New n-p Junction Floating Gate to Enhance the Operation Performance of a Semiconductor Memory Device.

To lower the charge leakage of a floating gate device and improve the operation performance of memory devices toward a smaller structure size and a higher component capability, two new types of floating gates composed of pn-type polysilicon or np-type polysilicon were developed in this study. Their microstructure and elemental compositions were investigated, and the sheet resistance, threshold voltages and erasing voltages were measured. The experimental results and charge simulation indicated that, by forming an n-p junction in the floating gate, the sheet resistance was increased, and the charge leakage was reduced because of the formation of a carrier depletion zone at the junction interface serving as an intrinsic potential barrier. Additionally, the threshold voltage and erasing voltage of the np-type floating gate were elevated, suggesting that the performance of the floating gate in the operation of memory devices can be effectively improved without the application of new materials or changes to the physical structure.

Association between Extreme Values of Markers of Chronic Kidney Disease: Mineral and Bone Disorder and 5-Year Mortality among Prevalent Hemodialysis Patients.

BACKGROUND/AIMS: We examined the association between markers of chronic kidney disease - mineral and bone disorder (CKD-MBD) and mortality in hemodialysis (HD) patients. METHODS: We retrospectively reviewed the association between markers of CKD-MBD and mortality in 1,126 HD patients from 2009 to 2013 with baseline (B), time-average (TA), and time-dependent (TD) Cox regression models. RESULTS: Hypercalcemia (10.9-11.9 mg/dL) indicated an increased risk of all-cause mortality (TA: hazard ratio [HR] 3.49; p = 0.01). Hypophosphatemia (2.0-2.5 mg/dL) was significantly associated with an increased risk of all-cause mortality (TA: HR 5.18; p = 0.01). Hypophosphatemia (<2.0 mg/dL) was significantly associated with an increased risk of cardiovascular mortality in all models. Intact parathyroid hormone levels <60 and >1,500 pg/mL indicated an increased risk of all-cause mortality (TA: HR 1.64; p = 0.02; TD: HR 2.26; p = 0.02). CONCLUSION: Extreme values of CKD-MBD markers are associated with mortality risk in HD patients. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=478972.

Proteinuria and baseline renal function predict mortality and renal outcomes after sirolimus therapy in liver transplantation recipients.

BACKGROUND: Chronic kidney disease is a significant complication after liver transplantation (LT), but the role of pre-existing renal insufficiency and proteinuria remains unclear among LT recipients receiving sirolimus. METHODS: We assessed the effects of proteinuria and baseline renal function on long-term renal and survival outcomes among 576 LT recipients who received SRL in a medical center between 2005 and 2014. Renal outcomes were the incidences of >50% reduction in their baseline estimated glomerular filtration rate and end stage kidney disease requiring renal replacement therapy. Proteinuria was identified using morning dipstick results (≥30 mg/dL) at baseline and within the first year after the initiation of SRL therapy. A Kaplan-Meier analysis was performed to estimate time to event. Factors associated with the outcomes were determined using the Cox proportional hazards model with a significance level set at P <0.05. RESULTS: During the study period, renal function deteriorated in 135 (25.3%) patients and 68 (11.8%) patients died. Persistent and new onset proteinuria contributed to a high rate of mortality and the deterioration of renal function (both log-rank tests, P <0.0001). After adjustments, new onset proteinuria within the first year after the initiation of SRL therapy increased the risk of deteriorating renal function, regardless of baseline estimated glomerular filtration rate. Moreover, pre-existing (hazard ratio = 1.91; P <0.001) and new onset diabetes (hazard ratio = 2.34; P <0.0001) were significantly associated with new onset proteinuria among SRL users. CONCLUSIONS: These findings support the effective monitoring and early management of the predictable risks for proteinuria among new SRL users in order to delay the progression of renal disease.

An association between time-varying serum alkaline phosphatase concentrations and mortality rate in patients undergoing peritoneal dialysis: a five-year cohort study.

