Beckwith-Wiedemann syndrome with multiple hepatic and cutaneous hemangiomas in a female patient of Albanian origin: Diagnostic and therapeutic considerations.

We describe a 2-month-old female infant with macroglossia, macrosomia, omphalocele, neonatal hypoglycemia, earlobe creases, low nasal bridge, midface retrusion, syndromic facies and multiple cutaneous and hepatic hemangiomas (HH). Genetic evaluation confirmed the diagnosis of Beckwith-Wiedemann Syndrome (BWS) with mosaic uniparental disomy 11 as the underlying genetic mechanism suggested by partial hypermethylation of H19/IGF2:IG-DMR and partial hypomethylation of KCNQ1OT1:TSS-DMR on chromosome 11p15.5. Pediatric endocrinology and cardiology assessments were normal. No malignant liver or renal tumors were detected during the follow-up period. Treatment with propranolol was started for the multiple HH, according to international recommendations. At 3-, 6-, and 9-month follow up, a gradual decrease in the size of the hemangiomas and AFP levels was observed, without side effects. This is the fifth case in the literature combining HH and BWS, and among these, the third case with this specific genetic defect suggesting a possible association between HH and BWS caused by 11 paternal uniparental disomy [upd(11)pat]. The case also highlights that if treatment is warranted, then oral propranolol can be used for the management of infantile HH in BWS patients similarly to non-BWS patients.

Pediatric Optic Pathway Gliomas: A Report From Northern Greece.

Optic pathway gliomas (OPGs) are the most common pediatric optic nerve tumors. Their behavior ranges between rapid growth, stability, or spontaneous regression. Τhey are characterized by low mortality albeit with significant morbidity. We present the characteristics, management, and outcome of 23 OPG patients (16 females, median age: 4.8 y) managed in a Pediatric Oncology Department in Northern Greece over a 25-year period. Overall, 57% had a background of neurofibromatosis type 1. Diagnosis was based on imaging (10 patients) or biopsy (13 patients). Presenting symptoms were mostly visual impairment/squint (52%). Proptosis/exophthalmos, raised intracranial pressure, and headache were also noted. In 2 occasions, it was detected with surveillance magnetic resonance imaging in the context of neurofibromatosis type 1. Eight patients had unilateral and 2 bilateral optic nerve tumors (Modified Dodge Classification, stage 1a/1b), 3 had chiasmatic (stage 2a/b), and 10 had multiple tumors (stage 3/4). Predominant histology was pilocytic astrocytoma (77%). Management included: observation (4), chemotherapy only (9), surgery only (3), or various combinations (7). Chemotherapy regimens included vincristine and carboplatin, vinblastine, or bevacizumab with irinotecan. Most patients demonstrated a slow disease course with complete response/partial response to chemotherapy and/or surgery, whereas 39% presented ≥1 recurrences. After a median follow-up of 8.5 years (range to 19 y), 20 patients (87%) are still alive with stable disease, in partial/complete remission, or on treatment.

Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection.

Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant pediatric inflammatory responses against SARS-CoV-2. We propose that signatures of complement missense coding SNPs associated with dysregulation could also be identified in children with multisystem inflammatory syndrome (MIS-C). We investigated 71 pediatric patients with RT-PCR validated SARS-CoV-2 hospitalized in pediatric COVID-19 care units (November 2020-March 2021) in three major groups. Seven (7) patients suffered from MIS-C (MIS-C group), 32 suffered from COVID-19 and were hospitalized (admitted group), whereas 32 suffered from COVID-19, but were sent home. All patients survived and were genotyped for variations in the C3, C5, CFB, CFD, CFH, CFHR1, CFI, CD46, CD55, MASP1, MASP2, MBL2, COLEC11, FCN1, and FCN3 genes. Upon evaluation of the missense coding SNP distribution patterns along the three study groups, we noticed similarities, but also considerably increased frequencies of the alternative pathway (AP) associated with SNPs rs12614 CFB, rs1061170, and rs1065489 CFH in the MIS-C patients. Our analysis suggests that the corresponding substitutions potentially reduce the C3b-inactivation efficiency and promote slower and weaker AP C3bBb pre-convertase assembly on virions. Under these circumstances, the complement AP opsonization capacity may be impaired, leading to compromised immune clearance and systemic inflammation in the MIS-C syndrome.

