Impact of Frailty on Short-Term Outcomes of Hepatic Lobectomy in Patients with Intrahepatic Cholangiocarcinoma: Evidence from the US Nationwide Inpatient Sample 2005-2018.

INTRODUCTION: This study aimed to evaluate associations between frailty and outcomes in patients with intrahepatic cholangiocarcinoma (ICC) undergoing hepatic lobectomy using a large, nationally representative sample. METHODS: This population-based, retrospective observational study extracted the data of adults ≥20 years old with ICC undergoing hepatic lobectomy from the US Nationwide Inpatient Sample database between 2005 and 2018. Frailty was assessed by the validated Hospital Frailty Risk Score (HFRS). Associations between frailty and surgical outcomes were analyzed using logistic regression analyses. RESULTS: After exclusions, 777 patients were enrolled, including 427 frail and 350 non-frail. Patients' mean age was 64.5 (±0.4) years and the majority were males (51.1%) and whites (76.5%). Frailty was significantly associated with increased odds of in-hospital mortality (aOR: 18.51, 95% CI: 6.70, 51.18), non-home discharge (aOR: 3.58, 95% CI: 2.26, 5.66), prolonged LOS (aOR: 5.56, 95% CI: 3.87, 7.99), perioperative cardiac arrest/stroke (aOR: 5.44, 95% CI: 1.62, 18.24), acute respiratory distress syndrome (ARDS)/respiratory failure (aOR: 3.88, 95% CI: 2.40, 6.28), tracheostomy/ventilation (aOR: 3.83, 95% CI: 2.23, 6.58), bleeding/transfusion (aOR: 1.67, 95% CI: 1.24, 2.26), acute kidney injury (AKI) (aOR: 14.37, 95% CI: 7.13, 28.99), postoperative shock (aOR: 4.44, 95% CI: 2.54, 7.74), and sepsis (aOR: 11.94, 95% CI: 6.90, 20.67). DISCUSSION/CONCLUSION: Among patients with ICC undergoing hepatic lobectomy, HFRS-defined frailty is a strong predictor of worse in-patient outcomes, including in-hospital death, prolonged LOS, unfavorable discharge, and complications (perioperative cardiac arrest/stroke, ARDS/respiratory failure, tracheostomy/ventilation, bleeding/transfusion, AKI, postoperative shock, and sepsis). Study results may help stratify risk in frail patients undergoing hepatic resection for ICC.

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.

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.

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.

Surgical treatment of a 72-year-old patient with headache, hyponatremia and oculomotor nerve palsy: a case report and literature review.

Pituitary apoplexy is a life-threatening syndrome caused by acute infarction of the pituitary gland. The most common symptoms associated with pituitary apoplexy are headache, nausea, vomiting, visual symptoms, hypopituitarism, and altered mental status. Both oculomotor nerve palsy and hyponatremia are relatively rare complications of pituitary apoplexy. The treatment of pituitary apoplexy is controversial. We report a case of a 72-year-old man with severe headache, nausea, vomiting, confusion and left oculomotor nerve palsy, who was initially considered as posterior communicating artery aneurysm (PCOAA) based on the presenting symptoms. Initial biochemical evaluation showed severe hyponatremia, hormonal evaluation identified multiple pituitary hormone deficiency and enhanced magnetic resonance imaging showed a large pituitary adenoma with signs of hemorrhage. A diagnosis of pituitary apoplexy and secondary hypopituitarism was finally made. The patient was treated with intravenous hydrocortisone 100 mg twice daily and oral levothyroxine 100 mg once daily. Appropriate venous transfusion with sodium was also used concomitantly to correct hyponatremia. After seven days of treatment, the patient's serum electrolytes normalized and he gradually recovered alertness. Then, the patient underwent transsphenoidal surgery for tumor removal. Left ptosis and oculomotor nerve palsy completely recovered three months after surgery. Postoperatively, hormone replacement therapy was essential for the patient with 20 mg hydrocortisone and 50 mg levothyroxine once daily. During the last follow up 4 years later, the patient was still on hormonal replacement and in good condition. So, for patients with pituitary apoplexy, we have shown that a semi-elective surgery after conservative treatment when the patient becomes clinically stable and hypopituitarism has been corrected is a good approach.

