Associations between body composition and vertebral fracture risk in postmenopausal women.

INTRODUCTION: Osteoporosis is a metabolic bone disease with low bone mineral density (BMD) and high incidence of vertebral fractures (VFs). Postmenopausal women with osteoporosis have decreased total fat and lean mass. This study aimed to investigate the associations between body composition and VF risk and explore the potential predictor of VF risk in postmenopausal women. METHODS: Enrolled 731 postmenopausal women were referred by various departments and outpatient clinics to assess vertebral status between October 2016 and November 2017. The main measures were total body lean mass, fat mass, and BMD. Patients were divided into osteopenia, osteoporosis, and normal groups based on T-scores. Logistic regression analyses were performed to evaluate associations between body composition parameters and VF. RESULTS: VF was significantly associated with increased age, lower height, and lighter weight in all participants, and higher BMI was observed in VF participants. Participants in the osteoporosis group were older and had lower height, weight, and BMD than those in normal and osteopenia groups. Femoral and total hip T-scores as well as T-scores for lumbar spine were significantly lower in participants with VF than in non-VF participants. Percentage of bone mass was also significantly lower in VF participants compared to that of non-VF participants. Women with increased BMD and lower bone mass had reduced odds for VF occurrence. Bone mass was significantly able to identify VF occurrence. CONCLUSIONS: Body composition analysis discerns differences in the bone status of postmenopausal women with and without VF. The cutoff value of the bone mass might be used effectively as an indicator of risk for VF occurrence.

Radiofrequency ablation compared with laparoscopic adrenalectomy for aldosterone-producing adenoma.

BACKGROUND: Radiofrequency ablation (RFA) is an emerging treatment for primary aldosteronism owing to aldosterone-producing adenoma. Whether RFA could be an alternative treatment to laparoscopic adrenalectomy is unknown. METHODS: This was a retrospective comparative study in patients with aldosterone-producing adenoma undergoing either laparoscopic adrenalectomy or CT-guided percutaneous RFA between 2004 and 2012. Short-term outcomes and long-term resolution rates of primary aldosteronism (normalized aldosterone to renin ratio), hypokalaemia and hypertension (BP lower than 140/90 mmHg without antihypertensive medical therapy) were evaluated. RESULTS: Some 63 patients were included, 27 in the laparoscopic adrenalectomy group and 36 in the RFA group. RFA was associated with shorter duration of operation (median 12 versus 124 min; P < 0·001), shorter hospital stay (2 versus 4 days; P < 0·001), lower analgesic requirements (13 of 36 versus 23 of 27 patients; P < 0·001) and earlier resumption of work (median 4 versus 14 days; P = 0·006). Morbidity rates were similar in the two groups. With median follow-up of 5·7 (range 1·9-10·6) years, resolution of primary aldosteronism was seen in 33 of 36 patients treated with RFA and all 27 patients who had laparoscopic adrenalectomy (P = 0·180). Hypertension was resolved less frequently after treatment with RFA compared with laparoscopic adrenalectomy (13 of 36 versus 19 of 27 patients; P = 0·007). Hypokalaemia was resolved in all patients. CONCLUSION: For patients with aldosterone-producing adenoma the efficacy of resolution of primary aldosteronism and hypertension was inferior after treatment with RFA compared with laparoscopic adrenalectomy.

Diagnostic value of apoptosis biomarkers in severe sepsis-A pilot study.

Severe sepsis is associated with significant mortality and massive immune cell lose, or apoptosis. It is unclear whether plasma apoptosis biomarkers could be used as a diagnostic test for severe sepsis. Forty patients with severe sepsis and 35 healthy controls were enrolled. The percentage and apoptosis of monocytes and lymphocytes were detected by flow cytometric analysis. Plasma levels of tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR), soluble Fas (sFas), Fas ligand (FasL), caspase-1, and procalcitonin (PCT) were measured. Plasma caspase-1 level was positively correlated with CD4 lymphocyte apoptosis in controls and patients, and with CD8 lymphocyte apoptosis in all subjects. Plasma FasL level was negatively correlated with CD4 and CD8 lymphocyte apoptosis in all subjects. The sFas/FasL ratio was positively correlated with CD4 and CD8 lymphocyte apoptosis and negatively with monocyte apoptosis in all subjects. Compared with PCT, caspase-1, FasL, and sFas/FasL ratio had better negative predictive value and likelihood ratio for a negative test. PCT had better positive predictive value and likelihood ratio for a positive test. This work demonstrated caspase-1, FasL, and sFas/FasL ratio could be candidates for diagnosis of severe sepsis and their diagnostic value was not inferior to that of PCT.