Challenges in the Diagnosis of Medulloblastoma Recurrence at an Unusual Site in a Patient With Prader-Willi Syndrome.

Medulloblastoma is the most common malignant pediatric brain tumor. Survival rates range between 50% and 80% depending on histology and other biologic features, metastases, and treatment approach. Prader-Willi syndrome (PWS) is a genetically inherited disorder characterized by dysmorphic features, mental retardation, obesity, and hypogonadism among other features. We describe a 10.5-year-old girl with PWS and previous standard-risk medulloblastoma that relapsed in the pons 3 years after the end of treatment. Diagnosis of relapse was delayed by a preceding varicella infection, an initial clinical/radiologic response to steroids and the unusual location, and was confirmed with a stereotactic biopsy. Second-line therapy was commenced, however, the patient rapidly deteriorated and died. This is the first report of medulloblastoma in a patient with PWS.

Neuroblastoma among children in Southern and Eastern European cancer registries: Variations in incidence and temporal trends compared to US.

Neuroblastoma comprises the most common neoplasm during infancy (first year of life). Our study describes incidence of neuroblastoma in Southern-Eastern Europe (SEE), including - for the first time - the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)/Greece, compared to the US population, while controlling for human development index (HDI). Age-adjusted incidence rates (AIR) were calculated for 1,859 childhood (0-14 years) neuroblastoma cases, retrieved from 13 collaborating SEE registries (1990-2016), and were compared to those of SEER/US (N = 3,166; 1990-2012); temporal trends were assessed using Poisson regression and Joinpoint analyses. The overall AIR was significantly lower in SEE (10.1/million) compared to SEER (11.7 per million); the difference was maximum during infancy (43.7 vs. 53.3 per million, respectively), when approximately one-third of cases were diagnosed. Incidence rates of neuroblastoma at ages <1 and 1-4 years were positively associated with HDI, whereas lower median age at diagnosis was correlated with higher overall AIR. Distribution of primary site and histology was similar in SEE and SEER. Neuroblastoma was slightly more common among males compared to females (male-to-female ratio: 1.1), mainly among SEE infants. Incidence trends decreased in infants in Slovenia, Cyprus and SEER and increased in Ukraine and Belarus. The lower incidence in SEE compared to SEER, especially in infants living in low HDI countries possibly indicates a lower level of overdiagnosis in SEE. Hence, increases in incidence rates in infancy noted in some subpopulations should be carefully monitored to avoid the unnecessary costs health impacts of tumors that could potentially spontaneously regress.

Prevalence of malnutrition and obesity among cystic fibrosis patients.

BACKGROUND: Optimal nutritional status (NS) in cystic fibrosis (CF) is associated with better lung function and increased overall survival. This study estimated the prevalence of malnutrition and obesity among CF patients in a tertiary center. METHODS: In a cross-sectional study of 68 CF patients (33 female; 37 children/adolescents) weight, height, body composition, respiratory function (% of the predicted forced expiratory volume in 1 s; FEV1%pred ) and serum lipids were measured; body mass index (BMI), BMI standard deviation score (BMI-SDS) and BMI percentiles were calculated; Pseudomonas colonization, pancreatic insufficiency, diabetes mellitus (CFDM), liver disease (CFLD) and genotype were recorded; NS was classified according to the 2005 Cystic Fibrosis Foundation (CFF) criteria. Frequency distributions and associations between anthropometric and clinical parameters (univariate/multivariate) were calculated. RESULTS: Mean age (±SD) was 19.81 ± 8.98 years. Regarding NS: 22.1% were malnourished, 13.2% overweight/obese and 29.4% had optimal NS. Pancreatic function (PF), Pseudomonas colonization, CFDM, CFLD and genotype differed significantly among the three groups. FEV1%pred was significantly higher among overweight/obese patients and correlated positively with anthropometric characteristics as well as serum cholesterol and negatively with age. BMI-SDS was associated with PF, FEV1%pred and CFDM. Among overweight/obese patients 89.9% had adequate PF and 66.7% carried mutations other than F508del. No patient had any traits of metabolic syndrome. CONCLUSIONS: Despite appropriate management only one-third of the present patients had optimal NS. One-fourth were malnourished and a significant percentage were overweight/obese. The latter were mostly carriers of mutations other than F508del and had better pulmonary function. CF patients require intensive monitoring for both malnutrition and overweight/obesity.

