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This study assessed the psychological wellbeing and its associated factors amongst ethnic minorities during the coronavirus disease 2019 (COVID-19) pandemic. A total of 310 Hong Kong South Asians aged 41.3 (SD 13.7) years completed an anonymous online survey between July 2020 and February 2021. The results showed an overall moderate level of stress and high levels of depression, anxiety and post-traumatic stress disorder (PTSD) symptoms amongst South Asian minorities. Multivariable regression analyses suggested that being single/divorced, following Hinduism or other non-Muslim religions, having lower perceived knowledge of COVID-19 and having worried about losing job were significant predictors of higher levels of depression, anxiety and/or stress; additionally, being male, having a low monthly household income, having worried about losing job and healthcare collapse were significant predictors of a higher level of PTSD symptoms. The findings suggest an urgent need to alleviate the psychological impacts of the COVID-19 pandemic on ethnic minorities, specifically for those most vulnerable to these impacts.

Background International guidelines on clinical staging of gastric cancer recommend the use of chest CT for the detection of pulmonary metastases. This study assessed the clinical value of routine chest CT in the staging of gastric cancer. Methods This retrospective study included patients identified from the gastric cancer registry of Chang Gung Memorial Hospital, Linkou, Taiwan. All patients who underwent clinical staging between 2008 and 2014 were included. The pattern, site and number of metastases at initial presentation and after surgery with curative intent were evaluated. Pulmonary metastases were defined as multiple small round pulmonary nodules with a random distribution or of variable size. Results Some 1669 patients were included, of whom 478 (28·6 per cent) had metastatic disease at clinical presentation. The majority of metastases were to the peritoneum (75·7 per cent of patients) or liver (30·5 per cent), and only 27 patients (5·6 per cent) had pulmonary metastases at presentation, none of which were isolated to the lung. Of these 27 patients, 11 had primary lesions located at the cardia/fundus. In 19 patients the lung metastases were also detected on the staging chest X-ray. After surgery there were 196 cancer recurrences. Some 15 patients (7·6 per cent) had lung metastasis and this was not the only site of metastases in any patient. The prevalence of lung metastasis at presentation of the disease and after surgery was 1·6 and 1·5 per cent respectively. Conclusion This study does not support the routine use of chest CT for staging of gastric cancer as isolated pulmonary metastasis in the absence of other metastatic sites could not be detected.

Emerging evidence implicates a role of the gut microbiota in colorectal cancer (CRC). Peptostreptococcus anaerobius (P. anaerobius) is an anaerobic bacterium selectively enriched in the faecal and mucosal microbiota from patients with CRC, but its causative role and molecular mechanism in promoting tumorigenesis remain unestablished. We demonstrate that P. anaerobius adheres to the CRC mucosa and accelerates CRC development in Apc

Cardiac fibroblasts are critical mediators of fibrotic remodeling in the failing heart and transform into myofibroblasts in the presence of profibrotic factors such as transforming growth factor-β. Myocardial fibrosis worsens cardiac function, accelerating the progression to decompensated heart failure (HF). We investigated the effects of a novel inhibitor (NM922; NovoMedix, San Diego, CA) of the conversion of normal fibroblasts to the myofibroblast phenotype in the setting of pressure overload-induced HF. NM922 inhibited fibroblast-to-myofibroblast transformation in vitro via a reduction of activation of the focal adhesion kinase-Akt-p70S6 kinase and STAT3/4E-binding protein 1 pathways as well as via induction of cyclooxygenase-2. NM922 preserved left ventricular ejection fraction ( P < 0.05 vs. vehicle) and significantly attenuated transverse aortic constriction-induced LV dilation and hypertrophy ( P < 0.05 compared with vehicle). NM922 significantly ( P < 0.05) inhibited fibroblast activation, as evidenced by reduced myofibroblast counts per square millimeter of tissue area. Picrosirius red staining demonstrated that NM922 reduced ( P < 0.05) interstitial fibrosis compared with mice that received vehicle. Similarly, NM922 hearts had lower mRNA levels ( P < 0.05) of collagen types I and III, lysyl oxidase, and TNF-α at 16 wk after transverse aortic constriction. Treatment with NM922 after the onset of cardiac hypertrophy and HF resulted in attenuated myocardial collagen formation and adverse remodeling with preservation of left ventricular ejection fraction. Future studies are aimed at further elucidation of the molecular and cellular mechanisms by which this novel antifibrotic agent protects the failing heart. NEW & NOTEWORTHY Our data demonstrated that a novel antifibrotic agent, NM922, blocks the activation of fibroblasts, reduces the formation of cardiac fibrosis, and preserves cardiac function in a murine model of heart failure with reduced ejection fraction.

Resection is the most widely used potentially curative treatment for patients with early hepatocellular carcinoma (HCC). However, recurrence within 2 years occurs in 30-50% of patients, being the major cause of mortality. Herein, we describe 2 models, both based on widely available clinical data, which permit risk of early recurrence to be assessed before and after resection.A total of 3,903 patients undergoing surgical resection with curative intent were recruited from 6 different centres. We built 2 models for early recurrence, 1 using preoperative and 1 using pre and post-operative data, which were internally validated in the Hong Kong cohort. The models were then externally validated in European, Chinese and US cohorts. We developed 2 online calculators to permit easy clinical application.Multivariable analysis identified male gender, large tumour size, multinodular tumour, high albumin-bilirubin (ALBI) grade and high serum alpha-fetoprotein as the key parameters related to early recurrence. Using these variables, a preoperative model (ERASL-pre) gave 3 risk strata for recurrence-free survival (RFS) in the entire cohort - low risk: 2-year RFS 64.8%, intermediate risk: 2-year RFS 42.5% and high risk: 2-year RFS 20.7%. Median survival in each stratum was similar between centres and the discrimination between the 3 strata was enhanced in the post-operative model (ERASL-post) which included 'microvascular invasion'.Statistical models that can predict the risk of early HCC recurrence after resection have been developed, extensively validated and shown to be applicable in the international setting. Such models will be valuable in guiding surveillance follow-up and in the design of post-resection adjuvant therapy trials.The most effective treatment of hepatocellular carcinoma is surgical removal of the tumour but there is often recurrence. In this large international study, we develop a statistical method that allows clinicians to estimate the risk of recurrence in an individual patient. This facility enhances communication with the patient about the likely success of the treatment and will help in designing clinical trials that aim to find drugs that decrease the risk of recurrence.

A surge of vascular endothelial growth factor (VEGF) after transarterial chemoembolization (TACE) may contribute to tumor progression. Axitinib is a potent antiangiogenic agent with main activity against VEGF receptors 1 to 3. To the authors' knowledge, its role in combination with TACE for the treatment of patients with inoperable hepatocellular carcinoma (HCC) is unclear.A phase 2 clinical trial (ClinicalTrials.gov identifier NCT01352728) was conducted to evaluate the combination treatment. Patients with inoperable HCC who were potential candidates for TACE initiated treatment with axitinib at a dose of 5 mg twice daily and were evaluated for the need for TACE every 8 weeks. Axitinib was withheld 24 hours before TACE, and resumed 24 hours afterward when fulfilling predefined criteria. Radiologic assessment was conducted every 8 weeks. The primary endpoint was the 2-year overall survival (OS) rate.A total of 50 patients were recruited from March 2011 to April 2014. The mean age of the patients was 61.8 years, and 46 patients (92%) had hepatitis B infection. The Barcelona Clinic Liver Cancer stage B/C percentage was 76% (38 cases)/24% (12 cases). The 2-year OS rate was 43.7%, and the median OS was 18.8 months in the intention-to-treat population. Among the evaluable population (44 patients), 40.9% (18 patients) and 27.3% (12 patients) achieved complete and partial responses, respectively. Common grade 3 or above axitinib-related complications included hand-foot skin reaction (14%) and hypertension (24%). The presence of hypertension during treatment was found to be an independent prognosticator (hazard ratio, 0.563; P = .0073) suggestive of a contributory role of axitinib to efficacy.The combination of axitinib and TACE was potentially efficacious for patients with inoperable HCC with a high radiologic response rate. Cancer 2017;123:3977-85. © 2017 American Cancer Society.

