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Abstract Background In order to estimate the causes of pediatric morbidity in our area, with particular emphasis on diseases with a genetic background, we retrospectively categorized the admissions of all children hospitalized in the Department of Pediatrics of the University General Hospital of Alexandroupolis, in the area of Evros, Thrace, Greece over the three year period 2005-2007. Finally, in order to guide health care administrators to improve the delivery of pediatric health care services, we estimated the percentage of hospitalized children who were uninsured and the type of health insurance of those who had medical coverage. Patients and Methods The causes of admission, as recorded in the medical records were categorized in terms of the major organ and/or system involved and/or the underlying pathology, with emphasis on diseases with a genetic background. Duplicate admissions, i.e., admissions of the same child for the same underlying disease were excluded. Additional information recorded was age, sex, and type of health insurance of all admitted children. Distribution of the causes of admission by study year was compared by chi-square. A p value < 0.05 was considered significant. Results Over the study period, there were 4,947 admissions in 2,818 boys and 2,129 girls. Respiratory diseases were the most common accounting for 30%, while infectious diseases followed with 26.4%. The frequency of chromosomal abnormalities among the hospitalized children was only 0.06%. However, if we consider diseases with an underlying genetic background, this percentage rises to 5%. Approximately 10.3% of the admitted children had no health insurance. Conclusions The percentage of children hospitalized in our area due to a disease with an underlying genetic background was 5%. This percentage pertains to a Department of Pediatrics that has no inpatient subspecialty units and which is located within a General hospital, because hospitalizations for genetic diseases are more frequent in specialized pediatric hospitals, with competence in clinical genetics. The double figure of uninsured children is worrisome and dictates the need for governmental efforts for universal pediatric health coverage in our country.

Abstract Background Female genital tuberculosis is an uncommon disease that is rarely diagnosed in developed countries. Case presentation A 61-year-old postmenopausal woman who had undergone surgery and treated with adjuvant chemotherapy for infiltrating ductal carcinoma of the breast five years ago, presented with bloody vaginal discharge, fatigue, weight loss, and low grade fevers at night for two months. Histological examination of the endometrium, done based on the suspicion of a second primary cancer due to the tamoxifen therapy, revealed a granulomatous reaction. Liquid and solid mycobacterial cultures of the tissues were performed. Although the acid fast staining was negative, the liquid culture was positive for Mycobacterium tuberculosis. Involvement of other systems was not detected. The patient was treated with a three-drug antituberculosis regimen for 9 months and recovered fully. Conclusion Female genital tuberculosis is a rare but curable disease that should be included in the differential diagnosis of women with menstrual problems. Early diagnosis is important and may prevent unnecessary invasive procedures for the patient.

A letter to the editor is presented which discusses a medical case of a 9.5-year-old girl with swollen feet for eight days after her hospitalization for diagnosed diabetes mellitus (DM) type 1 and ketoacidosis (DKA), diagnosed with insulin edema.

A letter to the editor is presented on chickenpox-associated immune thrombocytopenic purpura.

