Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency.

Background: Biallelic mutations in LIG4 encoding DNA-ligase 4 cause a rare immunodeficiency syndrome manifesting as infant-onset life-threatening and/or opportunistic infections, skeletal malformations, radiosensitivity and neoplasia. LIG4 is pivotal during DNA repair and during V(D)J recombination as it performs the final DNA-break sealing step.

Objectives: This study explored whether monoallelic LIG4 missense mutations may underlie immunodeficiency and autoimmunity with autosomal dominant inheritance.

Supportive Care During Pediatric Hematopoietic Stem Cell Transplantation: Prevention of Infections. A Report From Workshops on Supportive Care of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT).

Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions.

Transfusions in Aplastic Anemia Patients Cause HLA Alloimmunization: Comparisons of Current and Past Cohorts Demonstrate Progress.

Transfusions are the mainstay of supportive therapy in patients with aplastic anemia (AA) and may lead to anti- HLA alloimmunization, thereby also increasing the risk for donor-specific antibodies in the setting of HLA-mismatched transplantation. Historically, AA patients were thought to be at particularly high risk for HLA alloimmunization. In past decades, blood product manufacturing (leukoreduction) and HLA antibody testing have improved significantly by single antigen bead (SAB) technology.

Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families.

Very long-term follow-up of aplastic anemia treated with immunosuppressive therapy or allogeneic hematopoietic cell transplantation.

Introduction: Since the 1970s outcome of aplastic anemia (AA) patients has improved significantly due to the introduction of immunosuppressive therapy (IST) and allogeneic hematopoietic transplantation (HCT). However, patients may suffer from persistent disease, relapse, clonal evolution, graft-versus-host disease and other late effects. Here, we analyse very long-term outcome of all AA patients at our institution comparing not only survival, but also response status and complications.

Moving Beyond the Friend-Foe Myth: A Scoping Review of the Use of Social Media in Adolescent and Young Adult Oncology.

Adolescents and young adults (AYA) with cancer present a unique challenge to health care institutions. Their cancer diagnosis and treatment have a profound impact upon their health and well-being. Despite the various support services aimed at improving their quality of life, their needs and preferences are often underestimated or misjudged.

Bayesian spatial modelling of childhood cancer incidence in Switzerland using exact point data: a nationwide study during 1985-2015.

Background: The aetiology of most childhood cancers is largely unknown. Spatially varying environmental factors such as traffic-related air pollution, background radiation and agricultural pesticides might contribute to the development of childhood cancer. This study is the first investigation of the spatial disease mapping of childhood cancers using exact geocodes of place of residence.

Correction: Supportive care during pediatric hematopoietic stem cell transplantation: beyond infectious diseases. A report from workshops on supportive care of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Supportive care during pediatric hematopoietic stem cell transplantation: beyond infectious diseases. A report from workshops on supportive care of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT).

Hematopoietic stem cell transplantation (HSCT) is currently the standard of care for many malignant and nonmalignant blood diseases. As several treatment-emerging acute toxicities are expected, optimal supportive measurements critically affect HSCT outcomes. The paucity of good clinical studies in supportive practices gives rise to the establishment of heterogeneous guidelines across the different centers, which hampers direct clinical comparison in multicentric studies.

Physical activity and screen time in children who survived cancer: A report from the Swiss Childhood Cancer Survivor Study.

Background: Physical activity (PA) can reduce the risk of chronic adverse health conditions in childhood cancer survivors. We examined PA and sedentary screen time behavior in a nationwide study in Switzerland.

Procedures: The Swiss Childhood Cancer Survivor Study sent questionnaires to parents of all Swiss resident ≥5-year survivors diagnosed between 1995 and 2010.

Gonadal Function after Busulfan Compared with Treosulfan in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplant.

Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre- and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant.

Heart-sparing volumetric modulated arc therapy for whole lung irradiation.

Purpose: Whole lung irradiation (WLI) is indicated for subgroups of patients with lung metastases from Wilms' tumor (nephroblastoma). WLI has traditionally been performed with an anterior/posterior field arrangement with poor potential for heart sparing; thus, new techniques are desirable to achieve a lower dose to the heart.

Materials And Methods: We utilized volumetric modulated arc therapy (VMAT) for WLI with 18 Gy in a patient with metastatic nephroblastoma.

Fertility preservation issues in pediatric hematopoietic stem cell transplantation: practical approaches from the consensus of the Pediatric Diseases Working Party of the EBMT and the International BFM Study Group.

