Diameter Reduction Determined Through Carotid Ultrasound Associated With Cardiovascular and All-Cause Mortality: A Single-Center Experience of 38 201 Consecutive Patients in Taiwan.

Background Few studies have evaluated the prognostic significance of diameter-based carotid sonographic measurements for mortality. We investigated whether a reduction in diameter of different carotid anatomical segments is associated with cardiovascular and all-cause mortality in a hospital-based cohort with universal health care. Methods and Results We conducted a retrospective cohort study of 38 201 patients who underwent carotid duplex ultrasound at a medical center in Taiwan. Carotid sonographic parameters were the diameter reduction percentage in carotid bifurcation, the internal carotid artery, the common carotid artery, and the external carotid artery and the overall carotid atherosclerotic burden score, determined by summing the scores from all segments. The vital status was ascertained by linking data to National Death Registry until 2017. During a median follow-up of 4.2 years, 5644 participants died, with 1719 deaths attributable to cardiovascular diseases. The multivariable-adjusted hazard ratios (HRs; 95% CIs) for cardiovascular mortality were 1.33 (1.16‒1.53), 1.58 (1.361.84), and 1.89 (1.58, 2.26) for participants with 30% to <40%, 40% to <50%, and ≥50% reduction in carotid bifurcation diameter, respectively, compared with participants with <30% diameter reduction (P for trend <0.001). The corresponding HRs (95% CIs) for all-cause mortality were 1.25 (1.16‒1.34), 1.42 (1.31‒1.54), and 1.60 (1.45‒1.77), respectively. Diameter reduction at other carotid sites and the carotid atherosclerotic burden score exhibited the same dose-response relationship. Conclusions This study suggests that reduction in carotid artery diameter, which can be determined through routinely available sonography, is an independent risk factor for all-cause and cardiovascular mortality.

Effect of Temporal Difference on Clinical Outcomes of Patients with Out-of-Hospital Cardiac Arrest: A Retrospective Study from an Urban City of Taiwan.

Circadian pattern influence on the incidence of out-of-hospital cardiac arrest (OHCA) has been demonstrated. However, the effect of temporal difference on the clinical outcomes of OHCA remains inconclusive. Therefore, we conducted a retrospective study in an urban city of Taiwan between January 2018 and December 2020 in order to investigate the relationship between temporal differences and the return of spontaneous circulation (ROSC), sustained (≥24 h) ROSC, and survival to discharge in patients with OHCA. Of the 842 patients with OHCA, 371 occurred in the daytime, 250 in the evening, and 221 at night. During nighttime, there was a decreased incidence of OHCA, but the outcomes of OHCA were significant poor compared to the incidents during the daytime and evening. After multivariate adjustment for influencing factors, OHCAs occurring at night were independently associated with lower probabilities of achieving sustained ROSC (aOR = 0.489, 95% CI: 0.285-0.840, p = 0.009) and survival to discharge (aOR = 0.147, 95% CI: 0.03-0.714, p = 0.017). Subgroup analyses revealed significant temporal differences in male patients, older adult patients, those with longer response times (≥5 min), and witnessed OHCA. The effects of temporal difference on the outcome of OHCA may be a result of physiological factors, underlying etiology of arrest, resuscitative efforts in prehospital and in-hospital stages, or a combination of factors.

The Effect of Implementing Mechanical Cardiopulmonary Resuscitation Devices on Out-of-Hospital Cardiac Arrest Patients in an Urban City of Taiwan.

High-quality cardiopulmonary resuscitation (CPR) is a key element in out-of-hospital cardiac arrest (OHCA) resuscitation. Mechanical CPR devices have been developed to provide uninterrupted and high-quality CPR. Although human studies have shown controversial results in favor of mechanical CPR devices, their application in pre-hospital settings continues to increase. There remains scant data on the pre-hospital use of mechanical CPR devices in Asia. Therefore, we conducted a retrospective cohort study between September 2018 and August 2020 in an urban city of Taiwan to analyze the effects of mechanical CPR devices on the outcomes of OHCA; the primary outcome was attainment of return of spontaneous circulation (ROSC). Of 552 patients with OHCA, 279 received mechanical CPR and 273 received manual CPR, before being transferred to the hospital. After multivariate adjustment for the influencing factors, mechanical CPR was independently associated with achievement of any ROSC (OR = 1.871; 95%CI:1.195-2.930) and sustained (≥24 h) ROSC (OR = 2.353; 95%CI:1.427-3.879). Subgroup analyses demonstrated that mechanical CPR is beneficial in shorter emergency medical service response time (≤4 min), witnessed cardiac arrest, and non-shockable cardiac rhythm. These findings support the importance of early EMS activation and high-quality CPR in OHCA resuscitation.

