Relative lateral wall thickness is an improved predictor for postoperative lateral wall fracture after trochanteric femoral fracture osteosynthesis.

Lateral wall thickness is a known predictor for postoperative stability of trochanteric femoral fractures and occurrence of secondary lateral wall fractures. Currently, the AO/OTA classification relies on the absolute lateral wall thickness (aLWT) to distinguish between stable A1.3 and unstable A2.1 fractures that does not take interpersonal patient differences into account. Thus, a more individualized and accurate measure would be favorable. Therefore, we proposed and validated a new patient-specific measure-the relative lateral wall thickness (rLWT)-to consider individualized measures and hypothesized its higher sensitivity and specificity compared with aLWT. First, in 146 pelvic radiographs of patients without a trochanteric femoral fracture, the symmetry of both caput-collum-diaphyseal angle (CCD) and total trochanteric thickness (TTT) was assessed to determine whether the contralateral side can be used for rLWT determination. Then, data of 202 patients were re-evaluated to compare rLWT versus previously published aLWT. Bilateral symmetry was found for both CCD and TTT (p ≥ 0.827), implying that bone morphology and geometry of the contralateral intact side could be used to calculate rLWT. Validation revealed increased accuracy of the rLWT compared with the gold standard aLWT, with increased specificity by 3.5% (Number Needed to Treat = 64 patients) and sensitivity by 1% (Number Needed to Treat = 75 patients). The novel rLWT is a more accurate and individualized predictor of secondary lateral wall fractures compared with the standard aLWT. This study established the threshold of 50.5% rLWT as a reference value for predicting fracture stability in trochanteric femoral fractures.

Carcinogenesis of Male Oral Submucous Fibrosis Alters Salivary Microbiomes.

Most oral squamous cell carcinoma (OSCC) tumors arise from oral premalignant lesions. Oral submucous fibrosis (OSF), usually occurring in male chewers of betel quid, is a premalignant stromal disease characterized by a high malignant transformation rate and high prevalence. Although a relationship between the inhabited microbiome and carcinogenesis has been proposed, no detailed information regarding the oral microbiome of patients with OSF exists; the changes of the salivary microbiome during cancer formation remain unclear. This study compared the salivary microbiomes of male patients with OSCC and a predisposing OSF background (OSCC-OSF group) and those with OSF only (OSF group). The results of high-throughput sequencing of the bacterial 16S rRNA gene indicated that OSF-related carcinogenesis and smoking status significantly contributed to phylogenetic composition variations in the salivary microbiome, leading to considerable reductions in species richness and phylogenetic diversity. The microbiome profile of OSF-related malignancy was associated with increased microbial stochastic fluctuation, which dominated the salivary microbiome assembly and caused species co-occurrence network collapse. Artificial intelligence selection algorithms consistently identified 5 key species in the OSCC-OSF group: Porphyromonas catoniae, Prevotella multisaccharivorax, Prevotella sp. HMT-300, Mitsuokella sp. HMT-131, and Treponema sp. HMT-927. Robust accuracy in predicting oral carcinogenesis was obtained with our exploratory and validation data sets. In functional analysis, the microbiome of the OSCC-OSF group had greater potential for S-adenosyl-l-methionine and norspermidine synthesis but lower potential for l-ornithine and pyrimidine deoxyribonucleotide synthesis and formaldehyde metabolism. These findings indicated that the salivary microbiome plays important roles in modulating microbial metabolites during oral carcinogenesis. In conclusion, our results provided new insights into salivary microbiome alterations during the malignant transformation of OSF.

No infectious risk of COVID-19 patients with long-term fecal 2019-nCoV nucleic acid positive.

