Prevalence of ossification of the posterior longitudinal ligament (OPLL) in the Pacific populations in Auckland, New Zealand: A retrospective multicentre study.

INTRODUCTION: Primary objective was to investigate the prevalence of ossification of the posterior longitudinal ligament (OPLL) in a mixed demographic region, especially in the Pacific Island population. Secondary objective was to investigate the prevalence of diabetes mellitus and cervical diffuse skeletal hyperostosis (DISH) in patients with and without OPLL. METHODS: Using the local picture archiving and communication system (PACS), cervical spine computed tomography (CT) examinations over a 2-month period were retrospectively assessed for the presence of OPLL. Basic demographic data were recorded-gender, age, ethnicity, presence of cervical DISH and the presence or absence of diabetes mellitus. RESULTS: A total of 1692 CT examinations were included in the study. The distribution of the ethnic groups was 57.3% European, 12.09% Pacific peoples, 11.9% Maori, 11.53% Asian, 0.95% Middle Eastern/Latin American/African and 6.3% not specified. Overall, 47 cases of OPPL were identified (2.78%). The prevalence of OPPL in the Pacific ethnic groups was significantly higher than the European ethnic group 8.4% versus 0.6%, P < 0.05. The prevalence of OPLL was also significantly higher in the Asian (6.9%) and Maori (3.6%) than in the European ethnic group, P < 0.05. A significantly higher proportion of the patients with OPLL had underlying diabetes 20/47 (42.6%) compared with the study population 196/1692 (11.6%), P < 0.05. Seven cases of OPPL (14.9%) had associated cervical DISH, which was significantly higher compared with the study group (23/1692), P < 0.05. Using the Japanese Ministry of Health and Welfare classification system4, segmental type was the most common (34/47, 72.3%), followed by mixed (14.9%) and continuous types (12.8%). CONCLUSION: The prevalence of OPLL is significantly higher among the Pacific populations in Auckland. There is also increased prevalence in the Asian and Maori populations.

Dual-energy CT for occult pelvic fractures: An audit and roc analysis.

INTRODUCTION: There is an increasing incidence of hip and pelvic fractures with an ageing population. Accurate and timely diagnosis is important in the emergency setting. While magnetic resonance imaging (MRI) is the gold standard, it is a limited resource. Dual energy CT (DECT) is comparable to MRI in detection of bone marrow oedema. Our hospital was the first centre in our country to introduce DECT for occult pelvic fractures. We aimed to describe its utility in occult pelvic fractures since commencement. METHODS: Retrospective study of consecutive pelvic bone CT (conventional or DECT) performed to look for an occult fracture over a 10-month period. Sensitivity and specificity calculated based on clinical and imaging follow-up. ROC study performed where three observers visually interpreted pelvic radiographs, conventional CT and DECT and scored their confidence for an acute fracture from 1 to 5. The null hypothesis was that DECT would not improve observer performance compared with conventional CT. RESULTS: DECT studies were performed on 178 patients of whom 84 (47%) had acute fractures. Sensitivity on audit was 99% and specificity was 100%. ROC analysis showed that, for all observers, the area under curve increased from radiograph to conventional CT to DECT. The difference between conventional CT and DECT was statistically significant for all observers where metal implants were not present. CONCLUSION: DECT improves accuracy compared to conventional CT in the diagnosis of occult pelvic fractures and should be used for this indication when available.

Evaluation of the clinical significance of long non-coding RNA MALAT1 genetic variants in human lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most frequent histological subtype of lung cancer, which is the most common malignant tumor and the main cause of cancer-related mortality globally. Recent reports revealed that long non-coding RNA (lncRNA) of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a crucial role in tumorigenesis and metastasis development in lung cancer. However, the contribution of MALAT1 genetic variants to the development of LUAD is unclear, especially in epidermal growth factor receptor (EGFR) mutation status. In this study, 272 LADC patients with different EGFR status were recruited to dissect the allelic discrimination of the MALAT1 polymorphisms at rs3200401, rs619586, and rs1194338. The findings of the study showed that MALAT1 polymorphisms rs3200401, rs619586, and rs1194338 were not associated to LUAD susceptibility; however, rs3200401 polymorphisms was significantly correlated to EGFR wild-type status and tumor stages in LUAD patients in dominant model (p=0.016). Further analyses using the datasets from The Cancer Genome Atlas (TCGA) revealed that lower MALAT1 mRNA levels were associated with the advanced stage, and lymph node metastasis in LADC patients. In conclusion, our results showed that MALAT1 rs3200401 polymorphisms dramatically raised the probability of LUAD development.

FAM13A polymorphisms are associated with a specific susceptibility to clinical progression of oral cancer in alcohol drinkers.

