T cells: Friends and foes in NASH pathogenesis and hepatocarcinogenesis.

In association with the pandemic spreading of obesity and metabolic syndrome, the prevalence of NAFLD-related HCC is increasing almost exponentially. In recent years, many of the underlining multifactorial causes of NAFLD have been identified, and the cellular mechanisms sustaining disease development have been dissected up to the single-cell level. However, there is still an urgent need to provide clinicians with more therapeutic targets, with particular attention on NAFLD-induced HCC, where immune checkpoint inhibitors do not work as efficiently. Whereas much effort has been invested in elucidating the role of innate immune response in the hepatic NAFLD microenvironment, only in the past decade have novel critical roles been unraveled for T cells in driving chronic inflammation toward HCC. The metabolic and immune microenvironment interact to recreate a tumor-promoting and immune-suppressive terrain, responsible for resistance to anticancer therapy. In this article, we will review the specific functions of several T-cell populations involved in NAFLD and NAFLD-driven HCC. We will illustrate the cellular crosstalk with other immune cells, regulatory networks or stimulatory effects of these interactions, and role of the metabolic microenvironment in influencing immune cell functionality. Finally, we will present the pros and cons of the current therapeutic strategies against NAFLD-related HCC and delineate possible novel approaches for the future.

Outcomes of community-based and home-based pulmonary rehabilitation for pneumoconiosis patients: a retrospective study.

BACKGROUND: Pneumoconiosis patients receive community-based or home-based pulmonary rehabilitation (PR) for symptom management and enhancement of physical and mental well-being. This study aimed to review the clinical benefits of community-based rehabilitation programmes (CBRP) and home-based rehabilitation programmes (HBRP) for PR of pneumoconiosis patients. METHODS: Archival data of pneumoconiosis patients who participated in CBRP and HBRP between 2008 and 2011 was analysed. There were 155 and 26 patients in the CBRP and HBRP respectively. The outcome measures used in the pre- and post-tests were Knowledge, Health Survey Short Form-12 (SF-12), Hospital Anxiety and Depression Scale (HADS), 6-Min Walk Test (6MWT), and Chronic Respiratory Questionnaire (CRQ). Paired t-tests and the Analysis of Covariance (ANCOVA) using the patients' baseline lung functions as the covariates were performed to examine the changes in the outcomes after completing the programmes. Hierarchical multiple regression analyses were used to examine the relationships between patient's programme participation factors and different scores of the outcome measures. RESULTS: After controlling for patients' baseline lung capacities, significant improvements were revealed among patients participated in CBRP in the scores of the 6MWT, Knowledge, HADS, SF-12 PCS, and CRQ emotion and mastery. The different scores in the Knowledge and HADS were correlated with the patients' levels of programme participation. In contrast, significant improvements were only found in the scores of the Knowledge and 6MWT among patients who participated in HBRP. The gain scores of the 6MWT were correlated with the patients' levels of programme participation. CONCLUSIONS: Both CBRP and HBRP benefited patients' levels of exercise tolerance and knowledge about the disease. CBRP provided greater benefits to patients' mental and psychosocial needs. In contrast, HBRP was found to improve patients' physical function, but did not have significant impacts on patients' mental health and health-related quality of life. The attendance of patients and the participation of their relatives in treatment sessions were important factors in enhancing the positive effects of CBRP and HBRP. These positive outcomes confirm the value of pulmonary rehabilitation programmes for community-dwelling pneumoconiosis patients.

Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels.

Osteoprotegerin (OPG) is involved in bone homeostasis and tumor cell survival. Circulating OPG levels are also important biomarkers of various clinical traits, such as cancers and atherosclerosis. OPG levels were measured in serum or in plasma. In a meta-analysis of genome-wide association studies in up to 10 336 individuals from European and Asian origin, we discovered that variants >100 kb upstream of the TNFRSF11B gene encoding OPG and another new locus on chromosome 17q11.2 were significantly associated with OPG variation. We also identified a suggestive locus on chromosome 14q21.2 associated with the trait. Moreover, we estimated that over half of the heritability of OPG levels could be explained by all variants examined in our study. Our findings provide further insight into the genetic regulation of circulating OPG levels.

