Adjuvant anti-angiogenic therapy enhances chemotherapeutic uptake in a murine model of head and neck cancer.

Intratumoural metabolic demands result in excessive angiogenic cytokine release leading to unorganised vasculature. Resultant fluid dynamics oppose blood flow and drug penetration due to a marked increase in interstitial fluid hydrostatic pressure. It is hypothesised that anti-angiogenic therapy may function to 'prune' vasculature and lead to improved chemotherapeutic penetration.

C3a receptor antagonism as a novel therapeutic target for chronic rhinosinusitis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease with an unknown etiology. Recent studies have implicated the complement system as a potential modulator of disease immunopathology. We performed proteomic pathway enrichment analysis of differentially increased proteins, and found an enrichment of complement cascade pathways in the nasal mucus of individuals with CRSwNP as compared to control subjects.

Interventions for preventing distal intestinal obstruction syndrome (DIOS) in cystic fibrosis.

Background: Cystic fibrosis (CF) is the most common, life-limiting, genetically inherited disease. It affects multiple organs, particularly the respiratory system. However, gastrointestinal problems such as constipation and distal intestinal obstruction syndrome (DIOS) are also important and well-recognised complications in CF.

Utility of the Surgical Apgar Score in Head and Neck Squamous Cell Carcinoma.

Objectives To recognize the utility of the surgical Apgar score (SAS) in a noncutaneous head and neck squamous cell carcinoma (HNSCC) population. Study Design Retrospective case series with chart review. Setting Academic tertiary medical center.

Dasatinib Plus Intensive Chemotherapy in Children, Adolescents, and Young Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Results of Children's Oncology Group Trial AALL0622.

Purpose Addition of imatinib to intensive chemotherapy improved survival for children and young adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Compared with imatinib, dasatinib has increased potency, CNS penetration, and activity against imatinib-resistant clones. Patients and Methods Children's Oncology Group (COG) trial AALL0622 (Bristol Myers Squibb trial CA180-204) tested safety and feasibility of adding dasatinib to intensive chemotherapy starting at induction day 15 in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia age 1 to 30 years.

A randomised, controlled clinical trial of narrowband UVB phototherapy for clinically isolated syndrome: The PhoCIS study.

Background: The natural history of multiple sclerosis (MS) typically presents with the clinically isolated syndrome (CIS), an episode of neurological symptoms caused by central nervous system inflammation or demyelination that does not fulfil the diagnostic criteria for MS.

Objective: As preclinical studies have suggested that exposure to ultraviolet radiation (UVR) could regulate the development of MS, the Phototherapy for CIS (PhoCIS trial) was established to examine the effects of narrowband UVB phototherapy on patients with CIS, and their conversion to MS.

Methods: Of the 20 participants, half received 24 sessions of narrowband UVB exposure over eight weeks; participants in both arms were followed for 12 months.

Natural history of benign multiple sclerosis: Clinical and HLA correlates in a Western Australian cohort.

Background: Benign multiple sclerosis (BMS) is a controversial term that has been used for MS patients with minimal disability decades after disease onset. Herein, we evaluated disease status after 20 years in a Western Australian cohort defined as BMS based on an Expanded Disability Status Scale (EDSS) score ≤ 3.0 at 10 years from onset.

Higher carbohydrate intake is associated with increased risk of all-cause and disease-specific mortality in head and neck cancer patients: results from a prospective cohort study.

No studies have evaluated associations between carbohydrate intake and head and neck squamous cell carcinoma (HNSCC) prognosis. We prospectively examined associations between pre- and post-treatment carbohydrate intake and recurrence, all-cause mortality, and HNSCC-specific mortality in a cohort of 414 newly diagnosed HNSCC patients. All participants completed pre- and post-treatment Food Frequency Questionnaires (FFQs) and epidemiologic surveys.

Relapsed acute lymphoblastic leukemia-specific mutations in NT5C2 cluster into hotspots driving intersubunit stimulation.

Activating mutations in NT5C2, a gene encoding cytosolic purine 5'-nucleotidase (cN-II), confer chemoresistance in relapsed acute lymphoblastic leukemia. Here we show that all mutants became independent of allosteric effects of ATP and thus constitutively active. Structural mapping of mutations described in patients demonstrates that 90% of leukemia-specific allelles directly affect two regulatory hotspots within the cN-II molecule-the helix A region: residues 355-365, and the intersubunit interface: helix B (232-242) and flexible interhelical loop L (400-418).

Flow-cytometric vs. -morphologic assessment of remission in childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group (COG).

Minimal residual disease (MRD) after initial therapy is integral to risk stratification in B-precursor and T-precursor acute lymphoblastic leukemia (B-ALL, T-ALL). Although MRD determines depth of remission, remission remains defined by morphology. We determined the outcomes of children with discordant assessments of remission by morphology vs.

MSH6 haploinsufficiency at relapse contributes to the development of thiopurine resistance in pediatric B-lymphoblastic leukemia.

Survival of children with relapsed acute lymphoblastic leukemia is poor, and understanding mechanisms underlying resistance is essential to developing new therapy. Relapse-specific heterozygous deletions in , a crucial part of DNA mismatch repair, are frequently detected. Our aim was to determine whether deletion results in a hypermutator phenotype associated with generation of secondary mutations involved in drug resistance, or if it leads to a failure to initiate apoptosis directly in response to chemotherapeutic agents.