Objectives: The aim of our study was to elucidate the current pattern of acute poisoning among children admitted to a regional University Hospital in the prefecture of Evros in Northern Greece. We also compared the obtained findings with those of two previous studies performed in the same region.Methods: Demographic and clinical data, management, and outcome of children with acute poisoning were recorded in our region, during the past 5-years (2005-2009, period C) and compared to similar studies carried out in the periods 1985-1989 (period A) and 1995-1999 (period B).Results: Comparison between the three periods showed that in period Athe lower incidence of children's acute poisoning (CAP) was observed. Also this revealed a 20%-reduction in the frequency of poisoning over the past 5-years (period C) compared to period B (p = 0.219), a significant increase in tobacco intoxication over the years (in the order A-C; p < 0.001 for comparisons of periods A and B, and periods B and C), while poisoning from insecticides-pesticides decreased (p < 0.001). The incidence of poisoning via salicylates significantly reduced from 9.7% in period A to 6.2% in period B, and further to 4.7% in period C (p = 0.016), whereas during the same periods poisoning via paracetamol increased from 2.3% to 5.1% and then to 10.4%, respectively (p < 0.001). Atrend toward a higher incidence of suicide attempt via poisoning was found during the three periods (from 3.0% in period A to 4.7% and 6.6%, in periods B and C, respectively; p = 0.049).Conclusions: The frequency of acute poisoning among children has decreased over the past 5 years. The incidences of poisoning via paracetamol and tobacco, and attempted suicide have increased in recent years. Targeted and continuous educational preventive programs are mandatory. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency anemia (IDA) is a major public health problem among children worldwide. Iron deficiency without anemia (IDWA) is at least twice as common as IDA. Some studies propose that oral iron fortification can modify the infant's gut microbiome, leading to intestinal inflammation., Objectives: To determine whether oral iron therapy can lead to intestinal inflammation in children with IDA or IDWA., Patients and Methods: Fifty-six patients aged 6 months to 16 years (median age 7.6 years) with IDA or IDWA were randomly assigned to receive either iron (III)-hydroxide polymaltose complex (IPC) 5 mg/kg once daily (maximum dose 100 mg) or sucrosomial iron (SI)1.4 mg/kg once daily (maximum dose 29.4 mg). Safety and efficacy were studied after 30 and 90 days of treatment. In addition, fecal calprotectin as a marker of intestinal inflammation was measured simultaneously and compared to results obtained before therapy., Results: A significant increase in serum ferritin was noted in both groups as the median ferritin level at baseline was 6.7 μg/L in the IPC group and 6.6 μg/L in the SI group, increasing to 15.9 μg/L and 12.1 μg/L respectively, after 90 days of treatment. However, there was no significant change in fecal calprotectin in either group. In addition, no differences in the trend over time were observed between the two groups regarding fecal calprotectin, serum ferritin, and hemoglobin., Conclusions: IPC and SI were equally effective in treating IDA and IDWA. At the recommended doses, oral iron therapy does not seem to induce intestinal inflammation., Competing Interests: Competing interests: The authors declare no conflict of Interest.

We present a never-transfused girl with thalassemia intermedia who was admitted for febrile aplastic crisis due to human parvovirus B19. After a first transfusion of packed red blood cells, she developed pulmonary oedema. She improved with supportive care including the use of intravenous diuretics. Due to severe anaemia, she received a second blood transfusion, antibiotics for febrile neutropenia and intravenous γ globulin for control of the parvovirus infection. She had an uneventful recovery. The first of her male blood donors had an antibody against a patient's human leukocyte antigens type II antigen with a high mean fluorescent intensity. Our patient had clinical features and supportive laboratory evidence for mild transfusion-related acute lung injury (TRALI). However, she also met the criteria for transfusion-associated circulatory overload (TACO). We conclude that our patient likely suffered from TRALI/TACO, a consensus term proposed in 2019 for patients in whom TRALI cannot be distinguished from TACO or in whom both conditions occur simultaneously., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome, caused by genetic mutations that principally affect telomere biology. Approximately 35% of cases remain uncharacterised at the genetic level. To explore the genetic landscape, we conducted genetic studies on a large collection of clinically diagnosed cases of DC as well as cases exhibiting features resembling DC, referred to as 'DC-like' (DCL). This led us to identify several novel pathogenic variants within known genetic loci and in the novel X-linked gene, POLA1. In addition, we have also identified several novel variants in POT1 and ZCCHC8 in multiple cases from different families expanding the allelic series of DC and DCL phenotypes. Functional characterisation of novel POLA1 and POT1 variants, revealed pathogenic effects on protein-protein interactions with primase, CTC1-STN1-TEN1 (CST) and shelterin subunit complexes, that are critical for telomere maintenance. ZCCHC8 variants demonstrated ZCCHC8 deficiency and signs of pervasive transcription, triggering inflammation in patients' blood. In conclusion, our studies expand the current genetic architecture and broaden our understanding of disease mechanisms underlying DC and DCL disorders., (© 2024. The Author(s).)

Bone and joint infections (BJI) require prolonged antimicrobial treatment, leading to lengthy hospitalizations, high costs, the risk of nosocomial infections, and the development of antimicrobial resistance. Dalbavancin is a novel semisynthetic lipoglycopeptide approved for the treatment of adults and children with acute bacterial skin and skin structure infections. This narrative review aims to summarize the characteristics of dalbavancin and the current scientific evidence regarding its clinical efficacy and safety in the treatment of BJI. A literature search until June 2023 was performed to identify all published research about the role of dalbavancin in the management of BJI. Due to its unique pharmacokinetics characterized by prolonged half-life, high bactericidal activity against most Gram-positive bacteria, a good safety profile, and high tissue penetration, dalbavancin can be a valuable alternative to the treatment of BJI. Clinical studies have shown its non-inferiority compared to conventional therapies in BJI, offering potent activity against key pathogens and an extended dosing interval that may shorten hospitalization. In conclusion, dalbavancin represents a promising treatment option for BJI with a favorable safety profile, but further research in both adults and particularly children, who are ideal candidates for long-acting antibiotics, is necessary to evaluate the role of dalbavancin in BJI.