Post-genome wide association studies and functional analyses identify association of MPP7 gene variants with site-specific bone mineral density.

Our previous genome-wide association study (GWAS) in a Hong Kong Southern Chinese population with extreme bone mineral density (BMD) scores revealed suggestive association with MPP7, which ranked second after JAG1 as a candidate gene for BMD. To follow-up this suggestive signal, we replicated the top single-nucleotide polymorphism rs4317882 of MPP7 in three additional independent Asian-descent samples (n= 2684). The association of rs4317882 reached the genome-wide significance in the meta-analysis of all available subjects (P(meta)= 4.58 × 10(-8), n= 4204). Site heterogeneity was observed, with a larger effect on spine than hip BMD. Further functional studies in a zebrafish model revealed that vertebral bone mass was lower in an mpp7 knock-down model compared with the wide-type (P= 9.64 × 10(-4), n= 21). In addition, MPP7 was found to have constitutive expression in human bone-derived cells during osteogenesis. Immunostaining of murine MC3T3-E1 cells revealed that the Mpp7 protein is localized in the plasma membrane and intracytoplasmic compartment of osteoblasts. In an assessment of the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of transcriptional factor GATA2 to the risk allele 'A' but not the 'G' allele of rs4317882. An mRNA expression study in human peripheral blood mononuclear cells confirmed that the low BMD-related allele 'A' of rs4317882 was associated with lower MPP7 expression (P= 9.07 × 10(-3), n= 135). Our data suggest a genetic and functional association of MPP7 with BMD variation.

Genetic variant in vitamin D binding protein is associated with serum 25-hydroxyvitamin D and vitamin D insufficiency in southern Chinese.

Previous large-scale genome-wide meta-analysis identified four loci affecting 25-hydroxyvitamin D (25(OH)D) concentrations. However, whether these loci are associated with 25(OH)D concentration in southern Chinese remain unknown. Our primary aim was to examine whether the four top hits (rs2282679, rs10741657, rs12785878 and rs6013897) could be replicated in 712 southern Chinese women. The associations between these single-nucleotide polymorphisms (SNPs), serum 25(OH)D concentration (continuous variable) and vitamin D insufficiency (dichotomized variable) were examined using multivariable linear regression and logistic regression, respectively. Age, body mass index and season were adjusted in the model. Among these four SNPs, rs2282679 was associated with serum 25(OH)D levels (ß=-0.066; P=9 × 10(-5)) and vitamin D insufficiency (odds ratio (OR)=1.51, 95% confidence interval (CI) 1.19-1.93; P=8.6 × 10(-4)), whereas rs12785878 was nominally associated with vitamin D insufficiency only (OR=0.79, 95% CI 0.63-0.99; P=0.042). Genotype risk score (GRS), by summing risk variants of these two SNPs, had more significant association with vitamin D insufficiency (OR=1.38; 95% CI 1.17-1.64; P(trend)=1.76 × 10(-4)) than the model that included only either SNP. The areas under receiver operating characteristic curves of rs2282679 and GRS were 0.561 (P=0.005) and 0.576 (P=5 × 10(-4)), respectively. Our study provides an independent evidence of the associations of rs2282679 and probably rs12785878 with 25(OH)D and vitamin D insufficiency in southern Chinese.

Altered human gut virome in patients undergoing antibiotics therapy for Helicobacter pylori.

