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 .).

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.

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

Interleukin-10 (-592 C/A) and interleukin-12B (+16974 A/C) gene polymorphisms and the interleukin-10 ATA haplotype are associated with periodontitis in a Taiwanese population.

BACKGROUND AND OBJECTIVE: Single nucleotide polymorphisms are assumed to be associated with the differential production of cytokines. We evaluated gene polymorphisms of interleukin-10 (-592C>A, -819C>T and -1082G>A) and interleukin-12B (+16974) in patients with chronic periodontitis (n = 145) and generalized aggressive periodontitis (n = 65) in comparison with healthy controls (n = 126). MATERIAL AND METHODS: Gene promoter polymorphisms were analyzed by polymerase chain reaction with sequence-specific primers. Genotype and allele frequencies were analyzed using the chi-square test and logistic regression analysis. RESULTS: The interleukin-10 -592 polymorphism showed significant differences among the three groups (p = 0.0330). The genotype frequencies of the -592 locus between the chronic periodontitis and healthy control groups were significantly different (AC vs. AA: odds ratio = 0.33). The combination ATA/ATA seemed to be associated with susceptibility to generalized aggressive periodontitis (p = 0.0276). Patients with the composite ATA/ACC were less likely to develop chronic periodontitis (p = 0.0248). The CC genotype of interleukin-12B (+16974) was related to chronic periodontitis (CC vs. AA, p = 0.0211; CC vs. AA+AC, p = 0.0187). The AC heterozygosity of interleukin-12B was significantly lower in chronic periodontitis vs. healthy controls (p = 0.0500). CONCLUSION: The interleukin-10 gene polymorphism at position -592C>A may be associated with a lower risk for development of chronic periodontitis. The interleukin-10 haplotype ATA is associated with generalized aggressive periodontitis. On the other hand, interleukin-12B genetic variants at position +16974 are associated with susceptibility to chronic periodontitis.

Obesity and hepatitis B infection are associated with increased risk of metabolic syndrome in university freshmen.

OBJECTIVE: To investigate the prevalence of metabolic syndrome and its associated risk factors in a cohort of university freshmen. DESIGN: A cross-sectional study in a university health center in North Taiwan. SUBJECTS: A total of 8226 students (mean age: 19.2+/-2.3 years) receiving pre-entrance health examinations and lifestyle questionnaires during the 2005-2006 academic year were recruited. MEASUREMENTS: A fasting plasma glucose, lipids, uric acid and hepatitis B serology were measured for each subject. The prevalence of metabolic syndrome and its individual components were examined using the America Heart Association and National Heart Lung Blood Institute criteria. The risk factors for metabolic syndrome were identified using a multivariate logistic regression analysis. RESULTS: The prevalence of overweight, obesity and metabolic syndrome was 12.7% (17.0% in men and 7.6% in women), 13.0% (18.4% in men and 6.4% in women) and 4.6% (6.4% in men and 2.4% in women). The risk for metabolic syndrome increased with an increase of body mass index and plasma uric acid level, and decreased with the vigorous physical activity and current alcohol drinking. Furthermore, as compared to subjects with seroprotective titers from hepatitis B vaccination (anti-HBs(+) and anti-HBc(-)), those without protective titers of anti-HBs after vaccination or without hepatitis B infection (anti-HBs(-) and anti-HBc(-)) had 34% higher risk for metabolic syndrome, and those with natural infection of hepatitis B (anti-HBc(+)) had 58% higher risk for metabolic syndrome. CONCLUSIONS: Overweight, obesity and metabolic syndrome were more common among men than women in university freshmen. Hepatitis B vaccination with anti-HBs(+) was associated with a lower risk of metabolic syndrome as compared to anti-HBs(-). However, hepatitis B infection presented with anti-HBc(+) was associated with a higher risk of metabolic syndrome. The interplay between hepatitis B infection, hepatitis B vaccination and metabolic syndrome needs further investigation.

The metabolic syndrome increases cardiovascular mortality in Taiwanese elderly.