Childhood asthma is a chronic inflammatory airway disorder that can drive tissue remodeling. Neutrophils are amongst the most prominent inflammatory cells contributing to disease manifestations and may exert a potent role in the progression of inflammation to fibrosis. However, their role in asthma exacerbation is still understudied. Here, we investigate the association between neutrophil extracellular traps (NETs) and lung fibroblasts in childhood asthma pathophysiology using serum samples from pediatric patients during asthma exacerbation. Cell-based assays and NETs/human fetal lung fibroblast co-cultures were deployed. Increased levels of NETs and interleukin (IL)-17A were detected in the sera of children during asthma exacerbation. The in vitro stimulation of control neutrophils using the sera from pediatric patients during asthma exacerbation resulted in IL-17A-enriched NET formation. The subsequent co-incubation of lung fibroblasts with in vitro-generated IL-17A-enriched NETs led fibroblasts to acquire a pre-fibrotic phenotype, as assessed via enhanced CCN2 expression, migratory/healing capacity, and collagen release. These data uncover the important pathogenic role of the NET/IL-17A axis in asthma exacerbation, linking lung inflammation to fibroblast dysfunction and fibrosis.

Background: Adverse antibiotic reactions caused by an immunological mechanism are known as allergic reactions. The percentage of reported antibiotic allergies is likely to differ from the one validated after a drug provocation test (DPT) with the culprit antibiotic. This study aimed to compare the percentage of children who were thought to be allergic to a certain antibiotic with those who have a true allergy, as confirmed by DPTs. We also validated Skin Prick Tests (SPTs) and Intradermal Tests (IDTs) by assessing their sensitivity and specificity, in diagnosing antibiotic allergies using DPT as the gold standard. Furthermore, we investigated epidemiological risk factors such as personal and family history of atopic disease and eosinophilia., Methods: Children with a history of possible allergic reaction to an antibiotic underwent a diagnostic procedure that included: (1) Eosinophil blood count, (2) SPTs, (3) IDTs and (4) DPTs. The parameters were compared with Pearson's Chi-Square and Fisher's Exact Test. Several risk factors that were found significant in univariate analysis, such as personal and family history of atopic disease, and positive SPTs and IDTs were examined with multiple logistic regression analysis to see if they were related to a higher risk for a positive DPT., Results: Semi-synthetic penicillin was the most common group of antibiotics thought to cause allergic reactions in this study. Overall, 123 children with a personal history of an adverse reaction to a certain antibiotic, were evaluated. In 87.8% of the cases, the symptoms had occurred several hours after administration of the culprit antibiotic. Both SPTs and IDTs had low sensitivity but high specificity. Moreover, they had a high positive predictive value (PPV). In contrast, eosinophilia was not recognized as a risk factor. Seventeen patients (13.8%) had a true antibiotic allergy, as confirmed by a positive DPT. A positive IDT was a strong predictor of a positive DPT, along with a positive personal and family history of atopy., Conclusion: SPTs and IDTs are very reliable in confirming antibiotic allergy when found positive. A negative result of a SPT highly predicts a negative DPT. A positive IDT and a positive personal and family history of atopy were recognized as significant risk factors for antibiotic allergy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Kitsos, Cassimos, Trypsianis, Xinias, Roilides, Grivea, Mantadakis and Mavroudi.)

The aim of this review is to highlight mechanisms of immunosuppression for each agent, along with pooled analyses of infectious complications from the available medical literature. Rituximab confers no increase in grade ≥3 infectious risks, except in the case of patients with advanced-stage non-Hodgkin lymphoma. Gemtuzumab ozogamicin links with high rates of grade ≥3 infections which, however, are comparable with historical cohorts. Pembrolizumab exhibits a favorable safety profile in terms of severe infections. Despite high rates of hypogammaglobulinemia (HGG) with blinatumomab, low-grade ≥3 infection rates were observed, especially in the post-reinduction therapy of relapsed B-acute lymphoblastic leukemia. Imatinib and nilotinib are generally devoid of severe infectious complications, but dasatinib may slightly increase the risk of opportunistic infections. Data on crizotinib and pan-Trk inhibitors entrectinib and larotrectinib are limited. CAR T-cell therapy with tisagenlecleucel is associated with grade ≥3 infections in children and is linked with HGG and the emergence of immune-related adverse events. Off-label therapies inotuzumab ozogamicin, brentuximab vedotin, and venetoclax demonstrate low rates of treatment-related grade ≥3 infections, while the addition of bortezomib to standard chemotherapy in T-cell malignancies seems to decrease the infection risk during induction. Prophylaxis, immune reconstitution, and vaccinations for each targeted agent are discussed, along with comparisons to adult studies.