Apatinib as non-first-line treatment in patients with Intrahepatic Cholangiocarcinoma.

Purpose: There is limited standard treatment for patients with advanced cholangiocarcinoma after refractory of chemotherapy. Apatinib is a tyrosine kinase inhibitor targeting VEGFR-2, which exhibited broad-spectrum antitumor activities in previous studies. We aim to evaluate the efficacy and safety of apatinib as non-first-line treatment in patients with advanced cholangiocarcinoma. Methods: This was a prospective open-label phase II trial (NCT03251443). Patients with pathology-confirmed cholangiocarcinoma after prior systemic therapy were enrolled. Participants were treated with apatinib 500 mg orally once daily. The primary end point was overall response rate (ORR). Results: Between August 8, 2017 and November 13, 2018, 30 patients participated in this study, and 26 patients received apatinib treatment except 4 patients withdrew consent before the first dosage. For full analysis set, the ORR was 11.5% and the disease control rate was 50.0%. 3 patients (11.5%) achieved partial response and no patients achieved complete response. The median progression free time was 2.0 (95% CI: 0.7-3.3) months and median overall survival was 9. 0 (95% CI: 4.6-13.4) months. The most common adverse events of any grade were fatigue (80.8%), hypertension (73.1%) and decreased appetite (38.5%). Grade 3 adverse events occurred in 23.1% patients and no grade 4 adverse events occurred. The most common grade 3 adverse events were hypertension (23.1%) and elevated transaminase (11.5%). Conclusion: Apatinib as non-first-line monotherapy has potential therapeutic efficacy in patients with advanced cholangiocarcinoma.

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.

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.

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.

Safety, feasibility, and efficacy of associating liver partition and portal vein ligation for staged hepatectomy in treating hepatocellular carcinoma: a systematic review.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows radical resection of colorectal liver metastasis (CRLM). However, the effect of ALPPS on hepatocellular carcinoma (HCC) is not completely understood. This systematic review aimed to examine the existing data on the safety, feasibility, and oncologic effect of ALPPS on HCC. Electronic databases, including PubMed, Web of Science, and Embase, were systemically searched to identify articles on ALPPS and HCC. Additional articles were identified manually. The feasibility (liver hypertrophy between two stages), safety (90-day mortality), and therapeutic effect (long-term survival) were analyzed. Nine published articles that satisfied the retrieval standards were included, and these studies involved 176 patients. The evidence level of the enrolled studies was low, among which, the greatest Oxford evidence level was 2c. Additionally, the average median increase in future liver volume was 178 mL, the average interval between two stages was 11.2 days, the interval was remarkably longer in radiofrequency-assisted ALPPS (RALPPS) patients (28 days), and the average 90-day mortality was 17.6% (range, 0-50%). However, the oncological outcomes were not well documented. Survival following ALPPS was evidently improved compared with that after transcatheter arterial chemoembolization (TACE). This value was comparable to that following the one-stage hepatectomy and portal vein embolization (PVE), and it was similar to that in CRLM patients over the long term. Publication biases caused by case series and single-center reports are common in the review. It is concluded in this review that ALPPS is a safe and feasible approach to treat selected patients with unresectable HCC, but its oncological outcome requires further study. RALPPS is not recommended for HCC patients because of the long waiting time between the two stages.

N6-methyladenosine associated prognostic model in hepatocellular carcinoma.