The ratio and difference of urine protein-to-creatinine ratio and albumin-to-creatinine ratio facilitate risk prediction of all-cause mortality.

The role of the difference and ratio of albuminuria (urine albumin-to-creatinine ratio, uACR) and proteinuria (urine protein-to-creatinine ratio, uPCR) has not been systematically evaluated with all-cause mortality. We retrospectively analyzed 2904 patients with concurrently measured uACR and uPCR from the same urine specimen in a tertiary hospital in Taiwan. The urinary albumin-to-protein ratio (uAPR) was derived by dividing uACR by uPCR, whereas urinary non-albumin protein (uNAP) was calculated by subtracting uACR from uPCR. Conventional severity categories of uACR and uPCR were also used to establish a concordance matrix and develop a corresponding risk matrix. The median age at enrollment was 58.6 years (interquartile range 45.4-70.8). During the 12,391 person-years of follow-up, 657 deaths occurred. For each doubling increase in uPCR, uACR, and uNAP, the adjusted hazard ratios (aHRs) of all-cause mortality were 1.29 (95% confidence interval [CI] 1.24-1.35), 1.12 (1.09-1.16), and 1.41 (1.34-1.49), respectively. For each 10% increase in uAPR, it was 1.02 (95% CI 0.98-1.06). The linear dose-response association with all-cause mortality was only observed with uPCR and uNAP. The 3 × 3 risk matrices revealed that patients with severe proteinuria and normal albuminuria had the highest risk of all-cause mortality (aHR 5.25, 95% CI 1.88, 14.63). uNAP significantly improved the discriminative performance compared to that of uPCR (c statistics: 0.834 vs. 0.828, p-value = 0.032). Our study findings advocate for simultaneous measurements of uPCR and uACR in daily practice to derive uAPR and uNAP, which can provide a better mortality prognostic assessment.

Association Between Preoperative Blood Glucose Level and Hospital Length of Stay for Patients Undergoing Appendectomy or Laparoscopic Cholecystectomy.

OBJECTIVE: To evaluate the effect of preoperative blood glucose (POBG) level on hospital length of stay (LOS) in patients undergoing appendectomy or laparoscopic cholecystectomy. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study of patients aged ≥18 years who had undergone appendectomy or laparoscopic cholecystectomy procedures between 2005 and 2016 at a tertiary medical center in Taiwan. The association between POBG level and LOS was evaluated using a multivariable quasi-Poisson regression with robust variance. Multiple imputations were performed to replace missing values. RESULTS: We included 8,291 patients; 4,025 patients underwent appendectomy (appendectomy group) and 4,266 underwent laparoscopic cholecystectomy (laparoscopic cholecystectomy group). In the appendectomy group, patients with POBG levels of ≥123 mg/dL (adjusted relative risk [aRR] 1.19; 95% CI 1.06-1.33) had a 19% higher risk of having a LOS of >3 days than did those with POBG levels of <106 mg/dL. In the laparoscopic cholecystectomy group, patients with POBG levels of ≥128 mg/dL also had a significantly higher risk of having a LOS of >3 days (aRR 1.17; 95% CI 1.07-1.29) than did those with POBG levels of <102 mg/dL. A positive dose-response curve between POBG and an adjusted risk of a LOS of >3 days was observed, although the curve starts to flatten at a POBG level of ∼130 mg/dL. CONCLUSIONS: We demonstrated that a higher POBG level was significantly associated with a prolonged LOS for patients undergoing appendectomy or laparoscopic cholecystectomy. The optimal POBG level may be lower than that commonly perceived.

Joint Longitudinal Low Calcium High Phosphorus Trajectory Associates with Accelerated Progression, Acute Coronary Syndrome and Mortality in Chronic Kidney Disease.

