Efficacy and Safety of Cell-based Immunotherapy in The Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma - A Systematic Review and Meta-analysis.

BACKGROUND: Recurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is Gemcitabine and Cisplatin and second-line treatment options differ. The endemic variant of NPC is associated with Epstein-Barr Virus (EBV). Therefore, Cell-based Immunotherapy (CBI) targeting EBV-specific RM-NPC may be effective. METHODS: We systematically searched PubMed, Embase and the Cochrane Library for randomised or observational studies investigating the efficacy and safety of CBI in the treatment of RM-NPC. We performed all meta-analyses using the random-effects model. Studies were further stratified by endemicity, nature of disease and drug type to investigate for potential between-study heterogeneity and additional pre-specified tests were employed to assess for publication bias. RESULTS: We screened 1,671 studies and included 13 studies with 403 participants in the systematic review, of which nine studies were eligible for meta-analysis. The use of CBI monotherapy as second or subsequent line treatment for EBV-positive RM-NPC revealed an ORR of 10 % (95 %CI = 3 %-29 %), median PFS of 2.37 months (95 %CI = 1.23-3.51) and median OS of 10.16 months (95 %CI = 0.67-19.65). For EBV-specific Cytotoxic T-Lymphocyte monotherapy, the pooled PD rate was 54 % (95 %CI = 9 %-93 %), SD rate was 22 % (95 %CI = 2 %-75 %) and incidence rate of any grade adverse events was 45 %. For Dendritic Cell monotherapy, a PD rate of 80 % (95 % CI = 29 %-98 %), SD rate of 11 % (95 % CI = 0 %-82 %) and incidence rate of any grade adverse events of 29 % was achieved. CONCLUSION: CBI monotherapy demonstrates some activity in pre-treated RM-NPC. More trials are needed to better understand how to integrate CBI into RM-NPC care.

Preemptive anticoagulation of pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is a life-threatening disease where preemptive anticoagulation is recommended by guidelines for patients with intermediate to high pretest risk of PE. AIMS: The primary objective of our study was to describe the use of preemptive anticoagulation from the emergency department (ED) or inpatient wards stratified by risk assessment score. METHODS: We performed a retrospective observational cohort study of consecutive patients undergoing computed tomography pulmonary angiography (CTPA) for investigation of PE. Patients were classified as either ED patients or hospital ward patients based on where the CTPA was requested. The pretest risk of PE was calculated using the Revised Geneva Score (RGS) and patients were divided into low and intermediate to high risk. RESULTS: A total of 392 consecutive patients who underwent CTPA at Monash Health were reviewed. There were 108 (27.6%) patients who were categorised as low risk (RGS 0-3) and 284 (72.4%) categorised as intermediate to high risk (RGS >3). There were 29 (7.4%) patients overall who received preemptive anticoagulation. Diagnostic yield of CTPA in the ED was low, with only four of 144 (2.8%) CTPA scans positive for PE. The yield of CTPA was higher in ward patients, with 63 of 248 (25.4%) being diagnostic of PE. CONCLUSIONS: The use of preemptive anticoagulation for suspected PE was uncommon and was not influenced by the pretest probability of PE as determined by a validated clinical prediction tool. This may reflect concerns regarding haemorrhagic complications without any clear evidence of benefit. Diagnostic yield of CTPA performed in the ED was low.

Crossing the Innovation Chasm: Identifying Facilitators and Barriers to Early Adoption of the Global Health Starter Kit Curriculum.

Purpose: The Global Health Starter Kit (GHSK) is an interdisciplinary, competency-based, open access global health curriculum covering global disease and demographic trends, Millennium Development Goals (MDGs) and Sustainable Development Goals (SDGs), the connection between oral health and overall health, social determinants of health, and concepts of sustainable and ethical global health programs. In this study, we evaluate and describe barriers to and facilitators for using and implementing the GHSK curriculum across a variety of new users. Methods: This two-phase study uses the Roger's Adoption Curve concept to standardize this evaluation and inform a strategic plan for continuing to move the curriculum across the chasm from early adopters to an early majority of global oral health educators and learners. We utilized a theoretical adoption framework to identify facilitators and barriers under the domains of innovation and curricular, educator and learner, and institutional and structural factors. Under qualitative Phase 1, five early adopter institutions were interviewed to elicit understanding of factors that contribute to adoption of the GHSK curriculum. Common themes identified were next used to create a Phase 2 quantitative survey for early majority subscribers of the GHSK (N = 27). Results: These qualitative and quantitative results showed an overall high satisfaction with the quality of the GHSK materials, but also effectively identified barriers to its adoption, including inexperience of faculty in teaching global oral health, a lack of awareness and marketing, and absence of global health accrediting requirements. Conclusions: By identifying the barriers and facilitators of GHSK curriculum integration, this study provides concrete and specific opportunities to improve its format, relevance, content, and delivery. This study outlines next steps to creating a standardized approach to successfully adopting competency-based global oral health teaching and learning.

A cleft lip and palate gene, Irf6, is involved in osteoblast differentiation of craniofacial bone.

BACKGROUND: Interferon regulatory factor 6 (IRF6) plays a critical role in embryonic tissue development, including differentiation of epithelial cells. Besides orofacial clefting due to haploinsufficiency of IRF6, recent human genetic studies indicated that mutations in IRF6 are linked to small mandible and digit abnormalities. The function of IRF6 has been well studied in oral epithelium; however, its role in craniofacial skeletal formation remains unknown. In this study, we investigated the role of Irf6 in craniofacial bone development using comparative analyses between wild-type (WT) and Irf6-null littermate mice. RESULTS: Immunostaining revealed the expression of IRF6 in hypertrophic chondrocytes, osteocytes, and bone matrix of craniofacial tissues. Histological analysis of Irf6-null mice showed a remarkable reduction in the number of lacunae, embedded osteocytes in matrices, and a reduction in mineralization during bone formation. These abnormalities may explain the decreased craniofacial bone density detected by micro-CT, loss of incisors, and mandibular bone abnormality of Irf6-null mice. To validate the autonomous role of IRF6 in bone, extracted primary osteoblasts from calvarial bone of WT and Irf6-null pups showed no effect on osteoblastic viability and proliferation. However, a reduction in mineralization was detected in Irf6-null cells. CONCLUSIONS: Altogether, these findings suggest an autonomous role of Irf6 in regulating bone differentiation and mineralization. Developmental Dynamics 248:221-232, 2019. © 2019 Wiley Periodicals, Inc.