OBJECTIVE: It has recently been reported that some COVID-19 patients have long-term positive fecal nucleic acid after discharging from the hospital with negative nucleic acid in the respiratory tract, but it is unclear whether COVID-19 patients with positive long-term fecal nucleic acid tests have the risk of self-infection. PATIENTS AND METHODS: From January 25, 2020 to March 9, 2020, 5 COVID-19 patients with negative respiratory tract nucleic acid and positive fecal nucleic acid were observed and studied to explore whether these patients can re-infect themselves. Five patients with COVID-19 accompanied by diarrhea as the main gastrointestinal symptoms were carefully observed through clinical symptoms, imaging and other auxiliary examinations. The RT-PCR technology was used to continuously detect fecal and respiratory viral nucleic acids. The IgM antibody was detected on the 7th day of admission and IgM/IgG at the time of discharge. RESULTS: All 5 patients had symptoms of fever and diarrhea upon admission. The fecal nucleic acid was positive, as well as the throat swab was positive. All COVID-19 patients had positive IgM antibodies on the 7th day of admission and positive IgM and IgG at the time of discharge, and there were no abnormalities in the gastrointestinal examination on discharge. All 5 fecal nucleic acid tests were positive at the time of discharge. After continuous dynamic follow-up for 3-15 days, no clinical symptoms recurred, and the last nucleic acid test was negative. CONCLUSIONS: There is no risk of self-infection for COVID-19 patients with long-term 2019-nCoV nucleic acid positive in feces.

Deferred treatment with a fixed-dose combination of sofosbuvir-velpatasvir for chronic hepatitis C virus genotype 1, 2, 4 and 6 infection.

Sofosbuvir-velpatasvir is approved for the treatment of chronic hepatitis C virus (HCV) infection. In this single-arm, open-label, phase 3, deferred treatment study, we investigated the efficacy and safety of sofosbuvir-velpatasvir among patients randomized to the placebo group in the ASTRAL-1 study. Patients received sofosbuvir-velpatasvir (400/100 mg) once daily for 12 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response 12 weeks after the end of therapy (SVR12). The primary safety endpoint was any adverse events (AEs) leading to the permanent discontinuation of study drug. Overall, 108/111 (97%, 95% confidence interval [CI], 92%-99%) achieved SVR12, and only one patient had virological failure. SVR12 was achieved by 61/63 (97%, 95%CI, 89%-100%) genotype 1 patients, 20/20 (100%; 95%CI, 83%-100%) with genotype 2, 19/19 (100%; 95%CI, 82%-100%) with genotype 4 and 8/9 (89%; 95% CI, 52%-100%) with genotype 6. All (19/19; 95%CI, 82-100) patients with cirrhosis and all (31/31, 95%CI, 89-100) with prior treatment experience achieved SVR12. The safety profile during treatment was similar to that observed in patients receiving placebo treatment. The most common AEs were headache, fatigue and nausea. One patient (1%) discontinued treatment due to an AE of gallbladder carcinoma, which was not considered related to treatment. Of five reported serious AEs, none were considered related to study drug. Sofosbuvir-velpatasvir for 12 weeks was effective and well tolerated among untreated and previously treated patients with HCV genotype 1, 2, 4 or 6 infection, including those with compensated cirrhosis (ClinicalTrials.gov NCT02346721).

Baseline Factors Associated With Improvements in Decompensated Cirrhosis After Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection.

BACKGROUND & AIMS: Treatment with direct-acting antiviral (DAA) agents can reduce Model for End-Stage Liver Disease and Child-Pugh-Turcotte (CPT) scores in patients with decompensated cirrhosis caused by hepatitis C virus. However, many of these patients still die or require liver transplantation. We collected data on baseline features of patients and aimed to develop a scoring system to predict response to DAA therapy. METHODS: We performed a retrospective analysis of data from 4 trials on the effects of sofosbuvir-based therapy in patients with hepatitis C virus-associated decompensated cirrhosis (502 of CPT class B and 120 of CPT class C). In these trials, patients were given 12 or 24 weeks of treatment with ledipasvir, sofosbuvir, and ribavirin or velpatasvir, sofosbuvir, and/or ribavirin, or 48 weeks of treatment with sofosbuvir and ribavirin. We collected demographic, clinical, treatment response, and laboratory data from patients and tested their associations with patient outcomes at 36 weeks. The primary outcome was factors associated with reduction of CPT score to class A. RESULTS: The presence of ascites or encephalopathy, serum level of albumin <3.5 g/dL or alanine aminotransferase <60 U/L, and body mass index >25 kg/m2 were associated with an increased risk of not achieving a reduction in CPT to class A, independent of sustained viral response to therapy. Serum level of albumin <2.8 g/dL and abnormal level of bilirubin were associated with an increased risk of liver transplantation or death. We developed a scoring system based on 5 baseline factors (body mass index, encephalopathy, ascites, and serum levels of alanine aminotransferase and albumin) associated significantly with patient outcomes, which we called the "BE3A score." For patients with scores of 4-5, the hazard ratio for reduction of CPT score to class A was 52.3 (95% confidence interval, 15.2-179.7). CONCLUSIONS: We identified 5 baseline factors (body mass index, encephalopathy, ascites, and serum levels of alanine aminotransferase and albumin) associated with a reduction of CPT score to class A in patients with hepatitis C virus-associated decompensated cirrhosis receiving DAA therapy. We developed a predictive score using these factors, called the BE3A score, which can be used as a shared decision-making tool, quantifying the potential benefits of DAA therapy for patients with decompensated cirrhosis.

