Detection of significant liver fibrosis in Chinese psoriasis patients receiving methotrexate: a comparison between transient elastography and liver histology.

INTRODUCTION: Methotrexate (MTX) is effective for treating psoriasis and psoriatic arthritis, but its potential hepatoxicity remains a concern. Liver biopsy, the gold standard for detecting MTX-induced liver injury, is invasive and carries considerable risk. Transient elastography (TE) offers a non-invasive alternative for detecting advanced liver fibrosis. This study investigated the performance of TE in detecting MTX-induced liver fibrosis among Chinese psoriasis patients, compared with liver biopsy. METHODS: This study included adult patients with clinical psoriasis. Liver stiffness measurement using TE was performed in patients receiving MTX. Exclusion criteria were known liver cirrhosis, positive viral hepatitis carrier status, or conditions influencing TE performance. Liver biopsy was performed when liver stiffness was ≥7.1 kilopascals (kPa) or when the total cumulative dose (TCD) of MTX was ≥3.5 g. RESULTS: A total of 228 patients were screened; among 34 patients who met the inclusion criteria, nine (26.5%) had significant liver fibrosis (Roenigk grade ≥3a). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval=0.59-0.93; P=0.021), indicating that TE had satisfactory performance in detecting liver fibrosis. A cut-off value of 7.1 kPa of liver stiffness yielded 100% sensitivity and 68% specificity. Liver fibrosis was not correlated with the TCD of MTX or the duration of MTX use; it was significantly correlated with obesity and diabetes status (body mass index ≥30 kg/m2, waist circumference ≥138 cm, and glycated haemoglobin level ≥7.8%). CONCLUSION: Transient elastography is reliable and superior to the TCD for detecting liver fibrosis in Chinese psoriasis patients receiving MTX. Liver biopsy should be reserved for high-risk patients or patients with liver stiffness ≥11.7 kPa on TE.

Cutaneous manifestations, viral load, and prognosis among hospitalised patients with COVID-19: a cohort study.

INTRODUCTION: Various cutaneous manifestations have been reported as symptoms of coronavirus disease 2019 (COVID-19), which may facilitate early clinical diagnosis and management. This study explored the incidence of cutaneous manifestations among hospitalised patients with COVID-19 and investigated its relationships with viral load, co-morbidities, and outcomes. METHODS: This retrospective study included adult patients admitted to a tertiary hospital for COVID-19 from July to September 2020. Clinical information, co-morbidities, viral load (cycle threshold [Ct] value), and outcomes were analysed. RESULTS: In total, 219 patients with confirmed COVID-19 were included. Twenty patients presented with new onset of rash. The incidence of new rash was 9.1% (95% confidence interval=6.25%-14.4%). The most common manifestations were maculopapular exanthem (n=6, 42.9%, median Ct value: 24.8), followed by livedo reticularis (n=4, 28.6%, median Ct value: 21.3), varicella-like lesions (n=2, 14.3%, median Ct value: 19.3), urticaria (n=1, 7.1%, median Ct value: 14.4), and acral chilblain and petechiae (n=1, 7.1%, median Ct value: 33.1). The median Ct values for patients with and without rash were 22.9 and 24.1, respectively (P=0.58). There were no significant differences in mortality or hospital stay between patients with and without rash. Patients with rash were more likely to display fever on admission (P<0.01). Regardless of cutaneous manifestations, patients with older age, hypertension, and chronic kidney disease stage ≥3 had significantly higher viral load and mortality (P<0.05). CONCLUSION: This study revealed no associations between cutaneous manifestation and viral load or clinical outcomes. Older patients with multiple co-morbidities have risks of high viral load and mortality; they should be closely monitored.

Relationship between parathyroid hormone and subclinical myocardial dysfunction in patients with severe psoriasis.