Concurrent fatty liver in hepatitis B virus (HBV)-infected patients without significant alcohol intake is a frequent and increasingly alarming problem because of the non-alcoholic fatty liver disease pandemic. The risk of HBV-related hepatocellular carcinoma (HCC) development was increased by concomitant obesity and diabetes. Direct evidence of the hepatocarcinogenic effect of fatty liver in chronic HBV remains elusive. We aimed to evaluate the risk of concurrent histologically proven fatty liver in HBV hepatocarcinogenesis.We conducted a retrospective cohort study on a liver biopsy cohort of HBV-infected patients without significant alcohol intake to evaluate the prevalence of concurrent histologically proven fatty liver and its association with subsequent HCC development. We also examined nine polymorphisms on six non-alcoholic fatty liver disease-related candidate genes (ADIPOQ, APOC3, GCKR, LEPR, PNPLA3, and PPARG).Among 270 HBV-infected patients, concurrent fatty liver was found in 107 patients (39.6%) and was associated with metabolic risks, cirrhosis (P = 0.016) and PNPLA3 rs738409 CG/GG genotype (P = 0.002). At a median follow-up of 79.9 months, 11 patients (4.1%) developed HCC, and nine of them had concurrent fatty liver. By multivariable Cox analysis, concurrent fatty liver (HR 7.27, 95% confidence interval: 1.52-34.76; P = 0.013), age, cirrhosis, and APOC3 rs2854116 TC/CC genotype (HR 3.93, 95% confidence interval: 1.30-11.84; P = 0.013) were independent factors predicting HCC development.Concurrent fatty liver is common in HBV-infected patients and an independent risk factor potentiating HBV-associated HCC development by 7.3-fold. The risk of HBV-related HCC is increased by APOC3 gene polymorphism, and further characterization is required by its role.

The albumin-bilirubin (ALBI) grade is a recently emerging alternative of the Child-Pugh (CP) grade. The Cancer of the Liver Italian Program (CLIP) was demonstrated to be a useful prognostic model for hepatocellular carcinoma (HCC) in large prospective cohorts. We aimed to investigate the feasibility of substituting the CP grade by the ALBI grade in the CLIP system and compare the prognostic performance with other existing staging systems.A large cohort of 1973 Chinese patients with HCC was recruited to evaluate the prognostic performance of CP-based CLIP (CP-CLIP) and ALBI-based CLIP (ALBI-CLIP) systems and nine other staging systems by homogeneity likelihood chi-square, c-index, and corrected Akaike information criterion.The ALBI-CLIP system provided comparable prognostic performance than the CP-CLIP system, which was indicated by homogeneity likelihood chi-squares (ALBI-CLIP 1186.35 vs CP-CLIP 1145.54), c-indices (ALBI-CLIP 0.789 vs CP-CLIP 0.785) and AICs (ALBI-CLIP 15 493.47 vs CP-CLIP 15 534.28). Among 11 staging systems, ALBI-CLIP and CP-CLIP systems were associated with the highest homogeneity chi-squares and c-indices, and the lowest corrected Akaike information criterion. Patients in ALBI-CLIP score 0-4 had better median survival than those in corresponding CP-CLIP score.The ALBI grade performs as well as the CP grade when integrating into the CLIP system. ALBI-CLIP and CP-CLIP systems are the most accurate prognostic models among 11 existing staging systems.

The Japan Integrated Staging (JIS) for hepatocellular carcinoma (HCC) has been extensively studied in hepatitis virus C-endemic Japanese population but seldom evaluated outside Japan, while albumin-bilirubin (ALBI)-based JIS (ALBI-T) has never been externally validated. We evaluate the prognostic significance of the ALBI-T score among Chinese patients with hepatitis virus B (HBV)-related HCC, and to explore its potential therapeutic application in selecting patients for appropriate treatments in addition to the Barcelona Clinic Liver Cancer (BCLC) recommendation.A cohort of 1222 HBV-associated HCC patients was evaluated to compare the prognostic performance of JIS and ALBI-T scores by homogeneity likelihood chi-square and corrected Akaike information criterion. In the subgroup analysis of each BCLC stage, Kaplan-Meier method and log-rank statistics were used to compare overall survival of patients undergoing different treatment options.The ALBI-T score showed better prognostic performance than the JIS score, which were indicated by homogeneity likelihood chi-squares (ALBI-T 580.12 vs JIS 536.35) and Akaike information criteria (ALBI-T 9836.57 vs JIS 9880.23). Treatment options significantly influenced prognosis among patients of the same BCLC stage. With the use of ALBI-T score 4 as the cutoff, the current study identified that a portion of patients (14.7%, 25.2% and 28.6% of BCLC stage B, C and D, respectively) undergoing unnecessary therapy without survival advantage.The ALBI-T score is applicable to Chinese patients with HBV-related HCC to provide reasonable prognostic information as well as potentially helping clinicians to avoid offering non-beneficial aggressive treatments.

Aims Diabetes mellitus is the most common co-morbidity associated with necrotising fasciitis. This study aims to compare the clinical presentation, investigations, Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score, microbiology and outcome of management of this condition in diabetic and non-diabetic patients. Patients and Methods The medical records of all patients with surgically proven necrotising fasciitis treated at our institution between 2005 and 2014 were reviewed. Diagnosis of necrotising fasciitis was made on findings of ‘dishwater’ fluid, presence of greyish necrotic deep fascia and lack of bleeding on muscle dissection found intra-operatively. Information on patients’ demographics, presenting symptoms, clinical signs, investigations, treatment and outcome were recorded and analysed. Results A total of 127 patients with surgically proven necrotising fasciitis were included in this study. In all, 78 (61.4%) were diabetic and 49 (38.6%) were non-diabetic. Diabetics tended to have polymicrobial infections (p = 0.03), renal impairment (p < 0.001), end-stage renal disease (p = 0.001) and multiple co-morbidities (p < 0.001). They presented atypically, with less tenderness (p = 0.042) and less hypotension (p = 0.034). This resulted in higher rates of misdiagnosis (p = 0.038) and a longer time to surgery (p = 0.05) leading to longer hospital stays (p = 0.043) and higher rates of amputation (p = 0.045). However, the rate of mortality is comparable (p = 0.525). A LRINEC score of > 8 appears to be more sensitive in diabetic patients (p < 0.001). However, the increased sensitivity in diabetic patients may be related to hyperglycemia and electrolyte abnormalities associated with renal impairment in these patients. Conclusion The LRINEC score must be used with caution in diagnosing necrotising fasciitis in diabetic patients. A high index of suspicion is key to the early diagnosis and subsequent management of these patients. Cite this article: Bone Joint J 2016;98-B:1563–8.

The albumin-bilirubin (ALBI) grade is a recently reported, simpler, more objective, and evidence-based alternative to the Child-Pugh (CP) score for hepatocellular carcinoma (HCC). We aimed to study whether ALBI grade could substitute for CP score in Barcelona Clinic Liver Cancer (BCLC) for HCC.An international multicentre cohort (n = 3696) was accrued to compare the prognostic performance of the CP-based and ALBI-based BCLC system, in terms of homogeneity, discriminatory ability, and monotonicity of gradients that were numerically reflected by homogeneity likelihood, linear trend chi-squares, and c-indices, respectively.The ALBI grade performed as well as CP score when integrated into the BCLC staging system in terms of predicting clinical outcome of HCC regardless of regions, etiology, and treatment options. CP-based and ALBI-based BCLC systems were highly concordant with weighted kappa value of 0.917. All restaged patients showed significantly different clinical outcomes compared with their original stage classification. In particular, ALBI-based BCLC upstaged 83 (2.2%) patients from lower CP-based BC LC stages to ALBI-based BCLC stage D, whose median overall survival was only 3 months.The overall prognostic performance of ALBI-based and CP-based BCLC systems was similar. It also potentially allows more precise patient selection for clinical trials on systemic agents.

