Impact of fill volume on ultrafiltration with icodextrin in children on chronic peritoneal dialysis.

BACKGROUND: Icodextrin is a solution of glucose polymers developed to provide sustained ultrafiltration over an extended dwell. Our aim was to determine whether or not fill volume with icodextrin contributes to the ability to achieve ultrafiltration in children. METHODS: The charts of all children on chronic peritoneal dialysis between January 2000 and July 2014 were screened for the use of an icodextrin day dwell. Data were extracted from the electronic chart and the HomeChoice™ Pro card and corrected for body surface area (BSA). RESULTS: Fifty children had an icodextrin day dwell. A linear correlation was found between the daytime fill volume and net ultrafiltration (p < 0.001). More ultrafiltration was achieved with a fill volume above 550 ml/m(2) BSA (107 ± 75 ml/m(2) BSA) than with smaller fill volumes (-8 ± 99 ml; p = 0.004). Ultrafiltration was achieved in 88 % of children with a fill volume above 550 ml/m(2) BSA versus only 44 % of patients with a smaller fill volume (p = 0.001). Icodextrin was well tolerated. CONCLUSIONS: Our observations reveal that the larger the fill volume the higher the likelihood of achieving ultrafiltration with icodextrin and suggest that a minimum day dwell volume of 550 ml/m(2) BSA seems to facilitate ultrafiltration in children. To our knowledge this is the largest study addressing ultrafiltration with icodextrin in children.

Leukocyte adhesion deficiency type III: clinical features and treatment with stem cell transplantation.

Leukocyte adhesion deficiency type III (LADIII) is an autosomal recessive disorder that presents with a severe leukocyte adhesion defect and a Glanzmann-type thrombocytopathy. Hematopoietic stem cell transplantation (HSCT)--the only definitive treatment for LADIII--appears to have a high rate of complications. In this study, we describe a new group of patients with LADIII, highlighting further clinical and immunologic aspects of this disease, and reevaluating the effectiveness of HSCT for its treatment. The patients had clinical and laboratory findings consistent with LADIII. Molecular analysis confirmed the presence of a mutation in the kindlin-3 gene. HSCT was carried out in 3 patients and was successful in 2. The diagnosis of LADIII should be considered in all patients who present with recurrent infections and a bleeding diathesis, regardless of the leukocyte count. LADIII is a primary immune deficiency, which can be successfully corrected by bone marrow transplantation if applied early in the course of the disease using appropriate conditioning.

Hematopoietic Stem Cell Transplantations for Primary Immune Deficiencies: 3 Decades of Experience From a Tertiary Medical Center.

Hematopoietic stem cell transplantation (HSCT) remains the leading treatment for the majority of severe primary immune deficiency (PID). This study aims to analyze changes in outcome over time. We conducted a retrospective analysis of HSCT in children with PID in a tertiary medical center over the period of 1983 to 2012. We identified 93 children with PID with a median follow-up of 3.6 years (range, 29 d to 21.2 y) after HSCT. The 2-year survival rates after HSCT for children with severe combined immune deficiency, hemophagocytic lymphohistiocytosis/lymphoproliferative disease, Wiskott-Aldrich syndrome, granulocyte defect, and undefined PID were 65.7%±6.8%, 80%±10.3%, 83.3%±15.2%, 75%±12.5%, and 25%±21.7%, respectively. Survival was associated with year of HSCT and matching. The hazard ratio (HR) (95% CI) for HSCT done in 1983 to 1999 compared with 2000 to 2012 and for matched (related and unrelated) compared with mismatched donor were 2.14 (0.99 to 4.653) and 3.07 (1.46 to 6.4), respectively. Survival was not associated with age, sex of the recipient, underlying PID, conditioning regimen, and presence of acute graft-versus-host disease. After adjustment to the underlying PID, donor and use of fludarabine-based conditioning, the HR (95% CI) for HSCT from the year 2000 was 4.69 (range, 1.4 to 15.45). Advances in HSCT over time have improved the survival of children with PID.

Oct-3/4 regulates stem cell identity and cell fate decisions by modulating Wnt/ß-catenin signalling.