Transient gut microbiota alterations have been reported after antibiotic therapy for Helicobacter pylori. However, alteration in the gut virome after H. pylori eradication remains uncertain. Here, we apply metagenomic sequencing to fecal samples of 44 H. pylori-infected patients at baseline, 6-week (N = 44), and 6-month (N = 33) after treatment. Following H. pylori eradication, we discover contraction of the gut virome diversity, separation of virome community with increased community difference, and shifting towards a higher proportion of core virus. While the gut microbiota is altered at 6-week and restored at 6-month, the virome community shows contraction till 6-month after the treatment with enhanced phage-bacteria interactions at 6-week. Multiple courses of antibiotic treatments further lead to lower virus community diversity when compared with treatment naive patients. Our results demonstrate that H. pylori eradication therapies not only result in transient alteration in gut microbiota but also significantly alter the previously less known gut virome community.

A nomogram based on ultrasound radiomics for predicting the invasiveness of cN0 single papillary thyroid microcarcinoma.

Background: Up to 15.3% of papillary thyroid microcarcinoma (PTMC) patients with negative clinical lymph node metastasis (cN0) were confirmed to have pathological lymph node metastasis in level VI. Conventional ultrasound (US) focuses on the characteristics of tumor capsule and the periphery to determine whether the tumor has invasive growth. However, due to its small size, the typical features of invasiveness shown by conventional 2-dimensional (2D) US are not well visualized. US-based radiomics makes use of artificial intelligence and big data to build a model that can help improving diagnostic accuracy and providing prognostic implication of the disease. We hope to establish and assess the value of a nomogram based on US radiomics combined with independent risk factors in predicting the invasiveness of a single PTMC without clinical lymph node metastasis (cN0). Methods: A total of 317 patients with cN0 single PTMC who underwent US examination and operation were included in this retrospective cohort study. Patients were randomly divided into training and testing set in the ratio of 8:2. The US images of all patients were segmented, and the radiomics features were extracted. In the training dataset, the US with features of minimum redundancy maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) were selected and radiomics signatures were then established according to their respective weighting coefficients. Univariate and multivariate logistic regression analyses were employed to generate the risk factors of possible invasive PTMC. The nomogram is then made by combining high risk factors and the radiomics signature. The efficiency of the nomogram was evaluated by the receiver operating characteristic (ROC) curve and calibration curve, and its clinical application value was assessed by decision curve analysis (DCA). The testing dataset was used to validate the model. Results: In the model, seven radiomics features were selected to establish the radiomics signature. A nomogram was made by incorporating clinically independent risk factors and the radiomics signature. Both the ROC curve and calibration curve showed good prediction efficiency. The area under the curve (AUC), accuracy, sensitivity, and specificity of the nomogram in the training data were 0.76 [95% confidence interval (CI): 0.71-0.82], 0.811, 0.914, and 0.727, respectively whereas the results of the testing dataset were 0.71 (95% CI: 0.58-0.84), 0.841, 0.533, and 0.868. As such, the efficacy of the nomogram in predicting the invasiveness of PTMC was subsequently validated by the DCA. Conclusions: Nomogram based on thyroid US radiomics has an excellent predictive value of the potential invasiveness of a single PTMC without clinical lymph node metastasis. With these promising results, it can potentially be the imaging marker used in daily clinical practice.

Genomic characteristics and viral load dynamics of a SARS-CoV-2 Omicron BA.2.2 variant from a hospitalized patient treated with molnupiravir.

We sequenced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from nasal and throat swabs of a hospitalized patient during the fifth wave of coronavirus disease 2019 (COVID-19) pandemic in Hong Kong. Genomic characteristics and viral load dynamics of an Omicron BA.2.2 variant before and after molnupiravir treatment were presented.

Identification of QTL genes for BMD variation using both linkage and gene-based association approaches.

