Ming-Jen Sheu

Long-term survival and predictors for mortality among dialysis patients in an endemic area for chronic liver disease: a national cohort study in Taiwan

BackgroundPatients with end-stage renal disease (ESRD) are at a higher risk for chronic hepatitis, liver cirrhosis (LC) and mortality than the general population. Optimal modalities of renal replacement therapy for ESRD patients with concomitant end-stage liver disease remain controversial. We investigated the long-term outcome for chronic liver disease among dialysis patients in an endemic area.MethodsUsing Taiwan’s National Health Insurance claim data (NHRI-NHIRD-99182), We performed a longitudinal cohort study to investigate the impact of comorbidities on mortality in dialysis patients. We followed up 11293 incident hemodialysis (HD) and 761 peritoneal dialysis (PD) patients from the start of dialysis until the date of death or the end of database period (December 31, 2008). A Cox proportional hazards model was used to identify the risk factors for all-cause mortality.ResultsPatients receiving PD tended to be younger and less likely to have comorbidities than those receiving HD. At the beginning of dialysis, a high prevalence rate (6.16 %) of LC was found. Other than well-known risk factors, LC (hazard ratio [HR] 1.473, 95 % CI: 1.329-1.634) and dementia (HR 1.376, 95 % CI: 1.083-1.750) were also independent predictors of mortality. Hypertension and mortality were inversely associated. Dialysis modality and three individual comorbidities (diabetes mellitus, chronic lung disease, and dementia) interacted significantly on mortality risk.ConclusionsLC is an important predictor of mortality; however, the effect on mortality was not different between HD and PD patients.

Predictors of Longterm Mortality in Patients with and without Systemic Lupus Erythematosus on Maintenance Dialysis: A Comparative Study

Objective. To compare the prognosis of patients with and without systemic lupus erythematosus (SLE) on dialysis and to determine the factors that affect survival after dialysis. Methods. We used the Taiwan National Health Insurance Research Database (NHRI-NHIRD-99182) and collected data on patients who started maintenance dialysis between 2001 and 2003. Patients were followed from the initiation of dialysis until death, discontinuation of dialysis, or the end of 2008. We did a Kaplan-Meier analysis of the cohort and used multivariate Cox regression analysis to identify significant predictors of survival. Results. Of the 22,394 dialysis patients studied, 303 (1.35%) had SLE. Hypertension and diabetes were the 2 most common comorbidities associated with dialysis for patients with and without SLE. After adjusting for age, sex, dialysis modality, and comorbidities, we found no significant survival difference between the 2 patient groups after 8 years of followup. Multivariate analysis showed that increased mortality in the patient group without SLE (p < 0.05) was associated with older age (≥ 45 years), male sex, initial choice of hemodialysis, diabetes mellitus, heart failure, coronary artery disease, cerebrovascular disease, and malignancy. In the patient group with SLE, independent predictors of mortality (p < 0.05) were older age (≥ 65 years), male sex, and diabetes mellitus. Conclusion. The longterm survival outcome was similar between patients with and without SLE who were on dialysis. The factors affecting patient mortality were not identical in these 2 groups.

Epidemiology and mortality among dialysis patients with acute coronary syndrome: Taiwan National Cohort Study

