate for pregnancies resulting from assisted reproduction technologies (ART) than for spontaneous pregnancies (SP). A prospective interventional study was designed to address the performances of cfDNA compared with MSS in pregnancies with or without ART. Each patient was offered both MSS and cfDNA testing. The primary analysis cohort ultimately included 794 patients with a spontaneous pregnancy (SP) (n = 472) or pregnancy obtained after ART (n = 322). Overall, the false-positive rate and positive predictive value were 6.6% and 8.8% for MSS but 0% and 100% for cfDNA. MSS false-positive rate and positive predictive values were clearly poorer in the ART group (11.7% and 2.6%) than in the SP group (3.2% and 21.1%). The global rates of invasive procedures were 1.9% (15/794) with cfDNA but 8.4% (65/794) if MSS alone was proposed. cfDNA achieved better performance than MSS in both spontaneous and ART pregnancies, thus decreasing the number of invasive procedures. Our findings suggest that cfDNA should be considered for primary screening, especially in pregnancies obtained after ART.

BACKGROUND Hematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiencies. However, pre-HSCT conditioning entails unacceptably high risks if the liver is compromised. The presence of a recurrent opportunistic infection affecting the biliary tree and determining liver cirrhosis with portal hypertension posed particular decisional difficulties in a 7-year-old child with X-linked CD40-ligand deficiency. We aim at adding to the scanty experience available on such rare cases, as successful management with sequential liver transplantation (LT) and HSCT has been reported in detail only in 1 young adult to date. METHODS A closely sequential strategy, with a surgical complication-free LT, followed by reduced-intensity conditioning, allowed HSCT to be performed only one month after LT, preventing Cryptosporidium parvum recolonization of the liver graft. RESULTS Combined sequential LT and HSCT resolved the cirrhotic evolution and corrected the immunodeficiency so that the infection responsible for the progressive sclerosing cholangitis did not recur. CONCLUSIONS Hopefully, this report of the successful resolution of a potentially fatal combination of immunodeficiency and chronic opportunistic infection with end-stage organ damage in a child will encourage others to adapt a sequential transplant approach to this highly complex pathology. However, caution is to be exercised to carefully balance the risks intrinsic to transplant surgery and immunosuppression in primary immunodeficiencies.

Resume La decouverte d’un perimetre cephalique (PC) inferieur au 3epercentile (p), au meme titre que le femur court ou l’hyperclarte de nuque a caryotype normal, demeure l’une des situations les plus difficiles pour le praticien en diagnostic prenatal. La microcephalie constitue une porte d’entree d’eventuelles pathologies cerebrales diverses; cependant l’objectif principal est d’identifier les situations graves accessibles en periode prenatale. Une mesure standardisee du PC, l’utilisation d’outils et de courbes de references adaptes, un suivi longitudinal des biometries cephaliques dans les situations a risques, et une analyse systematisee du systeme nerveux central peuvent permettre d’augmenter les performances diagnostiques de l’echographie souvent decevantes pour la microcephalie. La distinction precoce entre microcephalie associee ou isolee permet d’orienter rapidement la conduite a tenir et le conseil prenatal. L’IRM fœtale et la consultation de genetique sont fondamentaux dans ce contexte, ils permettent de preciser, au mieux, le diagnostic etiologique et d’apporter une aide au neuropediatre dans l’etablissement d’un pronostic souvent incertain. La recente augmentation des cas de microcephalie concomitante a l’epidemie du virus ZIKA est un argument supplementaire pour ameliorer nos pratiques et l’apprehension au quotidien des PC

The detection of abnormalities of the fetal urinary system in the first trimester of pregnancy is constantly improving, namely owing to the improved resolution of the image, the use of the endovaginal approach and thanks to sonographers' constant training. The pathological aspects, usually detected in the second trimester of pregnancy, can be suspected early in the first trimester and range from kidneys' cavity dilation to bilateral renal agenesis, polycystic kidney disease, multi-cystic dysplasia and bladder megavessia or bladder exstrophy. A poly-malformative syndrome is to be found out. The detection of an abnormality of the urinary tract requires a close ultrasound check. Very often, the pathological aspects tend to disappear spontaneously. In particular, the non-visualization of the bladder requires repeated examinations during the same session or even a little later in the pregnancy. We will carry out a review of the literature by pointing out the usual and unusual aspects of the fetal urinary system visible in the first trimester and we will as well propose an algorithm describing how to deal with abnormalities of the urinary tract that can be found out at first trimester ultrasound.

Pulmonary lymphoid lesions span from benign to other forms of malignant diseases. Among these pulmonary lymphoid lesions, Nodular Lymphoid Hyperplasia (NLH) has an excellent prognosis. The surgical excision of NLH seems to be the only treatment, even if in some cases a spontaneous regression has been reported. Interestingly, these lesions may have similar clinical and radiographic presentations, making a histopathological examination vital for their differentiation. In this report we describe four cases of pediatric patients with a previous history of classical Hodgkin Lymphoma (HL) with documented or suspected NLH.