BACKGROUND: The prevalence of the metabolic syndrome (MetS) is high among the elderly. However, evidence that mortality increases with MetS is rare. In this study, we investigated the relationship between MetS, cardiovascular disease (CVD) and all cause mortality in the elderly. MATERIALS AND METHODS: A total 10 547 participants, aged 65 years and older, of baseline cohort were recruited from four nationwide Health Screening Centres in Taiwan from 1998 to 1999. The metabolic syndrome was defined according to the America Heart Association/National Heart Lung Blood Institute definition. Cox proportional hazards regression analyses were used to estimate the relative risks (RRs) of CVD and all cause mortality for those with MetS for up to 8 years of follow-up. RESULTS: The baseline prevalence of MetS was 50.1% (45.6% in men and 54.4% in women, respectively). A total of 1312 participants died; of these, 300 participants died from CVD. Adjusted for age, gender, smoking, total cholesterol and estimated glomerular filtration rate, the RRs for CVD and all cause mortality among participants with MetS were 1.48 (95% confidence interval = 1.16-1.90) and 1.16 (1.03-1.30), respectively, for participants compared to those without MetS. The mean RRs for CVD, however, ranged from 1.21 to 5.31 among different combinations of MetS components. CONCLUSION: The elderly with MetS, compared to those without MetS, had a higher CVD and all cause mortality in Taiwan. Furthermore, different combinations of MetS components posed different risks to the mortality, which deserves further research in the future.

Clinical implications of minimal residual disease monitoring by quantitative polymerase chain reaction in acute myeloid leukemia patients bearing nucleophosmin (NPM1) mutations.

To explore the validity and prognostic significance of minimal residual disease detection by quantitative polymerase chain reaction (qPCR) in patients of acute myeloid leukemia (AML) bearing Nucleophosmin (NPM1) mutations, we quantified mutants in 194 bone marrow samples from 38 patients with a median follow-up time of 20.6 months. Following induction chemotherapy, a median of 2.78 log decline in mutant copy number was observed. Relapse was always accompanied by significant increase of mutant numbers (P<0.001). After achieving complete remission (CR), the mutant copy number was significantly higher in patients with subsequent relapse than in those remaining in continuous CR (P<0.001). Presence of detectable mutants after treatment predicted relapse if no further chemotherapy was administered. Furthermore, the patients with any rise of mutant signals during serial follow-up had 3.2-fold increase of relapse risk compared to those with persistently low or undetectable signals (P<0.001). Patients who could achieve mutant reduction to <0.1% of internal control had significantly longer overall survival (OS) (P=0.004) and relapse-free survival (RFS) (P<0.001). Failure to achieve 2 logs of reduction after consolidation predicted shorter OS (P=0.01) and RFS (P=0.001). In conclusion, qPCR monitoring may have prognostic impact in AML patients with NPM1 mutations.

Comparison of the association of age with the infection of Salmonella and Salmonella enterica Serovar Typhimurium in Pekin ducks and Roman geese.

Nontyphoid Salmonella have a broad host range in poultry and mammals, and serovar Typhimurium is a threat to public health. In this study, normal and sick ducks and geese were collected from 12 farms in Taiwan to investigate the age-associated infection of Salmonella and Salmonella Typhimurium in Roman geese (Anser anser domesticus) and Pekin ducks (Anas platyrhynchos domesticus). In normal birds, the prevalence of Salmonella differed between species, and with age [e.g., 1-wk group, 37.5% (30/80) for ducks and 5.2% (6/116) for goslings (P < 0.05) vs. 4-wk group, 1% (1/96) for ducks and 12.1% (21/174) for geese]. Salmonella Typhimurium was identified from the visceral organs of moribund young geese suffering with colibacillosis and riemerellosis isolated from 2 goose farms (farm A and B, respectively). At farm B, 22.9% (27/118) of 4-wk geese with diarrhea were Salmonella Typhimurium-positive compared with 4.6% (8/174) of 4-wk normal geese. All Salmonella Typhimurium strains except one harbored a 94.7-kb virulence plasmid. Subcutaneous injection of Salmonella Typhimurium isolate 91NGL1 resulted in different clinical signs and pathogenesis between ducks and geese. In addition, the mean infectivity dose ratios of ducks to geese were 3.2 and 85.0 for 4- and 12-d birds, respectively, suggesting that goslings were more susceptible to Salmonella Typhimurium and resistance to Salmonella Typhimurium increased with age, especially for ducks. Therefore, Salmonella Typhimurium infection should be more common in goose farms than in duck farms, especially in the younger birds.