BACKGROUND Patients with end-stage renal disease (ESRD) on dialysis have poor outcomes after acute coronary syndrome (ACS). Epidemiological data for Asian patients are scarce. METHODS This longitudinal cohort study investigated the incidence, risk factors, and outcomes of ACS in 19,974 ESRD incident dialysis patients in the Taiwan National Health Insurance research Database between January 1999 and December 2001. The follow-up period was from the start of dialysis to the date of death, end of dialysis, or December 31, 2008. RESULTS ACS was diagnosed in 1785 patients during follow-up (1.78/100 person-years): 832 (46.6%) had acute myocardial infarction (AMI), 681 (38.2%) underwent cardiac catheterization, 398 (22.3%) underwent percutaneous transluminal coronary angioplasty (PTCA), and 50 (2.8%) underwent coronary artery bypass grafting. Male (HR 1.35, 95% CI: 1.23-1.49) and elderly (HR 3.289, 95% CI: 2.71-4.00) patients had a high rate of ACS. Patients with baseline comorbidities (diabetes mellitus, hypertension, congestive heart failure, coronary artery disease, dysrhythmia, and other cardiac and chronic obstructive lung diseases) had a higher incidence of ACS than did those without. Overall in-hospital mortality was 9.7%. The cumulative 6-month post-hospitalization survival rate was 79.3%; the 1-year rate was 72.3%. Being elderly (≥ 65 years old), and having DM or AMI were associated with an increased risk for mortality; PTCA was associated with a decreased risk (HR 0.77, 95% CI: 0.66-0.91). CONCLUSION ESRD dialysis patients had a high incidence of ACS and mortality. Being male, elderly and having baseline comorbidities were independent risk factors for ACS. Coronary intervention is the possible benefits for dialysis patients.

Deficiency in asparagine synthetase expression in rectal cancers receiving concurrent chemoradiotherapy: Negative prognostic impact and therapeutic relevance

Locally advanced rectal cancers are currently treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery, but risk stratification and final outcomes remain suboptimal. In this study, we identify and validate targetable metabolic drivers relevant to the prognosis of patients with rectal cancer treated with CCRT. Using a published transcriptome of rectal cancers, we found that asparagine synthetase (ASNS) gene significantly predicted the response to CCRT. From 172 patients with rectal cancer, the expression levels of ASNS, using immunohistochemistry assays, were further evaluated in tumor specimens initially obtained by using colonoscopy. Expression levels of ASNS were further correlated with major clinicopathological features and clinical survivals in this valid cohort. ASNS deficiency was significantly related to advanced posttreatment tumor (T3, T4; P = .015) and nodal status (N1, N2; P = .004) and inferior tumor regression grade (P < .001). In survival analyses, ASNS deficiency was significantly associated with shorter local recurrence-free survival (LRFS; P = .0039), metastasis-free survival (MeFS; P = .0001), and disease-specific survival (DSS; P = .0006). Furthermore, ASNS deficiency was independently predictive of worse outcomes for MeFS (P = .012, hazard ratio = 3.691) and DSS (P = .022, hazard ratio = 2.845), using multivariate analysis. ASNS deficiency is correlated with poor therapeutic response and worse survivals in patients with rectal cancer receiving neoadjuvant CCRT. These findings indicate that ASNS is a prognostic factor with therapeutic potential for treating rectal cancer.

Increased incidence of herpes zoster in adult patients with peptic ulcer disease: a population-based cohort study

BACKGROUND Peptic ulcer disease (PUD) has been linked to immunological dysfunctions and malnutrition—both are predictors of herpes zoster(HZ). We hypothesized that PUD patients might have a greater risk for developing HZ. METHODS Using the longitudinal National Health Insurance Research Database, we conducted a retrospective population-based cohort study to evaluate the incidence of HZ in adult PUD patients and controls matched by age and gender. Kaplan-Meier analysis and Cox regression were conducted to compare differences in the development of HZ. The effects of comorbidities on the risk of HZ and the associations between different risk factors of PUD and HZ were assessed by subgroup analyses. RESULTS We identified 41 229 adults PUD patients and 41 229 controls. Over an 8-year follow-up, the cumulative incidence of HZ in PUD patients(11.76/1000 person-years) was significantly higher than controls(6.56/1000 person-years) (P<0.001, by log-rank test). After adjusting for potential confounders, PUD was an independent predictor for HZ (adjusted hazard ratio: 1.77, 95% confidence interval 1.64–1.91, P<0.001). Major risk factors of PUD were non-selective nonsteroidal anti-inflammatory drugs (nsNSAID) usage and Helicobacter pylori infection. Subgroup analyses revealed that PUDis an independent predictor of HZ after excluding the potential confounding effects of the comorbidities; PUD associated with the combination of nsNSAID usage and Helicobacter pylori infection leads to greatest risk of HZ. CONCLUSIONS Adults with PUD are at increased risk of HZ independently compared with the general population. Further studies are required to clarify the nature of the associations between HZ and PUD.