Linezolid vs. vancomycin in treatment of methicillin-resistant staphylococcus aureus infections: a meta-analysis.

OBJECTIVE: This study aims to explore the treatment of methicillin-resistant staphylococcus aureus (MRSA) infection by using meta-analysis method. MATERIALS AND METHODS: Pubmed/Medline, ScienceDirect, CNKI and Wanfang database were comprehensively searched to obtain the randomized controlled trials (RCTs) on linezolid and vancomycin in the treatment of MRSA infections. We extracted features and information of included studies and selected appropriate effect models based on the heterogeneity test results. The funnel plot was used to analyze publication bias. RESULTS: A total of seven RCTs including 5376 cases met the inclusion criteria. Meta-analysis showed that the clinical cure rate of linezolid group was higher than that of vancomycin group after treatment (OR = 1.85; 95% CI: 1.33-2.59, p<0.001) and follow-up (OR = 1.49; 95% CI: 1.17-1.91, p=0.001). In the microbiologically evaluable patients, end of therapy (EOT) MRSA clearance rate, and test of cure (TOC) MRSA clearance rate of linezolid were superior to those of vancomycin. CONCLUSIONS: Based on the combined analysis of randomized controlled trials, the efficacy of linezolid should be better than that of vancomycin in the treatment of infections caused by MRSA, but conclusions still need to be further validated by more well-designed RCTs of a large sample.

Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection.

BACKGROUND: Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options. METHODS: We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks. Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir-voxilaprevir (163 patients) or sofosbuvir-velpatasvir (151 patients) for 12 weeks. An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. RESULTS: In the three active-treatment groups, 46% of the patients had compensated cirrhosis. In POLARIS-1, the rate of sustained virologic response was 96% with sofosbuvir-velpatasvir-voxilaprevir, as compared with 0% with placebo. In POLARIS-4, the rate of response was 98% with sofosbuvir-velpatasvir-voxilaprevir and 90% with sofosbuvir-velpatasvir. The most common adverse events were headache, fatigue, diarrhea, and nausea. In the active-treatment groups in both trials, the percentage of patients who discontinued treatment owing to adverse events was 1% or lower. CONCLUSIONS: Sofosbuvir-velpatasvir-voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed. (Funded by Gilead Sciences; POLARIS-1 and POLARIS-4 ClinicalTrials.gov numbers, NCT02607735 and NCT02639247 .).

Ledipasvir-Sofosbuvir Plus Ribavirin in Treatment-Naive Patients With Hepatitis C Virus Genotype 3 Infection: An Open-Label Study.

BACKGROUND: Patients chronically infected with genotype 3 hepatitis C virus (HCV) have faster disease progression and are less responsive to current direct-acting antiviral regimens than patients infected with other genotypes. We conducted an open-label trial to evaluate the safety, tolerability, and efficacy of ledipasvir and sofosbuvir plus ribavirin in patients with genotype 3 HCV infection. METHODS: We enrolled treatment-naive patients with and without compensated cirrhosis at 15 sites in Canada. All patients were treated with ledipasvir-sofosbuvir (90 mg and 400 mg) plus weight-based ribavirin for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Secondary endpoints included evaluation of baseline and treatment-emergent drug resistance. RESULTS: Of the 111 patients enrolled, 105 (95%) had subtype 3a HCV and 39 (35%) had compensated cirrhosis. SVR12 was achieved by 99 of 111 patients (89%; 95% confidence interval, 82%-94%). Of the 39 patients with cirrhosis, 31 (79%) achieved SVR12, compared with 68 of 72 (94%) patients without cirrhosis. No treatment-emergent resistance mutations occurred in those who failed treatment. One patient discontinued treatment due to liver cancer and died 22 days after treatment discontinuation. The most common adverse events were fatigue (51%), headache (36%), and nausea (23%). CONCLUSIONS: In this multicenter trial involving treatment-naive patients with genotype 3 HCV, 12 weeks of ledipasvir-sofosbuvir provided a high level of SVR in those without cirrhosis. CLINICAL TRIALS REGISTRATION: NCT02413593.

