Definitive chemoradiation alters the immunologic landscape and immune checkpoints in head and neck cancer.

BACKGROUND: Preclinical and clinical studies suggest potential synergy between high dose per fraction focal radiation and immunotherapy. However, conventionally fractionated radiation regimens in combination with concurrent chemotherapy are more commonly administered to patients as definitive treatment and may have both immune-stimulating and -suppressive effects. METHODS: We prospectively collected longitudinal samples from head and neck squamous cell carcinoma patients receiving definitive radiation therapy. We quantified changes in populations of circulating immune cells and chemokines CXCL9, 10, and 16. Analyses of humoral and cellular immune responses were conducted in select patients via proteomic analysis and T-cell receptor sequencing. RESULTS: Treatment not only increased circulating CD-8+ T-effector cells, but also myeloid-derived suppressor cells, regulatory T cells, and checkpoint receptor-expressing T cells, particularly PD-1+ T cells. Significant decreases in CXCL10 and increases in CXLC16 were noted. Treatment also increased the percentage of unique and dominant TCR clones, and increased humoral responses as measured by proteomic array. CONCLUSIONS: Our results suggest that fractionated chemoradiation leads to quantifiable effects in circulating immune mediators, including a balance of stimulatory and suppressive mechanisms. These results suggest future combinations with immune checkpoint blockade.

The Complex Diseases of Staphylococcus pseudintermedius in Canines: Where to Next?

Staphylococcus pseudintermedius is a pathogenic bacterium of concern within the veterinary sector and is involved in numerous infections in canines, including topical infections such as canine pyoderma and otitis externa, as well as systemic infections within the urinary, respiratory and reproductive tract. The high prevalence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) within such infections is a growing concern. Therefore, it is crucial to understand the involvement of S. pseudintermedius in canine disease pathology to gain better insight into novel treatment avenues. Here, we review the literature focused on S. pseudintermedius infection in multiple anatomic locations in dogs and the role of MRSP in treatment outcomes at these niches. Multiple novel treatment avenues for MRSP have been pioneered in recent years and these are discussed with a specific focus on vaccines and phage therapy as potential therapeutic options. Whilst both undertakings are in their infancy, phage therapy is versatile and has shown high success in both animal and human medical use. It is clear that further research is required to combat the growing problems associated with MRSP in canines.

Educating Nurses on the Use of the Clinical Opiate Withdrawal Scale to Improve Care of Adult Patients Undergoing Buprenorphine Induction.

INTRODUCTION: Opioid addiction disease has become a global health and social problem complicated by drug misuse and abuse (Pearlman, 2016; Rettig & Yarmolinsky, 1995; Watkins, 2016). Buprenorphine, a partial opioid agonist, is an effective treatment for opioid addiction disease (Loreck et al., 2016). Its induction can trigger severe precipitated withdrawal in opioid-dependent patients whose mu receptors are occupied opioids (American Society of Addiction Medicine, 2015). Knowledge of assessing a patient's level of withdrawal using a validated tool is key to successful transition from other opioids to buprenorphine. AIM: The aim of this study was to evaluate the effectiveness of training nurses on the use of the Clinical Opioid Withdrawal Scale (COWS) screening instrument by assessing their confidence in assessing and satisfaction with communicating withdrawal information crucial for patient safety. METHOD: Ten registered nurses and three nurse practitioners working at a mental health community service center completed two surveys at three time points (Pre, Post, and Post-90 days). The first survey measured nurses' confidence in assessing, whereas the second survey measured their satisfaction with communicating withdrawal symptoms. RESULTS: The means' (M) magnitude for both assessment and satisfaction scores increased with time (across Pre, Post, and Post-90). Standard deviations tended to become smaller. Improvements were noted in nurses' confidence in the assessment of and satisfaction in communicating withdrawal symptoms after the intervention. CONCLUSION: Participants expressed increased knowledge, confidence, and satisfaction with the COWS screening instrument. Ultimately, the patients benefited from the participants having more experience, education, skills, and confidence in monitoring withdrawal symptoms depicted by aggregate data of COWS screenings postintervention.

Effects of definitive chemoradiation on circulating immunologic angiogenic cytokines in head and neck cancer patients.

BACKGROUND: Preclinical studies suggest a synergistic effect between radiation, immunotherapy and anti-angiogenic therapy, although the mechanisms are unclear. Angiogenic cytokines are known to affect the immune system, and their levels may be associated with response to immunotherapy. Here, we assess changes in circulating VEGF, as well as angiogenic cytokines angiopoietin-1 and -2 (Ang1, Ang2), and placental growth factor (PLGF) that occur during definitive chemo-radiotherapy in HNSCC patients. METHODS: We prospectively collected blood samples from patients receiving definitive radiation with or without chemotherapy. Serum Ang1, Ang2, VEGF, and PLGF were measured via cytokine assays. RESULTS: The majority of patients had advanced stage, node positive HPV-associated oropharyngeal cancer, and received radiation to a median dose of 70 Gy with concurrent cisplatin. Over the course of treatment, serum VEGF and Ang1 levels decreased in 20/24 (84 %, p < 0.0001) and 21/24 (88 %, p < 0.0001) patients, respectively, and Ang2 and PLGF levels increased in 20/24 (83 %, p < 0.0001) patients. CONCLUSIONS: We find significant changes in angiogenic cytokines in the majority of HNSCC patients over the course of chemoradiation. Decreases in VEGF caused by radiation may represent one mechanism of potential synergy with immunotherapy. Increases in Ang2 and PLGF are interesting given their link to tumor associated angiogenesis and poor prognosis. Additional studies are needed to explore synergies between anti-angiogenic treatments, immunotherapy, and chemoradiation in HNSCC.