Opportunities and challenges in combining immunotherapy and radiotherapy in esophageal cancer.

BACKGROUND: Immunotherapy has shown promise in the treatment of esophageal cancer, but using it alone only benefits a small number of patients. Most patients either do not have a significant response or develop secondary drug resistance. The combination of radiotherapy and immunotherapy appears to be a promising approach to treating esophageal cancer. PURPOSE: We reviewed milestone clinical trials of radiotherapy combined with immunotherapy for esophageal cancer. We then discussed potential biomarkers for radiotherapy combined with immunotherapy, including programmed cell death-ligand 1 (PD-L1) status, tumor mutation burden (TMB), tumor-infiltrating lymphocytes, ct-DNA, imaging biomarkers, and clinical factors. Furthermore, we emphasize the key mechanisms of radiation therapy-induced immune stimulation and immune suppression in order to propose strategies for overcoming immune resistance in radiation therapy (RT). Lastly, we discussed the emerging role of low-dose radiotherapy (LDRT) , which has become a promising approach to overcome the limitations of high-dose radiotherapy. CONCLUSION: Radiotherapy can be considered a triggering factor for systemic anti-tumor immune response and, with the assistance of immunotherapy, can serve as a systemic treatment option and potentially become the standard treatment for cancer patients.

Experiences of caregivers and individuals living with traumatic brain injury in accessing health information: a qualitative investigation.

BACKGROUND/PURPOSE: Rehabilitation and treatment of chronic symptoms of traumatic brain injury (TBI) present life-long challenges. This qualitative study aimed to understand the experience of individuals with TBI and caregivers in finding and using health information and to understand their interest in participating in research. METHODS: Participants were recruited through hospital listservs, websites, social media, and word of mouth from across the US. A qualitative constructivism research method was used to analyze responses from semi-structured interviews with 24 individuals, 11 with TBI and 13 caregivers. RESULTS: Three major themes emerged from the analyses: 1) processes and resources for finding TBI-related health information, 2) reliability of information, and 3) participation in research. Study participants described using the internet, consulting with healthcare professionals, reading research articles, and seeking out information from other individuals with TBI or caregivers to search for information. Participants also shared their experiences related to evaluating the reliability of information and the impact of individuals with TBI and caregivers participating on research teams. CONCLUSION: Participants identified various needs in finding relevant health information and highlighted gaps in searching for and using health information. Participants identified an overarching need for improved dissemination of information that is both accessible and reliable.

Education on the consequences of traumatic brain injury for children and adolescents with TBI and families/caregivers: a systematic scoping review.

OBJECTIVE(S): To examine the breadth of education or training on the consequences of traumatic brain injury (TBI) for children and adolescents with TBI and their families/caregivers. METHODS: Systematic scoping review of literature published through July 2018 using eight databases and education, training, instruction, and pediatric search terms. Only studies including pediatric participants (age <18) with TBI or their families/caregivers were included. Six independent reviewers worked in pairs to review abstracts and full-text articles independently, and abstracted data using a REDCap database. RESULTS: Forty-two unique studies were included in the review. Based on TBI injury severity, 24 studies included persons with mild TBI (mTBI) and 18 studies focused on moderate/severe TBI. Six studies targeted the education or training provided to children or adolescents with TBI. TBI education was provided primarily in the emergency department or outpatient/community setting. Most studies described TBI education as the main topic of the study or intervention. Educational topics varied, such as managing TBI-related symptoms and behaviors, when to seek care, family issues, and returning to work, school, or play. CONCLUSIONS: The results of this scoping review may guide future research and intervention development to promote the recovery of children and adolescents with TBI.

Potential impact of WTAP and YTHDF2 on tumor immunity in lung adenocarcinoma.