Low bone mineral density (BMD) is a risk factor for osteoporotic fracture with a high heritability. Previous large scale linkage study in Northern Chinese has identified four significant quantitative trait loci (QTL) for BMD variation on chromosome 2q24, 5q21, 7p21 and 13q21. We performed a replication study of these four QTL in 1,459 Southern Chinese from 306 pedigrees. Successful replication was observed on chromosome 5q21 for femoral neck BMD with a LOD score of 1.38 (nominal p value = 0.006). We have previously identified this locus in a genome scan meta-analysis of BMD variation in a white population. Subsequent QTL-wide gene-based association analysis in 800 subjects with extreme BMD identified CAST and ERAP1 as novel BMD candidate genes (empirical p value of 0.032 and 0.014, respectively). The associations were independently replicated in a Northern European population (empirical p value of 0.01 and 0.004 for CAST and ERAP1, respectively). These findings provide further evidence that 5q21 is a BMD QTL, and CAST and ERAP1 may be associated with femoral neck BMD variation.

Metabolism-Associated Epigenetic and Immunoepigenetic Reprogramming in Liver Cancer.

Metabolic reprogramming and epigenetic changes have been characterized as hallmarks of liver cancer. Independently of etiology, oncogenic pathways as well as the availability of different energetic substrates critically influence cellular metabolism, and the resulting perturbations often cause aberrant epigenetic alterations, not only in cancer cells but also in the hepatic tumor microenvironment. Metabolic intermediates serve as crucial substrates for various epigenetic modulations, from post-translational modification of histones to DNA methylation. In turn, epigenetic changes can alter the expression of metabolic genes supporting on the one hand, the increased energetic demand of cancer cells and, on the other hand, influence the activity of tumor-associated immune cell populations. In this review, we will illustrate the most recent findings about metabolic reprogramming in liver cancer. We will focus on the metabolic changes characterizing the tumor microenvironment and on how these alterations impact on epigenetic mechanisms involved in the malignant progression. Furthermore, we will report our current knowledge about the influence of cancer-specific metabolites on epigenetic reprogramming of immune cells and we will highlight how this favors a tumor-permissive immune environment. Finally, we will review the current strategies to target metabolic and epigenetic pathways and their therapeutic potential in liver cancer, alone or in combinatorial approaches.

Application of droplet digital polymerase chain reaction of plasma methylated septin 9 on detection and early monitoring of colorectal cancer.

Methylated septin 9 (SEPT9) has been approved for non-invasive screening of colorectal cancer (CRC), but data on monitoring of CRC is sparse. Droplet digital polymerase chain reaction (ddPCR), with higher detection precision and simpler quantification than conventional PCR, has not been applied in SEPT9 detection. We explored the role of SEPT9 ddPCR for CRC detection and to measure serial SEPT9 levels in blood samples of CRC patients before and 3-month after surgery. SEPT9 methylated ratio, methylated abundance, and CEA levels were all higher in CRC patients than normal controls (all P < 0.05). The area under the curve (AUC) for methylated ratio and abundance to detect CRC was 0.707 and 0.710, respectively. There was an increasing trend for SEPT9 methylated abundance from proximal to distal cancers (P = 0.017). At 3-month after surgery, both methylated abundance and ratio decreased (P = 0.005 and 0.053, respectively), especially methylated abundance in stage III and distal cancer (both P < 0.01). We have developed a ddPCR platform for the quantitative detection of plasma SEPT9 in CRC patients. SEPT9 methylated abundance had an early post-operative decline, which may be useful in monitoring of treatment response.

XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are prevalent liver conditions that underlie the development of life-threatening cirrhosis, liver failure and liver cancer. Chronic necro-inflammation is a critical factor in development of NASH, yet the cellular and molecular mechanisms of immune dysregulation in this disease are poorly understood. Here, using single-cell transcriptomic analysis, we comprehensively profiled the immune composition of the mouse liver during NASH. We identified a significant pathology-associated increase in hepatic conventional dendritic cells (cDCs) and further defined their source as NASH-induced boost in cycling of cDC progenitors in the bone marrow. Analysis of blood and liver from patients on the NAFLD/NASH spectrum showed that type 1 cDCs (cDC1) were more abundant and activated in disease. Sequencing of physically interacting cDC-T cell pairs from liver-draining lymph nodes revealed that cDCs in NASH promote inflammatory T cell reprogramming, previously associated with NASH worsening. Finally, depletion of cDC1 in XCR1DTA mice or using anti-XCL1-blocking antibody attenuated liver pathology in NASH mouse models. Overall, our study provides a comprehensive characterization of cDC biology in NASH and identifies XCR1+ cDC1 as an important driver of liver pathology.