Background: As Greece is a country which has introduced the 13-valent pneumococcal conjugate vaccine (PCV13) both in the infant and in the adult immunization programs, the aim of the study was to investigate age-specific and serotype-specific trends of pneumococcal meningitis over an 11-year period (2010-2020)., Materials and Methods: Data are reported from pneumococcal meningitis cases [notified to the National Public Health Organization (NPHO)], with clinical samples and bacterial isolates sent for pneumococcal identification and serotyping at the National Meningitis Reference Laboratory (NMRL). Pneumococcal identification was performed directly on clinical samples or bacterial isolates by multiplex PCR (mPCR) assay, while serotyping was carried out by application of the Capsular Sequence Typing (CST) method with the combination of single tube PCR assays., Results: A total of 427 pneumococcal meningitis cases were notified to the NPHO between 2010 and 2020. Among those, 405 (94.8%) were microbiologically confirmed, while samples from 273 patients were sent to the NMRL for identification and/or further typing. The annual notification rate peaked at 0.47/100,000 in 2016 and since then has been decreasing. The incidence was highest in infants and in older adults. Pneumococcal serotypes were identified in 260/273 (95.2%) cases, where clinical samples were sent to the NMRL. The most prevalent serotypes (≥5%) were 3, 19A, 23B, 15B/C, 11A/D, 23A, 22F. During the study period there has been a decrease of PCV13 serotypes combined with an increase of non-PCV13 serotypes (p = 0.0045)., Conclusions: This is the first study to report serotypes for pneumococcal meningitis across all ages in the post-PCV13 era in Greece. There is a need to enhance surveillance, by close monitoring of the emerging serotypes and the impact of vaccination programs. Higher-valency PCVs may help to improve the coverage of pneumococcal disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Objective: Iron deficiency (ID) is a major public health problem with high prevalence in early childhood. We assessed the prevalence of anemia, ID, and iron deficiency anemia (IDA) in healthy children of Thrace, Greece, its correlation with several factors, and evaluated the diagnostic performance of hematologic and biochemical markers of sideropenia., Patients and Methods: For 202 healthy children 1-5 years old, a questionnaire was filled out describing their nutritional habits during infancy and early childhood. Venous hemograms along with serum ferritin, TIBC, %TS, and CRP were obtained from all studied children. In a subset of 156 children, the concentration of sTfR was also determined., Results: Children with ID and IDA had significantly lower beef consumption than children without sideropenia ( p =0.044). Using the WHO cutoff values of Hb <11g/dl and ferritin <12μg/l, the prevalence of anemia, ID, and IDA was 9.41%, 6.44%, and 3.47%, respectively. If Hb <12g/dl and ferritin<18μg/l were used as cutoffs, the prevalence of anemia, ID, and IDA was 26.73%, 16.33%, and 5.94%, respectively. ROC analysis revealed that at ferritin <12μg/l, the AUC of sTfR alone (0.827) was substantially better than that of TIBC (0.691), while at serum ferritin cutoff of 18μg/l, the AUC of TIBC (0.770) was better than that of sTfR (0.716)., Conclusions: The prevalence of ID and IDA in children 1-5 years old in Thrace is like in other developed countries. The chosen cutoff of serum ferritin affects the evaluation of the diagnostic significance of the different sideropenia markers., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Objective: We surveyed antimicrobials used in Greek pediatric hematology-oncology (PHO) and bone marrow transplant (BMT) units before and after an intervention involving education regarding the 2017 clinical practice guidelines (CPG) for the management of febrile neutropenia in children with cancer and hematopoietic stem-cell transplant recipients., Design: Antibiotic prescribing practices were prospectively recorded between June 2016 and November 2017., Intervention: In December 2017, baseline data feedback was provided, and CPG education was provided. Prescribing practices were followed for one more year. For antibiotic stewardship, days of therapy, and length of therapy were calculated., Setting: Five of the 6 PHO units in Greece and the single pediatric BMT unit participated., Participants: Admitted children in each unit who received the first 15 new antibiotic courses each month., Results: Administration of ≥4 antibiotics simultaneously and administration of antibiotics with overlapping activity for ≥2 days were significantly more common in PHO units in general hospitals compared to children's hospitals. Use of at least 1 antifungal was recorded in ∼47% of the patients before and after the intervention. De-escalation and/or discontinuation of antibiotics on day 6 of initial treatment increased significantly from 43% to 53.5% (P = .032). Although the number of patients requiring intensive care support for sepsis did not change, a significant drop was noted in all-cause mortality (P = .008)., Conclusions: We recorded the antibiotic prescribing practices in Greek PHO and BMT units, we achieved improved prescribing with a simple intervention, and we identified areas in need of improvement., (© The Author(s) 2022.)