A pediatric case of atypical hemolytic uremic syndrome (aHUS): Could any infection play a triggering role?

A 12-year-old boy was transferred to our pediatric department from a rural hospital for fever, cough, and vomiting associated with thrombocytopenia, non-immune hemolytic anemia, and acute kidney injury, leading to the diagnosis of hemolytic uremic syndrome (HUS). A nasopharyngeal swab and a lower respiratory sample detected Influenza A by polymerase chain reaction (PCR). The patient was treated with oseltamivir and intravenous fluids in addition to fresh frozen plasma (FFP). Enteropathogenic Escherichia coli (EPEC) was detected in a stool sample by PCR. Serum antibodies for Mycoplasma pneumoniae (IgM and IgG) and Helicobacter pylori (IgA and IgG) were increased. Further work-up revealed elevated serum C5b-9 suggesting a simultaneous viral and bacterial infection-mediated complement overactivation leading to the diagnosis of atypical HUS (aHUS). An association between aHUS and influenza A is reported in the literature, but the correlation of EPEC, Mycoplasma pneumoniae, and Helicobacter pylori with aHUS is not well-established. Fresh frozen plasma was administered for a total of 3 days, followed by clinical and laboratory improvement. The patient has remained asymptomatic until the latest follow-up, 5 months after discharge. This case demonstrates the potential triggering role of different pathogens in aHUS pathogenesis to raise awareness in the pediatric community.

Effect of apolipoprotein E (APOE) gene polymorphisms on the lipid profile of children being treated for acute lymphoblastic leukemia.

BACKGROUND: Medications used to treat acute lymphoblastic leukemia (ALL), such as L-asparaginase, can cause blood lipid disturbances. These can also be associated with polymorphisms of the lipoprotein lipase (LpL) and apolipoprotein E (APOE) genes. PROCEDURE: We aimed to investigate the association between lipid profile, certain LpL and APOE gene polymorphisms (rs268, rs328, rs1801177 and rs7412, rs429358 respectively) as well as the risk subgroup in 30 pediatric patients being treated for ALL, compared with 30 pediatric ALL survivors and 30 healthy controls. RESULTS: The only APOE gene polymorphism with significant allelic and genotypic heterogeneity was rs429358. Further analysis of this polymorphism showed that genotype (CC, CT, or TT) was significantly associated with (1) changes in the lipid profile at the end of consolidation (total cholesterol, LDL, apo-B100, and lipoprotein a) and during re-induction (total cholesterol and apo-B100), and (2) classification in the high risk-ALL subgroup (for CC genotype/C allele presence). CONCLUSIONS: Lipid abnormalities in children being treated for ALL may be associated with the APOE genotype, which is also possibly associated with risk stratification. Further research is needed to confirm the potential prognostic value of these findings.

Metabolic Fingerprint in Childhood Acute Lymphoblastic Leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy. Despite high cure rates, several questions remain regarding predisposition, response to treatment, and prognosis of the disease. The role of intermediary metabolism in the individualized mechanistic pathways of the disease is unclear. We have hypothesized that children with any (sub)type of ALL have a distinct metabolomic fingerprint at diagnosis when compared: (i) to a control group; (ii) to children with a different (sub)type of ALL; (iii) to the end of the induction treatment. MATERIALS AND METHODS: In this prospective case-control study (NCT03035344), plasma and urinary metabolites were analyzed in 34 children with ALL before the beginning (D0) and at the end of the induction treatment (D33). Their metabolic fingerprint was defined by targeted analysis of 106 metabolites and compared to that of an equal number of matched controls. Multivariate and univariate statistical analyses were performed using SIMCAP and scripts under the R programming language. RESULTS: Metabolomic analysis showed distinct changes in patients with ALL compared to controls on both D0 and D33. The metabolomic fingerprint within the patient group differed significantly between common B-ALL and pre-B ALL and between D0 and D33, reflecting the effect of treatment. We have further identified the major components of this metabolic dysregulation, indicating shifts in fatty acid synthesis, transfer and oxidation, in amino acid and glycerophospholipid metabolism, and in the glutaminolysis/TCA cycle. CONCLUSIONS: The disease type and time point-specific metabolic alterations observed in pediatric ALL are of particular interest as they may offer potential for the discovery of new prognostic biomarkers and therapeutic targets.

