Clinical RNA sequencing clarifies variants of uncertain significance identified by prior testing.

Purpose: Sequencing-based genetic testing often identifies variants of uncertain significance (VUS) or fails to detect pathogenic variants altogether. We evaluated the utility of RNA sequencing (RNA-seq) to clarify VUS or identify missing variants in a clinical setting.

Methods: Over a 2-year period, genetics providers at a single institution referred 26 cases for clinical RNA-seq.

Resilience Intervention Improves Stress-Related Gene Expression in Adolescent and Young Adult HCT Recipients.

Overactivation of the stress response can influence cancer outcomes through immune-related pathways. Adolescents and young adults (AYAs) undergoing hematopoietic cell transplantation (HCT) are at risk for poor outcomes, yet there are limited behavioral interventions and no psychosocial biomarker data for this population. The Conserved Transcriptional Response to Adversity (CTRA) is an inflammation-related pattern observed in conditions of heightened stress and is associated with HCT outcomes.

Resilience and distress among adolescents and young adults receiving hematopoietic cell transplantation: The Promoting Resilience in Stress Management randomized trial.

Background: Adolescents and young adults (AYAs) receiving hematopoietic cell transplantation (HCT) are at high risk of poor psychosocial health. This study aimed to determine whether the Promoting Resilience in Stress Management (PRISM) intervention mitigated these risks during the first 6 months posttransplant.

Methods: This multisite, parallel, randomized trial was conducted from April 2019 to March 2023.

Little patients, big impacts: a narrative review of palliative and emergent radiotherapy for pediatric cancers.

Background And Objective: The use of radiotherapy (RT) in the palliative and emergent settings for pediatric cancers is an under-utilized resource. Our objective was to provide an evidence-based review of the data to increase awareness of the benefit for this population along with providing guidance on pediatric specific treatment considerations for palliative care physicians, pediatric oncologists, and radiation oncologists.

Methods: A narrative review was performed querying PubMed, MEDLINE, ClinicalTrials.

Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis.

Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOHs), which can affect health outcomes through the stress response pathway. The conserved transcriptional response to adversity (CTRA) is a stress-mediated proinflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pretransplant CTRA with patient-reported SDOHs in allogeneic HCT recipients.

CD43-positive, EWSR1::FLI1 -rearranged Soft Tissue Sarcoma in a Pediatric Patient With History of B-Cell Acute Lymphoblastic Leukemia.

Ewing sarcoma is a small round blue cell tumor typically characterized by an EWSR1 rearrangement and expression of CD99 and NKX2.2, without expression of hematopoietic markers such as CD45. CD43 is an alternative hematopoietic immunohistochemical marker often utilized in the workup of these tumors and its expression typically argues against Ewing sarcoma.

Congenital pleuropulmonary blastoma in a newborn with a variant of uncertain significance in DICER1 evaluated by RNA-sequencing.

Background: Pleuropulmonary blastoma (PPB) is a rare mesenchymal malignancy of the lung and is the most common pulmonary malignancy in infants and children. Cystic PPB, the earliest form of PPB occurring from birth to approximately two years of age, is often mistaken for a congenital pulmonary airway malformation, as the two entities can be difficult to distinguish on imaging and pathology. Diagnosis of PPB should prompt workup for DICER1 syndrome, an autosomal dominant tumor predisposition syndrome.

Biobehavioral Implications of Chimeric Antigen Receptor T-cell Therapy: Current State and Future Directions.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable clinical responses in hematologic malignancies. Recent advances in CAR T-cell therapy have expanded its application into other populations including older patients and those with central nervous system and solid tumors. Although its clinical efficacy has been excellent for some malignancies, CAR T-cell therapy is associated with severe and even life-threatening immune-mediated toxicities, including cytokine release syndrome and neurotoxicity.

Biobehavioral Implications of Covid-19 for Transplantation and Cellular Therapy Recipients.

A growing body of literature has emphasized the importance of biobehavioral processes - defined as the interaction of behavior, psychology, socioenvironmental factors, and biological processes - for clinical outcomes among transplantation and cellular therapy (TCT) patients. TCT recipients are especially vulnerable to distress associated with pandemic conditions and represent a notably immunocompromised group at greater risk for SARS-CoV-2 infection with substantially worse outcomes. The summation of both the immunologic and psychologic vulnerability of TCT patients renders them particularly susceptible to adverse biobehavioral sequelae associated with the Covid-19 pandemic.

A Quantitative and Qualitative Literature Analysis of the Orthopedic Surgeons' Experience: Reflecting on 20 Years in the Global War on Terror.

Introduction: After over 20 years of war in the Middle East, orthopedic injuries have been among the most prevalent combat-related injuries, accounting for 14% of all surgical procedures at Role 2/3 (R2/R3) facilities according to the DoD Trauma Registry. To further delineate the role of the deployed orthopedic surgeon on the modern battlefield, a retrospective review was performed highlighting both quantitative and qualitative analysis factors associated with orthopedic surgical care during the war in the Middle East.

Methods: A retrospective review was conducted of orthopedic surgeons in the Middle East from 2001 to 2021.

The effect of tocilizumab on patient reported outcomes and inflammatory biomarkers in hematopoietic cell transplantation.

Inflammatory physiology has been linked to behavioral and emotional symptoms in a variety of contexts and experimental paradigms. Hematopoietic cell transplantation (HCT) represents an intersection of significant immune dysregulation and psychosocial stress, and this biobehavioral relationship can influence important clinical outcomes. For those undergoing HCT with inflammation-related neuropsychiatric symptoms, using targeted agents such as the IL-6 receptor antagonist tocilizumab may be an effective therapeutic approach.