WTAP and N6-methyladenosine (m6A) reader proteins (YTHDF2) are N6-methyladenosine (m6A) methyltransferase and m6A reading proteins, respectively. In recent years, the tumor immune environment has received more and more attention in the progress and treatment of cancer. The aim of this study was to investigate the relationship between N6-methyladenosine (m6A) methyltransferase (WTAP)/YTHDF2 and the immunological characteristics of lung adenocarcinoma (LUAD). Based on the expression of WTAP and YTHDF2 in the cancer genome atlas (TCGA) and gene expression omnibus (GEO) database, LUAD patients were divided into 2 clusters by coherently clustering method, and performed gene set enrichment analysis (GSEA) to identify the functional differences. Immunoinvasion analysis was performed using ESTIMATE, CIBERSORT, and single-sample GSEA (ssGSEA), and expression of immune checkpoint inhibitors (ICIs) targets was assessed, while tumor mutation burden (TMB) was calculated in tumor samples. Weighted gene co-expression network analysis (WGCNA) was used to identify the genes related to both WTAP/YTHDF2 expression and immunity. The immunological characteristics between the 2 clusters were externally verified based on GSE39582. The expression of WTAP was higher in cluster 1 and YTHDF2 was lower, but it was opposite in cluster 2. Cluster 1 had stronger immune infiltration, more ICIs target expression, more TMB. In addition, WGCNA identified 22 genes associated with WTAP/YTHDF2 expression and immune score, including TIM3 (HAVCR2) and CD86. WTAP and YTHDF2 influence immune contexture and may be novel prognostic and druggable targets associated with the immune system of LUAD.

Examination of Health Information Needs of Caregivers of and Individuals with Burn Injuries.

Burns are a leading cause of trauma worldwide with about 450,000 burn injuries being treated at medical facilities in the United States each year. Finding relevant information on the long-term consequences of burn injuries is a significant challenge for many individuals with burn injuries and their caregivers. This qualitative study aimed to identify how individuals with burn injuries and caregivers of individuals with burn injuries prefer to access and use health information, identify obstacles to accessing useful information, and identify information most needed by burn survivors and caregivers. Participants were recruited through hospital listservs, websites, social media, and word of mouth from across the United States. Semi-structured interviews were conducted with 23 individuals, 12 with burn injuries and 11 caregivers of individuals with burn injuries. Three specific needs were identified: (1) more direction from health professionals in finding health information relevant to burn injuries; (2) more internet-based access points that connect individuals to appropriate support networks; and (3) more support for long-term consequences of burn injuries, specifically with psychological, social, and other chronic physical issues. Participants identified various needs in finding relevant health information, thereby highlighting gaps in current literature and the dissemination of current literature. One potential way to address these deficiencies is to consider user-centered design principles in developing research, by more directly involving individuals with burn injuries and caregivers as part of the research team.

Scoping review of peer reviewed publications addressing rehabilitation for people sustaining traumatic spinal cord injury.

Study Design: Scoping review Objective: To study the design, clinical setting and outcome measures used in spinal cord injury rehabilitation publications. Methods: A literature search on PubMed and Medline was conducted focusing on articles published between 1990-2016 and using "traumatic SCI", "functional outcomes", "rehabilitation", "work" and "return to work" as outcomes. Studies were categorized based on design (intervention, including RCTs vs. non-intervention studies), settings (inpatient vs. outpatient vs. transition), and outcome measures used (impairment vs. function vs. participation/integration vs. quality of life vs. symptoms). Work-related studies were categorized independently. Results: Five hundred forty-four articles met the inclusion criteria. Of these, 234 were interventional studies, including 23 RCTs. Studies were evenly divided among inpatient, outpatient and transition settings. Of the 234 interventional studies, 143 used functional evaluations. Sixty-one different functional instruments were used, with a predominant use of the Functional Independence Measure (61 times) and an additional use of SCI-specific measures, i.e. Spinal Cord Independence Measure and Craig Handicap Assessment and Reporting Technique (13 times each). Fifty-one studies measured mobility, while only three measured hand functions. The work-related sub-analysis revealed 32 intervention studies (no RCTs), of which 15 used functional evaluations and only three focused on tetraplegia. Conclusion: Our study revealed a paucity of intervention trials and RCTs, indicating a dearth of knowledge that would be needed to establish evidence-based practice guidelines. This is particularly true for tetraplegia. While standard measures of function were frequently used, providing valuable data, there is no consensus about what exact outcome measure to use. Using newer measurement techniques, for instance based on the application of item response theory, should be considered to enhance uniformity.

Health status, difficulties, and desired health information and services for veterans with traumatic brain injuries and their caregivers: A qualitative investigation.