The effects of long-term disturbance of the mineral metabolism on patients with chronic kidney disease (CKD) are unclear. We investigated whether the longitudinal Ca-P (joint calcium and phosphorus) trajectories are associated with incident end-stage renal disease (ESRD), acute coronary syndrome (ACS), and all-cause mortality in patients with CKD. We conducted a prospective cohort study by using data from a 13-year multidisciplinary pre-ESRD care registry. The final study population consisted of 4,237 CKD patients aged 20-90 years with data gathered from 2003 to 2015. Individuals' Ca-P trajectories were defined using group-based multi-trajectory modeling into three distinct patterns: reference, moderately abnormal, and severely abnormal. Times to ESRD, ACS, and death were analyzed using multiple Cox regression. Compared with those with a "reference" Ca-P trajectory, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for incidental ESRD were 5.92 (4.71-7.44) and 15.20 (11.85-19.50) for "moderately abnormal" and "severely abnormal" Ca-P trajectories, respectively. The corresponding aHRs for ACS were 1.94 (1.49-2.52) and 3.18 (2.30-4.39), and for all-cause mortality, they were 1.88 (1.64-2.16) and 2.46 (2.05-2.96) for "moderately abnormal" and "severely abnormal" Ca-P trajectories, respectively. For outcomes of progression to ESRD, the detrimental effects of abnormal Ca-P trajectories were more substantial in patients with CKD stage 3 than those with CKD stage 4 or 5 (p-value for interaction < 0.001). Future studies should validate reliable longitudinal cut-offs of serum phosphorus and consider the "lowering phosphorus- the lower the better, the earlier the better" approach to phosphorus control in CKD.

Dialysis timing may be deferred toward very late initiation: An observational study.

The optimal timing to initiate dialysis among patients with an estimated glomerular filtration rate (eGFR) of <5 mL/min/1.73 m2 is unknown. We hypothesized that dialysis initiation time can be deferred in this population even with high uremic burden. A case-crossover study with case (0-30 days before dialysis initiation [DI]) and control (90-120 days before DI) periods was conducted in 1,079 hemodialysis patients aged 18-90 years at China Medical University Hospital between 2006 and 2015. The uremic burden was quantified based on 7 uremic indicators that reached the predefined threshold in case period, namely hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, potassium, phosphorus, and bicarbonate. Dialysis timing was classified as standard (met 0-2 uremic indicators), late (3-5 indicators), and very late (6-7 indicators). Median eGFR-DI of the 1,079 patients was 3.4 mL/min/1.73 m2 and was 2.7 mL/min/1.73 m2 in patients with very late initiation. The median follow-up duration was 2.42 years. Antibiotics, diuretics, antihypertensive medications, and non-steroidal anti-inflammatory drugs (NSAIDs) were more prevalently used during the case period. The fully adjusted hazards ratios of all-cause mortality for the late and very late groups were 0.97 (95% confidence interval 0.76-1.24) and 0.83 (0.61-1.15) compared with the standard group. It is safe to defer dialysis initiation among patients with chronic kidney disease (CKD) having an eGFR of <5 mL/min/1.73 m2 even when patients having multiple biochemical uremic burdens. Coordinated efforts in acute infection prevention, optimal fluid management, and prevention of accidental exposure to NSAIDs are crucial to prolong the dialysis-free survival.

Acute Kidney Injury in the Outpatient Setting Associates with Risk of End-Stage Renal Disease and Death in Patients with CKD.

Current acute kidney injury (AKI) diagnostic criteria are restricted to the inpatient setting. We proposed a new AKI diagnostic algorithm for the outpatient setting and evaluate whether outpatient AKI (AKIOPT) modifies the disease course among patients with chronic kidney disease (CKD) enrolled in the national predialysis registry. AKIOPT was detected when a 50% increase in serum creatinine level or 35% decline in eGFR was observed in the 180-day period prior to enrollment in the predialysis care program. Outcomes were progression to end-stage renal disease (ESRD) and all-cause mortality. Association analyses were performed using multiple Cox regression and coarsened exact matching (CEM) analysis. Among 6,046 patients, 31.5% (1,905 patients) had developed AKIOPT within the 180-day period before enrollment. The adjusted hazard ratios of the 1-year and overall risk of ESRD among patients with preceding AKIOPT compared with those without AKIOPT were 2.61 (95% CI: 2.15-3.18) and 1.97 (1.72-2.26), respectively. For 1-year and overall risk of all-cause mortality, patients with AKIOPT had respectively a 141% (95% CI: 89-209%) and 84% (56-117%) higher risk than those without AKIOPT. This statistical inference remained robust in CEM analysis. We also discovered a complete reversal in the eGFR slope before and after the AKIOPT from -10.61 ± 0.32 to 0.25 ± 0.30 mL/min/1.73 m2 per year; however, the loss of kidney function is not recovered. The new AKIOPT diagnostic algorithm provides prognostic insight in patients with CKD.