BACKGROUND: Single nucleotide polymorphism (SNP) is a genetic variation that occurs when a single nucleotide base in the DNA sequence varies between individuals and is present in at least 1% of the population. Genetic variants in FAM13A are associated with different types of chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and lung cancer. However, there is little literature on the association of FAM13A genotypes with oral cancer. Therefore, this project will explore the correlation between the FAM13A genotype and the formation of oral cancer. METHODS: In this project, we will examine the presence of gene polymorphisms gene polymorphisms of rs1059122, rs3017895, rs3756050, and rs7657817 in the FAM13A gene exon, and combine the expression of these genes to try to clarify the impact of the FAM13A gene polymorphism on oral cancer. First, four loci (rs1059122, rs3017895, rs3756050, and rs7657817) of the FAM13A SNP were genotyped using TaqMan allelic discrimination. RESULTS: By estimating OR and AOR, FAM13A exhibited different genotypic variables in four SNPs that were not statistically significant between controls and patients with oral cancer. The results of the general analysis showed that different distributions of allelic types did not affect clinical stage, tumour size, lymph node invasion, distant metastasis, and pathological differentiation status. However, in the alcohol drinking group specifically, patients with the rs3017895 SNP G genotype had a 3.17-fold (95% CI, 1.102-9.116; p = 0.032) increase in the well differentiated state of cells compared to patients with the A allele. CONCLUSIONS: Our results suggested that the SNP rs3017895 FAM13A could contribute to oral cancer. More sample studies are needed in the future to confirm our results and more functional studies are needed to investigate their relevant roles in the development of oral cancer.

Development of an efficient mAb quantification assay by LC-MS/MS using rapid on-bead digestion.

The use of monoclonal antibody (mAb) therapeutics is increasing rapidly, but mAb concentrations vary widely between individuals and might subsequently affect mAb exposure and treatment response. Precision medicine has gained much attention in recent years, but little is known about the personalized dosage of mAb therapeutics. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been demonstrated as a selective and sensitive approach to quantify mAb therapeutics in biological samples, but current methods to quantify mAbs are usually time-consuming and require tedious sample preparation. This study developed an efficient LC-MS/MS method using an on-bead trypsin digestion procedure at a higher digestion temperature. Five mAbs, bevacizumab, evolocumab, nivolumab, pembrolizumab, and trastuzumab, used for treating different diseases, were selected for method development. Tocilizumab was selected as the internal standard. The result of the on-bead digestion protocol was compared to the conventional low-pH elution method, and it showed better sensitivity and reproducibility for most mAbs. The optimized on-bead digestion protocol used 75 µL of digestion buffer at 60 °C for a 60 min digestion. The calibration curve was generated from 10 to 200 µg mL-1. The accuracies at the three QC levels of the 5 mAbs were all within 94.5 ± 5.2% to 111.6 ± 3.7%. The repeatability and intermediate precision of the 5 mAbs were all lower than 6.1 and 9.5% RSD, respectively. The newly developed method was successfully applied to quantify trastuzumab in six breast cancer patients under different treatment cycles, and the concentrations ranged from 66.4 to 173.2 µg mL-1. In conclusion, the developed method is more efficient and more practical for real-world analysis of a large number of clinical samples, it could be used for routine therapeutic drug monitoring, and it could contribute to personalized mAb treatment.

Development of efficient on-bead protein elution process coupled to ultra-high performance liquid chromatography-tandem mass spectrometry to determine immunoglobulin G subclass and glycosylation for discovery of bio-signatures in pancreatic disease.

Type 1 autoimmune pancreatitis (AIP) is a kind of IgG4-related disease in which higher IgG4 and total IgG levels have been found in patient serum. Due to the similar imaging features and laboratory parameters between AIP and pancreatic ductal adenocarcinoma (PDAC), a differential diagnosis is still challenging. Since IgG profiles can be potential bio-signatures for disease, we developed and validated a method which coupled on-bead enzymatic protein elution process to an efficient UHPLC-MS/MS method to determine IgG subclass and glycosylation. A stable-isotope labeled IgG was incorporated as internal standard to achieve accurate quantification. For calibration curves, the correlation coefficients for total IgG and the four IgG subclasses were higher than 0.995. Intraday (n = 5) and interday (n = 3) precisions of the peak area ratios of LLOQ, low, medium, and high QC samples were all less than 6.6% relative standard deviation (% RSD), and the accuracies were between 93.5 and 114.9%. Calibration curves, precision, and accuracy were also evaluated for 26 IgG glycopeptides. The method was applied to samples from healthy controls and patients with AIP and PDAC. Distinct IgG patterns were discovered among the groups, and 7 glycopeptides showed high potential in differentiating AIP and PDAC. The results demonstrated that the developed method is suitable for multi-feature analysis of human IgG, and the discovered IgG profiles can be used as bio-signatures for AIP and PDAC.