Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-versus-Host Disease Survivorship after Hematopoietic Cell Transplantation: Part II. Organ Dysfunction and Immune Reconstitution Considerations for children with chronic GVHD after Hematopoietic Cell Transplantation.

While highly morbid forms of chronic graft versus host disease (cGVHD) and severe late effects of allogeneic hematopoietic cell transplant (HCT) can impact children and adults alike, unique considerations arise in pediatric cases regarding diagnosis, monitoring, treatment, and likelihood of resolution. As children can present with atypical features of cGVHD, and with more significant disease due to inability to communicate symptoms, they may be at increased risk for highly morbid forms of cGVHD and incur greater subsequent late effects, which may be more pronounced in those with underlying chromosomal breakage syndromes, with higher prevalence in pediatric HCT recipients. The long-term effects of cGVHD and its therapies include impaired immune reconstitution, leading to increased risks of infection and secondary malignant neoplasms.

AMPK drives both glycolytic and oxidative metabolism in murine and human T cells during graft-versus-host disease.

Allogeneic T cells reprogram their metabolism during acute graft-versus-host disease (GVHD) in a process involving the cellular energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK). Deletion of AMPK in donor T cells limits GVHD but still preserves homeostatic reconstitution and graft-versus-leukemia effects. In the current studies, murine AMPK knock-out (KO) T cells decreased oxidative metabolism at early time points posttransplant and lacked a compensatory increase in glycolysis after inhibition of the electron transport chain.

Overexpression of AMPKγ2 increases AMPK signaling to augment human T cell metabolism and function.

Cellular therapies are currently employed to treat a variety of disease processes. For T cell-based therapies, success often relies on the metabolic fitness of the T cell product, where cells with enhanced metabolic capacity demonstrate improved in vivo efficacy. AMP-activated protein kinase (AMPK) is a cellular energy sensor which combines environmental signals with cellular energy status to enforce efficient and flexible metabolic programming.

AMPK Drives Both Glycolytic and Oxidative Metabolism in T Cells During Graft-versus-host Disease.

Unlabelled: Allogeneic T cells reprogram their metabolism during acute graft-versus-host disease (GVHD) in a process reliant on the cellular energy sensor AMP-activated protein kinase (AMPK). Deletion of AMPK in donor T cells limits GVHD but still preserves homeostatic reconstitution and graft-versus-leukemia (GVL) effects. In the current studies, murine T cells lacking AMPK decreased oxidative metabolism at early timepoints post-transplant and were also unable to mediate a compensatory increase in glycolysis following inhibition of the electron transport chain.

The role of AMP-activated protein kinase in GVHD-causing T cells.

Allogeneic stem cell transplantation is a curative therapy for multiple hematologic disorders. However, this life-saving procedure is often complicated by acute graft-versus-host disease (GVHD), where donor T cells attack tissues in the recipient's skin, liver, and gastrointestinal tract. Previous research has demonstrated that GVHD-causing T cells undergo significant metabolic reprogramming during disease pathogenesis, with an increased reliance on oxidative metabolism.

A chronic eyelid lesion in a child: multi-disciplinary approach to diagnosis, treatment and management of a highly atypical histiocytic lesion.

Malignant histiocytic neoplasm with histiocytic sarcoma phenotype is a rare malignant neoplasm, distinguished by malignant cells with phenotypic characteristics of mature tissue histiocytes. Histiocytic sarcoma typically presents as a primary malignancy, although can also present as a secondary malignancy, and is rarely seen in the pediatric population. Due to the rarity of this condition, diagnosis of histiocytic sarcoma is difficult and considered a diagnosis of exclusion.

Numerical analysis and design of a light-driven liquid crystal polymer-based motorless miniature cart.

Liquid crystal polymers are a special class of soft materials that can change their shape in response to numerous stimuli such as light, heat, electric field, and chemicals. The ability to tailor the deformed shape by tuning the alignment of mesogens across the film has enabled the researchers to generate unique motions from these liquid crystal polymer thin films. Simulating such motions might allow us to understand the underlying mechanisms better and could lead to novel designs.