Sofosbuvir-velpatasvir with ribavirin for 24 weeks in hepatitis C virus patients previously treated with a direct-acting antiviral regimen.

The optimal retreatment strategy for patients chronically infected with hepatitis C virus who experience virologic failure after treatment with direct-acting antiviral-based therapies remains unclear. In this multicenter, open-label, phase 2 study, we evaluated the efficacy and safety of a fixed-dose combination of sofosbuvir-velpatasvir (400 mg/100 mg) plus weight-adjusted ribavirin administered for 24 weeks in patients who did not achieve sustained virologic response after prior treatment with direct-acting antiviral regimens that included the nucleotide analogue nonstructural protein 5B inhibitor sofosbuvir plus the nonstructural protein 5A inhibitor velpatasvir with or without the nonstructural protein 3/4A protease inhibitor voxilaprevir. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response at 12 weeks after the cessation of treatment. In total, 63 of 69 (91%; 95% confidence interval, 82%-97%) patients achieved sustained virologic response at 12 weeks, including 36 of 37 (97%; 95% confidence interval, 86%-100%) patients with hepatitis C virus genotype 1 infection, 13 of 14 (93%; 95% confidence interval, 66%-100%) patients with genotype 2 infection, and 14 of 18 (78%; 95% confidence interval, 52%-94%) patients with genotype 3 infection. Most adverse events were of mild or moderate severity. The most frequently reported adverse events were fatigue, nausea, headache, insomnia, and rash. One patient (1%) with genotype 1a infection discontinued all study drugs due to an adverse event (irritability). CONCLUSION: Retreatment of patients who previously failed direct-acting antiviral-based therapies with sofosbuvir-velpatasvir plus ribavirin for 24 weeks was well tolerated and effective, particularly those with hepatitis C virus genotype 1 or 2 infection. (Hepatology 2017;66:1083-1089).

Severe hypoglycemia and hip fracture in patients with type 2 diabetes: a nationwide population-based cohort study.

Hypoglycemia is a major concern in glycemic control. Using the Taiwan National Health Insurance Research Database, we found that the risk of hip fracture was associated with emergency or hospitalization visits of severe hypoglycemia in patients with type 2 diabetes; greater visits were associated with higher incidence of hip fracture. INTRODUCTION: The objective of the study was to assess the risk of hip fracture among patients with type 2 diabetes mellitus (T2DM) and severe hypoglycemia. METHODS: Using the National Health Insurance Research database in Taiwan, we identified 2588 patients with T2DM who had developed severe hypoglycemia from 2001 to 2009. A comparison cohort who had never developed severe hypoglycemia was frequency matched at a ratio of approximately 1:2. Multivariate Cox proportional hazard regression analysis was used to evaluate the risk of hip fracture. RESULTS: During a median follow-up period of 3.9 years, there were 219 hip fracture events in 5173 comparison cohorts and 148 hip fracture events in 2588 hypoglycemia cohorts. The incidence of hip fracture was higher in patients with severe hypoglycemia than without severe hypoglycemia (17.19 vs. 8.83 per 1000 person-years; adjusted HR 1.71, 95% CI = 1.35-2.16). Approximately half of the individuals developed hip fracture within 2 years from the first occurrence of severe hypoglycemia. There was a significant associated trend towards increased hip fracture risk with increasing average visit of severe hypoglycemia per year (p for trend <0.001). Medication analysis showed that patients taking sulfonylurea alone, insulin alone, and insulin secretagogues combined with insulin had a higher associated risk to develop hip fracture. CONCLUSIONS: Severe hypoglycemia was associated with a higher risk to develop hip fracture. The more the visits of severe hypoglycemia per year indicated the higher associated risk in patients with T2DM. Fall is likely an important reason for severe hypoglycemia in relation to increased risk of hip fracture.

Sofosbuvir and Velpatasvir for the Treatment of Hepatitis C Virus in Patients Coinfected With Human Immunodeficiency Virus Type 1: An Open-Label, Phase 3 Study.