Overexpression of ANXA1 confers independent negative prognostic impact in rectal cancers receiving concurrent chemoradiotherapy

Neoadjuvant concurrent chemoradiation therapy (CCRT) is an increasingly common therapeutic strategy for rectal cancer. Clinically, it remains a major challenge to predict therapeutic response and patient outcomes after CCRT. Annexin I (ANXA1), encoded by ANXA1, is a Ca2+/phospholipid-binding protein that mediates actin dynamics and cellular proliferation, as well as suggesting tumor aggressiveness and predicting therapeutic response in certain malignancies. However, expression of ANXA1 has never been reported in rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of ANXA1 expression in patients with rectal cancer following neoadjuvant CCRT. We identified ANXA1 as associated with resistance to CCRT through data mining from a published transcriptomic dataset. Its immunoexpression was retrospectively assessed using H scores on pre-treatment biopsies from 172 rectal cancer patients treated with neoadjuvant CCRT followed by curative surgery. Results were correlated with clinicopathological features, therapeutic response, tumor regression grade (TRG), and metastasis-free survival (MeFS), as well as local recurrent-free survival (LRFS) and disease-specific survival (DSS). High expression of ANXA1 was associated with advanced pre-treatment tumor status (T3, T4, p = 0.022), advanced pre-treatment nodal status (N1, N2, p = 0.004), advanced post-treatment tumor status (T3, T4, p < 0.001), advanced post-treatment nodal status (N1, N2, p = 0.001) and inferior TRG (p = 0.009). In addition, high expression of ANXA1 emerged as an adverse prognosticator for DSS (p < 0.0001), LRFS (p = 0.0001) and MeFS (p = 0.0004). Moreover, high expression of ANXA1 also remained independently prognostic of worse DSS (hazard ratio [HR] = 3.998; p = 0.007), LRFS (HR = 3.206; p = 0.028) and MeFS (HR = 3.075; p = 0.017). This study concludes that high expression of ANXA1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients treated with neoadjuvant CCRT.

Dual view capsule endoscopic lens design

A dual view capsule endoscopic (DVCE) lens is proposed with front view and back view functions. This is a hybrid lens with a catadioptric mirror and an aspherical surface to support both view functions. The field of view (FOV) for the front view function is 90 degrees. The FOV for the back view function is 260 to 290 degrees. The TV distortion for the front view and back view function is under 30% and 25%. The corner relative illuminations for the two view functions are above 0.53. The Modulation Transfer Function (MTF) performance at the Nyquist Frequency for the two view functions can be kept above 0.35, even under tolerance they can remain above 0.2. Moreover, the telecentric conditions at the image plane of the DVCE system can support constant magnification through focusing. This condition can reduce the measurement error by slightly defocusing of the lens. Thus, the two view functions can offer physicians a wide viewing angle to deal with lesions over the fold.

Decrease in seroprevalence of Hepatitis A after the implementation of nationwide disposable tableware use in Taiwan

BackgroundTaiwan is an endemic area of viral hepatitis, including hepatitis A, which is transmitted mainly from the fecal-oral route. In order to reduce the transmission through food intake, the government implemented a policy of nationwide disposal tableware use in public eating places in 1982. We conducted a study to estimate the seroprevalence of Hepatitis A in a group of workers in Taiwan in 2005, determine the risk factors, and compare seroprevalence to published estimates in Taiwan to evaluate changes in the seroprevalence after the implementation of the nationwide disposal tableware use.MethodsWe recruited workers of an industrial park during their annual health examinations in 2005 and measured their anti-hepatitis A virus IgG titer using microparticle enzyme immunoassay. We compared the seroprevalence across different birth cohorts within the study population and also analyzed data from previous studies.ResultsThe overall sero-positive rate was 22.0% in the 11,777 participants. The rate was much lower among those who were covered by the program since birth (born after 1982) in comparison with those who were not (2.7% vs. 25.3%, p < 0.001). From the analyses of data from pervious studies, we found the age-specific rates were similar in cohorts born in or after 1982 across studies conducted in different time periods but decreased with the calendar year in cohorts born before 1982. In particular, the age-specific seroprevalence dropped to less than one third in a three-year period among those who were born around 1982.ConclusionsData from both the current and previous studies in different time periods supported the effectiveness of disposal tableware in preventing the transmission of hepatitis A.