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., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Despite the marked improvement in overall survival rates of paediatric patients with haematological malignancies that has been achieved during the last decades, there is still a pressing need for novel therapeutic approaches for the subset of patients with relapsed or refractory disease. Immune checkpoint inhibitors aim to induce potent anti-tumour immune responses by targeted blocking of inhibitory receptors and have shown promising results in preclinical models and studies on the adult population. However, paediatric malignancies present unique features, and so far, experience with these agents is limited. In the current review, we present an overview of efficacy and safety data from case reports, case series, and clinical trials employing the use of immune checkpoint inhibitors in children, adolescents, and young adults with haematological malignancies. We also discuss new possibilities involving novel targets and combination treatments and provide a summary of the currently registered clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cyclic vomiting syndrome (CVS) is a debilitating functional gastrointestinal disorder. Diagnosis is based on the Rome III criteria. There are no evidence-based guidelines for the management of paediatric CVS, although ondansetron and antimigraine medications are frequently tried. We describe a 13-year-old adolescent girl with severe CVS and numerous hospital admissions for dehydration because of cyclic vomiting. She had failed oral ondansetron therapy. Oral aprepitant (125 mg in the first, and 85 mg on the second and third days), a neurokinin 1 receptor antagonist that has been approved for preventing chemotherapy-induced vomiting or postoperative emesis, was tried in our patient at home during the first prodromal signs of an upset stomach. She had a dramatic response to it, with no further episodes of vomiting since its start. There is an urgent need for randomised clinical studies to assess the efficacy of available treatment options, including aprepitant in patients with severe CVS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

We present the case of a 7-year-old boy who fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). Prompt visualization of his bone marrow confirmed the diagnosis of visceral leishmaniasis (VL). He responded well to treatment with liposomal amphotericin-B. The patient had a false-negative enzyme-linked immunosorbent assay for Leishmania infantum and a false-positive immunoglobulin M test for Epstein Barr virus (EBV). Because age at presentation is similar in children with VL and familial HLH for whom EBV is the usual trigger, ruling out VL is extremely important because nonspecific serologic tests for EBV can lead to the inappropriate diagnosis of EBV-driven primary HLH and to the administration of unnecessary immunochemotherapy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that mostly affects children with suppressed cellular immunity. PJP was the most common cause of infectious death in children with acute lymphoblastic leukemia prior to the inclusion of cotrimoxazole prophylaxis as part of the standard medical care in the late 1980s. Children with acute leukemia, lymphomas, and those undergoing hematopoietic stem cell transplantation, especially allogeneic transplantation, are also at high risk of PJP. Persistent lymphopenia, graft versus host disease, poor immune reconstitution, and lengthy use of corticosteroids are significant risk factors for PJP. Active infection may be due to reactivation of latent infection or recent acquisition from environmental exposure. Intense hypoxemia and impaired diffusing capacity of the lungs are hallmarks of PJP, while computerized tomography of the lungs is the diagnostic technique of choice. Immunofluorescence testing with monoclonal antibodies followed by fluorescent microscopy and polymerase chain reaction testing of respiratory specimens have emerged as the best diagnostic methods. Measurement of (1-3)-β-D-glucan in the serum has a high negative predictive value in ruling out PJP. Oral cotrimoxazole is effective for prophylaxis, but in intolerant patients, intravenous and aerosolized pentamidine, dapsone, and atovaquone are effective alternatives. Ιntravenous cotrimoxazole is the treatment of choice, but PJP has a high mortality even with appropriate therapy.