Risk prediction for 30-day mortality among patients with Clostridium difficile infections: a retrospective cohort study.

Background: Current guidelines have unsatisfied performance in predicting severe outcomes after Clostridium difficile infection (CDI). Our objectives were to develop a risk prediction model for 30-day mortality and to examine its performance among inpatients with CDI. Methods: This retrospective cohort study was conducted at China Medical University Hospital, a 2111-bed tertiary medical center in central Taiwan. We included adult inpatients who had a first positive C. difficile culture or toxin assay and had diarrhea as the study population. The main exposure of interest was the biochemical profiles of white blood cell count, serum creatinine (SCr), estimated glomerular filtration rate, blood urea nitrogen (BUN), serum albumin, and glucose. The primary outcome was the 30-day all-cause mortality and the secondary outcome was the length of stay in the intensive care units (ICU) following CDI. A multivariable Cox model and a logistic regression model were developed using clinically relevant and statistically significant variables for 30-day mortality and for length of ICU stay, respectively. A risk scoring system was established by standardizing the coefficients. We compared the performance of our models and the guidelines. Results: Of 401 patients, 23.4% died within 30 days. In the multivariable model, malignancy (hazard ratio [HR] = 1.95), ≥ 1.5-fold rise in SCr (HR = 2.27), BUN-to-SCr ratio > 20 (HR = 2.04), and increased glucose (≥ 193 vs < 142 mg/dL, HR = 2.18) were significant predictors of 30-day mortality. For patients who survived the first 30 days of CDI, BUN-to-SCr ratio > 20 (Odds ratio [OR] = 4.01) was the only significant predictor for prolonged (> 9 days) length of ICU stay following CDI. The Harrell's c statistic of our Cox model for 30-day mortality (0.727) was significantly superior to those of SHEA-IDSA 2010 (0.645), SHEA-IDSA 2018 (0.591), and ECSMID (0.650). Similarly, the conventional c statistic of our logistic regression model for prolonged ICU stay (0.737) was significantly superior to that of the guidelines (SHEA-IDSA 2010, c = 0.600; SHEA-IDSA 2018, c = 0.634; ESCMID, c = 0.645). Our risk prediction scoring system for 30-day mortality correctly reclassified 20.7, 32.1, and 47.9% of patients, respectively. Conclusions: Our model that included novel biomarkers of BUN-to-SCr ratio and glucose have a higher predictive performance of 30-day mortality and prolonged ICU stay following CDI than do the guidelines.

Complete or partial split in associating liver partition and portal vein ligation for staged hepatectomy: A systematic review and meta-analysis.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been adopted by liver surgeons in recent years. However, high morbidity and mortality rates have limited the promotion of this technique. Some recent studies have suggested that ALPPS with a partial split can effectively induce the growth of future liver remnant (FLR) similar to a complete split with better postoperative safety profiles. However, some others have suggested that ALPPS can induce more rapid and adequate FLR growth, but with the same postoperative morbidity and mortality rates as in partial split of the liver parenchyma in ALPPS (p-ALPPS). AIM: To perform a systematic review and meta-analysis on ALPPS and p-ALPPS. METHODS: A systematic literature search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov was performed for articles published until June 2019. Studies comparing the outcomes of p-ALPPS and ALPPS for a small FLR in consecutive patients were included. Our main endpoints were the morbidity, mortality, and FLR hypertrophy rates. We performed a subgroup analysis to evaluate patients with and without liver cirrhosis. We assessed pooled data using a random-effects model. RESULTS: Four studies met the inclusion criteria. Four studies reported data on morbidity and mortality, and two studies reported the FLR hypertrophy rate and one study involved patients with cirrhosis. In the non-cirrhotic group, p-ALPPS-treated patients had significantly lower morbidity and mortality rates than ALPPS-treated patients [odds ratio (OR) = 0.2; 95% confidence interval (CI): 0.07-0.57; P = 0.003 and OR = 0.16; 95%CI: 0.03-0.9; P = 0.04]. No significant difference in the FLR hypertrophy rate was observed between the two groups (P > 0.05). The total effects indicated no difference in the FLR hypertrophy rate or perioperative morbidity and mortality rates between the ALPPS and p-ALPPS groups. In contrast, ALPPS seemed to have a better outcome in the cirrhotic group. CONCLUSION: The findings of our study suggest that p-ALPPS is safer than ALPPS in patients without cirrhosis and exhibits the same rate of FLR hypertrophy.