Signs and symptoms of childhood cancer: a guide for early recognition.

Although cancer in children is rare, it is the second most common cause of childhood mortality in developed countries. It often presents with nonspecific symptoms similar to those of benign conditions, leading to delays in the diagnosis and initiation of appropriate treatment. Primary care physicians should have a raised index of suspicion and explore the possibility of cancer in children who have worrisome or persisting signs and symptoms. Red flag signs for leukemia or lymphoma include unexplained and protracted pallor, malaise, fever, anorexia, weight loss, lymphadenopathy, hemorrhagic diathesis, and hepatosplenomegaly. New onset or persistent morning headaches associated with vomiting, neurologic symptoms, or back pain should raise concern for tumors of the central nervous system. Palpable masses in the abdomen or soft tissues, and persistent bone pain that awakens the child are red flags for abdominal, soft tissue, and bone tumors. Leukokoria is a red flag for retinoblastoma. Endocrine symptoms such as growth arrest, diabetes insipidus, and precocious or delayed puberty may be signs of endocranial or germ cell tumors. Paraneoplastic manifestations such as opsoclonus-myoclonus syndrome, rheumatic symptoms, or hypertension are rare and may be related to neuroblastoma, leukemia, or Wilms tumor, respectively. Increased suspicion is also warranted for conditions associated with a higher risk of childhood cancer, including immunodeficiency syndromes and previous malignancies, as well as with certain genetic conditions and familial cancer syndromes such as Down syndrome, Li-Fraumeni syndrome, hemihypertrophy, neurofibromatosis, and retinoblastoma.

Survival patterns of childhood neuroblastoma: an analysis of clinical data from Southern-Eastern European countries.

The prognosis of children with neuroblastoma (NBL) can be dismal with significant variations depending on the stage and biology of the tumor. We assessed the event-free (EFS) and overall (OS) survival using harmonized data from three Southern-Eastern European (SEE) countries. Data for 520 incident NBL cases (2009-2018) were collected from Greece, Slovenia and Russia. Kaplan-Meier curves were fitted, and EFS/OS were derived from Cox proportional models by study variables including the protocol-based risk-group (low/observation, intermediate, high). Over one-third of cases were coded in the high-risk group, of which 23 children (4.4%) received treatment with anti-ganglioside 2 (GD2) mAb. Survival rates were inferior in older (OS 5-year; 1.5-4.9 years: 61%; EFS 5-year; 1.5-4.9 years: 48%) compared to children younger than 1.5 years (OS 5-year; <1.5 years: 91%; EFS 5-year; <1.5 years: 78%). Predictors of poor OS included stage 4 (hazard ratio, HR OS : 18.12, 95% confidence intervals, CI: 3.47-94.54), N-myc amplification (HR OS : 2.16, 95% CI: 1.40-3.34), no surgical excision (HR OS : 3.27, 95% CI: 1.91-5.61) and relapse/progression (HR OS : 5.46, 95% CI: 3.23-9.24). Similar unfavorable EFS was found for the same subsets of patients. By contrast, treatment with anti-GD2 antibody in high-risk patients was associated with decreased risk of death or unfavorable events (HR OS : 0.11, 95% CI: 0.02-0.79; HR EFS : 0.19, 95% CI: 0.07-0.52). Our results confirm the outstanding prognosis of the early NBL stages, especially in children <1.5 years, and the improved outcomes of the anti-GD2 treatment in high-risk patients. Ongoing high-quality clinical cancer registration is needed to ensure comparability of survival across Europe and refine our understanding of the NBL biology.

A nationwide evaluation of bevacizumab-based treatments in pediatric low-grade glioma in the UK: Safety, efficacy, visual morbidity, and outcomes.