BACKGROUND: Psoriasis is associated with an increased risk of cardiovascular disease although the mechanism remains unclear. Recent studies have shown that such patients have a high prevalence of vitamin D (vit-D) deficiency and elevated parathyroid hormone (PTH) level. We hypothesized that vit-D deficiency and/or elevated PTH in psoriasis may contribute to left ventricular (LV) dysfunction. METHODS: Seventy-four patients with severe psoriasis with no known cardiovascular disease and 53 age- and gender-matched controls were recruited. All patients underwent detailed transthoracic echocardiography, including speckle tracking derived strains, and plasma levels of 25-hydoxyvitamin D (25-OHD), PTH and cardiac biomarkers including high sensitive C-reactive protein (hs-CRP), high sensitive troponin I (hs-TNI) and brain natriuretic peptide (BNP) were measured. RESULTS: Despite similar systolic and diastolic LV function, patients with severe psoriasis had impaired LV global longitudinal (-18.1 ± 2.6 vs.-19.6 ± 2.9%, P < 0.01) and circumferential strain (-18.7 ± 3.6 vs. -20.8 ± 4.3%, P < 0.01) compared with controls. Patients with severe psoriasis also had a significantly higher PTH (49.9 ± 18.0 vs. 40.5 ± 15.4 pmol/mL, P < 0.01) and hs-CRP (5.7 ± 6.9 vs. 1.9 ± 2.5 pg/mL, P < 0.01), but similar levels of 25-OHD, hs-TNI and BNP (all P > 0.05) compared with controls. Importantly, PTH level was negatively correlated with LV global longitudinal strain (R = -0.30, P < 0.01); and higher PTH level was independently associated with impaired global LV longitudinal strain (R = -0.33, P = 0.04), independent of cardiovascular risk factors, vit-D status and serum biomarkers. CONCLUSIONS: Severe psoriasis patients had an elevated PTH level and suffered from subclinical LV systolic dysfunction as detected by impaired global LV longitudinal strain. Importantly, a higher PTH level was independently associated with impaired global LV longitudinal strain.

Gaze and attention: Mechanisms underlying the therapeutic effect of optokinetic stimulation in spatial neglect.

Left smooth pursuit eye movement training in response to large-field visual motion (optokinetic stimulation) has become a promising rehabilitation method in left spatial inattention or neglect. The mechanisms underlying the therapeutic effect, however, remain unknown. During optokinetic stimulation, there is an error in visual localisation ahead of the line of sight. This could indicate a change in the brain's estimate of one's own direction of gaze. We hypothesized that optokinetic stimulation changes the brain's estimate of gaze. Because this estimate is critical for coding the locus of attention in the visual space relative to the body and across sensory modalities, its change might underlie the change in spatial attention. Here, we report that in healthy participants optokinetic stimulation causes not only a directional bias in the proprioceptive signal from the extraocular muscles, but also a corresponding shift of the locus of attention. Both changes outlasted the period of stimulation. This result forms a step in investigating a causal link between the adaptation in the sensorimotor gaze signals and the recovery in spatial neglect.

Prevalence and extent of subclinical atherosclerosis in patients with psoriasis.