Mesenchymal chondrosarcoma of the chest wall in an adolescent patient: A case report and brief review of the literature.

Background: Mesenchymal chondrosarcoma is a rare and aggressive bone tumor with few reports of primary tumor in the chest wall.

Case: We report a case of a 17-year-old male presenting with back pain and a posterior mediastinal mass. Imaging demonstrated what was thought to be a benign chondral tumor.

Thrombotic Microangiopathy: Multi-Institutional Review of Pediatric Patients Who Underwent HSCT.

Thrombotic microangiopathy (TMA) is a rare but serious complication of hematopoietic stem cell transplantation (HSCT). The purpose of our study is to estimate the incidence, prevalence, and analyze the risk factors and outcome of TMA in children receiving HSCT. Patients under the age of 21 who underwent HSCT at one of the 42 Pediatric Health Information System (PHIS) hospitals from 2000-2012 were analyzed, including demographics, hospitalizations, TMA, and other HSCT-related complications.

Light-Driven Continual Oscillatory Rocking of a Polymer Film.

Achieving oscillatory motion in polymers without requiring on/off switching of stimuli is a current challenge. Hereby, a free-standing liquid crystal polymer (LCP) is demonstrated to undergo a sustained oscillatory motion when triggered by light, moving back and forth, resembling the motion of a rocking-chair. Two polymer films having different azobenzene photo-switches have been studied, revealing photoswitch requirements as well as illumination conditions necessary to sustain oscillations.

Safety of allogeneic hematopoietic stem cell transplantation in beta-thalassemia patients with chronic hepatitis C infections treated at a pediatric center.

The outcome of allogeneic HCT in patients previously infected with HCV is a widely debated topic and rarely reported in the pediatric and young adult age group given the small population of affected patients. New medications directly targeting HCV have induced virologic cures for over 90% of patients, and their use in the pretransplant setting may improve outcomes for patients infected with HCV. We describe two patients with transfusion-dependent beta-thalassemia major who underwent matched sibling donor bone marrow transplantation, one with a myeloablative regimen and one with a reduced-intensity conditioning regimen.

Central Venous Line Associated Deep Vein Thrombosis in Hospitalized Children.

An increase in the incidence of deep vein thrombosis (DVT) has been reported in pediatric patients over the past decade. The presence of central venous line (CVL) is a major contributing risk factor with conflicting data on the relative risk of DVT with various types of central lines. We aimed to assess the incidence of and identify potential risk factors for DVT overall and with different types of CVL individually.

Association between Posterior Reversible Encephalopathy Syndrome and infection.

is a microbe known to affect numerous organ systems, and in particular, can cause neurological manifestations. We describe an otherwise healthy child who presented with acute onset intractable headache with magnetic resonance imaging (MRI) findings consistent with posterior reversible encephalopathy syndrome (PRES), a neurological manifestation that presents with headache, vision changes, altered mental status, or seizures. Our patient did not have any of the common etiologies for PRES reported but tested positive for acute infection.

Optimization of laccase production from Marasmiellus palmivorus LA1 by Taguchi method of Design of experiments.

Background: Fungal laccase has profound applications in different fields of biotechnology due to its broad specificity and high redox potential. Any successful application of the enzyme requires large scale production. As laccase production is highly dependent on medium components and cultural conditions, optimization of the same is essential for efficient product production.

Nuclear role of WASp in the pathogenesis of dysregulated TH1 immunity in human Wiskott-Aldrich syndrome.

The clinical symptomatology in the X-linked Wiskott-Aldrich syndrome (WAS), a combined immunodeficiency and autoimmune disease resulting from WAS protein (WASp) deficiency, reflects the underlying coexistence of an impaired T helper 1 (TH1) immunity alongside intact TH2 immunity. This suggests a role for WASp in patterning T(H) subtype immunity, yet the molecular basis for the TH1-TH2 imbalance in human WAS is unknown. We have discovered a nuclear role for WASp in the transcriptional regulation of the TH1 regulator gene TBX21 at the chromatin level.