Although the transcriptional regulatory events triggered by Oct-3/4 are well documented, understanding the proteomic networks that mediate the diverse functions of this POU domain homeobox protein remains a major challenge. Here, we present genetic and biochemical studies that suggest an unexpected novel strategy for Oct-3/4-dependent regulation of embryogenesis and cell lineage determination. Our data suggest that Oct-3/4 specifically interacts with nuclear ß-catenin and facilitates its proteasomal degradation, resulting in the maintenance of an undifferentiated, early embryonic phenotype both in Xenopus embryos and embryonic stem (ES) cells. Our data also show that Oct-3/4-mediated control of ß-catenin stability has an important function in regulating ES cell motility. Down-regulation of Oct-3/4 increases ß-catenin protein levels, enhancing Wnt signalling and initiating invasive cellular activity characteristic of epithelial-mesenchymal transition. Our data suggest a novel mode of regulation by which a delicate balance between ß-catenin, Tcf3 and Oct-3/4 regulates maintenance of stem cell identity. Altering the balance between these proteins can direct cell fate decisions and differentiation.

[How can asthma in children be controlled?].

Asthma is a disease manifested by recurrent episodes of shortness of breath, wheezing or cough that often require treatment at the emergency department or even hospitalization. These exacerbations are caused by an increased inflammatory process in the airways. This review focuses on the various daily long term control medications used to prevent exacerbations. The pharmacotherapy used to manage asthma is based mainly on inhaled corticosteroids (ICS and leukotriene receptor antagonists. In more severe cases, other drugs can be added, such as long-acting beta 2 agonists lare used only in conjunction with ICS] as well as additional drugs such as slow release theophylline, anti-lgE monoclonal antibodies, and more. The step-up step-down approach is used to decide on the controller medication needed. If the preventive therapy fails, it is essential to assess the adherence to therapy, the technique used, the existence of aggravating factors and the possibility that the cause of the symptoms is not asthma. For proper disclosure the third author (E.K.) has received payment in the past for lectures from Asthma drug companies.

Congenital SARS-CoV-2 Infection in Two Neonates with Confirmation by Viral Culture of the Placenta in One Case.

Congenital infections with SARS-CoV-2 are uncommon. We describe two confirmed congenital SARS-CoV-2 infections using descriptive, epidemiologic and standard laboratory methods and in one case, viral culture. Clinical data were obtained from health records. Nasopharyngeal (NP) specimens, cord blood and placentas when available were tested by reverse transcriptase real-time PCR (RT-PCR). Electron microscopy and histopathological examination with immunostaining for SARS-CoV-2 was conducted on the placentas. For Case 1, placenta, umbilical cord, and cord blood were cultured for SARS-CoV-2 on Vero cells. This neonate was born at 30 weeks, 2 days gestation by vaginal delivery. RT-PCR tests were positive for SARS-CoV-2 from NP swabs and cord blood; NP swab from the mother and placental tissue were positive for SARS-CoV-2. Placental tissue yielded viral plaques with typical morphology for SARS-CoV-2 at 2.8 × 102 pfu/mL confirmed by anti-spike protein immunostaining. Placental examination revealed chronic histiocytic intervillositis with trophoblast necrosis and perivillous fibrin deposition in a subchorionic distribution. Case 2 was born at 36 weeks, 4 days gestation. RT-PCR tests from the mother and infant were all positive for SARS-CoV-2, but placental pathology was normal. Case 1 may be the first described congenital case with SARS-CoV-2 cultivated directly from placental tissue.

Negative autoregulation of Oct3/4 through Cdx1 promotes the onset of gastrulation.

Gastrulation marks the onset of germ layer formation from undifferentiated precursor cells maintained by a network including the Pou5f1 gene, Oct3/4. Negative regulation of the undifferentiated state is a prerequisite for germ layer formation and subsequent development. A novel cross-regulatory network was characterized including the Pou5f1 and Cdx1 genes as part of the signals controlling the onset of gastrulation. Of particular interest was the observation that, preceding gastrulation, the Xenopus Oct3/4 factors, Oct60, Oct25, and Oct91, positively regulate Cdx1 expression through FGF signaling, and during gastrulation the Oct3/4 factors become repressors of Cdx1. Cdx1 negatively regulates the Pou5f1 genes during gastrulation, thus contributing to the repression of the network maintaining the undifferentiated state and promoting the onset of gastrulation. These regulatory interactions suggest that Oct3/4 initiates its own negative autoregulation through Cdx1 up-regulation to begin the repression of pluripotency in preparation for the onset of gastrulation and germ layer differentiation.