Targeted immunotherapy in the treatment of childhood and adolescent classic Hodgkin lymphoma.

Childhood and adolescent classic Hodgkin Lymphoma (cHL) has long been a model for how we balance improved outcomes with increased toxicities in pediatric cancer. The recognition that unacceptable short- and long-term toxicities come with increasing intensity of treatment has led to a decades-long attempt to better understand the patient-specific factors that dictate responses and outcomes. Targeted immunotherapy has emerged as a promising adjunct to cancer treatment; it has been shown to improve outcomes for poorly responding patients, to salvage relapsed disease, and more recently, to replace more toxic therapy modalities such as chemotherapy and radiation while maintaining excellent outcomes.

Apixaban versus no anticoagulation for the prevention of venous thromboembolism in children with newly diagnosed acute lymphoblastic leukaemia or lymphoma (PREVAPIX-ALL): a phase 3, open-label, randomised, controlled trial.

Background: Paediatric patients with acute lymphoblastic leukaemia or lymphoma are at increased risk of venous thromboembolism resulting in increased mortality and morbidity. We hypothesised that apixaban, a direct oral anticoagulant, would safely reduce venous thromboembolism in this patient population.

Methods: PREVAPIX-ALL was a phase 3, open-label, randomised, controlled trial conducted in 74 paediatric hospitals in 9 countries.

Serum miRNA profiles are altered in patients with primary sclerosing cholangitis receiving high-dose ursodeoxycholic acid.

Background & Aims: Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease that can lead to end-stage liver disease and cholangiocarcinoma. High-dose ursodeoxycholic acid (hd-UDCA, 28-30 mg/kg/day) was evaluated in a previous multicentre, randomised placebo-controlled trial; however, the study was discontinued early because of increased liver-related serious adverse events (SAEs), despite improvement in serum liver biochemical tests. We investigated longitudinal changes in serum miRNA and cytokine profiles over time among patients treated with either hd-UDCA or placebo in this trial as potential biomarkers for PSC and response to hd-UDCA, as well as to understand the toxicity associated with hd-UDCA treatment.

Late effects and frontline treatment selection for children with non-Hodgkin lymphoma.

Approximately 1 in 640 adults between 20 and 40 years of age is a survivor of childhood cancer. However, survival has often come at the expense of increased risk of long-term complications, including chronic health conditions and higher mortality rates. Similarly, long-term survivors of childhood non-Hodgkin lymphoma (NHL) experience significant morbidity and mortality related to prior cancer treatments, highlighting the importance of primary and secondary prevention strategies to mitigate late toxicity.

Diagnosis and management of Hodgkin lymphoma in children, adolescents, and young adults.

Advances in the management of Hodgkin lymphoma in children, adolescents and young adult have resulted in survival outcomes exceeding 90%. The risk of late toxicity, however, remains a significant concern for survivors of HL and the focus of modern trials have been to advance cure rates while reducing long term toxicity. This has been accomplished through response-adapted treatment approaches and the incorporation of novel agents, many of which target the unique interaction between the Hodgkin and Reed Sternberg cells and the tumor microenvironment.

Development and Validation of a Protocol for Pregnant Women Based on the Brazilian Dietary Guidelines.

Objective:  To develop and validate a protocol for the use of the Dietary Guidelines for the Brazilian Population (DGBP) in the individual dietary advice for pregnant women assisted in primary healthcare (PHC).

Methods:  Methodological study that involved the elaboration of a protocol in six steps: definition of the format, definition of the instrument to evaluate food consumption, systematization of evidence on food and nutrition needs of pregnant women, extraction of DGBP recommendations, development of messages of dietary guidelines and content, and face validity. The analyses of the validation steps were carried out by calculating the Content Validity Index (CVI) and thematic content analysis.

Photocurable Coatings to Improve the Mechanical Properties of 3D Printable Expanding Foams.

Recent developments of highly expandable foaming pre-polymer resins for lithographic additive manufacturing have allowed for the creation of structures larger than a printer's build envelope. To fully utilize the capabilities of this technology, the mechanical properties of these foams must be improved. This manuscript presents one method for strengthening these lightweight polymeric structures via aerosol spray application of a high-strength, low-viscosity photocurable coating.

Surface-Modified Melt Coextruded Nanofibers Enhance Blood Clotting In Vitro.

Blood loss causes an estimated 1.9 million deaths per year globally, making new methods to stop bleeding and promote clot formation immediately following injury paramount. The fabrication of functional hemostatic materials has the potential to save countless lives by limiting bleeding and promoting clot formation following an injury.

Risk-adapted chemoimmunotherapy using brentuximab vedotin and rituximab in children, adolescents, and young adults with newly diagnosed Hodgkin's lymphoma: a phase II, non-randomized controlled trial.

Background: Cure rates for Hodgkin's lymphoma are excellent, but excess short-term and long-term morbidities from treatment remain a concern. Immunotherapy targeting both tumor antigens and the immunosuppressive tumor microenvironment in children, adolescents, and young adults with Hodgkin's lymphoma may improve early response rates and eliminate toxic chemotherapy and radiation, thus minimizing toxicity. We conducted a phase II study to evaluate the safety and overall response rate of brentuximab vedotin and rituximab in combination with risk-adapted chemotherapy in children, adolescents, and young adults with newly diagnosed classic Hodgkin's lymphoma (cHL).

