Mental health symptoms are comparable in patients hospitalized with acute illness and patients hospitalized with injury.

BACKGROUND: High rates of mental health symptoms such as depression, anxiety, and posttraumatic stress disorder (PTSD) have been found in patients hospitalized with traumatic injuries, but little is known about these problems in patients hospitalized with acute illnesses. A similarly high prevalence of mental health problems in patients hospitalized with acute illness would have significant public health implications because acute illness and injury are both common, and mental health problems of depression, anxiety, and PTSD are highly debilitating. METHODS AND FINDINGS: In patients admitted after emergency care for Acute Illness (N = 656) or Injury (N = 661) to three hospitals across the United States, symptoms of depression, anxiety, and posttraumatic stress were compared acutely (Acute Stress Disorder) and two months post-admission (PTSD). Patients were ethnically/racially diverse and 54% female. No differences were found between the Acute Illness and Injury groups in levels of any symptoms acutely or two months post-admission. At two months post-admission, at least one symptom type was elevated for 37% of the Acute Illness group and 39% of the Injury group. Within racial/ethnic groups, PTSD symptoms were higher in Black patients with injuries than for Black patients with acute illness. A disproportionate number of Black patients had been assaulted. CONCLUSIONS: This study found comparable levels of mental health sequelae in patients hospitalized after emergency care for acute illness as in patients hospitalized after emergency care for injury. Findings of significantly higher symptoms and interpersonal violence injuries in Black patients with injury suggest that there may be important and actionable differences in mental health sequelae across ethnic/racial identities and/or mechanisms of injury or illness. Routine screening for mental health risk for all patients admitted after emergency care could foster preventive care and reduce ethnic/racial disparities in mental health responses to acute illness or injury.

Immature myeloid cells in the tumor microenvironment: Implications for immunotherapy.

Various preclinical studies have demonstrated that the success of immunotherapeutic strategies in inhibiting tumor progression in animal models of Glioblastoma multiforme (GBM). It is also evident that tumor-induced immune suppression drastically impacts the efficacy of immune based therapies. Among the mechanisms employed by GBM to induce immunosuppression is the accumulation of regulatory T cells (Tregs) and Myeloid derived suppressor cells (MDSCs). Advancing our understanding about the pathways regulating the expansion, accumulation and activity of MDSCs will allow for the development of therapies aimed at abolishing the inhibitory effect of these cells on immunotherapeutic approaches. In this review, we have focused on the origin, expansion and immunosuppressive mechanisms of MDSCs in animal models and human cancer, in particular GBM.

Single vs. combination immunotherapeutic strategies for glioma.

INTRODUCTION: Malignant gliomas are highly invasive tumors, associated with a dismal survival rate despite standard of care, which includes surgical resection, radiotherapy and chemotherapy with temozolomide (TMZ). Precision immunotherapies or combinations of immunotherapies that target unique tumor-specific features may substantially improve upon existing treatments. Areas covered: Clinical trials of single immunotherapies have shown therapeutic potential in high-grade glioma patients, and emerging preclinical studies indicate that combinations of immunotherapies may be more effective than monotherapies. In this review, the authors discuss emerging combinations of immunotherapies and compare efficacy of single vs. combined therapies tested in preclinical brain tumor models. Expert opinion: Malignant gliomas are characterized by a number of factors which may limit the success of single immunotherapies including inter-tumor and intra-tumor heterogeneity, intrinsic resistance to traditional therapies, immunosuppression, and immune selection for tumor cells with low antigenicity. Combination of therapies which target multiple aspects of tumor physiology are likely to be more effective than single therapies. While a limited number of combination immunotherapies are described which are currently being tested in preclinical and clinical studies, the field is expanding at an astounding rate, and endless combinations remain open for exploration.

Recent advances and future of immunotherapy for glioblastoma.

INTRODUCTION: Outcome for glioma (GBM) remains dismal despite advances in therapeutic interventions including chemotherapy, radiotherapy and surgical resection. The overall survival benefit observed with immunotherapies in cancers such as melanoma and prostate cancer has fuelled research into evaluating immunotherapies for GBM. AREAS COVERED: Preclinical studies have brought a wealth of information for improving the prognosis of GBM and multiple clinical studies are evaluating a wide array of immunotherapies for GBM patients. This review highlights advances in the development of immunotherapeutic approaches. We discuss the strategies and outcomes of active and passive immunotherapies for GBM including vaccination strategies, gene therapy, check point blockade and adoptive T cell therapies. We also focus on immunoediting and tumor neoantigens that can impact the efficacy of immunotherapies. EXPERT OPINION: Encouraging results have been observed with immunotherapeutic strategies; some clinical trials are reaching phase III. Significant progress has been made in unraveling the molecular and genetic heterogeneity of GBM and its implications to disease prognosis. There is now consensus related to the critical need to incorporate tumor heterogeneity into the design of therapeutic approaches. Recent data also indicates that an efficacious treatment strategy will need to be combinatorial and personalized to the tumor genetic signature.

Deep conservation of wrist and digit enhancers in fish.

There is no obvious morphological counterpart of the autopod (wrist/ankle and digits) in living fishes. Comparative molecular data may provide insight into understanding both the homology of elements and the evolutionary developmental mechanisms behind the fin to limb transition. In mouse limbs the autopod is built by a "late" phase of Hoxd and Hoxa gene expression, orchestrated by a set of enhancers located at the 5' end of each cluster. Despite a detailed mechanistic understanding of mouse limb development, interpretation of Hox expression patterns and their regulation in fish has spawned multiple hypotheses as to the origin and function of "autopod" enhancers throughout evolution. Using phylogenetic footprinting, epigenetic profiling, and transgenic reporters, we have identified and functionally characterized hoxD and hoxA enhancers in the genomes of zebrafish and the spotted gar, Lepisosteus oculatus, a fish lacking the whole genome duplication of teleosts. Gar and zebrafish "autopod" enhancers drive expression in the distal portion of developing zebrafish pectoral fins, and respond to the same functional cues as their murine orthologs. Moreover, gar enhancers drive reporter gene expression in both the wrist and digits of mouse embryos in patterns that are nearly indistinguishable from their murine counterparts. These functional genomic data support the hypothesis that the distal radials of bony fish are homologous to the wrist and/or digits of tetrapods.