Fertility preservation is an urgent challenge in the transplant setting. A panel of transplanters and fertility specialists within the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the International BFM Study Group provides specific guidelines. Patients and families should be informed of possible gender- and age-specific cryopreservation strategies that should be tailored according to the underlying disease, clinical condition and previous exposure to chemotherapy.

State-of-the-art fertility preservation in children and adolescents undergoing haematopoietic stem cell transplantation: a report on the expert meeting of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) in Baden, Austria, 29-30 September 2015.

Nowadays, allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment procedure and often the only cure for many patients with malignant and non-malignant diseases. Decrease in short-term complications has substantially contributed to increased survival. Therefore long-term sequelae are reaching the focus of patient care.

Fertility preservation practices in pediatric and adolescent cancer patients undergoing HSCT in Europe: a population-based survey.

Chemotherapy and irradiation can affect the gonads, leading to impairment of pubertal development and/or infertility. Fertility preservation (FP) is therefore a crucial endeavor in hematopoietic stem cell transplantation (HSCT) because of the severe impact of infertility on the quality of life of long-term survivors. Despite the existence of different international guidelines, FP counseling and procedures are not routinely implemented as part of patient care.

Fertility preservation in pediatric and adolescent cancer patients in Switzerland: A qualitative cross-sectional survey.

Fertility preservation (FP) is an important topic of discussion in the field of oncology, particularly in pediatric oncology. Despite the awareness of severe impact of infertility on quality of life and different guidelines available in this area, the options in FP are not routinely discussed with the pediatric cancer patients and their parents. To the best of our knowledge, this is the first survey report concerned to FP counseling and procedures in pediatric and adolescent cancer patients in Switzerland.

Intracranial Hemorrhage as the First Manifestation of Severe Congenital Factor X Deficiency in a 20-Month-Old Male: Case Report and Review of the Literature.

Factor X deficiency (FXD) is a rare bleeding disorder, which can result in severe bleeding symptoms such as intracranial hemorrhage (ICH). The most common bleeding symptoms are epistaxis and gum bleeding. ICH is reported in 9-26% of all patients with FXD, mostly during the first month of life.

Transient myeloproliferative disorder in neonates without Down syndrome: case report and review.

Transient myeloproliferative disorder (TMD) is a clonal proliferation of megakaryoblasts, typically occurring in newborns with Down syndrome. It is believed that TMD occurs in the presence of GATA1 mutation together with trisomy 21. However, a limited number of patients with TMD but without Down syndrome have been reported, all with a blast population with numeric or rarely structural chromosome 21 abnormalities.

Developmental changes in the electroencephalogram and responses to a noxious stimulus in anaesthetized tammar wallaby joeys (Macropus eugenii eugenii).

The tammar wallaby joey is born extremely immature and most of its neurological development occurs in the maternal pouch. It is not known at what in-pouch age functions such as conscious sensory perception commence. We determined the electroencephalographic (EEG) responses to noxious stimulation in lightly anaesthetized tammar wallaby joeys.

Electroencephalographic responses to tail clamping in anaesthetized rat pups.

We investigated electroencephalographic (EEG) responses to tail clamping in lightly anaesthetized rat pups (5-22 days) in order to determine the ontogeny of EEG activity and at what age they may be capable of experiencing pain. Median frequency (F50) and spectral edge frequency (F95) of the power spectrum in the range of 1-30 Hz were determined before and after the application of a noxious stimulus and power spectra were compared by multivariate analysis. There was a postnatal increase in EEG power as, before clamping, pups aged 5-7 days exhibited isoelectric traces, whereas those aged 12-14 days and 21-22 days had intermittent EEG activity where the power in all frequencies was significantly lower at the former than at the latter age.

Birth and hatching: key events in the onset of awareness in the lamb and chick.

The neuroanatomical and neurophysiological development of the embryo and fetus and unique features of the physiological environment of the fetal brain, features which are lost at birth, support recent conclusions that under normal circumstances awareness (or consciousness) is probably not exhibited by the ovine embryo-fetus before birth and that it appears for the first time only after birth. However, there has apparently been no evaluation of whether or not similar mechanisms modulate awareness-related functions in domestic chicks before and after hatching. This comparative review, in seeking to rectify this, arrived at the following conclusions.

The importance of 'awareness' for understanding fetal pain.

Our understanding of when the fetus can experience pain has been largely shaped by neuroanatomy. However, completion of the cortical nociceptive connections just after mid-gestation is only one part of the story. In addition to critically reviewing evidence for whether the fetus is ever awake or aware, and thus able to truly experience pain, we examine the role of endogenous neuro-inhibitors, such as adenosine and pregnanolone, produced within the feto-placental unit that contribute to fetal sleep states, and thus mediate suppression of fetal awareness.