BACKGROUND: A safe, simple, effective, and pan-genotypic regimen to treat hepatitis C virus (HCV) infection in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains a medical need. We assessed the efficacy and safety of the NS5B polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir for HCV in patients coinfected with HIV-1. METHODS: This phase 3, open-label, single-arm study at 17 sites in the United States enrolled patients with HCV of any genotype and HIV-1 coinfection, including those with compensated cirrhosis. All patients received sofosbuvir-velpatasvir once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Efficacy and safety were assessed in all patients receiving at least 1 dose of treatment. RESULTS: Of 106 patients, 91 (86%) were men, 48 (45%) were black, and 19 (18%) had cirrhosis. SVR12 was achieved by 101 of 106 (95% [95% confidence interval {CI}, 89%-99%]) patients: 74 of 78 (95% [95% CI, 87%-99%]) with genotype 1; all 11 (100% [95% CI, 72%-100%]) with genotype 2; 11 of 12 (92% [95% CI, 62%-100%]) with genotype 3; and all 5 (100% [95% CI, 48%-100%]) with genotype 4. All 19 patients with cirrhosis had SVR12. Two patients relapsed, 2 were lost to follow-up, and 1 withdrew consent. Two discontinued treatment due to adverse events and 2 had serious adverse events. The most common adverse events were fatigue (25%), headache (13%), upper respiratory tract infection (8%), and arthralgia (8%). CONCLUSIONS: Sofosbuvir-velpatasvir for 12 weeks was safe and provided high rates of SVR12 in patients coinfected with HCV and HIV-1. CLINICAL TRIALS REGISTRATION: NCT02480712.

The mortality and direct medical costs of osteoporotic fractures among postmenopausal women in Taiwan.

UNLABELLED: This study estimated the fracture-related mortality and direct medical costs among postmenopausal women in Taiwan by fracture types and age groups by utilizing a nationwide population-based database. Results demonstrated that hip fractures constituted the most severe and expensive complication of osteoporosis across fracture sites. INTRODUCTION: The aims of the study were to evaluate the risk of death and direct medical costs associated with osteoporotic fractures by fracture types and age groups among postmenopausal women in Taiwan. METHODS: This nationwide, population-based study was based on data from the National Health Insurance Research Database in Taiwan. Female patients aged 50 years and older in the fracture case cohort were matched in 1:1 ratio with randomly selected subjects in the reference control cohort by age, income-related insurance amount, urbanization level, and the Charlson comorbidity index. There were two main outcome measures of the study: age-differentiated mortality and direct medical costs in the first and subsequent years after osteoporotic fracture events among postmenopausal women. The bootstrap method by resampling with replacement was conducted to generate descriptive statistics of mortality and direct medical costs of the case and control cohorts. Student's t tests were then performed to compare mortality and costs between the two cohorts. RESULTS: A total of 155,466 postmenopausal women in the database met the inclusion criteria for the fracture case cohort, including 22,791 hip fractures, 72,292 vertebral fractures, 15,621 upper end humerus (closed) fractures, 36,774 wrist fractures, and 7,988 multiple fractures. Analytical results demonstrated that patients experiencing osteoporotic fractures were at considerable excess risk of death and incurred substantially higher treatment costs, notably for hip fractures. Furthermore, results also revealed that the risk of mortality increased with advancing age across the spectrum of fracture sites. CONCLUSIONS: The present study confirmed an excess mortality and higher direct medical costs associated with osteoporotic fractures. Moreover, hip fractures constituted the most severe and expensive complication of osteoporosis among fracture types.

Government Response to the Discovery of a Rabies Virus Reservoir Species on a Previously Designated Rabies-Free Island, Taiwan, 1999-2014.

Taiwan had been considered rabies free since 1961. In 2013, Taiwan confirmed the detection of rabies virus in wild Taiwan ferret-badgers. Up to December 2014, there have been 423 rabies-confirmed ferret-badgers and three cases of spillover infection into non-reservoir hosts. Genetic analysis indicates that TFBV is distinct from all other known rabies virus variants. To date, ferret-badger rabies is known to occur only in China and Taiwan. The temporal dynamics of rabid ferret-badgers in Taiwan suggests that the epizootic appears to have subsided to enzootic levels as of December 2014. According to the current epidemiologic data, there is only one TFBV strain in Taiwan. TFBV is still sequestered to the mountainous regions. Humans are at risk mainly through exposure to the virus from infected domestic meso-carnivores, mainly dogs and cats. Dogs and cats should be vaccinated to establish an immunological barrier to stop the spread of the disease from mountainous regions to domestic meso-carnivores.

