Ya-Wen Yang

Impact of timing of renal replacement therapy initiation on outcome of septic acute kidney injury

IntroductionSepsis is the leading cause of acute kidney injury (AKI) in critical patients. The optimal timing of initiating renal replacement therapy (RRT) in septic AKI patients remains controversial. The objective of this study is to determine the impact of early or late initiation of RRT, as defined using the simplified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification (sRIFLE), on hospital mortality among septic AKI patients.MethodsPatient with sepsis and AKI requiring RRT in surgical intensive care units were enrolled between January 2002 and October 2009. The patients were divided into early (sRIFLE-0 or -Risk) or late (sRIFLE-Injury or -Failure) initiation of RRT by sRIFLE criteria. Cox proportional hazard ratios for in hospital mortality were determined to assess the impact of timing of RRT.ResultsAmong the 370 patients, 192 (51.9%) underwent early RRT and 259 (70.0%) died during hospitalization. The mortality rate in early and late RRT groups were 70.8% and 69.7% respectively (P > 0.05). Early dialysis did not relate to hospital mortality by Cox proportional hazard model (P > 0.05). Patients with heart failure, male gender, higher admission creatinine, and operation were more likely to be in the late RRT group. Cox proportional hazard model, after adjustment with propensity score including all patients based on the probability of late RRT, showed early dialysis was not related to hospital mortality. Further model matched patients by 1:1 fashion according to each patients propensity to late RRT showed no differences in hospital mortality according to head-to-head comparison of demographic data (P > 0.05).ConclusionsUse of sRIFLE classification as a marker poorly predicted the benefits of early or late RRT in the context of septic AKI. In the future, more physiologically meaningful markers with which to determine the optimal timing of RRT initiation should be identified.

Multi-Dimensional Tumor Detection in Automated Whole Breast Ultrasound Using Topographic Watershed

Automated whole breast ultrasound (ABUS) is becoming a popular screening modality for whole breast examination. Compared to conventional handheld ultrasound, ABUS achieves operator-independent and is feasible for mass screening. However, reviewing hundreds of slices in an ABUS image volume is time-consuming. A computer-aided detection (CADe) system based on watershed transform was proposed in this study to accelerate the reviewing. The watershed transform was applied to gather similar tissues around local minima to be homogeneous regions. The likelihoods of being tumors of the regions were estimated using the quantitative morphology, intensity, and texture features in the 2-D/3-D false positive reduction (FPR). The collected database comprised 68 benign and 65 malignant tumors. As a result, the proposed system achieved sensitivities of 100% (133/133), 90% (121/133), and 80% (107/133) with FPs/pass of 9.44, 5.42, and 3.33, respectively. The figure of merit of the combination of three feature sets is 0.46 which is significantly better than that of other feature sets (p-value <; 0.05). In summary, the proposed CADe system based on the multi-dimensional FPR using the integrated feature set is promising in detecting tumors in ABUS images.

Heart Rate Variability During Hemodialysis and Following Renal Transplantation

Previous studies have shown awareness of uremic dysfunction in end-stage renal disease (ESRD) patients. Dysautonomia in ESRD patients may be reversible after renal transplantation. We used a power spectral analysis (PSA) of heart rate variability (HRV) to assess alterations of autonomic activity in 14 controls and 14 nondiabetic hemodialysis ESRD patients who had undergone renal transplantation. Compared with matched control subjects, the power frequency determinations of low frequency (LF; 3.42 ln(ms(2)) vs 6.38 ln(ms(2)); P < .05 high frequency (HF; 2.29 ln(ms(2)) vs 5.27 ln(ms(2)); P < .05)), and total power (TP; 5.39 ln(ms(2)) vs 7.53 ln(ms(2)); P < .05) were significantly suppressed in ESRD patients undergoing hemodialysis. ESRD patients showed significantly improved HRV after renal transplantation. After renal transplantation, there was no significant difference in the TP (6.82 ln(ms(2)) vs 7.53 ln(ms(2)); P = .15) component between measurements in both patient subgroups. We further divided the ESRD patients into 2 groups based on their pretransplantation HRV, observing alterations in HRV after renal transplantation. Patients with significantly improved HRV were those with more suppressed HRV before transplantation (HF <3 In(ms(2)). Autonomic dysfunction in ESRD patients was not irreversible even if severe, and recovery was observed as early as 6 months after transplantation.