The BALAD score is developed to provide an objective determination of prognosis for hepatocellular carcinoma (HCC) by incorporating five serum markers, namely albumin, bilirubin, alpha-fetoprotein (AFP), agglutinin-reactive alpha-fetoprotein (AFP-L3), and des-γ-carboxy prothrombin. We aim to study the applicability of BALAD score and prognostication of the three tumor markers in hepatitis B virus-related HCC.Patients with newly diagnosed HCC were prospectively enrolled. All of the baseline characteristics and serum albumin and bilirubin level were documented at baseline. The levels of the three tumor markers (AFP, AFP-L3, and des-γ-carboxy prothrombin) were determined in archival serum samples. Patients were followed up for survivals according to local practice. The prognostic performances of the three markers and BALAD score were studied in association with overall survival (OS).A total of 198 patients with hepatitis B-related HCC were recruited. AFP and AFP-L3 levels were independent prognostic factors. The number of elevated tumor markers was also predictive of worse OS. BALAD score could stratify the cohort into different patient groups with distinct median OS. The median OS of BALAD score of 0, 1, 2, 3, and 4 was not reached, 26.6, 8.3, 2.6, and 1.9 months, respectively (P 0.0001). BALAD score could further stratify outcomes in each Barcelona Clinic Liver Cancer (BCLC) subgroup. In particular, BALAD score of 3-4 had median OS of 2.6 months only in BCLC stage C patients.BALAD score is applicable in the population of hepatitis B virus-related HCC. The combined use of BALAD score and BCLC staging system could help identify more suitable candidates for clinical trial.

Serum albumin and bilirubin are the most significant independent prognostic factors to predict hepatic events in patients with primary biliary cirrhosis (PBC). We aimed to investigate the prognostic significance of a new prognostic score, the albumin-bilirubin (ALBI) score, among PBC patients.In a retrospective longitudinal cohort of 61 Chinese PBC patients with follow-up period up to 18.3 years, the prognostic performance of the ALBI in prediction of hepatic events was compared with other well-established prognostic scores: Child-Pugh score, model of end-stage liver disease, Mayo risk score, Yale, European, and Newcastle models.Fifteen patients (24.6%) developed hepatic events during follow-up. The c-index (0.894) and χ(2) by likelihood ratio test (36.34) of the ALBI score were highest in comparison to other models. The ALBI score was the only independent prognostic factor by multivariate analysis and its adjusted hazard ratio of developing hepatic event was 27.8 (P 0.001). There were three prognostically different groups stratified by the ALBI score: ALBI grade 1 (≤ -2.60), grade 2 ( -2.60 to -1.39), and grade 3 ( -1.39) groups. The 2-, 5-, and 10-year event-free survivals for grade 1, grade 2, and grade 3 groups were 100.0% versus 100.0% versus 57.1%, 100.0% versus 88.5% versus 14.3%, and 100.0% versus 81.7% versus 0.0%, respectively (P 0.001).The ALBI score is readily derived from a blood test without using those factors evaluated subjectively or obtained by invasive procedures. It is an independent prognostic factor for PBC patients and provides better/similar prognostic performance compared with other prognostic scores.

All aqueous humor draining through the conventional outflow pathway must cross the endothelium of Schlemm's canal (SC), likely by passing through micron-sized transendothelial pores. SC pores are non-uniformly distributed along the inner wall endothelium, but it is unclear how the distribution of pores relates to the non-uniform or segmental distribution of aqueous humor outflow through the trabecular meshwork. It is hypothesized that regions in the juxtacanalicular tissue (JCT) with higher local outflow should coincide with regions of greater inner wall pore density compared to JCT regions with lower outflow. Three pairs of non-glaucomatous human donor eyes were perfused at 8 mmHg with fluorescent tracer nanospheres to decorate local patterns of outflow segmentation through the JCT. The inner wall was stained for CD31 and/or vimentin and imaged en face using confocal and scanning electron microscopy (SEM). Confocal and SEM images were spatially registered to examine the spatial relationship between inner wall pore density and tracer intensity in the underlying JCT. For each eye, tracer intensity, pore density ( n ) and pore diameter ( D ) (for both transcellular “I” and paracellular “B” pores) were measured in 4–7 regions of interest (ROIs; 50 × 150 μm each). Analysis of covariance was used to examine the relationship between tracer intensity and pore density, as well as the relationship between tracer intensity and three pore metrics ( nD , nD 2 and nD 3 ) that represent the local hydraulic conductivity of the outflow pathway as predicted by various hydrodynamic models. Tracer intensity in the JCT correlated positively with local pore density when considering total pores ( p = 0.044) and paracellular B pores on their own ( p = 0.016), but not transcellular I-pores on their own ( p = 0.54). Local hydraulic conductivity as predicted by the three hydrodynamic models all showed a significant positive correlation with tracer intensity when considering total pores and B-pores ( p p −4 ) but not I-pores ( p > 0.38). These data suggest that aqueous humor passes through micron-sized pores in the inner wall endothelium of SC. Paracellular B-pores appear to have a dominant contribution towards transendothelial filtration across the inner wall relative to transcellular I-pores. Impaired pore formation, as previously described in glaucomatous SC cells, may thereby contribute to greater outflow heterogeneity, outflow obstruction, and IOP elevation in glaucoma.

Increasing evidence suggests that chronic, subclinical inflammation plays an important role in the pathogenesis of diabetic retinopathy. We recently reported that a glycosylating enzyme, core 2 beta-1,6-N-acetylglucosaminyltransferase (core 2 GlcNAc-T), is implicated in increased leucocyte-endothelial cell adhesion in diabetic retinopathy via an upregulation mechanism controlled by TNF-alpha.We examined the functional link between circulating TNF-alpha and the activity and phosphorylation of core 2 GlcNAc-T in polymorphonuclear leucocytes of patients with type 1 and type 2 diabetes.Plasma levels of TNF-alpha, although similar in patients with type 1 and type 2 diabetes, were significantly higher than in age-matched healthy controls, and correlated well with the severity of retinopathy. Core 2 GlcNAc-T activity followed the same trend and was associated with phosphorylation of the enzyme. Finally, the observation that TNF-alpha levels are also linked to glycaemic values suggests that in patients, as well as in vitro, the glycosylation-mediated cell adhesion process that plays a role in diabetic retinopathy may involve glucose- and TNF-alpha-induced protein kinase beta2 activation, and subsequently raise activity of core 2 GlcNAc-T through increased enzyme phosphorylation.Our results reveal a novel rationale towards a specific treatment of diabetic retinopathy, based on the inhibition of core 2 GlcNAc-T activity and/or the blockage of cognate glycans.

Single nucleotide polymorphism (SNP) of the excision repair cross-complementing group 1 (ERCC1) gene has been linked with sensitivity to platinum and radiation. The authors hypothesized that the ERCC1 genotype for the SNPs cytosine-to-thymine substitution at codon 118 (C118T) and cytosine-to-adenine substitution at codon 8092 (C8092A) is prognostic in patients with nasopharyngeal carcinoma (NPC) who receive either radiotherapy (RT) or cisplatin plus RT.The authors tested their hypothesis using biomarker screening samples from the Hong Kong NPC Study Group 0502 trial, which was a prospective, multicenter clinical trial that used post-RT plasma Epstein-Bar virus (EBV) DNA (pEBV) levels to screen patients with high-risk NPC for adjuvant chemotherapy.ERCC1 SNPs were analyzed in 576 consecutive patients who were screened by pEBV. In the total biomarker population, there was no significant association of ERCC1 C118T or C8092A genotype with relapse-free survival (RFS) or overall survival (OS). There also was no correlation between ERCC1 genotype and ERCC1 protein or messenger RNA expression in a subset of patients who had available paired biopsies. Post-RT pEBV status was the only independent prognosticator for RFS and OS in multivariate analyses. However, there was a significant interaction between ERCC1 C118T genotype and post-RT pEBV status (RFS, P = .0106; OS, P = .0067). The ERCC1 C118T genotype was significantly associated with both RFS (hazard ratio, 1.67; 95% confidence interval, 1.07-2.61; P = .024) and OS (hazard ratio, 2.31; 95% confidence interval, 1.22-4.40; P = .0106) in the post-RT pEBV-negative population, but not in the pEBV-positive population.The current results prospectively validate pEBV as the most significant prognostic biomarker in NPC that can be used to select high-risk patients for adjuvant therapy. The ERCC1 C118T genotype may help to identify a favorable subgroup (approximately 7%) of pEBV-negative patients with NPC who have an excellent prognosis and can be spared the toxicities of further therapy.

To examine the potential value of a creative art-based activity as a caring modality for promoting holistic well-being among chronic stroke patients, and to explore the feelings and meanings that stroke patients derived from their experience in leisure art-based creative engagement (LACE).Qualitative design.Participants were recruited through purposive and snowball sampling. Individual semi-structured interviews were conducted. Qualitative content analysis was performed. The design and implementation of LACE was guided by Watson's theory of caring.Twenty-four participants completed the study. Four themes emerged from participants' account of experiences with the LACE: (1) appreciation of opportunities, (2) appreciation of self, (3) appreciation of others, and (4) appreciation of life.From the perspective of the participants, engaging in LACE enhances their sense of enjoyment and self-expression. Furthermore, they perceived LACE as an affirmation of life and an empowering process strengthening their connection and appreciation with the self and others.This study adds evidence to existing literature on Watson's theory-guided design and implementation of caring initiatives for community rehabilitation and has laid the groundwork for developing further evidencebased research in leisure art-based caring occasions for promoting holistic well-being in stroke rehabilitation.

