Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality. Endotoxin is ...an important source and also another marker of inflammation in patients with chronic kidney disease. The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis (PD) patients. The decline of residual renal function, peritonitis episodes, and cardiovascular events were also recorded. From July 2011 to June 2012, a randomised, double-blind, placebo-controlled trial was conducted in PD patients. The intervention group received one capsule of probiotics containing 109 cfu Bifobacterium bifidum A218, 109 cfu Bifidobacterium catenulatum A302, 109 cfu Bifidobacterium longum A101, and 109 cfu Lactobacillus plantarum A87 daily for six months, while the placebo group received similar capsules containing maltodextrin for the same duration. Levels of serum TNF-α, interferon gamma, IL-5, IL-6, IL-10, IL-17, and endotoxin were measured before and six months after intervention. 39 patients completed the study (21 in the probiotics group and 18 in the placebo group). In patients receiving probiotics, levels of serum TNF-α, IL-5, IL-6, and endotoxin significantly decreased after six months of treatment, while levels of serum IL-10 significantly increased. In contrast, there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months. In addition, the residual renal function was preserved in patients receiving probiotics. In conclusion, probiotics could significantly reduce the serum levels of endotoxin, pro-inflammatory cytokines (TNF-α and IL-6), IL-5, increase the serum levels of anti-inflammatory cytokine (IL-10), and preserve residual renal function in PD patients.
Morbidity and mortality from tuberculosis (TB) are high in Taiwan. We conducted a nationwide population‐based matched cohort study using data retrieved from the Taiwan's National Health Insurance ...Research Database to determine the impact of TB after liver transplantation (LT). During 2000–2011, we identified 3202 liver transplant recipients and selected subjects from the general population matched for age, sex, and comorbidities on the same index date of recognition of LT with a 1:10 ratio. The data were analyzed using Cox proportional hazards models. Compared to the matched cohort, liver transplant patients had a higher risk for TB (adjusted HR 2.25, 95% CI 1.65–3.05, p < 0.001), and those with TB showed higher mortality (HR 2.27, 95% CI 1.30–3.97, p = 0.004). Old age (HR 2.64, 95% CI 1.25–5.54, p = 0.011) and mammalian target of rapamycin inhibitors (mTORis) (HR 3.09, 95% CI 1.68–5.69, p < 0.001) were significant risk factors for TB in LT; mTORis were also associated with mortality after adjusting for confounders (HR 2.13, 95% CI 1.73–2.62, p < 0.001). Therefore, regular surveillance of TB and treatment of latent TB infection in high‐risk patients after LT are important, especially in TB‐endemic areas.
The authors demonstrate the high risk of tuberculosis in liver transplant recipients and define old age and mammalian target of rapamycin inhibitors as risk factors for tuberculosis after liver transplantation, which provides a practical guide to selecting high‐risk liver transplant patients for regular surveillance and treatment of tuberculosis.
Summary
Hepatitis A virus (HAV) is the most common food‐borne hepatitis in the world. The study objectives were (i) to describe the epidemiology of HAV‐related hospitalizations during 1997–2011 in ...Taiwan, (ii) to examine the age effect on the length of stay (LOS) in hospital and (iii) to study the factors associated with death. The hospitalized cases were identified from the Taiwan National Health Insurance Research Database between 1997 and 2011 by ICD‐9‐CM code of 070.0/070.1. Patient sex, birthday, dates of hospitalization and death were analysed. A total of 3990 HAV‐hospitalized cases, males 2467 (62%), were identified. The LOS increased as patients’ age increased. The overall mortality rate was 16.8 per 1000 hospitalizations. Males had significantly higher case fatality rate than females (20.7 vs 10.5 per 1000 cases). The adjusted odds ratio (aOR) for death rose by age and increased rapidly over 40 years of age. The aOR and 95% confidence interval 95%CI for aged 40–59 years and aged over 60 years were 7.89 (1.06–58.98) and 14.88 (2.02–109.40) compared to aged 0–19 years, respectively. Patients with chronic liver disease and cirrhosis had significantly higher risk of death (aOR=1.03 1.01–1.04), compared to those without liver disease. However, patients with liver disease, but no cirrhosis did not have higher risk of death (aOR=1.00 0.99–1.01). The aOR 95%CI for LOS >9 day was 3.26 (1.96–5.40) compared to cases with LOS ≤9 days. Male sex, age over 40 years, cirrhotic liver and long LOS are significant factors associated with death in HAV‐hospitalized cases.