Mutational analysis of MED12 exon 2 in a spectrum of fibroepithelial tumours of the breast: implications for pathogenesis and histogenesis

Fibroadenomas (FAs) and phyllodes tumours (PTs) are fibroepithelial tumours. Mutations in MED12 exon 2 have been reported in FAs. This study investigated the MED12 mutations in a spectrum of fibroepithelial tumours.

Comparison of 24-h Urinary Aldosterone Level and Random Urinary Aldosterone-to-Creatinine Ratio in the Diagnosis of Primary Aldosteronism

Background Historically, urinary aldosterone level measurement was a commonly employed confirmatory test to detect primary aldosteronism (PA). However, 24-h urine collection is inconvenient and cumbersome. We hypothesized that random urinary aldosterone measurements with correction for creatinine concentration might be comparable to 24-h urinary aldosterone levels (Uald-24 h) in the diagnosis of PA. Methods The non-concurrent prospective study was conducted between June 2006 and March 2008 in patients admitted for confirmation of aldosteronism by salt loading test. A 24-h urine sample, which was collected during hospitalization on the day before saline infusion testing after restoration of serum hypokalemia, was collected from all subjects. Moreover, participants were asked to collect a first bladder voiding random urine sample during clinic visits. Uald-24 h and the random urinary aldosterone-to-creatinine ratio (UACR) were calculated accordingly. Results A total of 102 PA patients (71 patients diagnosed of aldosterone-producing adenoma, 31 with idiopathic hyperaldosteronism) and 65 patients with EH were enrolled. The receiver operating characteristic curve showed comparable areas under the curves of UACR and Uald-24 h. The Bland-Altman plot showed mean bias but no obvious heteroscedasticity between the two tests. When using random UACR >3.0 ng/mg creatinine as the cutoff value, we obtained a specificity of 90.6% to confirm PA from essential hypertension. Conclusions Our study reinforce that the diagnostic accuracy of random UACR was comparable to that of Uald-24 h in PA patients. With the quickness and simplicity of the UACR method and its equivalence to Uald-24 h, this assay could be a good alternative diagnostic tool for PA confirmation.

Longitudinal assessment of prognostic factors for patients with hepatorenal syndrome in a tertiary center

IntroductionHepatorenal syndrome (HRS) is one of the serious complications in patients with advanced cirrhosis and ascites. In tertiary centers, most patients were classified as having type 1 HRS for their rapid progressive diseases. However, no significant predictors have been assessed previously for patients with type 1 HRS. In addition to the initial model of end-stage liver disease (MELD) scores and biochemistry parameters, we want to further investigate the prognostic importance of changes in MELD scores and biochemistry parameters over time for patients with type 1 HRS.Materials and methodsData from type 1 HRS patients were incorporated, including their demographic, clinical progression, all recording biochemical parameters, therapeutic methods, and outcomes.ResultsA total of 103 patients were included in our study. According to the definition of the International Ascites Club, 67 patients (or 65%) had type 1 HRS whereas 36 (or 35%) had type 2 HRS. According to the multivariate COX proportional hazards regression model, either initial biochemistry parameters or MELD scores were not significantly associated with prognosis. By time-dependent proportional hazards model, each point elevated in creatinine (CRE) and total bilirubin (TBI) levels during the admission increased mortality risk by 29 and 4%, respectively. Increasing albumin level during the admission showed its protective value. Changes in MELD score simple during the admission, which were calculated by CRE and TBI [3.8 × log (bilirubin (mg/dl)] + 9.6 × log [Creatinine (mg/dl) + 6.43], were significant predictor for patients with type 1 HRS.ConclusionIn patients with type 1 HRS, changes in TBI, CRE, and albumin level during the admission were associated with prognosis. Changes in MELD score simple is superior to initial and changes in MELD scores to predict prognosis in patients with type 1 HRS.

Effect of Treatment on Body Fluid in Patients with Unilateral Aldosterone Producing Adenoma: Adrenalectomy versus Spironolactone.

Aldosterone affects fluid retention in the body by affecting how much salt and water that the kidney retains or excretes. There is limited information about the effect of prolonged aldosterone excess and treatment on body fluid in primary aldosteronism (PA) patients. In this study, body composition changes of 41 PA patients with unilateral aldosterone producing adenoma (APA) were assessed by a bio-impedance spectroscopy device. Patients with APA receiving adrenalectomy, as compared with those treated with spironolactone, had significantly lower relative overhydration (OH) and urine albumin excretion, and significantly higher urine sodium excretion four weeks after treatment. These differences dissipated 12 weeks after the initial treatment. Independent factors to predict decreased relative OH four weeks after treatment were male patients and patients who experienced adrenalectomy. Patients who underwent adrenaelctomy had significantly decreased TNF-α and increased serum potassium level when compared to patients treated with spironolactone 4 and 12 weeks after treatment. In this pilot study, we found that adrenalectomy leads to an earlier increase in renal sodium excretion and decreases in body fluid content, TNF-α, and urine albumin excretion. Adrenalectomy yields a therapeutic effect more rapidly, which has been shown to ameliorate overhydration in PA patients.