The relationship between serum alkaline phosphatase (ALP) concentrations and mortality in peritoneal dialysis (PD) patients is rarely reported. We enrolled 667 PD patients in one PD centre in Taiwan to retrospectively examine the association between three ALP concentrations (baseline, time-averaged, time-dependent) and mortality over a 5-year period (2011-2015). Baseline data collection included demographics, clinical, and laboratory parameters. Multivariable-adjusted Cox models were used to analyse the association. Four ALP quartiles were defined at the baseline: ≤62, 63-82, 83-118, and ≥119 U/L. Of 667 patients, 65 patients died, of which 8 patients died due to cardiovascular disease. Females were predominant in the higher ALP quartiles, and 24-h urine volume was significantly proportionately decreased in the higher ALP quartiles. ALP quartiles expressed by the three models were not associated with all-cause or cardiovascular mortalities after adjusting for demographics, liver function, bone metabolism, mortality, hemoglobin, and 24-h urine volume. In conclusion, ALP concentrations were not associated with death risk in PD patients over the 5-year period.

Association between the Achievement of Target Range CKD-MBD Markers and Mortality in Prevalent Hemodialysis Patients in Taiwan by Using the Kidney Disease: Improving Global Outcomes Clinical Guidelines.

Background. This study evaluated the association between achieving target chronic kidney disease-mineral and bone disorder (CKD-MBD) marker levels and mortality in Taiwanese hemodialysis (HD) patients. Target levels were based on the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Methods. We performed a retrospective medical record review of 1126 HD patients between 2009 and 2013. A logistic regression model was used to evaluate the relationship between achieving target marker levels and the risk for all-cause and cardiovascular (CV) mortality. Reference target ranges were 7.9 ≤ calcium (Ca) ≤ 9.9 mg/dL, 2.4 ≤ phosphate (P) ≤ 4.7 mg/dL, and 144 ≤ intact parathyroid hormone (iPTH) ≤ 648 pg/mL. Results. Achievement of target P levels was associated with a lower risk for all-cause mortality compared to achievement of either target Ca or iPTH levels. Achieving target P + iPTH levels (OR 1.32) was associated with a lower odds ratio for all-cause mortality compared to achieving target Ca + P (OR 1.66) and Ca + iPTH (OR 1.43) levels. Similar trends were observed for CV mortality risk. Conclusions. The present study demonstrated that achieving serum P levels within the KDIGO target range is the most important factor for lowering mortality in HD patients.

Serum Potassium Profile and Associated Factors in Incident Peritoneal Dialysis Patients.

BACKGROUND/AIMS: Abnormal potassium profiles are common in peritoneal dialysis (PD) patients. We studied the factors associated with serum potassium profiles in incident PD patients. METHODS: Patients were enrolled from two hospital-facilitated PD centers from May 2013 to May 2016 and January 2009 to December 2015. A total of 319 incident PD patients were examined for factors associated with serum potassium profile. Average serum potassium levels were obtained for analysis during the first 3 months after PD initiation. Clinically factors and parameters associated with PD were assessed by logistic regression. RESULTS: There were 168 men and 151 women (mean age, 50.8 years). Blood urea nitrogen (BUN), creatinine (Cr), and intact parathyroid hormone levels were significantly increased in patients in the higher serum potassium group. There were no significant risk factors for hypokalemia, including sex, age, diabetes, blood examination parameters, medication use, or PD-related parameters by multivariate logistic regression analysis. BUN (adjusted odds ratio [OR] 1.02, 95% CI 1.01-1.03, p = 0.001) and Cr (adjusted OR 1.08, 95% CI 1.01-1.16, p = 0.029) levels were significant risk factors for hyperkalemia by multivariate logistic regression analysis. CONCLUSION: Hyperkalemia and blood BUN and Cr levels were significantly associated in incident PD patients.

Serum Alkaline Phosphatase Levels are Not Associated with Increased Death Risk in Prevalent Hemodialysis Patients: 5-Year Experience in a Single Hemodialysis Center.