OBJECTIVE: Patients with psoriasis are prone to premature atherosclerosis and increased risk of cardiovascular disease events. However, the prevalence and extent of atherosclerosis in patients with psoriasis are unknown. DESIGN: A cross-sectional study. SETTING AND SUBJECTS: The prevalence and extent of coronary and carotid atherosclerosis were compared in 70 patients with psoriasis (46 ± 9 years, 71% male) without known cardiovascular disease or joint involvement and 51 age- and gender-matched healthy control subjects (45 ± 7 years, 71% male). Systemic inflammation was assessed by the level of high-sensitivity C-reactive protein (hs-CRP). Coronary atherosclerosis was determined by the coronary calcification score (CCS) measured by multi-detector computed tomography. Carotid atherosclerosis was assessed by high-resolution ultrasound-derived carotid intima-media thickness (cIMT). RESULTS: Patients with psoriasis had a higher prevalence of coronary atherosclerosis (CCS > 0; 28.6% vs. 3.9%, P < 0.01), and a higher degree of coronary atherosclerosis estimated by the mean CCS (67.4 ± 349.2 vs. 0.5 ± 3.0, P < 0.05) compared with controls. Similarly, cIMT was significantly greater in patients with psoriasis than in control subjects (0.73 ± 0.11 mm vs. 0.67 ± 0.08 mm, P < 0.01). Multiple logistic regression revealed that psoriasis [odd ratio (OR): 10.54, 95% confidence interval (CI) 1.89-58.67, P < 0.01] and serum total cholesterol level (OR 2.10, 95% CI 1.01-4.37) were associated with the presence of coronary atherosclerosis (CCS > 0). By contrast, only age was independently associated with increased cIMT. Amongst participants with no traditional cardiovascular disease risk factors, hs-CRP level was higher in patients with psoriasis than in controls. CONCLUSION: The present results demonstrate early-onset, diffuse arterial atherosclerosis in coronary and carotid arteries in patients with psoriasis, but not in age- and gender-matched control subjects. Low-grade inflammation could explain the presence of premature atherosclerosis in patients with psoriasis.

Global flash multifocal electroretinogram: early detection of local functional changes and its correlations with optical coherence tomography and visual field tests in diabetic eyes.

PURPOSE: To investigate the correlations of the global flash multifocal electroretinogram (MOFO mfERG) with common clinical visual assessments--Humphrey perimetry and Stratus circumpapillary retinal nerve fiber layer (RNFL) thickness measurement in type II diabetic patients. METHODS: Forty-two diabetic patients participated in the study: Ten were free from diabetic retinopathy (DR), while the remainder suffered from mild to moderate nonproliferative diabetic retinopathy. Fourteen age-matched controls were recruited for comparison. MOFO mfERG measurements were made under high- and low-contrast conditions. Humphrey central 30-2 perimetry and Stratus OCT circumpapillary RNFL thickness measurements were also performed. Correlations between local values of implicit time and amplitude of the mfERG components [direct component (DC) and induced component (IC)], and perimetric sensitivity and RNFL thickness were evaluated by mapping the localized responses for the three subject groups. RESULTS: MOFO mfERG was superior to perimetry and RNFL assessments in showing differences between the diabetic groups (with and without DR) and the controls. All the MOFO mfERG amplitudes (except IC amplitude at high contrast) correlated better with perimetry findings (Pearson's r ranged from 0.23 to 0.36, p < 0.01) than did the mfERG implicit time at both high and low contrasts across all subject groups. No consistent correlation was found between the mfERG and RNFL assessments for any group or contrast conditions. The responses of the local MOFO mfERG correlated with local perimetric sensitivity but not with RNFL thickness. CONCLUSION: Early functional changes in the diabetic retina seem to occur before morphological changes in the RNFL.

A retrospective analysis of the management of freckles and lentigines using four different pigment lasers on Asian skin.

BACKGROUND: The risk of post-inflammatory hyperpigmentation (PIH) is increased during freckles and lentigines treatment in Asians. OBJECTIVE: To determine the effectiveness and safety of using 595-nm long pulsed dye laser (LPDL), 755-nm LP Alexandrite laser, 532-nm QS Nd:YAG laser and 532-nm LP potassium-titanyl-phosphate (KTP) laser for the treatment of freckles or lentigines in Asian patients. METHODS: This is a retrospective study of 40 Chinese patients, who were divided into four groups based on treatment modality using four different pigment lasers. Each patient attended between 1 and 4 treatments (mean of 1.8), at 4-6 weeks intervals, depending on clinical response. Lesional clearance and PIH were assessed by two independent clinicians. RESULTS: Statistically significant improvement of global and focal facial pigmentation was found after treatment with LPDL, QS Nd:YAG and LP KTP lasers. No significant improvement was found after LP Alexandrite laser. PIH risk was 20% after LP Alexandrite treatment, 10% with QS Nd:YAG, and absent after LPDL and LP KTP treatment. CONCLUSION: A long pulse laser and small spot size appear to reduce the risks of lentigines treatment in darker skin types.