Quantitative breast mass classification based on the integration of B-mode features and strain features in elastography

BACKGROUND Elastography is a new sonographic imaging technique to acquire the strain information of tissues and transform the information into images. Radiologists have to observe the gray-scale distribution of tissues on the elastographic image interpreted as the reciprocal of Youngs modulus to evaluate the pathological changes such as scirrhous carcinoma. In this study, a computer-aided diagnosis (CAD) system was developed to extract quantitative strain features from elastographic images to reduce operator-dependence and provide an automatic procedure for breast mass classification. METHOD The collected image database was composed of 45 malignant and 45 benign breast masses. For each case, tumor segmentation was performed on the B-mode image to obtain tumor contour which was then mapped to the elastographic images to define the corresponding tumor area. The gray-scale pixels around tumor area were classified into white, gray, and black by fuzzy c-means clustering to highlight stiff tissues with darker values. Quantitative strain features were then extracted from the black cluster and compared with the B-mode features in the classification of breast masses. RESULTS The performance of the proposed strain features achieved an accuracy of 80% (72/90), a sensitivity of 80% (36/45), a specificity of 80% (36/45), and a normalized area under the receiver operating characteristic curve, Az=0.84. Combining the strain features with the B-mode features obtained a significantly better Az=0.93, p-value<0.05. CONCLUSIONS Summarily, the quantified strain features can be combined with the B-mode features to provide a promising suggestion in distinguishing malignant from benign tumors.

MED12 exon 2 mutation as a highly sensitive and specific marker in distinguishing phyllodes tumours from other spindle neoplasms of the breast.

Spindle neoplasms of the breast (SNB) primarily include metaplastic breast carcinoma (MBC), phyllodes tumour (PT), fibromatosis and primary nonspecific sarcoma (PNS). Mutations in MED12 exon 2 have been reported in PTs. Because spindle tumour components are shared by SNB, we assessed the diagnostic use of MED12 exon 2 mutation in SNB. We investigated MED12 exon 2 mutations in a total of 91 samples of SNB, including 49 PT cases that have been previously analysed. Mutations were identified using direct sequencing. MED12 exon 2 mutation was absent in all cases of MBC, fibromatosis and PNS, in contrast to the 71.4% positivity in PTs. MED12 mutations were identified in four of six previously diagnosed monophasic sarcomatous MCB cases, however, these four cases were revised as malignant PT based on additional bcl‐2 staining, albeit very focal. Consistence in the MED12 mutational status between a paired core biopsy and a surgical specimen was observed in all 20 tested PT cases. In conclusion, we demonstrated the restriction of MED12 exon 2 mutation to PTs (73.6%, 39/53) and its absence in other SNB. MED12 exon 2 mutational analysis can be included in the differential diagnosis between PT and other SNB, especially with limited specimen where diagnostic clues are not evident.

Ketoanalogues supplementation decreases dialysis and mortality risk in patients with anemic advanced chronic kidney disease

Background The benefit of alpha-Ketoanalogues (KA) supplementation for chronic kidney disease (CKD) patients that followed low-protein diet (LPD) remains undetermined. Methods We extracted longitudinal data for all CKD patients in the Taiwan National Health Insurance from January 1, 2000 through December 31, 2010. A total of 1483 patients with anemic advanced CKD treated with LPD, who started KA supplementation, were enrolled in this study. We analyzed the risks of end stage renal disease and all-cause mortality using Cox proportional hazard models with influential drugs as time-dependent variables. Results A total of 1113 events of initiating long-term dialysis and 1228 events of the composite outcome of long-term dialysis or death occurred in patients with advanced CKD after a mean follow-up of 1.57 years. Data analysis suggests KA supplementation is associated with a lower risk for long-term dialysis and the composite outcome when daily dosage is more than 5.5 tablets. The beneficial effect was consistent in subgroup analysis, independent of age, sex, and comorbidities. Conclusions Among advanced CKD patients that followed LPD, KA supplementation at an appropriate dosage may substantially reduce the risk of initiating long-term dialysis or of developing the composite outcome. KA supplementation represents an additional therapeutic strategy to slow the progression of CKD.