Variability of red blood cell size predicts all-cause mortality, but not progression to dialysis, in patients with chronic kidney disease: A 13-year pre-ESRD registry-based cohort.

BACKGROUND: Prognostic role of red blood cell distribution width (RDW) in patients with chronic kidney disease (CKD) is unclear. Little evidence provides a comprehensive predictive analysis considering both baseline values and longitudinal trajectories of RDW along with mean corpuscular volume (MCV). METHODS: We conducted a comprehensive risk assessment of RDW and MCV in a registry-based cohort of 4621 patients with CKD (age, 20-90 y) receiving multidisciplinary care during 2003 to 2015. Both baseline and longitudinal trajectories of RDW and MCV were modeled as predictors for end-stage renal disease (ESRD) and mortality by using multiple Cox proportional hazards regression models, incorporating time-varying covariates and adjustments for imperative confounding variables. RESULTS: Fully adjusted hazard ratio (HR; 95% CI) of progression to ESRD for each unit increase in RDW and MCV at baseline was 0.97 (0.93-1.02) and 1.00 (0.99-1.01), respectively. Longitudinally, neither RDW nor MCV trajectory was associated with progression to ESRD. For all-cause mortality, fully adjusted HRs (95%CI) were 1.09 (1.04-1.14) for each percent increase in RDW with a linear dose-response relationship and 1.95 (1.47-2.59) for a stable-high RDW trajectory compared with normal RDW trajectory. The effects of RDW on mortality were further augmented in patients with concomitantly high MCV status. Incorporating point-of-care RDW significantly improves the discrimination performance quantified using Harrell C statistics into the existing CKD mortality predictive equation (from 0.770 to 0.784, P = .018). CONCLUSIONS: We support the clinical utility of RDW in predicting all-cause mortality among patients with CKD. The mechanism underlying our findings is critical for CKD risk assessment and management, particularly from malnutrition, inflammation, and atherosclerosis perspectives.

Fruits and vegetables consumption and the risk of gallstone diasease: A systematic review and meta-analysis.

BACKGROUND: The role of fruit and vegetables (FVs) consumption in decreasing gallstone disease risk remains contradictory. We performed a meta-analysis to analyze this potential correlation, followed by investigation of dose-response relationship of FVs consumption with gallstone disease. MATERIALS AND METHODS: PubMed, Embase, as well as Web of Science were searched to determine all published researches about the connection of FVs consumption with gallstone disease before March 2018. Relative risks (RRs) or odds ratios (ORs) along with corresponding 95% confidence intervals (CIs) was pooled utilizing random effect models, aiming at examining the correlation of FVs consumption with gallstone disease risk. RESULTS: One cross-sectional study, our case-control studies as well as nine cohort studies were enrolled, covering approximately 33,983 patients with gallstone disease and 1,53,3752 participants. In a pooled analysis, vegetables consumption was significantly related to a decreased gallstone disease risk, (RR = 0.83, 95% CI, 0.74-0.94, I = 91.1%), and for fruits consumption, RR was similar (RR = 0.88, 95%CI, 0.83-0.92, I = 0.01%). This inverse correlation of FVs consumption with gallstone disease risk was solid in most subgroup analysis. The nonlinear dose-response correlation indicated that gallstone risk was reduced by 4% (RR = 0.96, 95%CI, 0.93-0.98) and 3% (RR = 0.97, 95%CI, 0.96-0.98) for every 200 g per day increment in vegetables consumption (P = .001) and fruits consumption (P = .001), respectively. CONCLUSION: This study suggests vegetables and fruits consumption is correlated with a significantly reduced risk of gallstone disease.

Albumin-to-alkaline phosphatase ratio: A novel prognostic index of overall survival in cholangiocarcinoma patients after surgery.

AIM: To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio (AAPR) in cholangiocarcinoma (CCA) subjects receiving surgery. METHODS: In this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics (including AAPR) were analyzed to determine predictors of post-operative overall survival and recurrence-free survival (RFS). In addition, univariate and multivariate Cox proportional hazards models were conducted, followed by application of time-dependent receiver operating curves to identify the optimal cut-off. RESULTS: Univariate and multivariate analyses revealed both decreased overall survival [hazard ratio (HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival (HR: 2.31, 95%CI: 1.40-3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥ 0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253 (83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low (< 0.41) AAPR group, which were significantly lower than those in the high (≥ 0.41) AAPR group (81.7%, 53.9%, and 33.4%, respectively) (P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor prognosis. CONCLUSION: Our outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients.