The impact of joint range of motion limitations on health-related quality of life in patients with haemophilia A: a prospective study.

In patients with haemophilia A, repeated occurrences of haemarthrosis and synovitis lead to limitations in range of motion (ROM) of major joints. However, the effect of limitations in joint ROM on health-related quality of life (HRQOL) in these patients has not been studied previously. The aim of this study was to assess the impact of ROM limitations of 10 major joints (bilateral shoulders, elbows, hips, knees and ankles), combined with other possibly influential factors, on HRQOL in patients with haemophilia A. The ROM limitations in 13 movements and pain intensity of the 10 major joints were measured. The socio-demographic and clinical data were recorded. Short-Form 36 was used as the HRQOL measurement. Eighteen patients (mean age: 36.9 years) were included. Hip ROM limitations, knee ROM limitations and hip pain intensity predicted physical functioning scale (P < 0.001; adjusted R2 = 0.553). Shoulder ROM limitations and age predicted role limitation were due to emotional problems scale (P < 0.001; adjusted R2 = 0.373). Elbow ROM limitations and haemophilia severity predicted mental health scale (P = 0.001; adjusted R2 = 0.320). Hip ROM limitations predicted social functioning scale (P = 0.041; adjusted R2 = 0.091). Educational level and elbow ROM limitations predicted vitality scale (P < 0.001; adjusted R2 = 0.416). The ROM limitations of hip, knee, shoulder and elbow could be predictors for HRQOL in patients with haemophilia A. Improving ROM of major joints could be an appropriate treatment strategy to enhance HRQOL in these patients.

ERG expression is associated with increased risk of biochemical relapse following radical prostatectomy in early onset prostate cancer.

PURPOSE: ERG expression has been proposed to signify molecular subtype of PCA. However, its significance in early onset prostate cancer (PCA) is not characterized. MATERIALS AND METHODS: ERG protein expression was investigated in a cohort of 121 men diagnosed with localized PCA at <50 years of age with a mean follow-up time of 65.7 months. ERG was correlated to patients' outcome and clinical-pathological parameters using univariate and multivariate analysis. RESULTS: ERG expression was detected in 76/118 (64.4 %) analyzable patients' samples and showed interfocal heterogeneity (differences between foci) in 17/118 (14.4 %) patients. There was significant association between ERG expression and Gleason score (p = 0.022), but not with any other clinical-pathologic parameter, including pre-surgical PSA levels, tumor volume, pathological stage, surgical margin or lymph-vascular invasion. ERG had significant effect on the rate of biochemical relapse following radical prostatectomy, with ERG positive patients showing higher relapse rates vs. ERG negative patients (p = 0.007). However, considering time till biochemical relapse post-radical prostatectomy, ERG expression showed positive insignificant trends (p = 0.071). Notably, and of great significance, in this cohort of early onset disease, none of the ERG negative PCA patients exhibited biochemical relapse. CONCLUSION: The study results suggest that ERG expression may be of added prognostic value in localized prostate cancer in patients with early onset PCA. However, the issue of ERG interfocal heterogeneity observed may require the evaluation of several tumor foci to assess ERG status per case. Incorporating ERG status into existing nomograms may be of added prognostic value in patients with early onset PCA.

Rosiglitazone is effective to improve renal damage in type-1-like diabetic rats.

A marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats) showing diabetic nephropathy. It has been documented that klotho is the target gene of PPARγ. However, the effect of PPARγ agonist on klotho expression in kidney of STZ rats remains obscure. Thus, we used rosiglitazone (TZD) as PPARγ agonist to investigate the effect on renal dysfunction in STZ rats. Treatment of TZD reversed the lower levels of PPARγ, klotho, and FGFR1 expressions in kidneys of STZ rats without the correction of hyperglycemia. Also, renal functions and structural defeats were improved by TZD treatment. Taken together, oral administration of TZD may improve STZ-induced diabetic nephropathy due to restoration of the expression of klotho axis through an increase in PPARγ expression without changing blood glucose in rats.

Lateral femoral wall thickness. A reliable predictor of post-operative lateral wall fracture in intertrochanteric fractures.