Increased arterial stiffness in patients with psoriasis is associated with active systemic inflammation.

BACKGROUND: Psoriasis is associated with premature atherosclerosis although the underlying mechanism remains unclear. OBJECTIVES: We sought to investigate the relationship between disease activity and systemic inflammation in patients with psoriasis, and macrovascular and microvascular function. METHODS: Fifty-two patients with psoriasis (mean ± SD age 44 ± 8 years; 38 men) were compared with 50 age- and sex-matched controls. Baseline demographics and high-sensitivity C-reactive protein (hs-CRP) level were recorded for each subject. Psoriatic disease activity was assessed using the Psoriasis Area and Severity Index (PASI). Arterial stiffness and endothelial function were assessed using brachial to ankle pulse wave velocity (baPWV) and digital hyperaemic response measured using the peripheral arterial tonometry (PAT) index. RESULTS: Patients with psoriasis had significantly higher hs-CRP (mean ± SD 5·3 ± 5·1 vs. 1·9 ± 1·6 mg L(-1), P < 0·01) and baPWV (mean ± SD 14·5 ± 2·5 vs. 13·2 ± 1·6 m s(-1) , P < 0·01) but not PAT index (mean ± SD 2·06 ± 0·59 vs. 2·10 ± 0·44, P = 0·70) than controls. There was significant correlation of hs-CRP with baPWV (r = 0·51, P < 0·01) and with PASI (r = 0·48, P < 0·01). Multiple linear regression analysis demonstrated that baPWV is independently correlated with age, fasting glucose and hs-CRP (P < 0·05), but does not predict PAT index. Each mg L(-1) increase in hs-CRP accounted for an increase in baPWV of +0·12 m s(-1) (95% confidence interval 0·01-0·22, P = 0·03). CONCLUSIONS: Young patients with psoriasis have increased arterial stiffness but not microvascular dysfunction compared with healthy controls. More importantly, hs-CRP positively correlated with, and independently predicted, arterial stiffness. This suggests that systemic inflammation in patients with psoriasis is associated with premature atherosclerosis.

A comparison of Q-switched and long-pulsed alexandrite laser for the treatment of freckles and lentigines in oriental patients.

BACKGROUND: Q-switched (QS) lasers are effective in the treatment of freckles and lentigines in Type I and II skin, with minimal adverse effects. Long pulsed (LP) lasers have been proposed to be more suitable for treatment of darker skin types. OBJECTIVES: To investigate the efficacy and adverse effects of using QS or LP Alexandrite laser for the treatment of freckles and lentigines in Oriental patients. METHODS: A prospective split-face study of 20 Chinese patients who were randomly assigned to undergo a single QS (50 nanosecond) or LP (100 microseconds) laser treatment to either side of their face was carried out. Two blinded physicians assessed clinical efficacy using visual analogue scales of pre- and post-treatment photographs. Subjective assessment was evaluated using questionnaires which detailed the degree of pain, erythema and edema sustained during treatment, and improvement and satisfaction levels at 4, 8, and 12 weeks. RESULTS: There was statistically significant improvement in pigmentation (P < 0.05) in both groups throughout the study, with no statistical difference found between the groups. Postinflammatory hyperpigmentation was more frequently found after QS treatment (22%), compared to LP treatment (6%). Majority of patients reported moderate to marked improvement in pigmentation throughout the study with both pulse widths, and correspondingly high levels of satisfaction rates. More severe pain, erythema and edema were experienced during QS Alexandrite treatment. CONCLUSION: LP Alexandrite is quick and effective, and carries a lower risk of adverse effects than QS Alexandrite, for the removal of freckles and lentigines in darker skin types.

A retrospective analysis of the management of acne post-inflammatory hyperpigmentation using topical treatment, laser treatment, or combination topical and laser treatments in oriental patients.