Longitudinal lipid trends and adverse outcomes in patients with CKD: a 13-year observational cohort study.

Studies on the effects of longitudinal lipid trajectories on end-stage renal disease (ESRD) development and deaths among patients with chronic kidney disease (CKD) are limited. We conducted a registry-based prospective study using data from a 13-year multidisciplinary pre-ESRD care program. The final study population comprised 4,647 patients with CKD. Using group-based trajectory modeling, we dichotomized longitudinal trajectories of total cholesterol (T-CHO), triglyceride (TG), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C). Time to ESRD or death was analyzed using multiple Cox regression. At baseline, higher levels of T-CHO and LDL-C were associated with rapid progression to ESRD, whereas only HDL-C was positively associated with all-cause mortality [adjusted hazard ratio (HR), 1.20; 95% CI, 1.06-1.36; P-value, 0.005]. Compared with those with a normal T-CHO trajectory, the fully adjusted HR of patients with a high T-CHO trajectory for ESRD risk was 1.21 (P-value, 0.019). Subgroup analysis showed that a high TG trajectory was associated with a 49% increase in mortality risk in CKD patients without diabetes (P-value for interaction, 0.012). In contrast to what was observed based on baseline HDL-C, patients with a trajectory of frequent hypo-HDL cholesterolemia had higher risk of all-cause mortality (adjusted HR, 1.53; P-value, 0.014). Thus, only T-CHO, both at baseline and over the longitudinal course, demonstrated a significant potential risk of incident ESRD. The inconsistency in the observed directions of association between baseline levels and longitudinal trajectories of HDL-C warrants further research to unveil specific pathogenic mechanisms underlying the HDL-C metabolism in patients with CKD.

First-year estimated glomerular filtration rate variability after pre-end-stage renal disease program enrollment and adverse outcomes of chronic kidney disease.

BACKGROUND: Scarce evidence associates the first-year estimated glomerular filtration rate (eGFR) variability and longitudinal change scales concomitantly to the risk of developing end-stage renal disease (ESRD), acute coronary syndrome (ACS) and death following pre-ESRD program enrollment in chronic kidney disease (CKD). METHODS: We conducted a prospective cohort study of 5092 CKD patients receiving multidisciplinary care between 2003 and 2015 with careful ascertainment of ESRD, ACS and death during the follow-up. First-year eGFR variability and longitudinal change scales that were based on all first-year eGFR measurements included coefficient of variation of eGFR (eGFR-CV), percent change (eGFR-PC), absolute difference (eGFR-AD), slope (eGFR-slope) and area under the curve (AUC). RESULTS: A total of 786 incident ESRD, 292 ACS and 410 death events occurred during the follow-up. In the multiple Cox regression, the fully adjusted hazard ratios (HRs) of progression to ESRD for each unit change in eGFR-CV, eGFR-PC, eGFR-AD, eGFR-slope, eGFR-AUC were 1.03 [95% confidence interval (CI) 1.02-1.04], 1.04 (1.03-1.04), 1.16 (1.14-1.18), 1.16 (1.14-1.17) and 1.04 (1.03-1.04), respectively. The adjusted HRs for incident ESRD comparing the extreme with the reference quartiles of eGFR-CV, eGFR-PC, eGFR-AD, eGFR-slope and eGFR-AUC were 2.67 (95% CI 2.11-3.38), 8.34 (6.33-10.98), 19.08 (11.89-30.62), 13.08 (8.32-20.55) and 6.35 (4.96-8.13), respectively. Similar direction of the effects on the risk of developing ACS and mortality was observed. In the 2 × 2 risk matrices, patients with the highest quartile of eGFR-CV and concomitantly with the most severely declining quartiles of any other longitudinal eGFR change scale had the highest risk of all outcomes. CONCLUSIONS: The dynamics of eGFR changes, both overall variability and longitudinal changes, over the first year following pre-ESRD program enrollment are crucial prognostic factors for the risk of progression to ESRD, ACS and deaths among patients with CKD. A risk matrix combining the first-year eGFR variability and longitudinal change scales following pre-ESRD enrollment is a novel approach for risk characterization in CKD care. Randomized trials in CKD may be required to ascertain comparable baseline eGFR dynamics.

Longitudinal progression trajectory of random urine creatinine as a novel predictor of ESRD among patients with CKD.