BACKGROUND/AIMS: Although high serum alkaline phosphatase (ALP) levels were reported as predictive factors for death risk in dialysis patients on the basis of large databank analyses, the real scenario in a single hemodialysis (HD) center is unknown. METHODS: In this study, a 5-year cohort of 1126 prevalent HD patients in the largest HD center in Taiwan was studied. The associations of ALP levels expressed as baseline, time-average, and time-dependent with all-cause mortality and cardiovascular mortality were evaluated by using adjusted Cox regression models. RESULTS: At baseline, levels of serum parathyroid hormone, calcium, and liver enzymes are increased in parallel with ALP quartiles. The hazard ratio (HR) for all-cause mortality was significantly increased in time-average and time-dependent ALP quartile in the unadjusted Cox analysis. The significance disappeared when multivariate adjusted Cox analysis was used. Similarly, HR was not significantly increased for cardiovascular mortality with ALP quartile expressed as baseline, time-average, and time-dependent in three models of Cox analyses. CONCLUSION: Our study demonstrated that serum ALP levels were not associated with increased death risk in prevalent HD patients over a 5-year interval.

Switch From Epoetin Beta to Darbepoetin Alfa Treatment of Anemia in Taiwanese Hemodialysis Patients: Dose Equivalence by Hemoglobin Stratification.

This multicenter study was designed to assess the hemoglobin (Hb) stability and conversion ratio of the switch from epoetin beta to darbepoetin alfa in Taiwanese hemodialysis (HD) patients. A total of 135 HD patients were enrolled and randomized with intravenous darbepoetin alfa or epoetin beta. The study duration was 24 weeks. Equivalent doses and conversion ratios were assessed with respect to Hb stratification: low Hb (≥8.0 g/dL to ≤10.0 g/dL) and high Hb (>10.0 g/dL to ≤11.0 g/dL). The results showed stable Hb levels in the study period. At week 24, the conversion ratio was higher for high Hb than low Hb (296.4 IU/dose epoetin beta: 1 µg/dose darbepoetin alfa. vs. 277.2 IU/dose epoetin beta: 1 µg/dose darbepoetin alfa). In conclusion, the conversion ratio in the present study was higher than 1 µg: 200 IU for darbepoetin alfa: epoetin for treating anemia in Taiwanese HD patients.

Diabetes mellitus is associated with gastroesophageal variceal bleeding in cirrhotic patients.

Diabetes mellitus (DM) has been reported to increase the risk of complications of liver cirrhosis of any etiology and subsequent survival. However, the impact of DM on the development of gastroesophageal variceal bleeding (GEVB) remains unclear. We aimed to elucidate whether DM is an independent risk factor for GEVB among cirrhotic patients. A total of 146 consecutive patients with liver cirrhosis (Child-Pugh Class A, n = 75; Class B, n = 40; and Class C, n = 31) were prospectively enrolled. Data on clinical and biochemical characteristics and history of ascites, GEVB, hepatic encephalopathy, and spontaneous bacterial peritonitis were retrospectively reviewed. Of these 146 patients, 37 (25%) had DM. Patients with DM had significantly higher ratio of Child-Pugh Class B/C (p = 0.043), renal insufficiency (p = 0.002), and history of GEVB (p = 0.006) compared with non-DM patients. GEVB was associated with Child-Pugh Class B/C (p = 0.001), ascites (p = 0.002), hepatic encephalopathy (p = 0.023), and low platelet counts (p < 0.001). Based on stepwise multiple logistic regression analysis, Child-Pugh class B/C [odds ratio (OR) = 4.90, p = 0.003] and DM (OR = 2.99, p = 0.022) were identified as independent predictors of GEVB. In the subgroup analysis, DM significantly correlated with GEVB in patients with Child-Pugh Class A (p = 0.042), but not in patients with Child-Pugh Class B/C (p = 0.128). DM is independently associated with GEVB in cirrhotic patients, especially in those with Child-Pugh Class A.

Discrepancy between effects of carbapenems and flomoxef in treating nosocomial hemodialysis access-related bacteremia secondary to extended spectrum beta-lactamase producing Klebsiella pneumoniae in patients on maintenance hemodialysis.