BACKGROUND: Post-inflammatory hyperpigmentation (PIH) is characterized by an acquired increase in pigmentation secondary to an inflammatory process, and is a commonly observed response to cutaneous injury in Fitzpatrick types III-VI patients. OBJECTIVES: To determine the effectiveness and safety of using topical treatment, laser treatment, or combination topical and laser treatments to treat acne PIH in Oriental patients. METHODS: This is a retrospective study of 34 randomly selected Chinese patients with acne PIH. They were divided into three groups, and treated with topical agents, 595 nm long pulsed dye laser and/or 1064 nm Q-switched Nd:YAG, or combination topical and laser treatments. An independent clinician assessed pre- and post-treatment photographs to determine efficacy and timing to visible and optimum improvement. RESULTS: There was significant global and focal improvement of acne PIH in patients in all three groups. However, no significant difference was found between the groups. An investigator global assessment showed improvement with all treatment modalities, with 70.6% moderate to marked improvement seen in the combination treatment group, compared to 55.6% in the laser only group, and 50% in the topical treatment only group. Visible and optimum improvement was seen by 3 months in majority of patients treated. One patient developed PIH as a result of laser treatment. CONCLUSION: Topical treatment, laser therapy, and combination topical and laser treatments all appear to be effective management strategies for acne PIH in Fitzpatrick types III and IV skin with little complications. Topical agents may be considered as first-line therapy for acne PIH, taking into consideration its effectiveness, ease of use and cost. Combined topical and laser therapy is also effective, and may be considered as second-line treatment.

Methotrexate versus traditional Chinese medicine in psoriasis: a randomized, placebo-controlled trial to determine efficacy, safety and quality of life.

BACKGROUND: Psoriasis is a common and chronic immune-mediated skin disorder, for which there is currently no cure. To our knowledge, this is the first randomized placebo-controlled trial comparing methotrexate and traditional Chinese medicine (TCM) in terms of efficacy, safety, and quality of life for the treatment of psoriasis. METHODS: In total, 61 patients with moderate to severe plaque psoriasis were randomized to receive treatment with methotrexate, TCM or placebo for 6 months. The primary outcome measure was the Psoriasis Area and Severity Index (PASI), and secondary outcome measures were the Physician's Global Assessment (PGA) and the Psoriasis Disability Index (PDI). RESULTS: In all, 50 patients completed the study and were included in the analysis. Dropout rates were highest in the TCM group. Mean PASI change from baseline at 6 months revealed an improvement of 73.9% of the methotrexate group, 15.1% of the TCM group and 32.0% of the placebo group. There was a significant difference between the three groups, with methotrexate showing greater effectiveness than the other two groups. No significant difference was found between the TCM and placebo groups. The methotrexate group also had greater improvement when assessed using the PGA and PDI. CONCLUSIONS: Our results verify the therapeutic effect of methotrexate for the management of psoriasis. Despite widespread belief and use of TCM in Asia for the treatment of psoriasis, we were unable to confirm the efficacy of TCM in this study.

Low-dose terlipressin plus banding ligation versus low-dose terlipressin alone in the prevention of very early rebleeding of oesophageal varices.

BACKGROUND: Very early rebleeding is frequently encountered in patients with acute oesophageal variceal bleeding. A trial was designed to assess the efficacy and safety in patients with no active bleeding at endoscopy, receiving banding ligation association with terlipressin to prevent very early rebleeding. METHODS: Patients with no active variceal bleeding at endoscopy were evaluated. Eligible patients were randomised to receive terlipressin infusion alone for 5 days (Terlipressin group) or banding ligation plus terlipressin infusion for 2 days (Combined group). Primary endpoints were treatment failure and very early rebleeding. RESULTS: The terlipressin group was composed of 46 patients and the Combined group was composed of 47 patients. Both groups were comparable in terms of baseline data. Forty-eight-hour haemostasis was achieved in 91% in the Terlipressin group and 98% in the Combined group (p = 0.20). Very early rebleeding within 48-120 h occurred in 7 patients (15%) in the Terlipressin group but not in any patients (0%) in the Combined group (p = 0.006). Treatment failure was 24% in the Terlipressin group and 2% in the Combined group (p = 0.002). Multivariate analysis revealed that treatment (OR 0.081; 95% CI 0.010 to 0.627) was the only predictive factor of very early rebleeding. Blood requirement was significantly lower in the Combined group than in the Terlipressin group. Complications and 6-week survival were similar in both groups. CONCLUSIONS: Combination of banding ligation and terlipressin infusion for 2 days was superior to only infusion of terlipressin for 5 days in the reduction of very early rebleeding and treatment failure in patients with inactive variceal bleeding at endoscopy. TRIAL REGISTRATION NUMBER: ISRCTN28353453.

Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan, and Singapore.

Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine whether an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R0) and the dispersion factor (k) from empirical data on clusters of epidemiologically linked coronavirus disease 2019 (COVID-19) cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.

Clinical trial: percutaneous acetic acid injection vs. percutaneous ethanol injection for small hepatocellular carcinoma--a long-term follow-up study.

BACKGROUND: The long-term outcome of percutaneous acetic acid injection (PAI) and percutaneous ethanol injection (PEI) for treating small hepatocellular carcinoma (HCC) remains unclear. AIM: To compare the long-term outcome of PAI vs. PEI for treating small HCC. METHODS: From July 1998 to July 2004, 125 patients with small HCC were enrolled. Seventy patients receiving PAI and 55 patients receiving PEI were enrolled. There were no significant differences in the clinical characteristics between the two groups. Tumour recurrence and survival rates were assessed. RESULTS: Mean follow-up time was 43 months. The local recurrence rate and new tumour recurrence rate were similar between the PAI and PEI groups. The PAI group had significantly better survival than the PEI group (P = 0.027). Multivariate analysis revealed that PAI was the significant factor associated with overall survival [PAI vs. PEI, RR: 0.639, 95% CI: (0.419-1.975), P = 0.038]. The treatment sessions required to achieve complete tumour necrosis were significantly fewer in the PAI group than in the PEI group (2.4 +/- 1.0 vs. 2.9 +/- 1.3, P = 0.018). CONCLUSION: Percutaneous acetic acid injection required fewer treatment sessions than PEI and provided better survival after long-term follow-up.

A prospective, randomized controlled trial of transjugular intrahepatic portosystemic shunt versus cyanoacrylate injection in the prevention of gastric variceal rebleeding.

BACKGROUND AND STUDY AIMS: Both endoscopic obturation and transjugular intrahepatic portosystemic shunts (TIPSs) have proven to be effective in preventing rebleeding from gastric varices. This study compared the efficacy and complications of these modalities. PATIENTS AND METHODS: Cirrhotic patients with acute bleeding from gastric varices were considered for inclusion. After initial control, eligible patients were randomly allocated to two groups: TIPS (n = 35) and obturation using cyanoacrylate (n = 37). In the cyanoacrylate group, treatment was repeated regularly until gastric varices were obliterated. Patients of both groups received regular follow-up. The end points were gastric variceal rebleeding or death. RESULTS: Stent shunt insertion was successful in all TIPS patients, and mean portal pressure gradient decreased from 21.4 +/- 7.5 mm Hg to 7.5 +/- 3.5 mm Hg ( P < 0.001). Variceal obliteration was achieved in 19 patients in the cyanoacrylate group (51 %) compared with seven TIPS patients (20 %) ( P < 0.02). After a median follow up of 33 months, upper gastrointestinal bleeding occurred in 15 TIPS patients (43 %) and 22 cyanoacrylate patients (59 %) ( P = 0.12). Rebleeding from gastric varices was encountered in four TIPS patients (11 %) and 14 cyanoacrylate patients (38 %) ( P = 0.014; odds ratio 3.6, 95 %CI 1.2 - 11.1). Blood transfusion requirements were lower in the TIPS group than in the cyanoacrylate group ( P < 0.01). Survival and frequency of complications were similar in both groups. CONCLUSIONS: TIPS proved more effective than glue injection in preventing rebleeding from gastric varices, with similar survival and frequency of complications.