Laboratory experiments indicate that direct growth of silicate grains via mutual collisions can only produce particles up to roughly millimeters in size. On the other hand, recent simulations of the ...streaming instability have shown that mm/cm-sized particles require an excessively high metallicity for dense filaments to emerge. Using a numerical algorithm for stiff mutual drag force, we perform simulations of small particles with significantly higher resolutions and longer simulation times than in previous investigations. We find that particles of dimensionless stopping time τs = 10-2 and 10-3 – representing cm- and mm-sized particles interior of the water ice line – concentrate themselves via the streaming instability at a solid abundance of a few percent. We thus revise a previously published critical solid abundance curve for the regime of τs ≪ 1. The solid density in the concentrated regions reaches values higher than the Roche density, indicating that direct collapse of particles down to mm sizes into planetesimals is possible. Our results hence bridge the gap in particle size between direct dust growth limited by bouncing and the streaming instability.
We studied paediatric patients with human adenovirus (HAdV) infection during the 2011 outbreak in northern Taiwan to define the clinical features of different HAdV genotypes in children.
Between ...January and December 2011, 637 patients <19 years of age exhibited culture-confirmed adenoviral infection in Chang Gung Memorial Hospital, and provided specimens available for genotyping by multiplex real-time PCR. Clinical data were collected retrospectively.
Excluding five cases with multiple genotypes, 632 cases were included for analysis. Three genotypes were identified, including HAdV-3 (429/632; 67.6%), HAdV-7 (144/632; 22.6%) and HAdV-2 (59/632; 9.8%). Median age was 4.58 years (range 2 months to 18 years), with children infected with HAdV-3 significantly older (82.9% >3 years; p <0.001). Of the 621 inpatients, 98.2% had fevers and all exhibited respiratory symptoms, 75 patients (12.1%) had lower respiratory tract infections, 20 (3.2%) required intensive care (HAdV-2: 1; HAdV-3: 8; and HAdV-7: 11), and three died (all HAdV-7-infected). HAdV-3-infected patients were significantly more likely to have upper respiratory symptoms and a high serum C-reactive protein level >100 mg/L, whereas leucocytosis (white blood cell count >15 000/mm3) was more common in HAdV-2-infected patients (p 0.007). HAdV-7 infections were significantly associated with a longer duration of fever, leucopenia (white blood cell count <5000/mm3), thrombocytopenia (platelet count <150 000/mm3), lower respiratory tract infections, a longer length of hospital stay, and requiring intensive care (all p <0.001).
Childhood HAdV-2, HAdV-3 and HAdV-7 infections may exhibit different clinical manifestations. Although HAdV-3 was the most prevalent genotype observed during the 2011 Taiwan outbreak, HAdV-7 caused more severe disease characteristics and outcomes.
Malignant pleural effusions (MPEs) are often observed in lung cancer, especially adenocarcinoma. Epidermal growth factor receptor (EGFR) gene mutations are usually detected in lung adenocarcinoma. ...The purpose of the present study was to investigate the EGFR mutation rate in MPEs of lung adenocarcinoma. Between June 2005 and December 2006, 136 MPEs from lung adenocarcinoma were collected for EGFR mutation detection. In addition, between April 2001 and November 2004, 91 surgically resected specimens of lung adenocarcinoma from patients without MPEs were assessed for EGFR mutation. The EGFR mutation rate was significantly higher in the patients with MPEs than in the patients without (68.4% versus 50.5%). The EGFR mutation rate in patients with MPEs was not associated with sex, smoking history, age or cancer stage. By multivariate analysis, an age of <65 yrs, never smoking, Eastern Cooperative Oncology Group performance status 0-1, and EGFR mutation were significantly associated with a longer overall survival for lung adenocarcinoma patients with MPEs. The patients with malignant pleural effusions related to lung adenocarcinoma had a higher epidermal growth factor receptor gene mutation rate than the patients from whom surgically resected specimens were taken. Epidermal growth factor receptor tyrosine kinase inhibitors may be the treatment of choice for lung adenocarcinoma with malignant pleural effusions in east Asia.
Summary
Background
Clearance of hepatitis B surface antigen (HBsAg) indicates clinical control of hepatitis B virus (HBV) infection. However, little is known about the impact of viral genomic ...variations on HBsAg loss.
Methods
We explored the association between viral genomic factors and HBsAg loss in 2121HBeAg‐negative patients. HBV pre‐core stop codon (1896) and basal core promoter (BCP) (1762/1764) sequences were determined in patients with HBV DNA ≥200 IU/mL (N = 1693). The effect of HBV genotype on HBsAg loss was further validated in the whole cohort of 3445 HBsAg carriers.
Results
The cumulative lifetime (age 28–75 years) incidence of HBsAg loss was 50.4% in 2121 HBeAg‐negative patients. We found that genotype C, but not pre‐core stop codon or BCP mutants, was associated with HBsAg loss. Compared to genotype B patients, genotype C patients had higher lifetime chance of HBsAg loss, with hazard ratio of 1.8 (95% confidence interval: 1.4–2.4). Multivariable analysis showed that male sex, elevated ALT levels, lower serum HBV DNA and HBsAg levels, and genotype C infection were associated with higher chance of HBsAg loss independently. We then performed sensitivity analysis, which re‐included HBeAg‐positive, cirrhotic and treatment‐experienced patients, and confirmed the robustness of our results in 3445 HBsAg carriers.