BACKGROUND: Hemodialysis (HD) patients are susceptible to extended spectrum beta-lactamase (ESBL)-producing bacterial infections. Because the optimal treatment and clinical significance of ESBL-producing Klebsiella pneumoniae (ESBL-Kp) HD access-related bacteremia remain unclear, we conducted this retrospective study to determine the clinical outcomes of patients treated with either flomoxef or a carbapenem. METHODS: The eligibility criterion was fistula or graft- or catheter- related ESBL-Kp bacteremia in patients on maintenance HD. The clinical characteristics and antibiotic management were analyzed. Outcome was determined by mortality resulting from bacteremia during the 14-day period after the first positive blood culture for flomoxef-susceptible ESBL-Kp. RESULTS: The 57 patients studied were predominantly elderly, malnourished, with a history of severe illnesses and broad-spectrum antibiotic use before the onset of bacteremia, and with severe septicemia as determined by the Pitt bacteremia score (PBS). The study population comprised 7 fistula, 8 graft, and 42 HD catheter-related bacteremia (CRB) cases, and the mortality rate was high (36/57, 63.2%) in these 57 patients. Of 42 patients with CRB, those in the deceased group (27/42, 64.3%) had significantly lower levels of serum albumin, longer prior hospital stay and duration of catheter-dependent HD, and higher PBS than patients in the survived group. Failure to receive effective antibiotics (flomoxef or a carbapenem) within 5 days after onset of bacteremia and treatment with flomoxef both significantly contributed to higher mortality. Multivariate analyses revealed that flomoxef use, PBS, and catheter-dependent HD >30 days were independently associated with increased mortality (OR, 3.52; 95% CI, 1.19-58.17, OR, 2.92; 95% CI, 1.36-6.26 and OR, 5.73; 95% CI, 1.21-63.2, respectively). CONCLUSIONS: Considering the high mortality rate, ESBL-Kp should be recognized as a possible pathogen in patients on maintenance HD at high risk of acquiring HD access infections associated with ESBL-producing bacteria. Carbapenems rather than flomoxef should be the therapy of choice in these critically vulnerable patients.

Refractory Salmonella enterica serotype choleraesuis-related renal cyst infection in a patient with autosomal dominant polycystic kidney disease undergoing hemodialysis treated successfully with intracystic ciprofloxacin infusion.

OBJECTIVE: To report a potential salvage therapy for refractory renal cyst infection secondary to Salmonellaenterica serotype choleraesuis (S. choleraesuis). CLINICAL PRESENTATION AND INTERVENTION: A 52-year-old male with autosomal dominant polycystic kidney disease undergoing hemodialysis experienced an episode of S. choleraesuis-related gastroenteritis subsequently complicated by bloodstream and refractory renal cyst infection with formation of multiple pyocysts. The patient was treated with intracystic indwelling diluted ciprofloxacin solution. CONCLUSION: In this patient, intracystic infusion of ciprofloxacin achieved a sufficient antibiotic level in infected renal cysts and hence completely eradicated S. choleraesuis. Therefore, intracystic antiobiotic infusion could be a potential salvage therapy for refractory renal cyst infection.

Early identification of leptospirosis as an ignored cause of multiple organ dysfunction syndrome.