The aim of the study was to test a hypothesised model that supportive care needs (SCNs) have a mediating effect on the relationship between characteristics of (Chinese) head and neck cancer (HNC) survivors and their quality of life (QoL).A total of 285 Chinese HNC survivors who had finished cancer treatment 1 year earlier completed a self-reported survey covering demographic and clinical characteristics, the Chinese version of the Short-Form Supportive Care Needs Questionnaire (SCNS-SF34-C), the supplementary module of access to healthcare and ancillary support services and the Functional Assessment of Cancer Therapy for Head and Neck Cancer (FACT-HN).The final path model showed that optimism, educational level, any coexisting disease, number of somatic symptoms, household income, eating ability, support from others, whether the cancer is under control or not and travelling time from home to hospital have direct or indirect effects, or both, on the QoL of HNC survivors, by way of unmet SCNs in the psychological, physical and/or health system information domains, which account for 64 % of the variance in the total FACT-HN score.Our study demonstrated the mediating effects of SCNs in the association between HNC survivors and their QoL. Early needs assessment may help healthcare professionals to identify the actual needs of these survivors, and providing the information that HNC survivors want is a significant factor in meeting their psychological needs and thereby improving their overall QoL.

Does the timing of treatment affect the ocular phenotype in patients with Mucopolysaccharidosis I homozygous for the L490P mutation?

The purpose of this study is to compare health-related quality of life (HRQoL) and emotional distress among diverse cancer survivors who had completed all treatment within the previous year. A convenience sample of 353 cancers survivors (lung, head and neck, breast and prostate cancers) were recruited to complete a survey, which consisted of (i) Hospital Anxiety and Depression Scales; (ii) Chinese version of the Functional Assessment of Cancer Therapy-General version; and (iii) demographic and clinical data. The HRQoL scores were similar among the four types of survivors. Mild anxiety and depression levels were reported, but no significant difference was noted. Younger females with financial burdens and uncertain prognosis were particularly associated with HRQoL and emotional distress. Further studies are essential to identify specific problems that cancer patients experience after cancer diagnosis that might lead to the early detection of those most at risk of ongoing problems.

Purpose. Kattan and Stephenson nomograms are based on the outcomes of patients with prostate cancer recruited in the USA, but their applicability to Chinese patients is yet to be validated. We aim at studying the predictive accuracy of these nomograms in the Chinese population.Patients and Methods. A total of 408 patients who underwent laparoscopic or open radical resection of prostate from 1995 to 2009 were recruited. The preoperative clinical parameters of these patients were collected, and they were followed up regularly with PSA monitored. Biochemical recurrence was defined as two or more consecutive PSA levels >0.4 ng/mL after radical resection of prostate or secondary cancer treatment.Results. The overall observed 5-year and 10-year biochemical recurrence-free survival rates were 68.3% and 59.8%, which was similar to the predicted values by the Kattan and Stephenson nomograms, respectively. The results of our study achieved a good concordance with both nomograms (Kattan: 5-years, 0.64; Stephenson: 5-years, 0.62, 10-years, 0.71).Conclusions. The incidence of prostate cancer in Hong Kong is increasing together with the patients’ awareness of this disease. Despite the fact that Kattan nomograms were derived from the western population, it has been validated in our study to be useful in Chinese patients as well.

BACKGROUND Although advanced cancer treatments prolong survivors' lives, a significant proportion experienced poorer health-related quality of life (HRQoL) than general populations. Identifying their needs is essential to develop a health service delivery model to improve patient outcomes. OBJECTIVE The objective of this study was to examine the perceived unmet needs and HRQoL of Chinese cancer survivors who completed treatment less than 1 year ago. METHODS Three hundred seventy-six participants completed a self-report survey: the 34-item Supportive Care Needs Survey, the supplementary module of access to healthcare and ancillary support services, and the Functional Assessment of Cancer Therapy: General. Descriptive statistics were used to examine the prevalence of unmet needs. Multivariable logistic regressions were conducted to identify participants' characteristics that were associated with unmet needs. Multiple linear regression was used to delineate which domains of unmet needs were significantly associated with HRQoL with adjustment for potential confounding factors. RESULTS Healthcare information was the most common unmet needs among the survivors. Age, stage of cancer, and remission were significantly associated with 1 or more unmet need domains. Participants with unmet needs in physical, psychological, and patient care domains, on average, have poorer HRQoL. CONCLUSIONS Chinese cancer survivors have various unmet needs that might have adverse effects on their HRQoL. Younger age, more advanced stages of cancer, and remission were factors contributing to further unmet needs. IMPLICATIONS FOR PRACTICE The results provided useful information on the special needs of survivors that may affect their HRQoL, enabling clinicians to plan better how to allocate existing limited resources to those who most require them.

The combined effect of uric acid, gamma-glutamyltransferase (GGT) and cardiovascular risk factors clustering in the youth remains under-explored.The objective of this study was to examine the association between uric acid, GGT, obesity and the individual components of metabolic syndrome in children and adolescents.We performed a cross-sectional observational study of 2067 children and adolescents (875 boys and 1192 girls) aged 6-20 years who were healthy volunteers and were recruited from primary and secondary schools in Hong Kong between 2007 and 2008. Subjects were divided into two strata (75th percentile as cut-off) for comparison between odds of cardiovascular risk factors.After adjustment by multivariable logistic regression, subjects in upper stratum, i.e.,75th percentile, of either serum uric acid or GGT levels were associated with obesity, low high-density lipoprotein cholesterol (HDL-C) level and high blood pressure (adjusted odds ratios [AOR] ranged from 1.63 to 5.82, all P 0.005) compared with those in the lower stratum. There were combined effect for upper stratum of both uric acid and GGT in the association with obesity, low HDL-C and high blood pressure (AOR ranged from 2.60 to 10.69, all P 0.05) after adjustment for age, sex and body mass index z-score (except for obesity status) as well as body height (for high blood pressure).Uric acid and GGT have combined effect in association with obesity and other cardiovascular risk factors in children and adolescents.

Previous literatures on young adult survivors of childhood cancer show inconsistent findings with regards to their psychological distress and health-related quality of life (HRQOL). Much of the available data focus on negative patient outcomes following cancer treatments prescribed from 1970 to 1990. In the present study, HRQOL and psychological distress of young adult survivors in Hong Kong was examined. It focused on subjects who had received cancer treatments prescribed in the last two decades.A structured telephone survey was conducted with 614 eligible survivors and 208 sibling controls in Hong Kong.The survivors reported significantly lower mean scores in physical role and functioning, whereas their mental, social, and psychological well-being was similar to that of their sibling controls. Being female, older age, longer survival time, and specific cancer diagnoses were the factors associated with poorer physical and mental adaptation. HRQOL was negatively correlated with psychological distress.Findings of the study suggest that most survivors adjusted fairly well in mental, psychological, and social aspects. Survivors with a higher risk of poor HRQOL could benefit from appropriate screening and counseling at an early stage to mitigate their survivorship difficulties. Prospective follow-up studies on childhood cancer survivors are recommended to detect changes over longer survival periods.