BACKGROUND: The clinical importance of random urine creatinine concentration in CKD population remains undetermined. Earlier studies found that lower 24-h urine creatinine excretion was associated with the risk of ESRD and all-cause mortality among CKD patients. METHODS: We modeled the longitudinal trajectories of serial random urine creatinine among 4689 CKD patients enrolled in a national registry-based pre-ESRD program between 2003 and 2015 at a tertiary medical center. Other biochemical parameters including kidney function and serum albumin were regularly evaluated. Primary study outcomes were ESRD requiring maintenance dialysis and all-cause mortality. RESULTS: By group-based trajectory modeling, the urine creatinine trajectories were characterized into three patterns: (1) stable low; (2) medium; and (3) high-declining. The adjusted hazard ratio of incident ESRD and all-cause mortality increased by 6% (95% CI: 1-12%) and 9% (95% CI: 2-17%), respectively, for each 20 mg/dL reduction in baseline random urine creatinine concentration. Consistently, there was a significant inverse linear dose-response relationship between baseline random urine creatinine and incident ESRD, but not all-cause mortality. Compared to patients with "medium" and "high-declining" urine creatinine trajectories combined, the adjusted hazard ratio for incidental ESRD among patients with a "stable-low" trajectory who had serial random urine creatinine concentrations stably below 100 mg/dL was 1.46 (95% CI: 1.00-2.12) after considering the competing risk of death. CONCLUSIONS: Random urine creatinine not only serves as a common urinary concentration corrector but has its own clinical significance in risk stratification and outcome prediction in patients with advanced CKD.

Nomogram to predict overall survival after gallbladder cancer resection in China.

AIM: To integrate clinically significant variables related to prognosis after curative resection for gallbladder carcinoma (GBC) into a predictive nomogram. METHODS: One hundred and forty-two GBC patients who underwent curative intent surgical resection at Peking Union Medical College Hospital (PUMCH) were included. This retrospective case study was conducted at PUMCH of the Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC) in China from January 1, 2003 to January 1, 2018. The continuous variable carbohydrate antigen 19-9 (CA19-9) was converted into a categorical variable (cCA19-9) based on the normal reference range. Stages 0 to IIIA were merged into one category, while the remaining stages were grouped into another category. Pathological grade X (GX) was treated as a missing value. A multivariate Cox proportional hazards model was used to select variables to construct a nomogram. Discrimination and calibration of the nomogram were performed via the concordance index (C-index) and calibration plots. The performance of the nomogram was estimated using the calibration curve. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate the predictive accuracy and net benefit of the nomogram, respectively. RESULTS: Of these 142 GBC patients, 55 (38.7%) were male, and the median and mean age were 64 and 63.9 years, respectively. Forty-eight (33.8%) patients in this cohort were censored in the survival analysis. The median survival time was 20 months. A series of methods, including the likelihood ratio test and Akaike information criterion (AIC) as well as stepwise, forward, and backward analyses, were used to select the model, and all yielded identical results. Jaundice [hazard ratio (HR) = 2.9; 95% confidence interval (CI): 1.60-5.27], cCA19-9 (HR = 3.2; 95%CI: 1.91-5.39), stage (HR = 1.89; 95%CI: 1.16-3.09), and resection (R) (HR = 2.82; 95%CI: 1.54-5.16) were selected as significant predictors and combined into a survival time predictive nomogram (C-index = 0.803; 95%CI: 0.766-0.839). High prediction accuracy (adjusted C-index = 0.797) was further verified via bootstrap validation. The calibration plot demonstrated good performance of the nomogram. ROC curve analysis revealed a high sensitivity and specificity. A high net benefit was proven by DCA. CONCLUSION: A nomogram has been constructed to predict the overall survival of GBC patients who underwent radical surgery from a clinical database of GBC at PUMCH.

Surgical treatment for metastasis from lymphoepithelioma-like cholangiocarcinoma in the liver: A case report.