Leptospirosis is the most common zoonosis in the world but remains underreported, owing to protean manifestations and ignorance about the disease among health care providers in Taiwan. From September 2000 to March 2006, surveillance of 455 patients with multiple organ dysfunction syndrome with unclear cause or clinical suspicion of leptospirosis was performed. Diagnosis was further confirmed by microscopic agglutination test or isolation of Leptospira. Cases were classified as excluded based on confirmed etiology other than leptospirosis or negative paired serologic test. Forty-two patients were confirmed as having leptospirosis, which accounted for 9.2% of total patients with multiple organ dysfunction syndrome. Forty-nine excluded cases were identified for a case-control analysis for clinical distinction. The most common presentations of leptospirosis were fever (97.6%), acute kidney injury (85.7%), and jaundice (61.9%). The leptospirosis group showed lower urine specific gravity (cutoff value, 1.0145) and enlarged kidney size (cutoff value, 11.05 cm) as compared with the excluded cases by multivariate logistics regression. Delayed antibiotic administration prolongs the duration of hospitalization (R2 = 0.486, P < 0.01). No mortality has been found in the leptospirosis group after initiation in 2003 of rapid immunoglobulin M serology assay that showed considerably high sensitivity and specificity. Leptospirosis accounts for a salient cause of multiple organ dysfunctions in Taiwan. Early awareness of leptospirosis by distinct presentations, followed by prompt antibiotics therapy, can dramatically save the patients. The easily performed rapid immunoglobulin M serology assay is suitable as a rapid screening test for the diagnosis of leptospirosis.

Clinical safety and anticoagulation efficacy of low-molecular-weight heparins in chronic hemodialysis patients: a single medical center experience.

BACKGROUND: In many countries low-molecular-weight heparins (LMWHs) are increasingly used for hemodialysis (HD). Low-range activated clotting time (ACT-LR) values and anti-Xa activity had been used to monitor the degree of anticoagulation caused by LMWH. However, the facilities are not easily available at most hospitals. Such data are limited in Taiwan. METHODS: A total of 76 patients receiving maintenance HD were prospectively enrolled. The HD patients were randomized to receive either nadroparin or enoxaparin and checked the ACT-LR values and anti-Xa activity. We aimed to analyze ACT-LR values and anti-Xa activity along with the clotting of the dialyzer or bleeding events associated with two LMWHs after they were administered. We also aimed to determine the dose necessary to reach maximum safety and efficacy. RESULTS: We found no significant differences in LMWH dosage, ACT-LR values, and anti-Xa activity between the two groups. There were no significant differences in bleeding/adverse events and extracorporeal circuit thrombosis between the two groups. Most of the bleeding and adverse events were subcutaneous minor bleeding. No major bleeding or mortality was found. We found significant differences in mean dosage, cost, bleeding/adverse effect, and extracorporeal circuit thrombosis between excessive and reduced nadroparin dosage groups. CONCLUSION: LMWH is not still routinely used due to its high cost in Taiwan. In our clinical experience, nadroparin and enoxaparin exhibited high levels of safety and efficacy in chronic HD patients. Reduced LMWHs dosage could promote patient's safety and decreased HD cost in HD patients with excessive dosage of LMWHs.

Association between interleukin-10 gene polymorphism -592 (A/C) and peritoneal transport in patients undergoing peritoneal dialysis.

AIM: The aim of this analysis was to know whether these three cytokine polymorphisms, including interleukin-6 (IL-6; -572 G/C), tumour necrosis factor-α (TNF-α; -308 G/A), and IL-10 (-592 A/C) have an effect on baseline peritoneal transport property and longitudinal evolution of peritoneal function. METHODS: A total of 141 stable peritoneal dialysis (PD) patients with mean treatment duration of 84.4 ± 34.2 months were enrolled. We genotyped these three cytokine polymorphisms, together with clinical parameters that were included as factors affecting longitudinal change of property of peritoneal transport over the first 3 year period after commencing therapy. RESULTS: There was no significant association between genotypes and baseline peritoneal transport property. The -592 A/C polymorphism of IL-10 was associated with longitudinal change of peritoneal transport. The ratio of D/P creatinine was significantly higher in patients with AA than those with CC/CA genotypes at 12 months (0.65 ± 0.11 vs 0.62 ± 0.09, P = 0.048) and 24 months (0.64 ± 0.12 vs 0.59 ± 0.09, P = 0.018). In addition, patients with increased peritoneal transport have greater frequency distribution of AA genotype and A allele. Logistic regression analysis revealed that -592 A allele was an independent predictor for the increase in D/P creatinine over the first 12 month period (odds ratio: 2.482, P = 0.017). There was no correlation between either polymorphism of IL-6 -572 (G/C) or TNF-α-308 (G/A) and longitudinal change of peritoneal function. CONCLUSIONS: Single nucleotide polymorphism of IL-10 -592 (A/C) was associated with longitudinal evolution of peritoneal transport rate in PD patients rather than the baseline peritoneal characteristics.