Conclusion
Genotype C infection, compared to genotype B, is associated with a higher lifetime chance of HBsAg loss in Asian HBV carriers.
This study aims to evaluate the efficacy of HBV vaccination as an alternative preventive measure against de novo HBV infection in pediatric living donor liver transplantation (LDLT). Sixty recipients ...were enrolled in this study. Thirty received grafts from anti‐HBc(+) donors, and another 30 received grafts from anti‐HBc(−) donors. HBV vaccine was given pretransplant to every candidate. Posttransplant, lamivudine was routinely given to recipients receiving anti‐HBc(+) grafts for about 2 years. Forty‐seven (78%) recipients achieved high levels of anti‐HBs titer (>1000 IU/L). Two (3.3%) recipients developed de novo HBV infection where one received an anti‐HBc(−) graft and another received an anti‐HBc(+) graft. Both recipients were in the lower anti‐HBs titer group (<1000 IU/L). The incidence of de novo HBV infection was significantly higher in the lower titer group (15.4% vs. 0%, p = 0.04). The median follow‐up period was 51 months in recipients with anti‐HBc(−) grafts and 57 months in those with anti‐HBc(+) grafts. Active immunization is an effective method to prevent de novo HBV infection. It can result in high levels of anti‐HBs titer (>1000 IU/L) which may prevent de novo HBV infection in pediatric patients with efficient primary vaccination undergoing LDLT.
Active immunization is an effective method to prevent de novo HBV infection in pediatric patients with efficient primary vaccination undergoing living donor liver transplantation.
Portal hyperperfusion in a small‐size liver graft is one cause of posttransplant graft dysfunction. We retrospectively analyzed the potential risk factors predicting the development of portal ...hyperperfusion in 43 adult living donor liver transplantation recipients. The following were evaluated: age, body weight, native liver disease, spleen size, graft size, graft‐to‐recipient weight ratio (GRWR), total portal flow, recipient portal venous flow per 100 g graft weight (RPVF), graft‐to‐recipient spleen size ratio (GRSSR) and portosystemic shunting. Spleen size was directly proportional to the total portal flow (p = 0.001) and RPVF (p = 0.014). Graft hyperperfusion (RPVF flow >250 mL/min/100 g graft) was seen in eight recipients. If the GRSSR was <0.6, 5 of 11 cases were found to have graft hyperperfusion (p = 0.017). The presence of portosystemic shunting was significant in decreasing excessive RPVF (p = 0.059). A decrease in portal flow in the hyperperfused grafts was achieved by intraoperative splenic artery ligation or splenectomy. Spleen size is a major factor contributing to portal flow after transplant. The GRSSR is associated with posttransplant graft hyperperfusion at a ratio of <0.6.
Spleen size is a major factor contributing to portal flow after transplant, and may predict graft hyperperfusion in live donor liver transplantation.
Sinus stenosis occasionally occurs in dural arteriovenous fistulas. Sinus stenosis impedes venous outflow and aggravates intracranial hypertension by reversing cortical venous drainage. This study ...aimed to analyze the likelihood of sinus stenosis and its impact on cerebral hemodynamics of various types of dural arteriovenous fistulas.
Forty-three cases of dural arteriovenous fistula in the transverse-sigmoid sinus were reviewed and divided into 3 groups: Cognard type I, type IIa, and types with cortical venous drainage. Sinus stenosis and the double peak sign (occurrence of 2 peaks in the time-density curve of the ipsilateral drainage of the internal jugular vein) in dural arteriovenous fistula were evaluated. "TTP" was defined as the time at which a selected angiographic point reached maximum concentration. TTP of the vein of Labbé, TTP of the ipsilateral normal transverse sinus, trans-fistula time, and trans-stenotic time were compared across the 3 groups.
Thirty-six percent of type I, 100% of type IIa, and 84% of types with cortical venous drainage had sinus stenosis. All sinus stenosis cases demonstrated loss of the double peak sign that occurs in dural arteriovenous fistula. Trans-fistula time (2.09 seconds) and trans-stenotic time (0.67 seconds) in types with cortical venous drainage were the most prolonged, followed by those in type IIa and type I. TTP of the vein of Labbé was significantly shorter in types with cortical venous drainage. Six patients with types with cortical venous drainage underwent venoplasty and stent placement, and 4 were downgraded to type IIa.
Sinus stenosis indicated dysfunction of venous drainage and is more often encountered in dural arteriovenous fistula with more aggressive types. Venoplasty ameliorates cortical venous drainage in dural arteriovenous fistulas and serves as a bridge treatment to stereotactic radiosurgery in most cases.