RATIONALE: Lymphoepithelioma-like cholangiocarcinoma (LEL-CC) is a rare variant of intrahepatic cholangiocarcinoma (ICC), which is characterized by the better outcome than normal ICC. There is no report about the treatment for the metastasis of the LEL-CC. Here, we describe a rare case of LEL-CC of the liver and report the treatment for metastasis of it. PATIENT CONCERNS: A 38-year-old woman with a chronic hepatitis B infection was referred to the department of liver surgery in our hospital with a mass in the liver. DIAGNOSES: A past ultrasound examination had revealed a 28 mm × 16 mm nodular lesion in the right posterior lobe of the liver in May 2013. She had undergone partial resection of the thyroid gland for papillary carcinoma 1 year earlier. INTERVENTION: Suspicious of the metastasis from thyroid cancer, she underwent surgery with liver segmentectomy. The pathologic diagnosis of the lesion was LEL-CC. After surgery, she regularly got checked in our hospital, and in the 6 months after surgery, there was enlargement of lymph node before the inferior vena cava in CT. The doctor did not detect the enlargement of the lymph node until June 2017. The PET-CT was done in June of 2017, which showed the lymph node was hypermetabolic. OUTCOMES: The patient got her second surgery for lymph node three years after the first surgery, which was proved that the lymph node was metastasis from LEL-CC. The patient was free from recurrence 9 months after surgery. LESSONS: We report the first case of surgery for metastasis from LEL-CC in the liver that was diagnosed 3 years after hepatectomy. Our findings suggest that surgery could be an effective way of treating lymph node metastasis of LEL-CC and early PET-CT can help to identify metastasis.

Comparative effectiveness of allopurinol, febuxostat and benzbromarone on renal function in chronic kidney disease patients with hyperuricemia: a 13-year inception cohort study.

Background: Direct comparisons of the effectiveness of allopurinol with that of other urate-lowering agents in chronic kidney disease (CKD) populations, as well as guideline recommendations for clinical practice, are lacking. Methods: We constructed a pharmacoepidemiology cohort study by including patients from Taiwan's long-term integrated CKD care program to compare the effectiveness among allopurinol, febuxostat and benzbromarone in reducing the risk of progression to dialysis. A total of 874 patients with hyperuricemia who were newly treated with allopurinol, febuxostat or benzbromarone were included. The primary and secondary outcomes were incident end-stage renal disease (ESRD) and the serum uric acid (SUA) changes from baseline, respectively. The results were analyzed using multiple Cox proportional models adjusted for multinomial propensity scores. For subgroup analyses, we further stratified patients according to whether their latest SUA level reached the therapeutic target. Results: Compared with allopurinol, benzbromarone therapy was associated with a reduced risk of progression to dialysis, the adjusted hazard ratio was 0.50 (95% confidence interval, 0.25-0.99). Patients who received allopurinol or febuxostat exhibited a comparable risk of ESRD [adjusted hazard ratio, 0.99 (0.40-2.44)]. Febuxostat was significantly more potent than allopurinol or benzbromarone in lowering SUA levels in the fully adjusted model. Among patients who reached the therapeutic target, those with febuxostat and benzbromarone initiation had a significantly lower risk of ESRD. Conclusions: In conclusion, compared with conventional allopurinol, febuxostat and benzbromarone may be more effective in reducing the risk of progression to dialysis and in lowering SUA levels in CKD populations.

Uric acid predicts adverse outcomes in chronic kidney disease: a novel insight from trajectory analyses.

Background: Very little is known about longitudinal trajectories of serum uric acid (SUA) over the course of chronic kidney disease (CKD). We aimed to determine whether longitudinal SUA trajectories are associated with the risk of end-stage renal disease (ESRD) and all-cause mortality among CKD patients. Methods: We conducted a prospective cohort study from a 13-year multidisciplinary pre-ESRD care registry. The final study population consisted of 5090 CKD patients aged 20-90 years between 2003 and 2015. An individual's SUA trajectory was defined by group-based trajectory modeling in four distinct patterns: high, moderate-high, moderate and low. Time to ESRD and death was analyzed by multiple Cox regression. Results: A total of 948 ESRD events and 472 deaths occurred with incidence rates of 57.9 and 28.7 per 1000 person-years, respectively. Compared with those with a low SUA trajectory, the adjusted hazard ratio of patients for incident ESRD was in a dose-response manner as follows: moderate, 1.89 [95% confidence interval (CI), 1.37-2.60]; moderate-high, 2.49 (1.75-3.55); and high, 2.84 (1.81-4.47); after considering the competing risk of death. For all-cause mortality, the corresponding risk estimate of the same SUA trajectory was 1.38 (95% CI, 0.89-2.12), 1.95 (1.22-3.10) and 4.52 (2.48-8.26), respectively. The unfavorable effect of elevated SUA trajectories on progression to ESRD was differentially higher among CKD patients without using urate-lowering agents at baseline (P for interaction = 0.018). Conclusions: Elevated SUA trajectories are associated with accelerated kidney failure and all-cause mortality in CKD patients. Adequate experimental evidence is urgently needed to inform when and how to optimize SUA in this population.