The interstitial chromosome (chr.) 1q21-q22 region is frequently amplified in human cancers, where it has been reported to carry prognostic significance for patients. We attempted to delineate chr. 1q21-q22 for affected gene(s) in hepatocellular carcinoma (HCC) by array-CGH and detected copy number gains of ρ-guanine nucleotide exchange factor-H1 (GEF-H1) as most significant event. Gene expression evaluation in the HCC cohort indicated common up-regulations of GEF-H1 in 64% tumours compared to adjacent non-tumoural liver (64/100; paired t-test p0.0001). Moreover, GEF-H1 over-expressions correlated with microvascular invasion and advanced-stage tumours (p0.05). High GEF-H1 levels also predict shorter disease-free and overall survival of HCC patients (p0.03). Functional knock-down of GEF-H1 by RNAi indicated marked reduction in cell invasion through matrigel and an inhibition of cell migration (p0.035), but an effect on cell viability was not apparent. More interestingly, a mesenchymal-epithelial transition (MET) was readily observed in GEF-H1 knock-down cells, where a concomitant re-expression of epithelial markers (E-cadherin and cytokeratin 18) and cell adhesion proteins (α-catenin and γ-catenin) was found but down-regulation of mesenchymal features (N-cadherin, vimentin and fibronectin). This phenotype was accompanied by reduced filamentous actin polymerizations and diminution of the stress fibre formation. In addition, reduced active form of GTP-RhoA, together with its downstream effectors, including cleaved ROCK1 and phosphorylated MLC2, were also detected in GEF-H1-depleted cells. Taken together, our findings underscore a potent oncogenic role for GEF-H1 in promoting the metastatic potentials of HCC, possibly through activation of RhoA signalling and the EMT phenomenon.

OBJECTIVE. To assess the accuracy of the Association of Coloproctology of Great Britain and Ireland scoring system in predicting the 30-day mortality after surgery for colorectal cancer in Hong Kong elderly (aged 80 years or more) patients. DESIGN. Early mortality outcome audit in a historical cohort. SETTING. Queen Elizabeth Hospital, Hong Kong. PATIENTS. All Chinese patients (aged 80 years or more) who underwent elective or emergency surgery for colorectal cancer in the Department of Surgery between January 2005 and December 2009. MAIN OUTCOME MEASURES. Receiver operating characteristic curve analyses were used to estimate the predictive ability of the score. RESULTS. In all, 180 patients with colorectal cancer were included in this review. The overall 30-day and hospital mortality rates were 29/180 (16%) and 31/180 (17%), respectively. The Association of Coloproctology of Great Britain and Ireland score was significantly higher among patients who died within 30 days (4.2 vs 3.1, P=0.0001), and was the only independent predictor for 30-day mortality by logistic regression (P=0.009; odds ratio=2.555; 95% confidence interval, 1.277-4.932). The mean score of this study population was 3.22 (median, 3.10), giving a predicted 30-day mortality rate of 16.0 to 17.4%, which corresponded with an observed 30-day mortality of 16.1% encountered in this study. The score had a significantly larger area under the curve for the 30-day mortality rates (odds ratio=0.811; 95% confidence interval, 0.722-0.849) as compared to the American Society of Anesthesiologists score (0.664; 0.589-0.735) [P=0.0001]. CONCLUSION. The Association of Coloproctology of Great Britain and Ireland scoring system can accurately predict the 30-day mortality rate of elderly Hong Kong Chinese patients (aged 80 years or more) operated on for colorectal cancer.

To assess the preference for the development of a Health Call Centre and the perceived needs of patients in Hong Kong.Cross-sectional, questionnaire-based survey.Two general out-patient clinics from health facilities in a geographical region in Hong Kong.Patients aged 18 years or above were recruited for the study, which was conducted between January and March 2009.Patients' perspectives of a Health Call Centre, perceived needs for services, perceived health status, and socio-demographic status.A total of 403 participants completed the questionnaire with a response rate of 78%. A total of 342 (85%) supported the development of a Health Call Centre. Providing basic health and chronic disease information, current health conditions and treatment information, and caregiver support advice were cited as the top perceived needs on the development of a Health Call Centre. Adjusting for age, education, and individual monthly income, participants aged 31 to 64 years (odds ratio=4.37; 95% confidence interval, 1.92-9.99; P0.001) and caregivers (odds ratio=3.41; 95% confidence interval, 1.21-9.59; P=0.020) were more likely to use the Health Call Centre. Presence of chronic illness had no significant correlation with the use of a Health Call Centre (odds ratio=1.43; 95% confidence interval, 0.69-3.00; P=0.340).This is the first study to assess the preferences for the development of a Health Call Centre and the perceived needs of patients in Hong Kong. The majority supported the development of a Health Call Centre. Services provided could meet the general needs of all patients and caregivers, and be accessible to old people.

Background Rebleeding from peptic ulcers is a major contributor to death. This study compared standard (40-mg intravenous infusion of omeprazole once daily for 3 days) and high-dose (80-mg bolus of omeprazole followed by 8-mg/h infusion for 72 h) in reducing the rebleeding rate (primary endpoint), need for surgery, duration of hospital stay and mortality in patients with peptic ulcer bleeding after successful endoscopic therapy. Methods This was a single-institution prospective randomized controlled study based on a postulated therapeutic equivalence of the two treatments. All patients who had successful endoscopic haemostasis of a bleeding peptic ulcer (Forrest classification Ia, Ib, IIa or IIb) were recruited. Informed consent was obtained and patients were randomized to receive standard- or high-dose infusions of intravenous omeprazole. Results Two (3 per cent) of 61 patients in the high-dose group and ten (16 per cent) of 61 in the standard-dose group exhibited rebleeding, a difference of − 13 (95 per cent confidence interval − 25 to − 2) per cent. The upper limit of the one-sided confidence interval exceeded a predefined equivalence absolute difference of 16 per cent. Equivalence of standard- and high-dose omeprazole in preventing rebleeding was not demonstrated. Conclusion Intravenous standard-dose omeprazole was inferior to high-dose omeprazole in preventing rebleeding after endoscopic haemostasis for peptic ulcer bleeding. Registration number: NCT00519519 (http://www.clinicaltrials.gov).

POU class 2 homeobox 1 (POU2F1), also known as octamer-binding transcription factor-1 (OCT-1), is a ubiquitous transcription factor that plays a key role in the regulation of genes related to inflammation and cell cycles. POU2F1 is located on chromosome 1q24, a region with linkage for Type 2 diabetes in Chinese and other populations. We examined the association of POU2F1 genetic variants with Type 2 diabetes in Hong Kong Chinese using two independent cohorts.We genotyped five haplotype-tagging single nucleotide polymorphisms at POU2F1 in 1378 clinic-based patients with Type 2 diabetes and 601 control subjects, as well as 707 members from 179 families with diabetes.We found significant associations of rs4657652, rs7532692, rs10918682 and rs3767434 (OR = 1.26-1.59, 0.0003P(unadjusted)0.035) with Type 2 diabetes in the clinic-based case-control cohorts. Rs3767434 was also associated with Type 2 diabetes (OR = 1.55, P(unadjusted) = 0.013) in the family-based cohort. Meta-analysis revealed similar associations. In addition, the risk G allele of rs10918682 showed increased usage of insulin treatment during a mean follow-up period of 7 years [hazard ratio = 1.50 (1.05-2.14), P = 0.025].Using separate cohorts, we observed consistent results showing the contribution of multiple variants at POU2F1 to the risk of Type 2 diabetes.

Non-invasive assessments of liver fibrosis in chronic hepatitis B were well established.To develop a combined algorithm of liver stiffness measurement (LSM) and serum test formula to predict advanced liver fibrosis in chronic hepatitis B.We reported an alanine aminotransferase (AST)-based LSM algorithm for liver fibrosis in 156 chronic hepatitis B patients, which formed the training cohort to evaluate the performance of APRI (AST-to-platelet-ratio-index), Forns index, FIB-4 and Fibroindex against liver histology. The best combined LSM-serum formula algorithm would be validated in another cohort of 82 chronic hepatitis B patients.In the training cohort, LSM has the best performance of diagnosing advanced (or =F3) fibrosis [area under the receiver operating characteristics curve (AUROC) 0.88, 95% confidence interval (CI) 0.85-0.91], while Forns index has the best performance among the various serum test formulae (AUROC 0.70, 95% CI 0.62-0.78). In the combined algorithm, low LSM or low Forns index could be used to exclude advanced fibrosis as both of them had high sensitivity (90%). To confirm advanced fibrosis, agreement between high LSM and high Forns index could improve the specificity (from 99% to 100% and from 87% to 98% in the training and validation cohorts respectively).A combined LSM-Forns algorithm can improve the accuracy to predict advanced liver fibrosis in chronic hepatitis B.