Automation of etch pit analyses on solid-state nuclear track detectors with machine learning for laser-driven ion acceleration.

Solid-state nuclear track detectors (SSNTDs) are often used as ion detectors in laser-driven ion acceleration experiments and are considered to be the most reliable ion diagnostics since they are sensitive only to ions and measure ions one by one. However, ion pit analyses require tremendous time and effort in chemical etching, microscope scanning, and ion pit identification by eyes. From a laser-driven ion acceleration experiment, there are typically millions of microscopic images, and it is practically impossible to analyze all of them by hand. This research aims to improve the efficiency and automation of SSNTD analyses for laser-driven ion acceleration. We use two sets of data obtained from calibration experiments with a conventional accelerator where ions with known nuclides and energies are generated and from actual laser experiments using SSNTDs. After chemical etching and scanning the SSNTDs with an optical microscope, we use machine learning to distinguish the ion etch pits from noises. From the results of the calibration experiment, we confirm highly accurate etch-pit detection with machine learning. We are also able to detect etch pits with machine learning from the laser-driven ion acceleration experiment, which is much noisier than calibration experiments. By using machine learning, we successfully identify ion etch pits ∼105 from more than 10 000 microscopic images with a precision of ≳95%. A million microscopic images can be examined with a recent entry-level computer within a day with high precision. Machine learning tremendously reduces the time consumption on ion etch pit analyses detected on SSNTDs.

3D track extraction from a fluorescent nuclear track detector via machine learning and an application to diagnostics of laser-driven ions.

We have developed an ion diagnostic method for laser-driven ion acceleration experiments that uses fluorescent nuclear track detectors (FNTDs). An FNTD records the particle tracks as color centers and does not require chemical etching, unlike CR-39 track detectors. The color centers are observed using a confocal laser microscope, and 3D particle tracks can be obtained by changing its focal position. The intensity of the color centers corresponds to the energy deposited by the ions. The nuclides of the ions can be determined from the intensity distribution of the color centers as a function of depth and the distance between the stopping point and the surface of the detector. To extract the intensity distribution, we must track the same ion tracks in the depth-layered microscopic images from the surface to the stopping point, even if they overlap with those of other ions. In addition, since an FNTD is sensitive not only to ions but also to electrons and photons, we must identify ion tracks among those from the latter particles. To analyze a statistical number of ion tracks, it is necessary to automate these processes. We have thus developed a method for automated ion detection and 3D tracking that relies on a support vector classifier and a kernelized correlation filter. This method was tested on a laser ion acceleration experiment performed using the J-KAREN-P laser. The method automatically detects ion tracks on FNTDs and tracks them in the depth direction. The training data are sampled from the Heavy-Ion Medical Accelerator in Chiba.

Basal core promoter mutation is associated with progression to cirrhosis rather than hepatocellular carcinoma in chronic hepatitis B virus infection.

BACKGROUND: As most cases of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have concurrent cirrhosis, viral factors identified to be associated with HCC might be related to cirrhosis rather than HCC. METHODS: Hepatitis B virus DNA levels, genotypes and precore/basal core promoter (BCP) mutants were compared between cirrhotic HCC and non-cirrhotic HCC patients. Age- and sex-matched case-control studies were performed to identify the risk factors. RESULTS: Hepatitis B virus DNA levels showed no significant difference between non-cirrhotic HCC patients (n=20) and cirrhotic HCC patients (n=140) or 1 : 3 age- and sex-matched cirrhotic HCC patients (n=60), but genotype C and BCP mutant were significantly more prevalent in the latter than in the former. In multiple logistic regression, BCP mutant but not genotype C correlated significantly with the presence of cirrhosis in HCC patients. Compared with inactive carriers (n=60), non-cirrhotic HCC patients (n=20) had significantly higher HBV DNA levels but no difference in HBV genotypes and precore/BCP mutants. Furthermore, HBV DNA levels, the distribution of HBV genotypes and the prevalence of precore/BCP mutants all failed to show any significant difference between cirrhotic HCC patients (n=60) and cirrhotic patients without HCC (n=60). CONCLUSION: Basal core promoter mutant is associated with progression to cirrhosis rather than HCC in chronic HBV infection.