Iron deficiency and iron-deficiency anemia (IDA) affects approximately two billion people worldwide, and most of them reside in low- and middle-income countries. In these nations, additional causes of anemia include parasitic infections like malaria, other nutritional deficiencies, chronic diseases, hemoglobinopathies, and lead poisoning. Maternal anemia in resource-poor nations is associated with low birth weight, increased perinatal mortality, and decreased work productivity. Maintaining a normal iron balance in these settings is challenging, as iron-rich foods with good bioavailability are of animal origin and either expensive and/or available in short supply. Apart from infrequent consumption of meat, inadequate vitamin C intake, and diets rich in inhibitors of iron absorption are additional important risk factors for IDA in low-income countries. In-home iron fortification of complementary foods with micronutrient powders has been shown to effectively reduce the risk of iron deficiency and IDA in infants and young children in developing countries but is associated with unfavorable changes in gut flora and induction of intestinal inflammation that may lead to diarrhea and hospitalization. In developed countries, iron deficiency is the only frequent micronutrient deficiency. In the industrialized world, IDA is more common in infants beyond the sixth month of life, in adolescent females with heavy menstrual bleeding, in women of childbearing age and older people. Other special at-risk populations for IDA in developed countries are regular blood donors, endurance athletes, and vegetarians. Several medicinal ferrous or ferric oral iron products exist, and their use is not associated with harmful effects on the overall incidence of infectious illnesses in sideropenic and/or anemic subjects. However, further research is needed to clarify the risks and benefits of supplemental iron for children exposed to parasitic infections in low-income countries, and for children genetically predisposed to iron overload., Competing Interests: Competing interests: The authors declare no conflict of Interest.

An 8-year-old girl with subacute submandibular lymphadenitis and no other complaints is described. After failure of parenteral antistaphylococcal therapy, she underwent incision and drainage of the involved lymph node. The responsible pathogen was identified as Mycobacterium malmoense by GenoType CM assay and sequencing of the 16S ribosomalRNA (rRNA) gene. The patient remains healthy, 11 months after surgery, even though it took approximately 4 months for the surgical incision to heal completely. While M. malmoense is a relatively common cause of non-tuberculous mycobacteria (NTM) lymphadenitis in Northern Europe, this is the first reported case from Greece. We conclude that in a young child with lymphadenitis without systemic symptoms, the microbiology laboratory should be notified in advance in order to extend the duration of mycobacterial cultures. Application of molecular methods will increase the number of reported cases of rare NTM in the future., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Hemolytic anemia occurs in only 1% to 3% of hospitalized patients with infectious mononucleosis. The authors describe an 8-year-old girl without cervical lymphadenopathy or splenomegaly, who presented with conjugated hyperbilirubinemia and was diagnosed with cold agglutinin disease caused by an immunoglobulin M autoantibody with anti-i specificity. Acute Epstein-Barr virus infection was confirmed by serologic and molecular methods. She recovered uneventfully after a 3-week course of methylprednisolone. Epstein-Barr virus infection should be considered in any case of hemolytic anemia associated with hepatic dysfunction, especially when direct antiglobulin test is positive for C3d. In these cases, a course of corticosteroids seems safe and may be beneficial.

Candidemia is the leading cause of invasive fungal infections in hospitalised children. The highest rates of candidemia have been recorded in neonates and infants <1 year of age. Candidemia is more frequent in neonates and young infants than in adults, and is associated with better clinical outcomes, but higher inpatient costs. Over the last 10 years, a declining trend has been noted in the incidence of paediatric candidemia in the US and elsewhere due to the hospital-wide implementation of central-line insertion and maintenance bundles that emphasise full sterile barrier precautions, chlorhexidine skin preparation during line insertion, meticulous site and tubing care, and daily discussion of catheter necessity. Additional interventions aiming at reducing gut-associated candidemia are required in immunocompromised and critically ill children., (© 2018 Blackwell Verlag GmbH.)

Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau ( VHL ) gene. Since this discovery, additional VHL mutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. VHL is a major tumor suppressor gene, mutations in which were first described in patients presenting with VHL disease, which is characterized by the development of highly vascularized tumors. Here, we identify a new VHL cryptic exon (termed E1') deep in intron 1 that is naturally expressed in many tissues. More importantly, we identify mutations in E1' in 7 families with erythrocytosis (1 homozygous case and 6 compound-heterozygous cases with a mutation in E1' in addition to a mutation in VHL coding sequences) and in 1 large family with typical VHL disease but without any alteration in the other VHL exons. In this study, we show that the mutations induced a dysregulation of VHL splicing with excessive retention of E1' and were associated with a downregulation of VHL protein expression. In addition, we demonstrate a pathogenic role for synonymous mutations in VHL exon 2 that altered splicing through E2-skipping in 5 families with erythrocytosis or VHL disease. In all the studied cases, the mutations differentially affected splicing, correlating with phenotype severity. This study demonstrates that cryptic exon retention and exon skipping are new VHL alterations and reveals a novel complex splicing regulation of the VHL gene. These findings open new avenues for diagnosis and research regarding the VHL-related hypoxia-signaling pathway., (© 2018 by The American Society of Hematology.)

Primary Evans syndrome (ES) is defined by the concurrent or sequential occurrence of immune thrombocytopenia and autoimmune hemolytic anemia in the absence of an underlying etiology. The syndrome is characterized by a chronic, relapsing, and potentially fatal course requiring long-term immunosuppressive therapy. Treatment of ES is hardly evidence-based. Corticosteroids are the mainstay of therapy. Rituximab has emerged as the most widely used second-line treatment, as it can safely achieve high response rates and postpone splenectomy. An increasing number of new genetic defects involving critical pathways of immune regulation identify specific disorders, which explain cases of ES previously reported as "idiopathic".

This article has been retracted by the authors under the agreement between the Editor-in-Chief, Masayuki Saijo and authors.

Background: Acinetobacter baumannii has emerged as a major cause of nosocomial outbreaks. It is particularly associated with nosocomial pneumonia and bloodstream infections in immunocompromised and debilitated patients with serious underlying pathologies. Over the last two decades, a remarkable rise in the rates of multidrug resistance to most antimicrobial agents that are active against A. baumannii has been noted worldwide. We evaluated the rates of antimicrobial resistance and changes in resistance over a 5-year period (2010-2014) in A. baumannii strains isolated from hospitalized patients in a tertiary Greek hospital., Materials and Methods: Identification of A. baumannii was performed by standard biochemical methods and the Vitek 2 automated system, which was also used for susceptibility testing against 18 antibiotics: ampicillin/sulbactam, ticarcillin, ticarcillin/clavulanic acid, piperacillin, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, meropenem, gentamicin, amikacin, tobramycin, ciprofloxacin, tetracycline, tigecycline, trimethoprim/sulfamethoxazole, and colistin. Interpretation of susceptibility results was based on the Clinical and Laboratory Standards Institute criteria, except for tigecycline, for which the Food and Drug Administration breakpoints were applied. Multidrug resistance was defined as resistance to ≥3 classes of antimicrobial agents., Results: Overall 914 clinical isolates of A. baumannii were recovered from the intensive care unit (ICU) (n = 493), and medical (n = 252) and surgical (n = 169) wards. Only 4.9% of these isolates were fully susceptible to the antimicrobials tested, while 92.89% of them were multidrug resistant (MDR), i.e., resistant to ≥3 classes of antibiotics. ICU isolates were the most resistant followed by isolates from surgical and medical wards. The most effective antimicrobial agents were, in descending order: colistin, amikacin, trimethoprim/sulfamethoxazole, tigecycline, and tobramycin. Nevertheless, with the exception of colistin, no antibiotic was associated with a susceptibility rate >40% for the entire study period. The most common phenotype showed resistance against ampicillin/sulbactam, cephalosporins, carbapenems, aminoglycosides, ciprofloxacin, and tigecycline. An extremely concerning increase in colistin-resistant isolates (7.9%) was noted in 2014, the most recent study year., Conclusion: The vast majority of A. baumannii clinical isolates in our hospital are MDR. The remaining therapeutic options for critically ill patients who suffer from MDR A. baumannii infections are severely limited, with A. baumannii beginning to develop resistance even against colistin. Scrupulous application of infection control practices should be implemented in every hospital unit. Lastly, given the lack of available therapeutic options for MDR A. baumannii infections, well-controlled clinical trials of combinations of existing antibiotics are clearly needed., Competing Interests: No conflicts of interest.