Developing a protocol based on the Brazilian Dietary Guidelines for individual dietary advice in the primary healthcare: theoretical and methodological bases.

To describe the methodology of development of a protocol for application of the Brazilian Dietary Guidelines by primary healthcare professionals in individual dietary advice. A five-step approach was followed: (1) format definition; (2) definition of the instrument for assessment of individuals' food consumption; (3) Dietary Guidelines' content extraction; (4) protocol content development; (5) content and face validity. An example from Brazil was displayed with the development of a protocol to guide healthcare professional decision-making when providing nutrition advice based on the Brazilian Dietary Guidelines.

Bioconjugation of Active Ingredients to Plant Viral Nanoparticles Is Enhanced by Preincubation with a Pluronic F127 Polymer Scaffold.

Proteinaceous nanoparticles can be used to deliver large payloads of active ingredients, which is advantageous in medicine and agriculture. However, the conjugation of hydrophobic ligands to hydrophilic nanocarriers such as plant viral nanoparticles (plant VNPs) can result in aggregation by reducing overall solubility. Given the benefits of hydrophilic nanocarrier platforms for targeted delivery and multivalent ligand display, coupled with the versatility of hydrophobic drugs, contrast agents, and peptides, this is an issue that must be addressed to realize their full potential.

Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis.

Background And Aims: Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes.

Approach And Results: We analyzed retrospective data from the Pediatric PSC Consortium.

Obinutuzumab (GA101) vs. rituximab significantly enhances cell death, antibody-dependent cytotoxicity and improves overall survival against CD20+ primary mediastinal B-cell lymphoma (PMBL) in a xenograft NOD-scid IL2Rgnull (NSG) mouse model: a potential targeted agent in the treatment of PMBL.

Primary mediastinal large B-cell lymphoma (PMBL), a distinct mature B-cell lymphoma, expresses CD20 and has recently been successfully treated with the combination of a type I anti-CD20 monoclonal antibody, rituximab, with multiple combination chemotherapy regimens. Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody (mAb), recognizing a unique CD20 extracellular membrane epitope with enhanced antibody dependent cellular cytotoxicity (ADCC) vs rituximab. We hypothesize that obinutuzumab vs rituximab will significantly enhance and cytotoxicity against PMBL.

The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children.

Background And Aims: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC.

Colorectal Dysplasia and Cancer in Pediatric-Onset Ulcerative Colitis Associated With Primary Sclerosing Cholangitis.

Inflammatory bowel disease (IBD), especially when associated with primary sclerosing cholangitis (PSC), is a risk factor for developing colorectal cancer (CRC). We aimed to determine the incidence of CRC in a large cohort of pediatric-onset PSC-ulcerative colitis (UC) patients.

Highly Expandable Foam for Lithographic 3D Printing.

In modern manufacturing, it is a widely accepted limitation that the parts patterned by an additive or subtractive manufacturing process (i.e., a lathe, mill, or 3D printer) must be smaller than the machine itself that produced them.

Long-term survivors of childhood, adolescent and young adult non-Hodgkin lymphoma.

Progress in overall survival rates for childhood non-Hodgkin lymphoma (NHL) can be largely attributed to effective development and conduct of a number of international treatment studies. Knowledge gained from these studies has shifted the treatment paradigm from a "one-size fits all" strategy to a histologically dependent approach. More specifically, many now adhere to a risk-stratified approach, prescribing cumulative doses and intensities of chemotherapeutic exposures based upon the aggressiveness of disease.

Lymphoma in Adolescents and Young Adults: Current Perspectives.

Lymphomas in adolescents and young adults represent approximately one quarter of all cancers in this age group. Historically, adolescent and young adult cancer patients represent a unique population with diverging issues surrounding psychosocial hardships/barriers, economics, and lack of standardization of therapeutic approaches.Furthermore, the biologic differences within the adolescent and young adult population seen in various lymphoma subtypes likely play a role in overall outcomes for this group.

The safety and efficacy of clofarabine in combination with high-dose cytarabine and total body irradiation myeloablative conditioning and allogeneic stem cell transplantation in children, adolescents, and young adults (CAYA) with poor-risk acute leukemia.

Acute leukemias in children with CR3, refractory relapse, or induction failure (IF) have a poor prognosis. Clofarabine has single agent activity in relapsed leukemia and synergy with cytarabine. We sought to determine the safety and overall survival in a Phase I/II trial of conditioning with clofarabine (doses 40 - 52 mg/m), cytarabine 1000 mg/m, and 1200 cGy TBI followed by alloSCT in children, adolescents, and young adults with poor-risk leukemia.

NHL in adolescents and young adults: A unique population.

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoid malignancies with high incidence in adolescents and young adults (AYAs). The most common diseases include diffuse large B-cell lymphoma, anaplastic large cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, and primary mediastinal large B-cell lymphoma. In comparison to younger children and adults, AYAs (15-39 years) with NHL present a specific set of challenges including variations in tumor biology, inconsistent treatment, pharmacodynamics, and psychosocial barriers.