Traumatic brain injury (TBI) is considered the signature injury among military service member and Veterans who served in Operation Iraqi Freedom and Operation Enduring Freedom with over 360,000 individuals sustaining a first-time TBI in the military. These service members and Veterans, and their caregiver(s), must navigate multiple health systems and find experts across many fields of expertise to recover and optimize functionality. Twenty-two individuals, 10 caregivers of Veterans with TBI, 12 Veterans with TBI, participated in semi-structured interviews. Responses were coded using NVivo. Participants from both groups reported difficulties finding community supportive services (support groups) in local communities. Most participants identified the need for an advocate or point-person to help guide them to needed services and provide ongoing support in the post-acute health care recovery phase. Caregivers and Veterans desired a more personalized recovery plan from their medical professionals. When describing their ideal health information and services model most identified interactivity and twenty-four-hour availability as essential components. To provide Veterans and caregivers with optimal support and resources to navigate a complicated health services system, advocates and personalized care plans are needed. Future research should examine the feasibility and cost-effectiveness of these services.

Traumatic brain injury education for adult patients and families: a scoping review.

Traumatic brain injury (TBI) is increasingly viewed as a chronic condition, bringing long-term needs for patient and caregiver knowledge pertaining to symptom and problem management over time. In light of these needs, we performed a scoping review of the literature on brain injury education provided to adult patients and/ or family members affected by TBI. Objectives were to describe the types of educational interventions that have been developed; to review the effects of these interventions; and to determine gaps that might be filled by future research efforts. Of 88 articles meeting search criteria and subjected to data extraction, 34 concerned education about mild TBI and 54, moderate to severe TBI. Most mild TBI articles focused on education in the Emergency Room, while most moderate/ severe TBI education was directed toward family members/ caregivers and was frequently combined with other treatment components, making the effects of education difficult to discern. Only 1 article incorporated elements of self-management training (SMT), a model proved effective in other chronic health conditions. We recommend further exploration of SMT principles in long-term TBI care, as well as more precise definition of treatment components in all patient and family interventions, so that the specific effects of education and other treatment elements may be more readily evaluated.

A qualitative study examining methods of accessing and identifying research relevant to clinical practice among rehabilitation clinicians.

PURPOSE: Research examining the utilization of evidence-based practice (EBP) specifically among rehabilitation clinicians is limited. The objective of this study was to examine how various rehabilitative clinicians including physical therapists, occupational therapists, rehabilitation counselors, and physiatrists are gaining access to literature and whether they are able to implement the available research into practice. METHODS: A total of 21 total clinicians were interviewed via telephone. Using NVivo, a qualitative analysis of the responses was performed. RESULTS: There were similarities found with respect to the information-seeking behaviors and translation of research across the different clinician types. Lack of time was reported to be a barrier for both access to literature and implementation of research across all clinician types. The majority of clinicians who reported having difficulty with utilizing the published literature indicated that the literature was not applicable to their practice, the research was not specific enough to be put into practice, or the research found was too outdated to be relevant. In addition, having a supportive work environment aided in the search and utilization of research through providing resources central to assisting clinicians in gaining access to health information. CONCLUSION: Our study identified several barriers that affect EBP for rehabilitation clinicians. The findings suggest the need for researchers to ensure that their work is applicable and specific to clinical practice for implementation to occur.

Identifying and Understanding the Health Information Experiences and Preferences of Caregivers of Individuals With Either Traumatic Brain Injury, Spinal Cord Injury, or Burn Injury: A Qualitative Investigation.

BACKGROUND: In order to meet the challenges of caring for an injured person, caregivers need access to health information. However, caregivers often feel that they lack adequate information. Previous studies of caregivers have primarily focused on either their time and emotional burdens or their health outcomes, but the information needs of caregivers have not been thoroughly investigated. OBJECTIVE: The purpose of this investigation was to identify the preferred sources of health information for caregivers supporting individuals with injuries and to explore how access to this information could be improved. METHODS: A total of 32 caregivers participated in semistructured interviews, which were used in order to develop a more in-depth understanding of these caregivers' information needs. Digital audio recordings of the interviews were used for analysis purposes. These audio recordings were analyzed using a thematic analysis or qualitative content analysis. All of participant's interviews were then coded using the qualitative analysis program, Nvivo 10 for Mac (QSR International). RESULTS: The caregivers endorsed similar behaviors and preferences when seeking and accessing health information. Medical professionals were the preferred source of information, while ease of access made the Internet the most common avenue to obtain information. The challenges faced by participants were frequently a result of limited support. In describing an ideal health system, participants expressed interest in a comprehensive care website offering support network resources, instructive services about the injury and caregiving, and injury-specific materials. CONCLUSIONS: According to the participants, an ideal health information system would include a comprehensive care website that offered supportive network resources, instructive services about the injury and caregiving, and materials specific to the type of patient injury.