Homozygous deletion screening has been widely utilized to define tumour suppressor genes (TSGs) in cancers. Although these biallelic deletions are infrequent, their identification has facilitated the discovery of many important TSGs. We have systematically examined the genome of hepatocellular carcinoma (HCC), a highly malignant tumour that is rapidly fatal, for the presence of homozygous deletions. Array-CGH analysis on early passage of HCC cultures and cell lines led us to identify six homozygous deleted (HD) regions. A high concordance between array-CGH and expression of HD genes was demonstrated, where crystallin Lambda1 (CRYL1; located on chromosome 13q12.11) displayed the most frequent down-regulation. We found that reduced mRNA expression of CRYL1 was common in HCC tumours when compared with their adjacent non-tumoural liver (p = 0.0097). Significant associations could also be drawn between repressed CRYL1 and advanced tumour staging, increased tumour size, and shorter disease-free survival of patients (p0.037). Moreover, homozygous deletions on CRYL1 could be detected in 36% of HCC cases, where recurrent HDs were identified on exons 1, 5, and 8. Examination of other causal events suggested histone deacetylation and promoter hypermethylation to be likely inactivating mechanisms as well. Re-expression of CRYL1 in the SK-Hep1 cell line, where biallelic loss of CRYL1 was found, induced profound inhibition of cellular proliferation and cell growth (p0.0015). By Annexin V staining, CRYL1 restoration readily increased pro-apoptotic cells with an induction of PARP cleavage. Flow cytometry further revealed that CRYL1 could prolong the G(2)-M phase, possibly through interruption of the Cdc2/cyclin B pathway. Given that regional chromosome 13q12-q14 loss is a causal genomic event in HCC tumourigenesis, our finding may have implications for identifying a novel TSG CRYL1 within this important locus.

We report our experience of the first use of nocturnal home haemodialysis in Hong Kong. The patient, a 40-year-old man with end-stage renal failure, was recruited into the Nocturnal Home Haemodialysis Programme at Princess Margaret Hospital in 2006. He received haemodialysis at home on alternate nights (3.5 sessions per week) for 5.5 to 6 hours per session. After 1 year of nocturnal home haemodialysis, his recombinant human erythropoietin requirement had been reduced by more than 50%. His serum phosphate level decreased by 35% and calcium phosphate product by 34%. After nocturnal home haemodialysis, his blood pressure control has been excellent and he was able to cease taking anti-hypertensive medications soon after commencing nocturnal home haemodialysis. Regression of his left ventricular hypertrophy has also been noted, with a 39% decrease in his left ventricular mass index. The haemodialysis adequacy index, weekly single-pool Kt/V, increased by 59% after switching to nocturnal home haemodialysis and his quality-of-life indices also showed significant improvement. Nocturnal home haemodialysis holds promise as an alternative dialytic therapy for patients on chronic haemodialysis in Hong Kong.

To summarise our experience of laparoscopic radical prostatectomy in a single centre in Hong Kong over 5 years.Retrospective study.Urology Division, Department of Surgery, Tuen Mun Hospital, Hong Kong.A total of 87 patients who underwent laparoscopic radical prostatectomy from March 2002 to May 2007.Peri-operative data and follow-up information.The operative procedure used entailed Montsouris technique and its modifications, including the latest method involving the extraperitoneal descending technique. In all, 87 patients underwent the operation; in two, the procedure was converted to open surgery. Peri-operative parameters which showed improvement included: operating time, blood loss, resort to blood transfusions, and the complication rate. There was no operation-related mortality. In organ-confined disease, a clear surgical margin was achieved in 93% of the patients, but in those whose disease was not organ-confined, the positive margin rate was 87%. Among patients with organ-confined disease, 13% had evidence of biochemical recurrence. Hormonal therapy was started in five patients, none of whom died during the follow-up period (mean, 24 months). Continence recovered in 69% of the patients by 6 months and in 92% by 12 months post-surgery. Assessment of erectile function before and after the surgery was problematic and estimated to be 20% among patients having the nerve-sparing procedure performed.Although Hong Kong has a relatively low incidence for prostate cancer, it was possible to develop laparoscopic radical prostatectomy with acceptable early results. Further follow-up is warranted before formulating definitive conclusions about this procedure.

Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide. This study aimed to validate the NAFLD fibrosis score in the Chinese population.NAFLD patients were prospectively recruited for liver biopsy and blood tests. The NAFLD fibrosis score was calculated as -1.675 + 0.037 x age (yr) + 0.094 x BMI (kg/m(2)) + 1.13 x impaired fasting glucose/diabetes (yes = 1, no = 0) + 0.99 x AST/ALT ratio-0.013 x platelet (x10(9)/L)-0.66 x albumin (g/dL). Advanced fibrosis was defined as stage 3 to 4 fibrosis.One hundred sixty-two patients (age 46 +/- 10 yr, male 59%) were included in the study. Advanced fibrosis was found in 18 (11%) patients. Only 11 of 128 patients with the NAFLD fibrosis score below the proposed low cutoff point (-1.455) were under-staged, resulting in a high negative predictive value of 91%. Only two patients exceeded the proposed high cutoff point (0.676), but neither had advanced fibrosis. If the NAFLD fibrosis score was implemented in the Chinese population, 79% of liver biopsies could be avoided.The NAFLD fibrosis score has high negative predictive value in excluding advanced fibrosis in the Chinese population, and can reduce the burden of liver biopsy in the vast majority of cases. Since there were few cases of advanced fibrosis in this cohort, this study had limited power in validating the high cutoff point.

Using polymerase chain reactions, this study aimed to evaluate the incidence of neonatal chlamydial conjunctivitis in our region of Hong Kong and explore any association between such conjunctivitis and nasopharyngeal colonisation with Chlamydia trachomatis.Prospective epidemiological study.Regional hospital, Hong Kong.Consecutive patients with neonatal conjunctivitis presenting to our hospital were recruited from May 2004 to April 2005 inclusive. Both eyes were investigated separately for Chlamydia trachomatis by polymerase chain reaction, direct immunofluorescent assay, and cell culture by two assigned ophthalmologists. Neonates diagnosed to have ocular Chlamydia trachomatis infection were subjected to additional nasopharyngeal investigations. Complete sets of ocular and nasopharyngeal investigations were also undertaken 1 week after oral erythromycin treatment to confirm complete eradication of Chlamydia trachomatis.Of 192 patients with neonatal conjunctivitis, 24 were diagnosed to have chlamydial conjunctivitis. Fifteen of them had nasopharyngeal colonisation with Chlamydia trachomatis. Among the 20 neonatal chlamydial conjunctivitis patients that completed the follow-up study, one suffered treatment failure. None had clinically diagnosed systemic Chlamydia trachomatis infection 3 months after oral erythromycin.The incidence of neonatal chlamydial conjunctivitis in our region of Hong Kong was 4 in 1000 live births, of whom 63% had nasopharyngeal presence of Chlamydia trachomatis. Owing to the high rate of nasopharyngeal isolation and possibility of treatment failure, post-treatment ocular and nasopharyngeal polymerase chain reaction testing for Chlamydia trachomatis may be considered to confirm complete eradication.

Tuberculous involvement of the oesophagus is rare, and is usually caused by direct spread from adjacent afflicted structures. We report an 83-year-old male patient with oesophageal tuberculosis secondary to tuberculous mediastinal lymphadenitis who presented with non-specific symptoms of anorexia and lethargy. Upper gastro-intestinal endoscopy revealed an ulcerative tumour-like lesion in the mid-oesophagus suggesting oesophageal carcinoma. Repeated endoscopic biopsies revealed a non-specific acute-on-chronic inflammation consisting of non-caseating granulomas, with no evidence of malignancy. Endoscopic ultrasonography demonstrated that the oesophageal lesion was secondary to direct extension of mediastinal lymphadenopathy. The diagnosis of tuberculosis was eventually confirmed by histological and microbiological analysis of a surgically excised cervical lymph node. The patient responded promptly to treatment with antituberculous drugs. We suggest that oesophageal tuberculosis has to be kept in mind in the differential diagnosis of oesophageal ulcerohypertrophic lesions.