Pigmentary disorders in Asian skin: treatment with laser and intense pulsed light sources.

The development of selective photothermolysis has enabled removal of targets such as melanin. Both lasers and intense pulsed light (IPL) sources have been used in the treatment of pigmented lesions, however careful selection is important to ensure success. This is especially true in darker skinned individuals where the risk of postinflammatory hyperpigmentation (PIH) is high. The advent of the Q-switched laser, IPL, and now fractional photothermolysis (Fraxel, Reliant Technologies) offers a variety of ways to treat epidermal and dermal pigmentary disorders.

YM155 down-regulates survivin and XIAP, modulates autophagy and induces autophagy-dependent DNA damage in breast cancer cells.

BACKGROUND AND PURPOSE: The aim of this study was to determine the potency and molecular mechanism of action of YM155, a first-in-class survivin inhibitor that is currently under phase I/II clinical investigations, in various drug-resistant breast cancers including the oestrogen receptor positive (ER(+) ) tamoxifen-resistant breast cancer and the caspase-3-deficient breast cancer. EXPERIMENTAL APPROACH: The potency of YM155 in SK-BR-3, MDA-MB-231, MCF7 and its tamoxifen-resistant sublines, TamR6, TamR7, TamR8, TamC3 and TamC6, were determined by MTT assay. Western blot analysis, flow cytometric analysis, reverse transcription-PCR, fluorescent microscopy and comet assay were used to determine the molecular mechanism of action of YM155 in different breast cancer cell lines. KEY RESULTS: YM155 was equally potent towards the parental ER(+) /caspase-3-deficient MCF7 breast cancer cells and its tamoxifen-resistant sublines in vitro. The ER(-) /HER2(+) SK-BR-3 breast cancer cells and the triple-negative/caspase-3-expressing metastatic aggressive MDA-MB-231 breast cancer cells were also sensitive to YM155 with IC50 values in the low nanomolar range. Targeting survivin by YM155 modulated autophagy, induced autophagy-dependent caspase-7 activation and autophagy-dependent DNA damage in breast cancer cells. Interestingly, YM155 also induced XIAP degradation and the degradation of XIAP might play an important role in YM155-induced autophagy in breast cancer cells. CONCLUSIONS AND IMPLICATIONS: YM155 is a potent survivin inhibitor that has potential for the management of various breast cancer subtypes regardless of the expression of ER, HER2 and caspase-3. Importantly, this study provides new insights into YM155's molecular mechanism of action and therapeutic potential in the treatment of tamoxifen-resistant breast cancer.

Normal ranges for vertebral height ratios and prevalence of vertebral fracture in Hong Kong Chinese: a comparison with American Caucasians.

We have established the normal ranges for vertebral height ratios and studied the prevalence of vertebral fracture in 481 Chinese women aged 70-79. Our results were compared with those of an American study with a similar methodology. Lateral spine radiographs centered at T8 and L3 were taken, and the anterior, middle, and posterior vertebral heights of each vertebra from T5 to L4 were measured. The means and standard deviations (SDs) of the anterior to posterior, middle to posterior, and posterior to posterior vertebral height ratios were derived after trimming the extreme values from the distribution. The Chinese had smaller vertebral size than the American Caucasians at all levels. Moreover, the anterior to posterior vertebral height ratios were consistently smaller in the Chinese than in the Americans from T10 onward. The means of other vertebral height ratios in the Chinese were similar to the American Caucasians, but the SDs were greater in the Chinese. The prevalence of vertebral fracture was 29% in the Chinese and 25% in the American Caucasians if a cut-off of 3 SD below the mean for vertebral height ratios was used. We conclude that population-specific means and SD should be used for defining vertebral fracture and that the prevalence of vertebral fracture is similar in Hong Kong Chinese and American Caucasians.