Serial HBV DNA levels in patients with persistently normal transaminase over 10 years following spontaneous HBeAg seroconversion.

Earlier studies addressing the hepatitis B virus (HBV) DNA cut-off level for inactive chronic HBV infection largely involved patients with normal alanine aminotransferase (ALT) for only 1-2 years and based on a single time HBV DNA assay. This study was conducted to address this issue using serial HBV DNA assays in patients with persistently normal ALT (PNALT) over 10 years following spontaneous hepatitis B e antigen (HBeAg) seroconversion. Serial serum specimens (mean 9 samples per patient) of 62 patients with PNALT and no disease progression over 10 years (median 18.1 years) after spontaneous HBeAg seroconversion were assayed for HBV DNA. Excluding assays within 1 year after HBeAg seroconversion, 21% and 82.3% of the patients with PNALT had HBV DNA levels persistently lower than 4 log(10) and 5 log(10) copies/mL, respectively, and only 8% had a level ≥ 5 log(10) copies/mL in at least two assays. Of the 27 patients with PNALT defined by ALT <30 U/L for male and <19 U/L for female, only 33% had serum HBV DNA level persistently <4 log(10) copies/mL. There was no significant difference in the serial HBV DNA changes among patients with different gender, HBV genotype or age at HBeAg seroconversion. Liver biopsy in nine patients invariably showed minimal necroinflammation and one showed Ishak fibrosis score 4. These results suggest that 5 log(10) copies/mL (20,000 IU/mL) is a more appropriate cut-off HBV DNA level for inactive chronic HBV infection in the setting of PNALT.

Prevalence of allergic rhinitis and its associated morbidity in adults with asthma: a multicentre study.

OBJECTIVES: To assess the prevalence of allergic rhinitis in adult patients with asthma in Hong Kong, and to compare the morbidity endured by asthma patients with and without allergic rhinitis. DESIGN: Cross-sectional study. SETTING: Respiratory clinics of four major public hospitals in Hong Kong. PATIENTS: A total of 600 adults with asthma were recruited from March to May 2007. MAIN OUTCOME MEASURES: Doctors and patients completed separate questionnaires evaluating symptoms, treatment, and health care utilisation. Spirometry data were obtained for a subgroup of patients at the time of survey completion. RESULTS: The patients consisted of 267 males and 333 females, with 251 having spirometry data. The mean pre-bronchodilator 1-second forced expiratory volume predicted among those who had spirometry performed was 88% (standard deviation, 28%). In all, 50% of the patients had intermittent and 50% had persistent asthma. Over three quarters (463/600; 77%) of patients had experienced allergic rhinitis symptoms in the past 12 months, of whom 96% had a previous diagnosis of allergic rhinitis. Asthmatics without allergic rhinitis symptoms had higher rates of visits to doctors, pharmacy visits, emergency department attendances, and hospitalisations for asthma than those with both conditions. Among subjects with asthma and allergic rhinitis, those taking nasal steroid (226/463; 49%) had lower rates of emergency department visits (13 vs 25%, P=0.002) and hospitalisations (7 vs 13%, P=0.045) for asthma than those who were not. CONCLUSION: Allergic rhinitis is a common co-morbid condition of asthma in this hospital clinic cohort. Treatment of allergic rhinitis with intra-nasal steroid was associated with less health care utilisation for asthma.

Assessment of capsular laxity in patients with recurrent anterior shoulder dislocation using MRI.