Although the importance of lateral femoral wall integrity is increasingly being recognised in the treatment of intertrochanteric fracture, little attention has been put on the development of a secondary post-operative fracture of the lateral wall. Patients with post-operative fractures of the lateral wall were reported to have high rates of re-operation and complication. To date, no predictors of post-operative lateral wall fracture have been reported. In this study, we investigated the reliability of lateral wall thickness as a predictor of lateral wall fracture after dynamic hip screw (DHS) implantation. A total of 208 patients with AO/OTA 31-A1 and -A2 classified intertrochanteric fractures who received internal fixation with a DHS between January 2003 and May 2012 were reviewed. There were 103 men and 150 women with a mean age at operation of 78 years (33 to 94). The mean follow-up was 23 months (6 to 83). The right side was affected in 97 patients and the left side in 111. Clinical information including age, gender, side, fracture classification, tip-apex distance, follow-up time, lateral wall thickness and outcome were recorded and used in the statistical analysis. Fracture classification and lateral wall thickness significantly contributed to post-operative lateral wall fracture (both p < 0.001). The lateral wall thickness threshold value for risk of developing a secondary lateral wall fracture was found to be 20.5 mm. To our knowledge, this is the first study to investigate the risk factors of post-operative lateral wall fracture in intertrochanteric fracture. We found that lateral wall thickness was a reliable predictor of post-operative lateral wall fracture and conclude that intertrochanteric fractures with a lateral wall thickness < 20.5 mm should not be treated with DHS alone.

The effects of an injury to the brain on bone healing and callus formation in young adults with fractures of the femoral shaft.

In patients with traumatic brain injury and fractures of long bones, it is often clinically observed that the rate of bone healing and extent of callus formation are increased. However, the evidence has been unconvincing and an association between such an injury and enhanced fracture healing remains unclear. We performed a retrospective cohort study of 74 young adult patients with a mean age of 24.2 years (16 to 40) who sustained a femoral shaft fracture (AO/OTA type 32A or 32B) with or without a brain injury. All the fractures were treated with closed intramedullary nailing. The main outcome measures included the time required for bridging callus formation (BCF) and the mean callus thickness (MCT) at the final follow-up. Comparative analyses were made between the 20 patients with a brain injury and the 54 without brain injury. Subgroup comparisons were performed among the patients with a brain injury in terms of the severity of head injury, the types of intracranial haemorrhage and gender. Patients with a brain injury had an earlier appearance of BCF (p < 0.001) and a greater final MCT value (p < 0.001) than those without. There were no significant differences with respect to the time required for BCF and final MCT values in terms of the severity of head injury (p = 0.521 and p = 0.153, respectively), the types of intracranial haemorrhage (p = 0.308 and p = 0.189, respectively) and gender (p = 0.383 and p = 0.662, respectively). These results confirm that an injury to the brain may be associated with accelerated fracture healing and enhanced callus formation. However, the severity of the injury to the brain, the type of intracranial haemorrhage and gender were not statistically significant factors in predicting the rate of bone healing and extent of final callus formation.

Elevated serum dehydroepiandrosterone sulphate level correlates with increased risk for metabolic syndrome in the elderly men.

BACKGROUND: The previous studies regarding the association between endogenous dehydroepiandrosterone (DHEA) sulphate level and metabolic syndrome are inconsistent. This study aimed to investigate such relationship in elderly Taiwanese men. MATERIALS AND METHODS: Five hundred and eighty-five elderly Taiwanese men (mean age 68.7 +/- 8.3 years) were enrolled as the baseline cohort population in 2000. In addition to a questionnaire, body mass index (BMI), blood pressure, fasting blood glucose, lipids, albumin and serum DHEA-S levels were measured for each participant. Metabolic syndrome was based on the definition by the America Heart Association/National Heart Lung Blood Institute. RESULTS: The prevalence of metabolic syndrome was 33.3%. Using multivariate logistic regression analyses with adjustments for age, smoking, alcohol, physical activities, albumin and BMI, there was a positive relationship between serum DHEA-S level and metabolic syndrome. The highest DHEA-S quartile group had increased risk for metabolic syndrome (odds ratio = 2.68, 95% confidence interval: 1.44-5.01, P < 0.01) compared with the lowest quartile group. The mean serum DHEA-S level increased with increasing number of metabolic syndrome components. CONCLUSIONS: The prevalence of metabolic syndrome increases with elevated DHEA-S levels among elderly Taiwanese men. Thus, elevated serum DHEA-S level should be treated as an important risk factor for metabolic syndrome in elderly men.