Pediatric Stroke Presenting as a Seizure.

Background. Childhood arterial ischemic stroke (AIS) is rare and may be difficult to diagnose. Management of acute stroke in any age group is time sensitive, so awareness of the manifestations and appropriate diagnostic procedures for pediatric AIS is vital to establishing care. We present a pediatric case of arterial ischemic stroke that presented to the emergency department (ED) after two seizures. Case Report. A five-year-old female with an existing seizure disorder presented to a pediatric ED after having two seizures. Postictal upon arrival, she underwent a computed tomography (CT) scan of her head. Family reported that she had complained of a severe headache and vomited; her seizures were described as different from those she had experienced in the past. Loss of grey white matter differentiation on the CT warranted magnetic resonance imaging (MRI), which demonstrated a right-sided stroke. After a complicated course in the hospital, the patient was discharged to a rehabilitation hospital. Why Should an Emergency Physician Be Aware of This? It is important that emergency physicians recognize that a seizure may be the initial symptom of a pediatric stroke regardless of an established seizure history. Pediatric seizures are relatively common; however consideration of the diagnosis of pediatric stroke may prevent unnecessary delays in treatment

Anti-PD-1 increases the clonality and activity of tumor infiltrating antigen specific T cells induced by a potent immune therapy consisting of vaccine and metronomic cyclophosphamide

BACKGROUND: Future cancer immunotherapies will combine multiple treatments to generate functional immune responses to cancer antigens through synergistic, multi-modal mechanisms. In this study we explored the combination of three distinct immunotherapies: a class I restricted peptide-based cancer vaccine, metronomic cyclophosphamide (mCPA) and anti-PD-1 treatment in a murine tumor model expressing HPV16 E7 (C3). METHODS: Mice were implanted with C3 tumors subcutaneously. Tumor bearing mice were treated with mCPA (20 mg/kg/day PO) for seven continuous days on alternating weeks, vaccinated with HPV16 E7(49-57) peptide antigen formulated in the DepoVax (DPX) adjuvanting platform every second week, and administered anti-PD-1 (200 μg/dose IP) after each vaccination. Efficacy was measured by following tumor growth and survival. Immunogenicity was measured by IFN-γ ELISpot of spleen, vaccine draining lymph nodes and tumor draining lymph nodes. Tumor infiltration was measured by flow cytometry for CD8α(+) peptide-specific T cells and RT-qPCR for cytotoxic proteins. The clonality of tumor infiltrating T cells was measured by TCRβ sequencing using genomic DNA. RESULTS: Untreated C3 tumors had low expression of PD-L1 in vivo and anti-PD-1 therapy alone provided no protection from tumor growth. Treatment with DPX/mCPA could delay tumor growth, and tri-therapy with DPX/mCPA/anti-PD-1 provided long-term control of tumors. We found that treatment with DPX/mCPA/anti-PD-1 enhanced systemic antigen-specific immune responses detected in the spleen as determined by IFN-γ ELISpot compared to those in the DPX/mCPA group, but immune responses in tumor-draining lymph nodes were not increased. Although no increases in antigen-specific CD8α(+) TILs could be detected, there was a trend for increased expression of cytotoxic genes within the tumor microenvironment as well as an increase in clonality in mice treated with DPX/mCPA/anti-PD-1 compared to those with anti-PD-1 alone or DPX/mCPA. Using a library of antigen-specific CD8α(+) T cell clones, we found that antigen-specific clones were more frequently expanded in the DPX/mCPA/anti-PD-1 treated group. CONCLUSIONS: These results demonstrate how the efficacy of anti-PD-1 may be improved by combination with a potent and targeted T cell activating immune therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40425-016-0169-2) contains supplementary material, which is available to authorized users

Upregulation of Circulating PD-L1/PD-1 Is Associated with Poor Post-Cryoablation Prognosis in Patients with HBV-Related Hepatocellular Carcinoma

BACKGROUND: The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association between circulating PD-L1/PD-1 and prognosis after cryoablation in patients with HBV-related hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: In the present study, 141 HBV-related HCC patients were enrolled and of those 109 patients received cryoablation. Circulating PD-L1/PD-1 expression was tested by flow cytometry, and 23 patients were simultaneously evaluated for intratumoral PD-L1 expression by immunohistochemical staining. Circulating PD-1/PD-L1 expression was associated with severity of diseases in patients with HCC, and the circulating PD-L1 expression was closely correlated with intratumoral PD-L1 expression. Of the clinical parameters, PD-1/PD-L1 expression was associated with tumor size, blood vessel invasion and BCLC staging. Moreover, PD-1/PD-L1 expression dropped after cryoablation while being elevated at the time of tumor recurrence. Patients with higher expression of circulating PD-L1, as well as circulating PD-1, had a significantly shorter overall survival and tumor-free survival than those with lower expression. Multivariate analysis confirmed that circulating PD-L1 could serve as an independent predictor of overall survival and tumor-recurrence survival in HCC patients after cryoablation. CONCLUSIONS/SIGNIFICANCE: Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma

Association between self-efficacy and quality of life in women with breast cancer undergoing chemotherapy

Background: Self-efficacy is known as a factor which influences health behaviors, chronic diseases management and quality of life in patients with cancer. Objective: The aim of this study was to investigate the association of self-efficacy and quality of life in women with breast cancer undergoing chemotherapy. Methods: This cross sectional study was conducted in 100 women with breast cancer referred to Seyed Al-Shohada Hospital, Isfahan in 2015. The study subjects were selected by simple random sampling method. The measurement tools were the Sherer self-efficacy scale and the World Health Organization WHOQOL-BREF quality of life assessment. Data were analyzed using one-way ANOVA and Pearson’s correlation coefficient. Findings: Mean age was 48.25±11.93 years. The mean self-efficacy score and quality of life score were 55.78± 11 and 75.91±15.28, respectively and both of them were average. There was positive significant correlation between self-efficacy and quality of life. There was also significant association between self-efficacy and quality of life domains including physical health, mental health, social relationships and environment. Conclusion: With regards to the results, it seems that activities such as workshops for patients, presence of a psychologist in department of chemotherapy, and providing health facilities can be effective for increasing self-efficacy and quality of life in patients with cancer