We assess the performance of different break detection methods on three sets of benchmark data sets, each consisting of 120 daily time series of integrated water vapor differences. These differences are generated from the Global Positioning System (GPS) measurements at 120 sites worldwide, and the numerical weather prediction reanalysis (ERA‐Interim) integrated wáter vapor output, which serves as the reference series here. The benchmark includes homogeneous and inhomogeneous sections with added nonclimatic shifts (breaks) in the latter. Three different variants of the benchmark time series are produced, with increasing complexity, by adding autoregressive noise of the first order to the white noise model and the periodic behavior and consecutively by adding gaps and allowing nonclimatic trends. The purpose of this “complex experiment” is to examine the performance of break detection methods in a more realistic case when the reference series are not homogeneous. We evaluate the performance of break detection methods with skill scores, centered root mean square errors (CRMSE), and trend differences relative to the trends of the homogeneous series. We found that most methods underestimate the number of breaks and have a significant number of false detections. Despite this, the degree of CRMSE reduction is significant (roughly between 40% and 80%) in the easy to moderate experiments, with the ratio of trend bias reduction is even exceeding the 90% of the raw data error. For the complex experiment, the improvement ranges between 15% and 35% with respect to the raw data, both in terms of RMSE and trend estimations. The research has been undertaken in the framework of the European COST Action ES1206 GNSS4SWEC (GNSS for Severe Weather and Climate monitoring; http://www.cost.eu/COST_Actions/essem/ES1206), which also funded two dedicated workshops on this activity.

International audience

Diamond-Blackfan anaemia (DBA) is a rare and heterogeneous disease characterised by hypoplastic anaemia, congenital anomalies and a predisposition for malignancies. The aim of this paper is to report the findings from the Italian DBA Registry, and to discuss the Registry's future challenges in tackling this disease. Our 20-year long work allowed the connection of 50 Italian Association of Paediatric Haematology and Oncology (AIEOP) centres and the recruitment of 283 cases. Almost all patients have been characterised at a molecular level (96%, 271/283), finding a causative mutation in 68% (184/271). We confirm the importance of determination of erythrocyte adenosine deaminase activity (eADA) and of ribosomal RNA assay in the diagnostic pipeline and characterisation of a remission state. Patients with mutations in large ribosomal subunit protein (RPL) genes had a significant correlation with the incidence of malformations, higher eADA levels and more severe outcomes, compared to patients with mutations in small ribosomal subunit protein (RPS) genes. Furthermore, as a consequence of our findings, particularly the incidence of malignancies and the high percentage of patients aged >18 years, we stress the importance of collaboration with adult clinicians to guarantee regular multi-specialist follow-up. In conclusion, this study highlights the importance of national registries to increase our understanding and improve management of this complex disease.

Over the last decade, next-generation sequencing technologies have improved our ability to assess biological aspects, at genomic and transcriptomic levels, on a large scale- and have been increasingly used for the management of adult cancers. However, their efficacy and feasibility within pediatrics is still under investigation. "Omic" approaches represent an opportunity to understand the oncogenic mechanisms driving the onset and progression of bone sarcoma and improve the clinical management of young patients with bone sarcomas. This review focuses on the current genomic and transcriptomic characteristics of managing pediatric patients, affected by Ewing sarcoma and osteosarcoma.

Liver disease in X-linked hyper IgM syndrome (XHIGM) is an important predictor of mortality. In case liver transplantation (LT) is required, a survival benefit is observed when LT is combined with HSCT. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:143 issue:5 pages:1952-+ ispartof: location:United States status: published

Purpose To study the feasibility of perinatal post-mortem computed tomography angiography (PMCTA) and to evaluate the informations provided. Material and methods From January to March 2014, we included all fetuses referred to our fetopathology unit for intra-uterine fetal death or termination (IUFD) or pregnancy (TOP). We noted sex, gestational age in weeks׳ gestation (WG) at referral, and reason for TOP. All bodies were scanned with the same CT device using the same protocol, before and after contrast injection. We analyzed the success rate of the injection, the quality of vascular filling and the informations provided compared to prenatal data and confirmed by standard autopsy for all patients. Results We prospectively included 17 consecutive attempts of PMCTA in fetuses aged 16–37 WG (mean 28), 9 were male and 8 were female, originating from intra-uterine fetal death ( n =4, 23.5%) or termination of pregnancy ( n =13, 76.5%). Injection failed in 4 cases (23%). In the 13 successful others (77%), injection was quoted sub-optimal in 2 cases (15%). Overall, additional informations were provided by PMCTA in 5 cases (29%), meaning 38% of cases when injection was successful. Conclusion Perinatal PMCTA is feasible and provides additional data compared to prenatal imaging. We strongly believe it is a very promising technique, especially in association with ultrasound, more or less dedicated brain MRI.

Relapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively investigated the prognostic role of minimal residual disease (MRD) before and after HSCT in 119 children transplanted in complete remission (CR). MRD was measured by polymerase chain reaction in bone marrow samples collected pre-HSCT and during the first and third trimesters after HSCT (post-HSCT1 and post-HSCT3). The overall event-free survival (EFS) was 50%. The cumulative incidence of relapse and non-relapse mortality was 41% and 9%. Any degree of detectable pre-HSCT MRD was associated with poor outcome: EFS was 39% and 18% in patients with MRD positivity

Objectives To evaluate the added value of fetal magnetic resonance imaging (MRI) in diagnosing and assessing isolated orofacial clefts and compare MRI with second-line diagnostic ultrasound. Materials and methods In a two-year prospective bicenter study, fetuses with isolated orofacial clefts were reassessed using second-line diagnostic ultrasound and MRI. The results of second line ultrasound and those MRI were compared to each other. The gestational age at the time of ultrasound and MRI, and the final diagnosis for each of the imaging modalities were recorded. Finally, the results of second line ultrasound and those of MRI were compared to the results of neonatal clinical examination after delivery that served as standard of reference. Results Twenty-two women were included after informed consent was obtained. On average, diagnostic ultrasound was performed at 25.5 weeks of gestation (range: 24–34 weeks) and MRI at 29.5 weeks of gestation (range: 27–34 weeks). The results of ultrasound and those of MRI findings were strictly consistent in 20 women (20/22; 91%) but differed in 2 women (2/22; 9%). For all fetuses, the final radiological diagnosis was confirmed by clinical examination after delivery. Conclusion If ultrasound examination proves technically challenging, fetal MRI can be used to obtain the same diagnostic information in 91% of cases and can help surgeons and interdisciplinary teams provide appropriate antenatal counseling.

Background CHARGE syndrome is a multiple congenital anomaly syndrome caused by mutations in CHD7. Diagnostic criteria have been proposed to improve diagnosis in fetuses at clinicopathological survey, but no criteria exist for fetal diagnosis during pregnancy. Method We collected prenatal findings of 12 children with CHARGE syndrome diagnosed in the first 3 months and a CHD7 mutation. We retrieved data on prenatal ultrasound (US) follow-up, fetal supplementary investigations, and results of postnatal evaluation. Result Seven pregnancies were complicated by the identification of isolated or multiple congenital anomalies. CHARGE syndrome was suspected in three fetuses but could not be confirmed despite additional examinations. Retrospectively, several postnatal findings could have been seen if they had been specifically searched. Intrauterine growth restriction, previously proposed as an exclusion criterion, complicated two pregnancies and is thus compatible with the diagnosis. Conclusion Diagnosis of CHARGE syndrome remains difficult during pregnancy. If the diagnosis of CHARGE syndrome is raised in utero, we suggest a careful US examination to identify typical external ears, choanal atresia, or microphthalmia. Fetal brain magnetic resonance imaging can be helpful, but a normal result does not exclude the diagnosis. When CHARGE syndrome is highly suspected, CHD7 molecular analysis must be proposed to confirm the diagnosis. © 2016 John Wiley & Sons, Ltd.

Introduction Transabdominal chorionic villus sampling (CVS) is an invasive procedure for prenatal diagnosis reported to be associated with anxiety and pain. In this context, the need for analgesia during CVS has been considered useful. Even though several authors have been interested in pain management during amniocentesis, no study has been published on pain reduction during CVS. Our objective was to evaluate pain and anxiety management during transabdominal CVS using nitrous oxide (N2 O) and local anesthesia. Material and methods In a randomized controlled noninferiority trial, self-administered nitrous oxide (N2 O) inhalation (equimolar premix of oxygen and nitrous oxide) was compared with local anesthesia (1% lidocaine) before CVS. Primary outcome was pain and secondary outcome was anxiety, both measured on a visual analog scale 30-60 minutes before, immediately after (5-10 minutes) and 30-60 minutes after CVS. With a statistical power of 90%, type I error of 5% and two-sided test and potential exclusions, a sample size of 96 patients per group was enrolled and randomized. No patient was enrolled before the trial registration date. Results From 13 March 2013 through 10 February 2015, 192 patients (96 per group) were screened and randomized. Most characteristics were similar across groups. Pain in the N2 O group was 2.65 ± 0.22 vs 3.32 ± 0.26 in local anesthesia group [mean ± standard error of mean (SEM)]. Mean anxiety in the N2 O group was 3.17 ± 0.27 vs 5.19 ± 0.30 in the local anesthesia group. Conclusion N2 O was as efficient and even superior to local anesthesia for both pain and anxiety reduction during CVS, as the 95% confidence intervals were both below the prespecified noninferiority margin of 0.8 and below zero.