Aim To compare the treatment outcomes of a clinical pharmacist-managed anticoagulation service with physician-managed service in Chinese patients. Methods A prospective, randomized clinical trial was conducted at the anticoagulation clinic of a teaching hospital in Hong Kong. Patients aged ≥ 18 years who would required warfarin therapy for at least 3 months were recruited. Patients were randomized to the pharmacist-managed or physician-managed group. Primary clinical outcome was assessed by the percentage of patient time spent within the target international normalized ratio (INR) range. The incidence of major thromboembolic events (TEs) and major bleeding was assessed as secondary clinical outcomes. The cost per patient per month (cPPPM) was calculated and patient satisfaction was assessed by patient satisfaction questionnaire (PSQ)-18. Results One hundred and forty-one patients were recruited at the anticoagulation clinic and 137 patients completed the study. Patients in the pharmacist-managed group (n = 68) were in the target INR 64% of patient time vs. 59% in the physician-managed group (n = 69) (P

Poor glycaemic control and the duration of diabetes mellitus are known to accelerate development and progression of neuropathy. Diabetic co-morbidities: hypertension and hyperlipidaemia, have been postulated to associate with development of neuropathy. A diabetic foot with low temperature and frequent exposure to low temperature environment has recently been hypothesized to be at higher risk to develop early neuropathy. This cross-sectional study is undertaken to identify risk factors for diabetic neuropathy and the association between foot temperature and development of diabetic neuropathy by using simple clinical examination in the outpatient setting. From April 18, to April 30, 2005, universal sampling method was used to select 134 diabetic patients (type 1 or type 2 for1 year) with peripheral neuropathy. Excluded are those with chronic alcoholism, drug-induced neuropathy, dietary history of vitamin B deficiency and family history of porphyria and hereditary sensorimotor neuropathy. The patient's duration of diabetes, glycaemic control status and the presence of co-morbids: hypertension and hyperlipidemia, were recorded. The temperature of the foot was measured by using thermo buddy. Of 134 patients representing Malaysian ethnic distribution with an equal number of males and females, 20.1% were in the age group of 61 to 65 years and, 85.1% and 67.9% belonged to lower socioeconomic and educational groups respectively. Associations between diabetic neuropathy and glycaemic control (p = 0.018) and duration of diabetes (p0.05) were significant. However, hypertension, hyperlipidaemia and low foot temperature were not significantly associated with development of diabetic neuropathy. Poor glycaemic control is significantly associated with diabetic neuropathy. Foot temperature alteration is merely an effect of autonomic neuropathy with a cold foot is attributed to co-existing peripheral arterial disease.

Summary Background Non-alcoholic fatty liver disease is prevalent in affluent countries and is strongly associated with metabolic syndrome. Aim To study the prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease. Methods 73 consecutive patients with biopsy-proven non-alcoholic fatty liver disease and no history of diabetes underwent comprehensive metabolic screening. Diagnosis of diabetes and impaired glucose regulation was based on the 2006 American Diabetes Association criteria. Results The prevalence of undiagnosed diabetes and impaired glucose tolerance in non-alcoholic fatty liver disease patients was 33% and 29%, respectively. Among patients with 2-h plasma glucose above 7.8 mm, 47% had normal fasting glucose (below 5.6 mm). Impaired glucose tolerance was more common in patients with non-alcoholic steatohepatitis than those with simple hepatic steatosis (P = 0.036), and 2-h plasma glucose correlated with fibrosis stage (Spearman coefficient: 0.25, P = 0.046). In a binary logistic regression analysis, high fasting glucose and low high-density lipoprotein cholesterol were independent factors associated with diabetes. Nevertheless, if oral glucose tolerance test was only performed in non-alcoholic fatty liver disease patients with impaired fasting glucose, 20.8% of diabetes cases would be missed. Conclusions Isolated postchallenge hyperglycaemia is common among Chinese non-alcoholic fatty liver disease patients without history of diabetes. It is associated with histological severe disease, and cannot be accurately predicted by any fasting glucose cut-off.

To study the clinical and pathological characteristics of patients with intestinal tuberculosis.Retrospective study.United Christian Hospital, Hong Kong.Patients with intestinal tuberculosis diagnosed between January 1995 and December 2004 inclusive.The median age of the 13 male and 9 female patients was 53 years (range, 12-81 years). Nineteen (86%) had a definitive diagnosis of intestinal tuberculosis confirmed by the presence of caseating granulomas and/or acid-fast bacilli in histological specimens. In three (14%) the diagnosis was based on histology revealing non-caseating granulomas and a positive response to anti-tuberculous treatment. Common symptoms included abdominal pain (82%), diarrhoea (55%), weight loss (55%), and fever (45%). Three (14%) of the patients were complicated by intestinal obstruction, and another two (9%) had intestinal perforation. Four (18%) had concomitant active pulmonary tuberculosis. The most frequently involved site was the ileocaecal region, which was affected in 19 (86%) patients. Other sites included the jejunum, ascending and sigmoid colon. The diagnosis of intestinal tuberculosis was facilitated by examination of colonoscopic biopsy specimens (11 patients), and by examination of resected surgical specimens in the remainder. Two patients died from terminal malignancy. The remainder completed anti-tuberculous therapy and responded satisfactorily.The diagnosis of intestinal tuberculosis is difficult due to the lack of specific signs or symptoms. Colonoscopy with ileoscopy are useful tools in the search for colonic and terminal ileal tuberculosis. Surgical exploration is reserved for equivocal cases and for those who present as emergencies.

To evaluate the effectiveness of sodium ramping (profiling) in reducing hypotensive episodes and symptoms during haemodialysis.Prospective study.Regional hospital, Hong Kong.Thirteen patients who experienced frequent episodes of hypotension and/or symptoms such as cramps, dizziness, chest pain, nausea, vomiting, and headache during haemodialysis in the preceding 4 weeks.Each patient was switched from standard haemodialysis with a constant dialysate sodium concentration of 135 to 140 mmol/L to a ramped sodium haemodialysis for a period of 4 weeks. During this time the dialysate sodium concentration was ramped linearly downwards from 150 mmol/L at the beginning of dialysis to 140 mmol/L at the end of dialysis.Intradialytic hypotensive episodes, intradialytic symptoms, nursing interventions, systolic and diastolic blood pressures, and interdialytic weight gain.A total of 248 haemodialysis sessions undertaken by 13 patients were analysed. Switching from constant sodium haemodialysis to ramped sodium haemodialysis resulted in a significant reduction in the number of intradialytic hypotensive episodes from 5.8 (standard deviation, 6.4) to 2.2 (3.3) [P0.05], the total number of intradialytic symptoms from 7.1 (3.4) to 0.9 (1.3) [P0.01], and nursing interventions from 11.3 (6.3) to 1.7 (3.9) [P0.01]. Post-dialysis systolic and diastolic blood pressures were higher during ramped sodium haemodialysis compared with constant sodium haemodialysis (systolic blood pressure, 139 [standard deviation, 23] vs 133 [22] mm Hg, P0.001; diastolic blood pressure, 77 [11] vs 74 [13] mm Hg, P0.01), and there was a trend towards a smaller drop in blood pressure after dialysis. The interdialytic weight gain with sodium ramping haemodialysis was greater compared with constant sodium haemodialysis (3.1 [standard deviation, 1.0] vs 2.7 [1.1] kg, P0.001).Sodium ramping during haemodialysis effectively reduces hypotensive episodes and intradialytic symptoms. Post-dialysis blood pressure is better maintained. A side-effect of sodium ramping is a greater interdialytic weight gain.

Congenital Langerhans cell histiocytosis (LCH) encompasses a wide spectrum of disease involvement and severity. Congenital "self-healing" cutaneous LCH represents one end of the spectrum, whereas the case we encountered represents the other extreme. A rare case of congenital LCH with severe multiorgan involvement presenting as hydrops fetalis is described in this report. Hydrops fetalis has not previously been associated with congenital LCH. The overall clinical features of this infant closely mimicked those of disseminated congenital infection, and he ran a fulminant and rapidly fatal course.A high index of suspicion is required to diagnose congenital LCH in the early neonatal period. Hydrops fetalis is an ominous sign and probably reflects severe systemic disease compromising the well-being of the fetus.

To characterize the in situ distribution of actin in Schlemm's canal endothelium (SCE) and juxtacanalicular tissue (JCT) cells in glaucomatous human eyes, and compare to the distribution in normal eyes. Fresh human eye bank eyes were perfused and fixed at pressure (n=27 normal eyes and 22 confirmed glaucomatous eyes). Schlemm's canal was opened by microdissection and outflow tissues were labelled for confocal microscopy to visualize F-actin, nuclei, laminin and/or CD31. Images were acquired in Z-series from the inner wall of Schlemm's canal, juxtacanalicular tissue and outer corneoscleral meshwork. In normal eyes, inner wall Schlemm's canal endothelial (SCE) cells showed a dense peripheral F-actin band, as previously described. JCT cells showed a more random and amorphous F-actin distribution. In glaucoma eyes, peripheral F-actin bands were less common in inner wall SCE cells; instead, F-actin was more centrally located within the cell and appeared "tangled". These actin tangles were also prominent in JCT cells of glaucoma eyes. Glaucoma eyes also demonstrated structures with features of cross-linked actin networks (CLANs), and more frequent occurrence of punctuate actin concentrations. There was a significant degree of heterogeneity, with some regions from glaucomatous eyes appearing normal and vice versa. F-actin architecture in human outflow pathway cells in situ differs between normal and glaucoma eyes, with glaucomatous tissue showing a more "disordered" actin architecture overall. Some of these changes are likely due to effects secondary to administration of anti-glaucoma medications. Most of the changes that we observed could potentially affect the biomechanical properties of the outflow pathway tissues in glaucoma, but their role in the pathogenesis of ocular hypertension remains unclear.