OBJECTIVE: The purpose of our study was to investigate the usefulness of MRI in assessing capsular laxity in patients with recurrent shoulder dislocation. MATERIALS AND METHODS: The records of 64 consecutive patients (the study group consisted of 58 patients, 45 male and 13 female; average age, 39.3 years; range, 13-82 years) who underwent MR arthrography between October 2002 and May 2008 were retrospectively reviewed. The patients were divided into three groups: group A, no shoulder dislocation; group B, first dislocation; and group C, recurrent dislocation. The maximum capsular widths at the anterior, anteroinferior, and inferior regions in the neutral and abducted and externally rotated (ABER) positions were measured on oblique sagittal images. The relationship of capsular width with the number of dislocations, type of capsular attachment, presence of anteroinferior labral tear, and patient sex were evaluated. The sensitivity and specificity of MRI and clinical tests in detecting capsular laxity were also calculated. RESULTS: Among all three patient groups, there were significant differences (p < 0.05) in the widths with the shoulder in the ABER position and the degree of capsular tightening at the anterior region. The average maximum width was largest in group C and smallest in group A. There was a significant difference in the degree of anterior capsular tightening in groups B and C. A moderate correlation of capsular width and anterior tightening (R = -0.45) with number of shoulder dislocations was found. There was a significant difference in capsular width and capsular tightening in relation to the presence of an anteroinferior labral tear. The sensitivity and specificity to detect capsular laxity were 92% and 100%, respectively, for clinical tests and 85% and 96% for MRI. CONCLUSION: MRI is a useful and objective method to assess capsular laxity in patients with recurrent shoulder dislocation.

The first novel influenza A (H1N1) fatality despite antiviral treatment and extracorporeal membrane oxygenation in Hong Kong.

We report the first fatality caused by novel influenza A (H1N1) infection despite having the diagnosis confirmed and being given antiviral treatment after hospitalisation. This patient was also the first with influenza A (H1N1) to be supported with extracorporeal membrane oxygenation in Hong Kong. Although extracorporeal membrane oxygenation is an effective means of supporting patients with refractory hypoxaemia on high mechanical ventilatory support, it is labour-intensive and technically demanding. We also discuss the challenges faced when managing this case.

Successful treatment of leflunomide-induced acute pneumonitis with cholestyramine wash-out therapy.

Drug-induced acute pneumonitis is a rare but potentially fatal adverse drug reaction. A high index of suspicion is needed for early diagnosis as it mimics community acquired pneumonia and interstitial lung disease that can occur in rheumatoid arthritis. We report a 32-year-old Chinese lady who suffered from leflunomide-induced pneumonitis and improved dramatically after receiving cholestyramine wash-out therapy. This case illustrates the need for clinical alertness to this potentially fatal complication. When in doubt, discontinuation of leflunomide and empirical wash-out therapy should be administered without delay.

Role of polymorphisms of the inflammatory response genes and DC-SIGNR in genetic susceptibility to SARS and other infections.

1. A genetic risk-association study involving more than 1200 subjects showed individuals homozygous for L-SIGN tandem repeats are less susceptible to SARS infection. 2. This was supported by in vitro binding studies that demonstrated homozygous L-SIGN, compared to heterozygous, had higher binding capacity for SARS coronavirus (SARS-CoV), with higher proteasome-dependent viral degradation. In contrast, homozygous L-SIGN demonstrated lower binding capacity for HIV1-gp120.3. Genetic-association studies for single nucleotide polymorphisms of the inflammatory response genes, namely TNF-alpha, INF-alpha, INF-beta, INF-gamma, IL1-alpha, IL1-beta, IL-4, IL-6 and iNOS, failed to show a significant association with SARS clinical outcomes or susceptibility.

Purification and characterization of a naturally processed hepatitis B virus peptide recognized by CD8+ cytotoxic T lymphocytes.

In vitro studies in patients with hepatitis B virus (HBV) infection have suggested that hepatocytolysis induced by CD8+ cytotoxic T lymphocytes (CTLs) is the most important effector pathway in eliminating infected cells. The recognition is implicated in the endogenously processed HBV antigens in the context of HLA class I molecules presented on the liver cell membrane. However, the naturally occurring HBV peptide antigens have not yet been demonstrated. We report here that a naturally processed peptide antigen P2 was isolated from HLA class I molecules of HBV-infected liver cell membrane. The P2 peptide exhibited the activity of sensitizing target cells for lysis by CD8+ CTLs. The P2 sequence (YVNVNMGLK) purified from liver tissue was in concordance with that encoded by the viral genome for the HBV nucleocapsid antigen or HBcAg 88-96. P2 peptide could also be isolated from the EBV-transformed B cells that were transfected by HBcAg-expressing vector. The P2 epitope, sharing the HLA-A11 binding motifs, was recognized by HLA-A11-restricted CD8+ CTLs. The data provided direct evidence that, in hepatitis B patients, antigenic peptides of HBV were processed by hepatocytes, presented with the class I MHC molecules, and recognized by CD8+ CTLs.