BACKGROUND: Bevacizumab is increasingly used in children with pediatric low-grade glioma (PLGG) despite limited evidence. A nationwide UK service evaluation was conducted to provide larger cohort "real life" safety and efficacy data including functional visual outcomes. METHODS: Children receiving bevacizumab-based treatments (BBT) for PLGG (2009-2020) from 11 centers were included. Standardized neuro-radiological (RANO-LGG) and visual (logMAR visual acuity) criteria were used to assess clinical-radiological correlation, survival outcomes and multivariate prognostic analysis. RESULTS: Eighty-eight children with PLGG received BBT either as 3rd line with irinotecan (85%) or alongside 1st/2nd line chemotherapies (15%). Toxicity was limited and minimal. Partial response (PR, 40%), stable disease (SD, 49%), and progressive disease (PD, 11%) were seen during BBT. However, 65% progressed at 8 months (median) from BBT cessation, leading to a radiology-based 3 yr-progression-free survival (PFS) of 29%. Diencephalic syndrome (P = .03) was associated with adverse PFS. Pre-existing visual morbidity included unilateral (25%) or bilateral (11%) blindness. Improvement (29%) or stabilization (49%) of visual acuity was achieved, more often in patients' best eyes. Vision deteriorated during BBT in 14 (22%), with 3-year visual-PFS of 53%; more often in patients' worst eyes. A superior visual outcome (P = .023) was seen in neurofibromatosis type 1-associated optic pathway glioma (OPG). Concordance between visual and radiological responses was 36%; optimized to 48% using only best eye responses. CONCLUSIONS: BBTs provide effective short-term PLGG control and delay further progression, with a better sustained visual (best > worst eye) than radiological response. Further research could optimize the role of BBT toward a potentially sight-saving strategy in OPG.

In vitro fertilization and risk of childhood leukemia in Greece and Sweden.

BACKGROUND: Cancer risk in children born after in vitro fertilization (IVF) remains largely unknown. We aimed to investigate risk of leukemia and lymphoma following IVF using two nationwide datasets. METHODS: The hospital-based case-control study in Greece derived from the National Registry for Childhood Hematological Malignancies (1996-2008, 814 leukemia and 277 lymphoma incident cases with their 1:1 matched controls). The Swedish case-control study was nested in the Swedish Medical Birth Register (MBR) (1995-2007, 520 leukemia and 71 lymphoma cases with their 5,200 and 710 matched controls) with ascertainment of incident cancer cases in the National Cancer Register. Study-specific and combined odds ratios (OR) were estimated using conditional logistic regression, with adjustment for possible risk factors. RESULTS: Nationwide studies pointed to similar size excess risk of leukemia following IVF, but to a null association between IVF and lymphoma. The proportion of leukemia cases conceived through IVF was 3% in Greece and 2.7% in Sweden; prevalence of IVF in matched controls was 1.8% and 1.6%, respectively. In combined multivariable analyses, the increased risk of leukemia was confined to age below 3.8 years (OR = 2.21; 95% confidence interval, CI: 1.27-3.85) and to acute lymphoblastic leukemia (ALL) (OR = 1.77; 95% CI: 1.06-2.95) with no sufficient evidence of excess risk for other leukemias (OR = 1.34; 95% CI: 0.38-4.69). Following IVF, OR for ALL was 2.58 (95% CI: 1.37-4.84) before age 3.8 and 4.29 (95% CI: 1.49-12.37) before age 2 years. CONCLUSIONS: IVF seems to be associated with increased risk of early onset ALL in the offspring.

Survival from breast cancer in relation to access to tertiary healthcare, body mass index, tumor characteristics and treatment: a Hellenic Cooperative Oncology Group (HeCOG) study.

Apart from tumour, treatment and patient characteristics at diagnosis, access to healthcare delivery may as well play a significant role in breast cancer prognosis. This study aimed to assess the additional impact exerted on survival by travel burden-a surrogate indicator of limited access to healthcare- expressed as geographical distance and/or time needed to reach the tertiary healthcare center from the patient's residence. Between 1997 and 2005, 2,789 women participated in therapeutic clinical trials conducted by the Hellenic Cooperative Oncology Group. The effect of geographical distance and travel time between patient's residence and treating hospital on survival was estimated using Cox proportional hazards regression adjusting for age, menopausal status, tumour size/grade, positive nodes (number), hormonal receptor status, HER2 overexpression, surgery type/treatment protocol as well as for body mass index>30 kg/m2. More aggressive tumour features, older treatment protocols and modifiable patient characteristics, such as obesity (HR: 1.27) adversely impacted on breast cancer survival. In addition, less studied indicators of access to healthcare, such as geographic distance>350 km and travel time>4 h were independently and significantly associated with worse outcomes (HR=1.43 and 1.34 respectively). In conclusion, to address inequalities in breast cancer survival, improvements in access to healthcare services related to increased travel burden especially for patients of lower socioeconomic status should be considered, more than ever at times of financial crisis and independently of already known modifiable patient characteristics.