Utility of the Modified Surgical Apgar Score in a Head and Neck Cancer Population.

Objective The Surgical Apgar Score (SAS) is a validated postoperative complication prediction model. The purpose of this study was to investigate the utility of the SAS in a diverse head and neck cancer population and to compare it with a recently developed modified SAS (mSAS) that accounts for intraoperative transfusion. Study Design Case series with chart review.

Preclinical efficacy of daratumumab in T-cell acute lymphoblastic leukemia.

As a consequence of acquired or intrinsic disease resistance, the prognosis for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) is dismal. Novel, less toxic drugs are clearly needed. One of the most promising emerging therapeutic strategies for cancer treatment is targeted immunotherapy.

TP53 Germline Variations Influence the Predisposition and Prognosis of B-Cell Acute Lymphoblastic Leukemia in Children.

Purpose Germline TP53 variation is the genetic basis of Li-Fraumeni syndrome, a highly penetrant cancer predisposition condition. Recent reports of germline TP53 variants in childhood hypodiploid acute lymphoblastic leukemia (ALL) suggest that this type of leukemia is another manifestation of Li-Fraumeni syndrome; however, the pattern, prevalence, and clinical relevance of TP53 variants in childhood ALL remain unknown. Patients and Methods Targeted sequencing of TP53 coding regions was performed in 3,801 children from the Children's Oncology Group frontline ALL clinical trials, AALL0232 and P9900.

Measurable residual disease detection by high-throughput sequencing improves risk stratification for pediatric B-ALL.

Early response to induction chemotherapy is an important prognostic factor in B-lymphoblastic leukemia (B-ALL). Here, we compare high-throughput sequencing (HTS) of and genes vs flow cytometry (FC) for measurable residual disease (MRD) detection at the end of induction chemotherapy in pediatric patients with newly diagnosed B-ALL. Six hundred nineteen paired pretreatment and end-of-induction bone marrow samples from Children's Oncology Group studies AALL0331 (clinicaltrials.

Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria.

The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions.

Cost comparison by treatment arm and center-level variations in cost and inpatient days on the phase III high-risk B acute lymphoblastic leukemia trial AALL0232.

The Children's Oncology Group (COG) develops and implements multi-institutional clinical trials with the primary goal of assessing the efficacy and safety profile of treatment regimens for various pediatric cancers. However, the monetary costs of treatment regimens are not measured. AALL0232 was a COG randomized phase III trial for children with acute lymphoblastic leukemia that found that dexamethasone (DEX) was a more effective glucocorticoid than prednisone (PRED) in patients younger than 10 years, but PRED was equally effective and less toxic in older patients.

Toxicity associated with intensive postinduction therapy incorporating clofarabine in the very high-risk stratum of patients with newly diagnosed high-risk B-lymphoblastic leukemia: A report from the Children's Oncology Group study AALL1131.

Background: Children, adolescents, and young adults with very high-risk (VHR) B acute lymphoblastic leukemia (B-ALL) have poor outcomes, and novel therapies are needed for this subgroup. The AALL1131 study evaluated postinduction therapy using cyclophosphamide (CPM), etoposide (ETOP), and clofarabine (CLOF) for patients with VHR B-ALL.

Methods: Patients who were 1 to 30 years old and had VHR B-ALL received modified Berlin-Frankfurt-Münster therapy after induction and were randomized to 1) CPM, cytarabine, mercaptopurine, vincristine (VCR), and pegaspargase (control arm), 2) CPM, ETOP, VCR, and pegaspargase (experimental arm 1), or 3) CPM, ETOP, CLOF (30 mg/m /d × 5), VCR, and pegaspargase (experimental arm 2) during the second half of consolidation and delayed intensification.

Voice and swallowing outcomes following reoperative anterior cervical discectomy and fusion with a 2-team surgical approach.

OBJECTIVE Dysphagia and vocal cord palsy (VCP) are common complications after anterior cervical discectomy and fusion (ACDF). The reported incidence rates for dysphagia and VCP are variable. When videolaryngostroboscopy (VLS) is performed to assess vocal cord function after ACDF procedures, the incidence of VCP is reported to be as high as 22%.

Severe pegaspargase hypersensitivity reaction rates (grade ≥3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children's oncology group (COG) clinical trials.

PEGylated asparaginase (pegaspargase) can be administered via intramuscular (IM) injection or intravenous (IV) infusion with a hypersensitivity reaction (HSR) incidence ranging 3-41%. We evaluated grade ≥3 HSRs when given IM vs. IV on six Children's Oncology Group (COG) leukemia trials (2003-2015) to determine differences in HSR rates.

Longitudinal analysis of quality-of-life outcomes in children during treatment for acute lymphoblastic leukemia: A report from the Children's Oncology Group AALL0932 trial.

Background: Children with average-risk acute lymphoblastic leukemia (AR-ALL) face many challenges that can adversely affect their quality of life (QOL). However, to the authors' knowledge, patterns and predictors of QOL impairment during therapy have not been well characterized to date.

Methods: Patients with AR-ALL who were enrolled on the Children's Oncology Group AALL0932 trial were offered participation in this prospective cohort study if they were aged ≥4 years at the time of diagnosis and had an English-speaking parent.