The Counterintuitive Relationship between Telomerase Activity and Childhood Emotional Abuse: Culture and Complexity.

BACKGROUND: A burgeoning literature has found relationships between telomere length, telomerase activity, and human health and longevity. Although some research links a history of childhood adversity with shortened telomere length, our review found no prior research on the relationship between child maltreatment history and telomerase activity in adulthood. We hypothesized a negative relationship between child maltreatment and telomerase activity and hypothesized that the association would be moderated by sex. METHODS: These relationships were tested on a sample of 262 Hong Kong Chinese adults (200 females versus 62 males) with mild to moderate depression. RESULTS: Counterintuitively, emotional abuse was positively associated with telomerase activity, while other maltreatment types were non-significant. The positive relationship between emotional abuse and telomerase activity was significantly moderated by the sex of the participant. CONCLUSIONS: We advance two possible explanations for this finding (1) a culturally informed resilience explanation and (2) a homeostatic complexity explanation. The two explanations are not mutually exclusive. This trial is registered under Hong Kong Clinical Trial Register number HKCTR-1929. SIGNIFICANCE STATEMENT: Emotional abuse was significantly positively associated with telomerase activity. There are at least two non-mutually exclusive explanations for the findings. Simply put, either (1) in the cultural context of Hong Kong emotional abuse was not a risk factor, and/or (2) the conceptualization of telomerase activity as a straightforward indicator of longevity is overly simplistic. The first story we might term a "resilience explanation" while the second we might call a "homeostatic complexity" story.

Development of salient medication reminders to facilitate information transfer during transition from inpatient to primary care: the Delphi process.

OBJECTIVE: Transitional care is important to successful hospital discharge. Providing patients with a clear and concise summary of medication-related information can help improve outcomes, in particular, among older adults. The present study aimed to propose a framework for the development of salient medication reminders (SMR), which include drug-related risks and precautions, using the Delphi process. DESIGN: Identification of potential SMR statements for 80% of medication types used by older adult patients discharged from geriatric medicine departments, followed by a Delphi survey and expert panel discussion. SETTINGS: Medical and geriatric departments of public hospitals in Hong Kong. PARTICIPANTS: A panel of 13 geriatric medical experts. OUTCOME MEASURE: A Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree) points, scoring item relevance, importance and clarity. The minimum of 70% consensus was required for each statement to be included. RESULTS: The expert panel achieved consensus through the Delphi process on 80 statements for 44 medication entities. Subsequently, the SMR steering group endorsed the inclusion of these statements in the SMR to be disseminated among older adults at the time of discharge from geriatric medicine departments. CONCLUSIONS: The Delphi process contributed to the development of SMR for older adult patients discharged from public hospitals in Hong Kong. Patient experience with and staff response to the SMR were assessed at four hospitals before implementation at all public hospitals.

Impact of Locally Adopted Simulation-Based Crew Resource Management Training on Patient Safety Culture: Comparison Between Operating Room Personnel and General Health Care Populations Pre and Post Course.

Crew resource management (CRM) was introduced to enhance patient safety and reduce medical errors through multidisciplinary learning experience. This study investigates the impact of locally adopted simulation-based CRM training on participants' perceptions and knowledge. A 32-item web-based questionnaire was administered pre course, 1 month, and 1 year post course to assess changes in perceptions and knowledge. Another 12-item paper-based questionnaire was administered immediately post course to assess reactions. Among 712 participants analyzed, 165 were operating room staff. The majority agreed that the training is useful and relevant in daily practice. All participants showed significant improvements in perception and knowledge 1 month post course; however, these improvements declined 1 year post course. The CRM course is associated with satisfactory reaction (Kirkpatrick level 1) and improvement in attitude and knowledge (level 2) toward patient safety. However, the effect may be short-lived and regular refresher courses should be mandatory to sustain momentum of ongoing change.