Urinary UMOD excretion and chronic kidney disease in gout patients: cross-sectional case-control study.

Patients with gout often have concurrent chronic kidney disease (CKD); the relationship between the two conditions is still unclear. Previous studies have identified an association between low level of urinary uromodulin (UMOD) and CKD within the setting of diabetes and lupus. The aim of this study was to examine the association between urinary UMOD excretion and CKD in patients with gout. A total of 53 Taiwanese gout patients with stable disease activity were enrolled. Patients were divided into a CKD group (n = 25) and a non-CKD group (n = 28). Using Pearson correlation analysis, urinary UMOD excretion was positively correlated with estimated glomerular filtration rate (Ha: ρ > 0, p = 0.004). Using multivariate analysis, patients with CKD and gout were associated with lower urinary UMOD excretion than those who have gout alone [odds ratio (95% CI): 0.826 (0.694-0.985), p < 0.001]. Patients with CKD and gout were also more likely to be older (p < 0.001) and have higher uric acid levels (p < 0.001). This study implicates that UMOD might play a role in the relationship between gout and CKD. Further studies with animal models of gout and CKD would be recommended.

Low-molecular-weight heparin successfully used to treat a nephrotic patient complicated by superior mesenteric vein thrombosis and portal vein thrombosis.

OBJECTIVES: To report the success of treatment with low- molecular-weight heparins (LMWHs) in a case of nephrotic syndrome complicated by mesenteric vein thrombosis (MVT) and portal vein thrombosis (PVT). CLINICAL PRESENTATION AND INTERVENTION: A 53-year-old man with nephrotic syndrome developed persistent mild abdominal pain for 3 days. Hepatic-portal venous system thrombosis of nephrotic syndrome was suspected due to new-onset superficial vein engorgement of the abdomen without liver cirrhosis. Abdominal computed tomography revealed MVT concomitant with PVT. He was successfully treated with LMWH without thrombolytic therapy. After discharge on day 9, he received continuous anticoagulation by LWMH on an outpatient basis at the nephrology clinic. Venous thromboembolic events or proteinuria did not recur within the 6-month follow-up. CONCLUSION: This report showed a case of MVT concomitant with PVT, a critical complication of nephrotic syndrome that was diagnosed in time and successfully treated with LMWH. A high index of clinical suspicion and timely management are crucial to tackle thrombotic complications in nephrotic syndrome.

Comparison of clinical characteristics between automated peritoneal dialysis and continuous ambulatory peritoneal dialysis: a 2-year single-center observational study.

AIMS: To date, there is convincing evidence for the preservation of residual renal function (RRF) in peritoneal dialysis (PD) patients; however, substantially variable data exist on the incidence rate of infectious complications and the decline of RRF for automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD). The purpose of our study was to investigate the relative merits or demerits of APD compared with CAPD. METHODS: From November 1998 to November 2007, we retrospectively reviewed 32 patients on APD and 140 patients on CAPD. We compared incidences of infectious complications during the entry period. RRF and other PD parameters were determined and compared over 2 years of therapy. In addition, the period of hospitalization was also included for clinical outcome analysis. RESULTS: There were no significant differences between the two modalities with regard to the incidence of peritonitis (1.42/100 patient-months for APD vs. 1.23/100 patient-months for CAPD, p = 0.66). At the end of the second year, there were no significant differences between APD and CAPD with regard to the decline of RRF (14.8 vs. 15.3 L/week/1.73 m(2), p = 0.84). However, APD significantly increased the value of total weekly Kt/V during this period. Furthermore, we observed a significant reduction in hospitalized days of APD compared with CAPD. CONCLUSIONS: We concluded that the selection of the PD modality is not a major determinant of the decline in RRF. APD can be adapted to the targeted adequacy and is at least as efficacious as CAPD when it is expertly applied.