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The diagnosis of an abnormal fetal posterior fossa is usually done during the second trimester scan. However, some forms of open spina bifida with Arnold-Chiari malformation can be detected from the first trimester ultrasound with a precise examination of the posterior fossa and intracranial translucency. Furthermore, other abnormalities of the posterior fossa such as cystic malformations also seem to be accessible to early detection. This work detailed the possible usual and unusual aspects of the posterior fossa individualized during the first trimester ultrasound scan. Identifying an unusual appearance may identify high-risk fetus to present an abnormality of the posterior fossa. Then, thorough analysis of the fetal brain from 18 weeks will often differentiate a normal variant of a real brain malformation.

Objectives The purpose of this study was to assess the feasibility and reproducibility of transabdominal ShearWaveTM elastography of fetal organs in pregnant baboons. Materials and methods Fetal ultrasounds of all pregnant baboons in a single primate research center were performed prospectively during 9 months. The visualization of fetal targeted organs (liver, proximal and distal lungs, brain white matter and periventricular gray matter) was initially performed using 2D ultrasound, and then elastography mode was activated. For each organ, three measurements were carried out by two operators. Intra-observer and inter-observer intra-class correlation coefficients (ICC) were calculated. Results During the study period (03/2013–12/2013), 21 pregnant baboons (21 fetuses) were included. One to three ultrasound scans were performed for each fetus. The measurements were feasible by the two operators in all cases. The intra-observer and inter-observer ICC were 0.654, 95% CI (0.606 to 0.699) and 0.645, 95% CI (0.553 to 0.721) respectively. Conclusion Transabdominal ShearWaveTM Elastography of fetal organs can be achieved in pregnant baboons. The intra-observer and inter-observer reproducibility is correct but vary according to the targeted organs. © 2015 John Wiley & Sons, Ltd.

Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.

Paediatric patients with acute myeloid leukaemia (AML) who fail induction due to primary resistance to chemotherapy account for a significant proportion of cases and have a particularly dismal prognosis. We report the clinical and biological data, and final outcome of 48 paediatric patients with primary-resistant AML enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 clinical trial. These patients had a significantly higher white blood cell count at diagnosis compared to other AML patients. Cytogenetic and molecular features did not differ between patients with primary induction failure and patients allocated to the high-risk group. For the whole patient population, the probability of overall survival, event-free survival (EFS) and disease-free survival (DFS) was 21·8% ± 6·2, 20·4% ± 5·9, and 49·5% ± 11·3, respectively. Twenty-eight (58%) patients received haematopoietic stem cell transplantation (HSCT); 3 were autologous and 25 were allogeneic. Patients who underwent HSCT had improved EFS (31·2% vs. 5%, P < 0·0001). Only one of the 20 patients who did not receive HSCT is alive and disease free. The 19 patients in complete remission at time of HSCT showed significantly better DFS than the 9 with active disease (46% vs. 0%, P = 0·02). This study represents one of the largest series with long-term follow up of paediatric AML patients with primary refractory disease. Children who underwent transplantation had an encouraging long-term outcome. Disease recurrence remains the major cause of treatment failure; a better understanding of the disease biology is desirable to develop more effective treatment strategies. © 2015 John Wiley

HX575 was approved in the European Union in August 2007 as the first-ever biosimilar epoetin-α product. The present study extended the safety database on HX575 by monitoring adverse events (AEs) in clinical practice. Hemoglobin (Hb) levels and HX575 doses were recorded for the assessment of efficacy. This open, 6-month single-arm study was conducted in 10 European countries with a target enrollment of 1,500 patients with anemia due to chronic kidney disease (CKD). HX575 was intravenously (i.v.) administered aiming at an Hb target of 10 - 12 g/dl. Most patients (92.3%) had already received erythropoiesis stimulating agents (ESAs) treatment before enrolment into this study; the recorded treatments mainly comprised i.v. or subcutaneous (s.c.) administration of epoetin-α, epoetin-β or darbepoetin. The study period covered 770 patient years. The observed AE profile was in line with expectations for this patient population. Thrombotic vascular events (TVEs) were reported in 11.9% of patients (0.2612 per patient year). Tumor incidence was 1.4% (0.0299 per patient year). No subject developed anti-epoetin antibodies. Mean Hb levels were effectively maintained between 11.2 and 11.3 g/dl following the conversion from a broad spectrum of pre-study ESA treatments with stable overall mean i.v. HX575 doses. The proportion of patients within the Hb target range increased from 57.5% at baseline to 66.8% at study end.