Combined Use of Common Fecal and Blood Markers for Detection of Endoscopically Active Inflammatory Bowel Disease.

INTRODUCTION: Monitoring of disease activity is essential in patients with inflammatory bowel disease. Although endoscopic remission is the ideal therapeutic goal, noninvasive biomarkers (blood and fecal) are more acceptable to patients and are less costly. We evaluated the performance of combinations of fecal and blood markers on the detection of endoscopically active disease. METHODS: Patients with ulcerative colitis (UC) or Crohn's disease (CD) on stable medications were recruited. Blood markers included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, platelet count (PLT), and hemoglobin. Fecal biomarkers included fecal calprotectin (FCT) and fecal immunochemical test (FIT). These markers were compared with the endoscopic Mayo score for UC and the Simple Endoscopic Score for CD. RESULTS: One hundred thirteen patients (mean age 44.7 years, 63.7% men, 54.9% patients with UC and 45.1% patients with CD) were recruited. FCT correlated well with FIT (r = 0.58), CRP (r = 0.56), ESR (r = 0.40), albumin (r = -0.54), PLT (r = 0.61), and hemoglobin (r = -0.35; all Ps < 0.001). Among 66 patients with endoscopic evaluation, 39.4% with endoscopically active disease had higher FCT, FIT, CRP, ESR, PLT, lower albumin, and hemoglobin compared with those in endoscopic remission (all Ps < 0.01). All 7 markers demonstrated good area under receiver operating characteristics (>0.7), with FCT being the best (0.91) for endoscopically active disease. Combining FCT and FIT improved the specificity to 95%, but the sensitivity decreased to 65.4%. In the subgroup analysis of UC, adding PLT to FIT improved the sensitivity and specificity to 100% and 90.9%, respectively. DISCUSSION: The combined use of fecal biomarkers and blood indexes is superior to the use of fecal biomarkers alone in identifying endoscopically active disease.

Trust as a mediator in the relationship between childhood sexual abuse and IL-6 level in adulthood.

Childhood sexual abuse (CSA) has been shown to predict the coupling of depression and inflammation in adulthood. Trust within intimate relationships, a core element in marital relations, has been shown to predict positive physical and mental health outcomes, but the mediating role of trust in partners in the association between CSA and inflammation in adulthood requires further study. The present study aimed to examine the impact of CSA on inflammatory biomarkers (IL-6 and IL-1ß) in adults with depression and the mediating role of trust. A cross-sectional survey data set of adults presenting with mood and sleep disturbance was used in the analysis. CSA demonstrated a significant negative correlation with IL-6 level (r = -0.28, p<0. 01) in adults with clinically significant depression, while trust showed a significant positive correlation with IL-6 level (r = 0.36, p < .01). Sobel test and bootstrapping revealed a significant mediating role for trust between CSA and IL-6 level. CSA and trust in partners were revealed to have significant associations with IL-6 level in adulthood. Counterintuitively, the directions of association were not those expected. Trust played a mediating role between CSA and adulthood levels of IL-6. Plausible explanations for these counterintuitive findings are discussed.

Factors associated with lower quality of life among patients receiving palliative care.