Traumatic hand amputations among children in Greece: epidemiology and prevention potential.

BACKGROUND: Traumatic hand and finger amputations frequently lead to permanent disability. OBJECTIVE: To investigate their epidemiological characteristics and estimate the prevention potential among children 0-14 years old, through a cross-sectional survey. METHODS: Nationwide extrapolations were produced based on data recorded between 1996 and 2004 in the Greek Emergency Department Injury Surveillance System and existing sample weights. Incident and injury related characteristics were analysed to identify preventable causes. RESULTS: Among 197,417 paediatric injuries, 28,225(14%) involved the hand and fingers resulting in 236 amputations (∼1% of hand injuries). The annual probability to seek emergency department care for a hand injury was 3%. The estimated incidence rate (IR) of hand amputations was 19.7/100,000 person-years. Over 50% concerned children 0-4 years old (male:female=2:1), peaking at 12-24 months. Male preschoolers suffered the highest IR (38.7/100,000). Migrant children were overrepresented among amputees. Of all amputations, 64% occurred in the house/garden and 14% in day-care/school/sports activities, usually between 08:00 and 16:00 (61%). Doors were the product most commonly involved (55% overall; 72% in day-care/school/gym) followed by furniture/appliances (15%) and machinery/tools (7%). Crushing was the commonest mechanism. Inadequate supervision and preventive measures were also frequently reported. 5% of the amputees were referred to specialised units for replantation/reconstructive surgery. CONCLUSIONS: The majority of paediatric hand and finger amputations could be prevented in Greece, particularly among preschoolers, by a single product modification, namely door closure systems, coupled with improved supervision. Paediatricians should incorporate this advice into their routine child-safety counselling. This country-specific profile supports the need for maintaining similar databases as an indispensable tool for assisting decision-making and preventing disabling and costly injuries.

Evaluating posaconazole, its pharmacology, efficacy and safety for the prophylaxis and treatment of fungal infections.

INTRODUCTION: Invasive fungal diseases (IFDs) are a significant cause of morbidity and mortality among immunocompromised patients. Safe and effective antifungal medications used for prophylaxis and treatment are pivotal in their management. Posaconazole is a promising triazole antifungal agent. AREAS COVERED: The authors discuss the pharmacological properties of posaconazole, including pharmacokinetics/pharmacodynamics, safety and tolerability profile, together with efficacy data for prophylaxis and treatment as well as its use in special populations based on current literature. EXPERT OPINION: Posaconazole has a favorable safety and tolerability profile; however, caution is advised when co-administered with agents that are CYP3A4 inhibitors, because their concentration may significantly increase, and their levels should be closely monitored. It has an extended spectrum of activity against yeasts and filamentous fungi. It is successfully used as prophylaxis for patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and post-hematopoietic cell transplantation (HCT) with graft-versus-host disease (GVHD). It is the first line treatment for oropharyngeal candidiasis and is also used as a salvage treatment for refractory IFDs. Currently available formulations include the oral suspension, delayed-release tablets and solution for intravenous infusion, all with different PK/PD properties and indications. Its use in children and adolescents is currently being examined in Phase-II clinical trials.

Iron Deficiency and Blood Donation: Links, Risks and Management.