Is peptic ulcer disease a risk factor of postherpetic neuralgia in patients with herpes zoster

Postherpetic neuralgia is the most common complication of herpes zoster which is caused by a reactivation of latent varicella zoster virus. The pathogenesis of postherpetic neuralgia may involve peripheral and central mechanisms. Reported risk factors for postherpetic neuralgia include female gender, old age, diminished cell-mediated immunity and nutritional deficiencies. Based on our clinical observation which revealed that peptic ulcer disease (PUD) is one of the common comorbidities in patients with postherpetic neuralgia, we hypothesize that herpes zoster patients with PUD may be at a greater risk for the development of postherpetic neuralgia due to their impaired cellular immunity and depressed nutritional status. Major causes of PUD include Helicobacter pylori infection and usage of ulcerogenic medications. Patients with H. pylori infection may develop T cell dysfunctions and nutritional deficiencies including vitamin C, iron, cobalamin, carotenes and alpha-tocopherol. Ulcerogenic medications such as nonsteroidal anti-inflammatory drugs and steroids have been found not only to be ulcerogenic but also immunosuppressive to T cells. In addition, usage of steroids and nonsteroidal anti-inflammatory drugs may cause deficiencies of alpha-tocopherol, carotenes, cobalamin, iron, zinc and vitamin C. Vitamin C, carotenes and alpha-tocopherol are anti-inflammatory and the major oxidant scavengers in the aqua phase and biomembranes. Deficiencies of these nutrients may induce dysregulated inflammation and oxidative damage leading to neuropathic pain in patients with herpes zoster. Furthermore, nutrient deficiencies including zinc, iron, cobalamin and vitamin C are associated with dysregulation of Ca(v)3.2 T-channels and N-methyl-D-aspartate receptors, upregulation of nitric oxide synthase, the increase of nitric oxide formation and dysfunction of central norepinephrine inhibitory pain pathway. Prospective cohort studies are suggested to test the hypothesis. We further propose that a follow-up study that contains two groups of herpes zoster patients, i.e., with or without gastroendoscopy-proven PUD, be conducted to determine their incidence of postherpetic neuralgia. In addition, despite of the high proportion of zoster patients having been treated with antiviral therapies, prevention and treatment of postherpetic neuralgia remain challenging in clinical practice. The potential risk of postherpetic neuralgia in zoster patients with PUD could mean that physicians need to pay more attention to the comorbidity--PUD in patients with herpes zoster and treat PUD earlier in order to prevent the development of postherpetic neuralgia.

Design of a bi-directional illumination system for a dual view capsule endoscope

ABSTRACT The capsule endoscope is an important tool for the intestinal examination. But the main disadvantage of the traditional capsule endoscope is the limited field of view. In order to solve this problem, the dual view capsule endoscope (DVCE) was developed. In this work, a dual view illumination system is designed for a DVCE. The dual view illumination system is divided into two sub-systems with a front view illumination lens and a back view illumination lens. The Bézier curves for the front view and back view illumination lenses are used for optimization, based on which we change the radiation pattern of the LED so that the dual view illumination design can support energy for the front view and back view simultaneously while achieving low power consumption and high efficiency. Moreover, a non-uniform illumination process is used to compensate for the problem of uniformity and relative illumination for the DVCE lens. Through this design, we can obtain a uniformity of 91% and an efficiency of 25.2% for front view illumination and uniformity of 91% and an efficiency of 23.5% for back view illumination. Finally, tolerance analysis can also be completed for mass production.