Grief Trajectories of Bereaved Parents of Adolescents and Young Adults With Advanced Cancer: A Qualitative Analysis Using Phenomenology.

Different parents grieve differently. However, research directed at understanding the important contextual or individual factors that influence the path each bereaved parent takes is lacking. In this qualitative analysis we seek to understand the array of bereaved parent experiences more completely.

Heart rate variability and psychosocial symptoms in adolescents and young adults with cancer.

Background: Heart Rate Variability (HRV) is a valid, scalable biomarker of stress. We aimed to examine associations between HRV and psychosocial outcomes in adolescents and young adults (AYAs) with cancer.

Methods: This was a secondary analysis of baseline data from a randomized trial testing a resilience intervention in AYAs with cancer.

Bilateral Pseudo-hypopyon as Presenting Symptom of Acute Monocytic Leukemia in an 8-Month-Old Infant.

A previously healthy 8-month-old female infant presenting with lethargy and bilateral eye redness and cloudiness had bilateral hypopyon uveitis, which persisted despite topical steroids. Cytology of the anterior chamber and cerebrospinal fluid and flow cytometry of cerebrospinal fluid revealed malignant cells consistent with acute monocytic leukemia. Bone marrow aspirates and biopsies showed no evidence of disease.

The biology of stress in cancer: Applying the biobehavioral framework to adolescent and young adult oncology research.

The stress response influences the development and trajectory of cancer through a host of complex neuroimmune mechanisms. Basic, translational, and clinical research has elucidated these biobehavioral connections and offers a new paradigm for scientific investigation and patient care. Using a biobehavioral approach could offer new diagnostic and therapeutic opportunities in oncology, and this approach will be particularly impactful for adolescent and young adult (AYA) patients with cancer.

Biobehavioral Research and Hematopoietic Stem Cell Transplantation: Expert Review from the Biobehavioral Research Special Interest Group of the American Society for Transplantation and Cellular Therapy.

Hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for many hematologic conditions. Despite advances in conditioning and supportive measures, however, there remain significant comorbidities that threaten survivorship. Adverse effects of stress-related biobehavioral processes-defined here as the interactions of behavioral, psychological, and socioenvironmental factors with biology-impact immune recovery and function and are particularly salient in the HCT context, given the importance of immune reconstitution for improved survivorship.

Objectifying the Subjective: The Use of Heart Rate Variability as a Psychosocial Symptom Biomarker in Hospice and Palliative Care Research.

Measuring psychosocial symptoms in hospice and palliative care research is critical to understanding the patient and caregiver experience. Subjective patient-reported outcome tools have been the primary method for collecting these data in palliative care, and the growing field of biobehavioral research offers new tools that could deepen our understanding of psychosocial symptomatology. Here we describe one psychosocial biomarker, heart rate variability (HRV), and simple techniques for measurement in an adolescent and young adult cancer population that are applicable to palliative care studies.

Stuck Moments and Silver-Linings: The Spectrum of Adaptation Among Non-Bereaved and Bereaved Parents of Adolescents and Young Adults With Advanced Cancer.

Context: With advances in treatments that have resulted in children living longer with serious illness, it is essential to understand how parents adapt to changes during the final stages of their child's life or after their child's death.

Objective: To examine the process by which parents adapt to their child's serious illness and death among a group of non-bereaved and bereaved parents of adolescents and young adults (AYAs) with advanced cancer.

Methods: Qualitative study exploring the experiences of parents of AYAs who were being treated for recurrent or refractory advanced cancer (nonbereaved parents) or had died from their disease (bereaved parents) at one large academic center.

Parent Perspectives after the PRISM-P Randomized Trial: A Mixed-Methods Analysis.

Parents experience high distress following their child's diagnosis of cancer. We previously tested two delivery models (group and one-on-one) of the "Promoting Resilience in Stress Management for Parents" (PRISM-P) intervention in a randomized trial: one-on-one delivery improved resilience and benefit finding at three months when compared to usual care (UC). The objective of this analysis was to evaluate quantitative and qualitative outcomes at six months.

"It's My Job to Love Him": Parenting Adolescents and Young Adults With Advanced Cancer.

Background: Parents of adolescents and young adults (AYAs) with serious illness experience enormous stress as they navigate their child's illness. In this study, we aimed to elucidate AYA parental perspectives on the advanced cancer experience, including what parents find challenging and their sources of strength.

Methods: Parents of AYAs aged 14 to 24 years old being treated for recurrent or refractory advanced cancer at a large academic center completed demographic surveys and 1:1 semi-structured interviews between December 2017 and July 2018.

Adverse childhood experiences (ACEs) and medically traumatic events (TEs) in adolescents and young adults (AYAs) with cancer: a report from the Promoting Resilience in Stress Management (PRISM) randomized controlled trial.

Objective: In adolescents and young adults (AYAs) with cancer, we examined (1) the distribution and type of traumatic events (TEs) experienced prior to baseline assessment and (2) how a resilience intervention, Promoting Resilience in Stress Management (PRISM), impacted changes in patient-reported outcomes (PROs) for AYAs with and without TEs.

Methods: AYAs (12-25 years) within 1-10 weeks of diagnosis of new malignancy or ever diagnosed with advanced cancer were enrolled and randomly assigned to usual care (UC) with or without PRISM. To assess TEs, we screened medical records for traditionally defined adverse childhood experiences (ACEs) and medical traumatic events.