Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.     

A multi-institutional analysis of clinical outcomes and patterns of care of 1p/19q codeleted oligodendrogliomas treated with adjuvant or salvage radiation therapy

Journal of Neuro-Oncology - Practice patterns vary for adjuvant treatment of 1p/19q-codeleted oligodendroglioma patients. This study evaluates the outcomes of adjuvant (aRT) versus salvage...     

Post‐Traumatic Heterotopic Ossification: An Old Problem in Need of New Solutions

Heterotopic ossification (HO) is the formation of pathological bone in ectopic sites and it can have serious consequences for functional outcomes. For many years, its main clinical relevance was as a rare complication of elective joint arthroplasty or CNS injury and a number of prophylaxes were developed to mitigate against it in these settings. As a consequence of changes in patterns of wounding and survival in conflicts since the turn of the century, post‐traumatic HO has become much more common and case severity has increased. It represents one of the main barriers to rehabilitation in a large cohort of combat‐injured patients. However, extant prophylaxes have not been shown to be effective or appropriate in this patient cohort. In addition, the lack of reliable early detection or means of predicting which patients will develop HO is another barrier to effective prevention. This review examines the current state of understanding of post‐traumatic HO including the historical context, epidemiology, pathophysiology, clinical issues, currently prophylaxis and detection, management, and potential future approaches. Our aims are to highlight the current lack of effective means of early detection and prevention of HO after major trauma and to stimulate research into novel solutions to this challenging problem. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1061–1068, 2018.     

Evaluating the swelling,erosion, and compaction properties of cellulose ethers

Swelling, erosion, deformation, and consolidation properties can affect the performance of cellulose ethers, the most commonly used matrix former in hydrophilic sustained tablet formulations. The present study was designed to comparatively evaluate the swelling, erosion, compression, compaction, and relaxation properties of the cellulose ethers in a comprehensive study using standardised conditions. The interrelationship between various compressional models and the inherent deformation and consolidation properties of the polymers on the derived swelling and erosion parameters are consolidated. The impact of swelling (K_w) on erosion rates (K_E) and the inter-relationship between Heckel and Kawakita plasticity constants was also investigated. It is evident from the findings that the increases in both substitution and polymer chain length led to higher K_w, but a lower K_E; this was also true for all particle size fractions regardless of polymer grade. Smaller particle size and high substitution levels tend to increase the relative density of the matrix but reduce porosity, yield pressure (P_y), Kawakita plasticity parameter (b^?1) and elastic relaxation. Both K_W versus K_E (R²?=?0.949–0.980) and P_y versus. b^?1 correlations (R²?=?0.820–0.934) were reasonably linear with regards to increasing hydroxypropyl substitution and molecular size. Hence, it can be concluded that the combined knowledge of swelling and erosion kinetics in tandem with the in- and out-of-die compression findings can be used to select a specific polymer grade and further to develop and optimize formulations for oral controlled drug delivery applications.     

Have patients with esophagitis got an increased risk of adenocarcinoma？ Results from a population-based study

AIM: To examine an increased risk of esophageal adenocarcinoma is restricted to patients who develop Barrett's esophagus or whether esophagitis per is a risk factor for adenocarcinoma. METHODS: A population-based cohort of patients with histological evidence of esophagitis without Barrett's esophagus was constructed using electronic pathology reports relating to all esophageal biopsies in Northern Ireland between 1993 and 1996. Person-years of follow-up and incident cases of esophageal cancer were calculated by linking the cohort to death files and the Northern Ireland Cancer Registry records. Standardized incidence ratios (SIR) were calculated for esophageal cancers (adenocarcinoma, squamous cell carcinoma (SCC), and historically unspecified cancers). RESULTS: A total of 2 013 patients in the cohort provided 13 559 patient-years of follow-up (mean follow-up 6.7 years). None of the patients developed adenocarcinoma. Three patients developed SCC, and six developed histologically unspecified cancers. The SIR for all esophageal cancers and for SCC were 2.73 (95%CI 1.25-5.19) and 2.93 (95%CI 0.61-8.59), respectively. In a sensitivity analysis in which all unspecified esophageal cancers were treated as adenocarcinomas, the SIR for adenocarcinoma was 2.64 (0.97-5.75). CONCLUSION: The risk of adenocarcinoma is not elevated in patients with histological evidence of esophagitis without Barrett's esophagus; however, these patients may have a moderately increased risk of SCC. Further studies are required to confirm these findings, which suggest that Barrett's esophagus, not esophagitis, is the key precursor lesion in the development of adenocarcinoma.     

Effect of calcium alginate concentration on viability and proliferation of encapsulated fibroblasts

Alginate hydrogels have been used widely in tissue engineering for cell encapsulation for several reasons: low toxicity, the ability to gel under gentle condition and compatibility with cells. In this study, we determined the effect of different concentrations of alginate on encapsulation of 3T3 fibroblast cells at two different cell seeding densities. Live/dead staining and MTT assay were performed at regular intervals up to 4 weeks. A Hoechst 33258 assay was done to validate the MTT results. There were more dead cells on day 1 for the higher concentrations of alginate while at, the lower concentration of alginate, cell proliferation and spheroid formation occurred more quickly. Furthermore, at low cell seeding density, cell proliferation was prolonged compared to the intermediate seeding density. In conclusion, by altering both alginate concentration and cell seeding density, proliferation and spheroid formation can be controlled.