Background: Intravenous iron sucrose is not recommended by its manufacturers for use in children despite extensive safety and efficacy data in adults., Methods: We reviewed the experience of our department between January, 2011 and February, 2014 with the use of intravenous iron sucrose in children ≤14 years of age who failed in oral iron therapy for iron deficiency anemia (IDA)., Results: Twelve children (6 females) aged 1.2-14 years (median age 8.9 years) received at least one dose of intravenous iron sucrose. Ten patients had IDA inadequately treated or non-responsive to oral iron therapy. One patient received therapy for blood transfusion avoidance and one for presumed iron refractory iron deficiency anemia (IRIDA). Iron sucrose infusions were given on alternate days up to three times per week. The number of infusions per patient ranged from 2 to 6 (median, 3), the individual doses from 100 mg to 200 mg (median, 200 mg), and the total doses from 200 mg to 1200 mg (median, 400 mg). Iron sucrose was effective in raising the hemoglobin concentration to normal in all patients with IDA, i.e., from 7.6±2.38 g/dL to 12.4±0.64 g/dL, within 31-42 days after the first infusion. The single patient with IRIDA demonstrated a 1.8 g/dL rise. Injection site disorders in three cases and transient taste perversion in one case were the only side effects., Conclusion: Intravenous iron sucrose appears to be safe and very effective in children with IDA who do not respond or cannot tolerate oral iron therapy.

Iron deficiency anemia (IDA) continues to be very common worldwide. Intravenous (IV) iron is an infrequently used therapeutic option in children with IDA despite numerous studies in adults and several small but notable pediatric studies showing efficacy and safety. Presently, the availability of newer IV iron products allows for replacement of the total iron deficit at a single setting. These products appear safer compared to the high molecular weight iron dextrans of the past. Herein, we review the medical literature and suggest that front line use of IV iron should be strongly considered in diseases associated with IDA in children., (© 2015 Wiley Periodicals, Inc.)

Urinary tract infections (UTIs) are common infections associated with considerable morbidity and mortality, particularly in paediatric patients. The alarmingly increasing antimicrobial resistance of contemporary uropathogens in children necessitates the re-evaluation of antibiotic treatment. We evaluated uropathogens isolated from children hospitalised due to a community-acquired UTI over a 5.5-year period in a university hospital of Northern Greece and their antibiotic susceptibility patterns. The antibiotic susceptibility of uropathogens was compared by patient sex and age. Bacterial identification and antibiotic susceptibility testing were performed by the automated VITEK ® 2 system and the Kirby-Bauer method. Overall, 221 urinary isolates were identified from 218 children with a documented UTI, including 170 (76.9%) Escherichia coli, 17 (7.7%) Proteus spp., 15 (6.8%) Klebsiella spp., 9 (4.1%) Pseudomonas aeruginosa, 4 (1.8%) Enterococcus faecalis, 2 (0.9%) Enterobacter spp., 2 (0.9%) Morganella morganii and 2 (0.9%) Serratia fonticola. Comparing antibiotic susceptibilities of E. coli isolates by age [≤2 years vs. >2 years] and sex did not show any significant differences. Only 80 (49.1%) of the 163 tested E. coli isolates were found to be susceptible to ampicillin, whereas susceptibility to amoxicillin/clavulanic acid (AMC), ampicillin/sulbactam, trimethoprim/sulfamethoxazole and nitrofurantoin was 78.3%, 78.9%, 75.3% and 96.9%, respectively. Parenteral second- and third-generation cephalosporins, aminoglycosides and carbapenems were highly active against almost all uropathogens. We conclude that ampicillin should not be used for empirical therapy of paediatric community-acquired UTIs in our region. AMC and oral second-generation cephalosporins cover ca. 80% of uropathogenic E. coli, whilst nitrofurantoin is an appealing option for UTI chemoprophylaxis., (Copyright © 2015 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

We investigated the antibiotic susceptibility of glycopeptide-resistant enterococci (GRE). Seventy consecutive GRE were tested. Sixty-two isolates were identified as Enterococcus faecium (88.6%), and 8 (11.4%) as Enterococcus faecalis. All strains were susceptible to linezolid and daptomycin, while 17.1% (12/70) and 11.4% (8/70) were resistant to quinupristin/dalfopristin (QD) and tigecycline, respectively. All E. faecalis isolates were resistant to QD, while 4 of 62 (6.5%) E. faecium isolates were resistant to QD. All E. faecalis isolates were susceptible to tigecycline, while 14.5% (9/62) E. faecium isolates were resistant. Continued surveillance of GRE antibiotic susceptibilities is important for combating these multi-resistant nosocomial pathogens.