Comparison of clinical staging systems in predicting survival of hepatocellular carcinoma patients receiving major or minor hepatectomy.

AIM: To compare the utility of seven commonly used staging systems in the prediction of survival among patients with hepatocellular carcinoma (HCC) undergoing major or minor hepatectomy. METHODS: All patients were classified by the Okuda, the TNM, the CLIP, the BCLC, the CUPI, the JIS and the MELD classifications to estimate the probabilities of survival. Survival curves were calculated using the Kaplan-Meier method and were examined using log-rank testing. The overall predictive power for patient survival with each staging system was evaluated using linear trend chi(2) tests and from the area under the receiver operating characteristic (ROC) curve. RESULTS: In our patient cohort, the log-rank test and the linear trend chi(2) test of the CLIP and JIS systems gave better results than did the other staging systems. The discriminatory ability of the CLIP and JIS staging for death, evaluated by ROC curve areas, was also better. In the subgroups of major hepatectomy patients with a non-cirrhotic liver or minor hepatectomy patients with a cirrhotic liver, the CLIP and JIS systems showed similar better performances in these three tests. The discriminatory ability of the CLIP system was the best in major hepatectomy patients with a non-cirrhotic liver while JIS score discriminated best in minor hepatectomy patients with a cirrhotic liver. CONCLUSION: Among the seven staging systems, the CLIP and JIS systems perform better than do the others. While the CLIP system should be considered to stage major hepatectomy patients, the JIS system could be chosen to stage minor hepatectomy patients.

Complicated parapneumonic effusion and empyema thoracis: microbiology and predictors of adverse outcomes.

OBJECTIVES: To describe the microbiological characteristics of a cohort of patients with complicated parapneumonic effusion and empyema thoracis, and to identify the potential risk factors for adverse outcomes, with particular reference to the choice of empirical antibiotics, intrapleural fibrinolytics, adherence to management guidelines, and input from pulmonologists. DESIGN: Retrospective review. SETTING: Regional hospital, Hong Kong. PATIENTS: All patients with a diagnosis of complicated parapneumonic effusion/empyema thoracis admitted between January 2003 and June 2005. MAIN OUTCOME MEASURES: Microbiological characteristics, mortality, and surgery-free survival. RESULTS. There were 63 patients, with a mean age of 64 (standard deviation, 16) years and a male-to-female ratio of 45:18. The pleural fluid culture positivity rate was 68%; Streptococcus milleri (19%), Bacteroides (14%), Klebsiella pneumoniae (12%), and Peptostreptococcus (7%) were the most common organisms. Thirteen (21%) patients died during their index admission. Use of intrapleural fibrinolytics according to the guideline was associated with survival (P=0.001) while discordant initial antibiotic use was associated with mortality (P=0.002). Discordant initial antibiotic use was also independently associated with reduced surgery-free survival (P<0.001). Subgroup analysis showed that early intrapleural fibrinolytic use (within 4 days of diagnosis) was associated with decreased mortality (P<0.001), increased surgery-free survival (P=0.005), and shorter hospital stay (P=0.039). CONCLUSION: Organisms identified from complicated parapneumonic effusion and empyema thoracis differ from those giving rise to community-acquired pneumonia. In these patients, adherence to guidelines, early concordant antibiotic treatment, intrapleural fibrinolytics, and input from a pulmonologist were associated with improved outcomes.

MgZnO/ZnO Two-Dimensional Electron Gas Photodetectors Fabricated by Radio Frequency Sputtering.