AIM: This paper is a report of a study conducted to (1) assess the quality of life (QoL) and physical functioning status of patients diagnosed with advanced cancer and receiving palliative care; (2) determine if there was a statistically significant relationship between their physical functioning and QoL and (3) identify the demographic and disease-related variables related to their QoL. BACKGROUND: Achieving the best possible QoL is a major goal in palliative care. However, research findings about the relationship between QoL and demographic variables have been inconsistent. METHOD: Three hundred patients with advanced cancer were recruited from four district hospitals in Hong Kong between February 2005 and July 2006. Their QoL and physical functioning status were assessed by face-to-face interview, using the McGill Quality of Life Questionnaire (Hong Kong version) and the Palliative Performance Scale respectively. RESULTS: Participants reported reduced ambulation, inability to perform hobbies or housework, and the need for occasional assistance in self-care (mean: 64.6 out of 100, sd: 19.3, range: 20-100). QoL was fair (mean: 6.2 out of 10, sd: 1.5, range: 0.9-10). There was a weak positive association between physical functioning and QoL scores. Multiple regression analysis showed that patients who were older, female, had ever been married, or had higher physical functioning tended to have better QoL. CONCLUSION: More could be done in symptom and psychosocial management to improve patients' QoL, in particular for those who are younger, male or single, or who have lower physical functioning.

Methylated Septin 9 and Carcinoembryonic Antigen for Serological Diagnosis and Monitoring of Patients with Colorectal Cancer After Surgery.

With the increasing incidence and mortality of colorectal cancer (CRC), early and accurate diagnosis is of paramount priority to combat this cancer. Epigenetic alterations such as DNA methylation are innovative biomarkers for CRC, due to their stability, frequency, and accessibility in bodily fluids. In this study, blood samples were prospectively collected from patients before and after operation for CRC for determination of methylated septin 9 (mSEPT9) and compared to carcinoembryonic antigen (CEA). The sensitivity of using mSEPT9 methylation status for diagnosing CRC was significantly higher than using elevated CEA levels (73.2% vs 48.2%; p value < 0.001). The sensitivities of both tests increased with higher tumor staging (P = 0.004 and 0.04 respectively). Combined mSEPT9 and CEA had higher accuracy than single CEA or mSEPT9 (P = 0.009 and 0.532 separately). An increase in the methylation level of mSEPT9 detected in the post-operative samples was associated with a higher mortality rate (15.2% vs 1.8%; P = 0.024) and the presence of metastasis (27.3% vs 7.0%; P = 0.013). mSEPT9 was more sensitive than CEA for diagnosing CRC, and combined mSEPT9 and CEA was more accurate. After curative resection, detection of increased mSEPT9 methylation level may indicate adverse outcomes.

Variability of the prevalence of undiagnosed airflow obstruction in smokers using different diagnostic criteria.

PURPOSES: To estimate the prevalence of undiagnosed airflow obstruction (AFO) in Hong Kong smokers with no previous diagnosis of respiratory disease, and to assess its variability when applying different prediction equations and diagnostic criteria. METHODS: A multicenter, population-based, cross-sectional prevalence study was performed in smokers aged 20 to 80 years. Three different criteria (fixed 70% [Global Initiative for Chronic Obstructive Lung Disease and British Thoracic Society], fixed 75%, and European Respiratory Society [ERS]) were applied to define a lower limit of normal (LLN) of the FEV(1)/FVC ratio to compare with the Hong Kong Chinese reference equation (criterion 1), which had used a distribution-free method to obtain the lower fifth percentile of FEV(1)/FVC ratio as the LLN. RESULTS: In 525 male patients, using criterion 1 (local internal prediction equation) and defining AFO as FEV(1)/FVC less than LLN, the overall prevalence of AFO was 13.7%: 8.3% in age > or = 20 to 40 years, 14.0% in age > or = 40 to 60 years, and 17.8% in age > or = 60 to 80 years. When the local internal prediction equation was used as the comparison reference, the fixed-ratio methods tended to miss AFO in younger age groups and overdiagnose AFO in old age, while the ERS criteria, which uses an almost lower fifth percentile-equivalent method, showed less of such a trend but still only showed moderate agreement with criterion 1. CONCLUSIONS: Undiagnosed AFO was prevalent in Hong Kong smokers. Estimated prevalence rates were highly affected by the criteria used to define AFO. The predicted lower fifth percentile values calculated from a local reference equation as the LLN of FEV(1)/FVC ratio should be used for the diagnosis of AFO.