Long Noncoding RNA ROR Regulates Proliferation, Invasion, and Stemness of Gastric Cancer Stem Cell.

Gastric cancer remains an incurable malignance and the second leading cause of cancer death globally. Recent progress in gastric cancer research has demonstrated the crucial roles of cancer stem cells (CSCs) in the development, metastasis, and drug resistance of this disease. Various studies have highlighted the role of long noncoding RNAs (lncRNAs) in the pathogenesis of gastric cancer. In this study, through fluorescence-activated cell sorting, we isolated gastric CSCs (GCSCs) from MKN-45 cells and demonstrated for the first time that lncRNA ROR was highly expressed in CD133+ GCSCs. Overexpression of lncRNA ROR significantly increased, but knockdown of lncRNA ROR inhibited the proliferation and invasion of GCSCs. Most importantly, lncRNA ROR led to upregulation of several key stemness transcriptional factors, such as OCT4, SOX2, and NANOG, as well as CD133 GCSC. Our data demonstrated that lncRNA ROR was associated with core stemness transcriptional factors and the pluripotent state of GCSCs. These results further improved our understanding of the functional cross talking network during development of GCSCs and may provide novel target for the diagnostics and therapeutics of gastric cancer.

Systematic review of interventions for fatigue after traumatic brain injury: a NIDRR traumatic brain injury model systems study.

OBJECTIVE: To conduct a systematic review of the evidence on interventions for posttraumatic brain injury fatigue (PTBIF). METHODS: Systematic searches of multiple databases for peer-reviewed studies published in English on interventions targeting PTBIF as a primary or secondary outcome through January 22, 2014. Reference sections were also reviewed to identify additional articles. Articles were rated using the 2011 American Academy of Neurology Classification of Evidence Scheme for therapeutic studies. RESULTS: The searches yielded 1526 articles. Nineteen articles met all inclusion criteria: 4 class I, 1 class II/III, 10 class III, and 4 class IV. Only 5 articles examined fatigue as a primary outcome. Interventions were pharmacological and psychological or involved physical activity, bright blue light, electroencephalographic biofeedback, or electrical stimulation. Only 2 interventions (modafinil and cognitive behavioral therapy with fatigue management) were evaluated in more than 1 study. CONCLUSIONS: Despite areas of promise, there is insufficient evidence to recommend or contraindicate any treatments of PTBIF. Modafinil is not likely to be effective for PTBIF. Piracetam may reduce it, as may bright blue light. Cognitive behavioral therapy deserves additional study. High-quality research incorporating appropriate definition and measurement of fatigue is required to explore the potential benefits of promising interventions, evaluate fatigue treatments shown to be effective in other populations, and develop new interventions for PTBIF.

Parent and teacher agreement on child behavior checklist items in a sample of preschoolers from low-income and predominantly African American families.

In this study we examined parent and teacher agreement at the item level of the newly revised Child Behavior Checklist/1 1/2-5 (CBCL/1 1/2-5) and Caregiver-Teacher Report Form/1 1/2-5 (CTRF/1 1/2-5) in 505 preschool children from low-income and predominantly African American families. Parents generally rated more children as having problem behaviors than did teachers. Lack of agreement between parents and teachers at the item level was indicated by low correlation coefficients, kappa values, and co-identification of children with specific behavior problems. High levels of parent-teacher agreement were obtained only when rank orders of problem behaviors were compared. No significant sex effect was found on parent and teacher agreement at the item level. Problem behaviors most often indicated by parents and teachers reflected the roles and responsibilities of parents and teachers in the home and school settings. Our findings suggest informant and setting specificity of parent- and teacher-identified problem behaviors in young children.