MgZnO/ZnO two-dimensional electron gas (2DEG) structures with ZnO annealed at various temperatures (600-900 °C) and photodetectors (PDs) with and without a 2DEG structure were fabricated using a radio frequency magnetron sputtering system. It was found that the carrier concentration and mobility increase with the annealing temperature owing to the improved crystalline in ZnO; however, high-temperature (800 °C or higher) annealing can degrade the crystalline of the ZnO layer. Hall measurements showed that compared with that of bulk ZnO, the sheet carrier concentration of the 2DEG sample increased from 1.3 × 1013 to 1.2 × 1014 cm-2, and the mobility was enhanced from 5.1 to 17.5 cm2/V s. This is because the channel layer is the total thickness (300 nm) in bulk ZnO, whereas the carriers are confined to a 45 nm region beneath the MgZO layer in the 2DEG sample, confirming the 2DEG behavior at the MgZnO/ZnO interface. The PDs with 2DEG structures demonstrate a higher ultraviolet (UV) response and a UV/visible rejection ratio that is six times larger than that of the PDs without a 2DEG structure. The 2DEG structure also induces a photocurrent gain, which results in a 240% quantum efficiency for the 310 nm incident wavelength. The related mechanism is elucidated with a band diagram.

Lymphopenia at presentation is associated with increased risk of infections in patients with systemic lupus erythematosus.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) frequently suffer from infections, but the predisposing risk factors, as well as the exact frequency and nature of such infections, are not fully understood. AIM: To describe the frequency, types and risk factors for infections in a group of Chinese patients in the early stage of SLE in Hong Kong. DESIGN: Retrospective record study. METHODS: We reviewed the case records of 91 Chinese SLE patients, presenting <12 months after SLE diagnosis. Details of major infections (requiring intravenous antimicrobial therapy, or any confirmed mycobacterial infection) and minor infections were reviewed. Clinical and laboratory features, the systemic lupus erythematosus disease activity index (SLEDAI) at presentation and drug treatment were recorded and analysed. RESULTS: There were 48 major infections and 62 minor infections during 260 patient-years of follow-up. A lymphocyte count < or =1.0 x 10(9)/l at presentation was independently associated with an increased risk for major infection: hazard ratio 4.7 (95%CI 1.6-13.7), p = 0.005. SLEDAI, use of corticosteroids and immunosuppressive therapy were all not associated with increased risk of infection. DISCUSSION: Lymphopenia was an important risk factor for major infections in this group of Chinese patients in the early stages of SLE. SLE patients with lymphopenia at presentation should be closely monitored for the development of infective complications.

Clinical outcomes after spontaneous and nucleos(t)ide analogue-treated HBsAg seroclearance in chronic HBV infection.

BACKGROUND: Both spontaneous and nucleos(t)ide analogue (Nuc)-treated hepatitis B surface antigen (HBsAg) seroclearance are associated with excellent clinical outcomes. AIM: To conduct a case-control study to explore whether there is difference of clinical outcomes between these two groups. METHODS: A total of 312 chronic hepatitis B patients with spontaneous HBsAg seroclearance and 110 patients with Nuc-treated HBsAg seroclearance were recruited retrospectively. Propensity score (PS) matching method produced 98 patients in each group for comparison. The development of hepatocellular carcinoma (HCC), hepatic complications and cumulative incidence of antibody to HBsAg (anti-HBs) was compared. RESULTS: During a mean follow-up period of 107 months after HBsAg seroclearance, five patients developed HCC after a mean period of 75.3 months (four and one patients with spontaneous and Nuc-treated HBsAg seroclearance, respectively) in overall population. One died of pneumonia with sepsis and one experienced variceal bleeding in Nuc-treated patients but none in spontaneous group. The incidence of anti-HBs seroconversion was comparable between spontaneous and Nuc-treated HBsAg seroclearance (69.6% vs. 66.4%, respectively, P = 0.617). There were no significant differences in HCC development (2% vs. 1.1%), overall mortality (0% vs. 1%), variceal bleeding (0% vs. 4.2%) and 6-year cumulative incidence of anti-HBs seroconversion (62.3% vs. 61.5%) among PS-matched patients with spontaneous and Nuc-treated HBsAg seroclearance. CONCLUSIONS: The clinical outcomes between patients with spontaneous and Nuc-treated HBsAg seroclearance are comparable. HCC can develop at a low rate during long-term follow-up and periodic surveillance after HBsAg seroclearance is still mandatory.