Death-associated protein kinase (DAP-kinase) is a serine/threonine kinase and a positive mediator of apoptosis. Down-regulation of DAP-kinase was associated with increased metastatic potential of tumors. Gene promoter hypermethylation could lead to down-regulation of DAP-kinase. We aimed to investigate the frequency of gene promoter methylation of DAP-kinase in gastric carcinoma (GCA) and assessed its association with clinicopathological features. One hundred and seven cases of gastric carcinoma were examined. The relevant clinical and pathological features, including survival data were reviewed. Methylation status was assessed by methylation-specific PCR (MSP). Seventy-four cases (69.2%) of GCA demonstrated promoter methylation of DAP-kinase. Methylation of DAP-kinase was observed in intestinal, diffuse and mixed type of GCA. It also occurred in similar frequency among antral, body and cardiac gastric cancer. No association between methylation status and age or gender was demonstrated. However, the methylated cases correlated with the presence of nodal metastasis (p=0.041), advance stage of disease (p=0.029) and a poorer event-free survival (log-rank test p=0.0141). DAP-kinase promoter methylation as a potential prognostic marker for gastric cancer patients deserved further evaluation.

Synovial fibroblasts (SFs) play a critical role in the pathogenesis of rheumatoid arthritis (RA) and are directly involved in joint destruction. Both SF-resident matrix metalloproteases and cathepsins have been implicated in cartilage degradation although their identities and individual contributions remain unclear. The aims of this study were to investigate the expression of cathepsin K in SFs, the correlation between cathepsin K expression and disease severity, and the contribution of cathepsin K to fibroblast-mediated collagen degradation. Immunostaining of joint specimens of 21 patients revealed high expression of cathepsin K in SFs in the synovial lining and the stroma of synovial villi, and to a lesser extent in CD68-positive cells of the synovial lining. Cathepsin K-positive SFs were consistently observed at sites of cartilage and bone degradation. Expression levels of cathepsin K in the sublining and vascularized areas of inflamed synovia showed a highly significant negative correlation with results derived from the Hannover Functional Capacity Questionnaire (r = 0.78, P = 0.003; and r = 0.70, P = 0.012, respectively) as a measure of the severity of RA in individual patients. For comparison, there was no correlation between Hannover Functional Capacity Questionnaire and cathepsin S whose expression is limited to CD-68-positive macrophage-like synoviocytes. The expression of cathepsin K was also demonstrated in primary cell cultures of RA-SFs. Co-cultures of SFs on cartilage disks revealed the ability of fibroblast-like cells to phagocytose collagen fibrils whose intralysosomal hydrolysis was prevented in the presence of a potent cathepsin K inhibitor but not by an inhibitor effective against cathepsins L, B, and S. The selective and critical role of cathepsin K in articular cartilage and subchondral bone erosion was further corroborated by the finding that cathepsin K has a potent aggrecan-degrading activity and that cathepsin K-generated aggrecan cleavage products specifically potentiate the collagenolytic activity of cathepsin K toward type I and II collagens. This study demonstrates for the first time a critical role of cathepsin K in cartilage degradation by SFs in RA that is comparable to its well-known activity in osteoclasts.

Correction to: Eye (2011) 25, 119–120; doi: 10.1038/eye.2010.159; published online 19 November 2010

Background: A positive oesophageal margin is frequently encountered in total and proximal gastrectomies. It is controversial as to whether a positive oesophageal margin in gastrectomy predisposes to anastomotic dehiscence and loco-regional recurrence. Its independent impact on survival has not been fully addressed. Methods: A retrospective review of 137 total and proximal gastrectomies for adenocarcinoma was undertaken. Independent prognostic factors were identified in a bivariate and Cox proportional hazards regression model. Results: The prevalence of positive oesophageal margin was 18.2%. A positive oesophageal margin was not associated with increased anastomotic leak (8.0 vs 10.7%; P = 0.51), operative morbidity (32.0 vs 27.7%; P = 0.85) or 30-day mortality (8.0 vs 5.4%; P = 0.48) rates when compared with a negative margin. In addition, it did not predispose to anastomotic (13.0 vs 10.4%; P = 0.47) or regional (22.7 vs 24.5%; P = 0.51) recurrences. In the multivariate analysis the TNM stage and status of the oesophageal margin were the only independent prognostic factors for survival. Conclusions: A positive oesophageal margin is an independent poor prognostic factor for long-term survival in stomach cancer. All efforts should therefore be made to clear the oesophageal margin in total and proximal gastrectomies.

The 5-year survival rate after resection of oesophageal cancer is still poor, reported to be between 5% to 34% in the literatures. We conducted this retrospective study to determine the prognostic factors and long-term survival rate for surgical resection of oesophageal carcinoma in Singapore.Sixty-seven consecutive patients who underwent surgical resection of oesophageal carcinoma from January 1989 to December 1996 were reviewed.Majority of the patients were Chinese (94%), males (81%) with a history of dysphagia (96%), cigarette smoking (84%) and alcohol ingestion (58%). The median age at surgery was 63.6 (range 29 to 81) years. Sixty-four patients had squamous cell carcinoma of the oesophagus and 3 patients had adenocarcinoma. The lower one-third of the oesophagus was the most common site (48.6%) followed by the middle third (46%). Postoperative complications included pneumonia (43.3%), vocal cord paralysis/paresis (19.4%) and anastomotic leakage (17.9%). Thirty-day postoperative mortality was 7.5%. There was an almost equal number of patients undergoing transhiatal (34 patients) and transthoracic approach (33 patients). There was no significant difference in postoperative complications and survival outcome for both approaches. The median survival was 15.3 months after surgery. Tumour features such as depth of involvement and TNM stage were useful in predicting survival (P0.05, log-rank test).We conclude that the poor outcome of surgical resection (5-year survival rate was 18% by Kaplan-Meier survival plots) was mainly attributed to late presentation (80% patients had T3 or T4 tumour).

Patients who receive cardiac procedures, in particular "redo" ones, often suffer complications from massive bleeding, largely due to bypass-induced coagulopathies. Cardiopulmonary bypass (CPB) may cause damage of the blood components, both in terms of quality and quantity. In order to investigate the qualitative changes of blood constituents with special regard to coagulation resulting from the complex insult of previous cardiac surgery, thromboelastography (TEG) was used to analyze the whole clotting process.Seventy-four patients who underwent cardiac surgery with CPB were prospectively studied. Of them, 32 patients received "redo" cardiac surgery. Blood samples for routine laboratory coagulation tests (RCT) and TEG examination were drawn before and after cardiopulmonary bypass. Clinically significant bleeding was defined if the chest tube drainage was greater than 100 ml/h for 3 consecutive h or greater than 300 ml in 1 h during the first 8 h after surgery. Prebypass and postbypass coagulation parameters were compared and the percentage of accuracy, false positive and false negative rate were deduced from calculation.In the TEG tracings, preoperative alpha angle and maximum amplitude were significantly decreased in the "redo" group when compared with primary group, indicating less competent platelet function and platelet-fibrin interaction. Lower platelet count was also found by conventional coagulation tests in "redo" patients. Postoperatively, higher percentage of excessive hemorrhage was also noted in the "redo" group (42.8% vs. 27.5% in primary group). However, a much lower predictive accuracy was found in "redo" patients in comparison with primary cardiac patients (53.5% vs. 90%).We concluded that thromboelastography failed to predict postoperative hemorrhage in "redo" cardiac patients and the graphic recordings derived could not be treated as a guide of transfusion therapy. We thought that inferior preoperative hemostatic status and severer coagulopathy might be responsible for the differences between "redo" and primary cardiac patients.