The purpose of this review is to raise awareness about the frequently underappreciated association of blood donation with iron deficiency, and to describe methods for its prevention and management. Blood donors cannot expect any health benefits from the donation but have justified expectations of no harm. Iron deficiency without anemia (IDWA) and iron deficiency anemia (IDA) are common consequences of regular blood donation, and this activity is the most important factor affecting iron status in regular blood donors. Awareness of blood donation as a primary cause of sideropenia is surprisingly low among physicians. Blood donation screening identifies potential donors with IDA but is frequently inadequate to detect IDWA. For the assessment of body iron stores, plasma or serum ferritin, transferrin saturation (TSAT) and soluble transferrin receptors (sTfR) concentrations are the most widely used biochemical markers, although the percentage of hypochromic mature erythrocytes and the hemoglobin content of reticulocytes are also useful. IDWA can be prevented by limiting the total volume of blood collected, by iron deficiency screening and deferral of sideropenic donors, by prolonging the interdonation intervals, and by iron supplementation between donations. IDWA tends to be more prevalent in younger people, females, and high-intensity donors. A potentially effective strategy to address sideropenia in blood donors is serum ferritin testing, but this may lead to a higher rate of deferral. Most regular blood donors cannot replenish their iron deficit by an iron-rich diet alone and will benefit from low-dose oral iron administration with various commercially available products post-donation, a well-tolerated strategy. However, valid concerns exist regarding the possibility of worsening the iron overload in donors with undiagnosed hemochromatosis or masking the symptoms of a clinically important gastrointestinal hemorrhage or other underlying medical condition. Finally, educational efforts should be intensified to improve the awareness of blood donation as a primary cause of iron deficiency among physicians of all specialties.

Maternal lifestyle factors and risk of neuroblastoma in the offspring: A meta-analysis including Greek NARECHEM-ST primary data.

The etiology of childhood neuroblastoma remains largely unknown. In this systematic review and meta-analysis, we summarized and quantitatively synthesized published evidence on the association of maternal modifiable lifestyle factors with neuroblastoma risk in the offspring. We searched MEDLINE up to December 31, 2020 for eligible studies assessing the association of maternal smoking, alcohol consumption and nutritional supplementation during pregnancy with childhood (0-14 years) neuroblastoma risk. Random-effects models were run, and summary odds ratios (OR) and 95% confidence intervals (95% CI) on the relevant associations were calculated, including estimates derived from primary data (n = 103 cases and n = 103 controls) of the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) case control study (2009-2017) in Greece. Twenty-one eligible studies amounting 5163 cases participating in both case-control and cohort/linkage studies were included in the meta-analysis. Maternal smoking and alcohol consumption were not statistically significantly associated with neuroblastoma risk (summary ORsmoking: 1.08, 95% CI: 0.96-1.22, I2 =12.0%, n = 17 studies; summary ORalcohol: 1.01, 95% CI: 0.82-1.18, I2 =0.0%, n = 8 studies). By contrast, maternal vitamin intake during pregnancy was associated with significantly lower neuroblastoma risk (summary OR: 0.57, 95% CI: 0.34-0.95, I2 =58.9%, n = 4 studies). The results of the largest to-date meta-analysis point to an inverse association between vitamin intake during pregnancy and childhood neuroblastoma risk. Future longitudinal studies are needed to confirm and further specify these associations as to guide preventive efforts on modifiable maternal risk factors of childhood neuroblastoma.

Safety of Ferric Carboxymaltose in Children: Report of a Case Series from Greece and Review of the Literature.

BACKGROUND: Parenteral iron is generally considered safe in adults, and severe adverse events are extremely rare. Ferric carboxymaltose (FCM), a third-generation parenteral iron product, is not licensed for pediatric use. OBJECTIVE: The aim of this study was to present our data on the safety of FCM in children with iron deficiency (ID) and/or iron deficiency anemia (IDA) and to investigate through a systematic literature review articles reporting on the safety of FCM use in children with ID/IDA. PATIENTS AND METHODS: Safety data regarding children treated with FCM for ID/IDA from four pediatric departments in Greece over a 26-month period are presented. Additionally, a literature search was performed in PubMed, Scopus, and Google Scholar on December 4, 2021 for articles reporting on the use of FCM in children with ID/IDA. Review articles, guidelines, case reports/case series, and reports on the use of FCM for conditions other than ID/IDA were excluded. Identified articles were screened for all reported adverse events (AE) that were graded according to the Common Terminology Criteria for Adverse Events, version 5.0. RESULTS: In our cohort, 37 children with ID/IDA received 41 FCM infusions. All infusions were tolerated well. In addition, 11 articles reporting 1231 infusions of FCM in 866 children were identified in the literature. Among them, 52 (6%) children developed AE that were graded as mild or moderate (grades I-III). CONCLUSIONS: Our patient cohort and this literature review provide further evidence for the good safety profile of FCM in children, although well-designed prospective clinical trials with appropriate safety endpoints are still required.