BACKGROUND: N6-methyladenosine (m6A), the most internal mRNA modification, is involved in various cancers. However, the function of m6A in hepatocellular carcinoma (HCC) is still not well explored. Here, we aimed to develop a prognostic model consist of m6A associated genes in HCC. METHODS: The mRNA expression profiles and the corresponding clinical information from the patients with HCC were obtained from The Cancer Genome Atlas (TCGA) database, m6A differentially expressed genes (DEGs) were screened by univariate, Lasso and multivariate Cox regression analyses to develop the prognostic model. The differentially expressed m6A genes in HCC tissues were verified by quantitative reverse transcription PCR (qRT-PCR). RESULTS: The DEGs were obtained between the HCC (n=374) and normal tissues (n=50). Nine m6A genes were correlated with the prognosis, and five of them (KIAA1429, METTL3, YTHDF1, YTHDF2, ZC3H13) were included in the prognostic model by Lasso regression analyses. Four genes (KIAA1429, METTL3, YTHDF1, YTHDF2) were proved significantly high expression in our ten pairs of matched HCC and normal tissues by PCR. The HCC patients were divided into two groups (high- and low-risk) according to the risk score. The high-risk group associated with a significant poor prognosis (P=1.72×10-4). The time-dependent receiver operating characteristic (ROC) curve analysis confirmed the good performance of this prognostic model (AUC =0.617). After univariate [P<0.001, 1.213 (1.136-1.295)] and multivariate Cox regression analyses [P<0.001, 1.198 (1.115-1.288)] by combined with other clinical factors, this prognostic model was identified as an independent prognostic factor of HCC patients. CONCLUSIONS: The m6A genes were differentially expressed between HCC and normal tissues, and associated with the prognosis of HCC.

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.

Application of associating liver partition and portal vein ligation for staged hepatectomy for hepatocellular carcinoma related to hepatitis B virus: comparison with traditional one-stage right hepatectomy.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been suggested to cause rapid liver hypertrophy among patients having inadequate future liver remnant (FLR). However, ALPPS is still considered as a controversial hepatocellular carcinoma (HCC) treatment, especially for those with cirrhosis. This is ascribed to the high mortality and morbidity. The present study aimed to evaluate the ALPPS safety and feasibility for HCC patients related to hepatitis B virus (HBV). METHODS: This was a retrospective observational study. Consecutive HCC cases undergoing ALPPS or RH at our hospital between September 2014 and June 2018 were included. The demographic and clinical data of patients were collected, and oncological results of ALPPS patients were compared with those receiving right hepatectomy (RH). RESULTS: A total of 14 ALPPS patients and 21 RH patients were consecutively collected between September 2014 and June 2018. All ALPPS patients received stage II operations, with 100% resection of R0. The median growth of FLR between operations was 48% (range, ‒0.06% to 100%) in 17 days (range, 9-30 days). 3 ALPPS patients (21.4%) suffered from severe complications (grade ≥IIIb) according to the Clavien-Dindo grade, including 1 with renal failure, and 2 with the FLR/SLV of <30% and liver failure, and 1 (4.8%) with severe complication (liver failure) after the stage I RH. Difference in the long-term survival, either overall survival (OS) or disease-free survival (DFS), between ALPPS and RH was not statistically significant. CONCLUSIONS: Our results suggest that ALPPS should be performed in highly selected patients with cirrhosis. Patients with 30%< the FLR/SLV <30% and ages <60 years old are recommended. And a longer interval time between stages is suggested to improve the safety of ALPPS. Because the long-term survival after ALPPS is similar to that after RH, which indicates that the long waiting time between stage does not increase the risk of tumor progression.

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 after associating liver partition and portal vein ligation for staged hepatectomy for hepatocellular carcinoma: two case reports and a literature review.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is used for avoiding postoperative live failure caused by insufficient future liver remnant (FLR) after major liver resection. However, ALPPS accompanied by high morbidity and mortality. The surgeons focus their attention mainly on the common complications such as bile leak, bleeding, infection and liver failure. Acute kidney injury (AKI) is a relatively rare postoperative complication, and get less attention. However, once AKI occurred after the surgery, it will seriously affect the prognosis of patients. We firstly report two cases of postoperative AKI after ALPPS in hepatocellular carcinoma with liver cirrhosis. Case 1, a 61-year-old male, chief complaint upper abdominal pain for half a month, medical examination found a huge liver space-occupying lesion. The clinical diagnosis was liver cancer, and ALPPS was performed. After the first step of surgery, delayed renal replacement therapy (RRT) was initiated when stage 3 AKI diagnosed. Although the second step surgery completed successfully, the patient eventually died of multiple organ dysfunction syndrome (MODS) induced by gastrointestinal bleeding. Case 2, a 64-year-old male chief complaint right liver mass present to our hospital, with a small FLR. Stage 2 AKI was diagnosed after the first step of ALPPS, early RRT was started immediately. Renal function gradually recovered, and the second step surgery was completed. The patient discharged with a good condition, found no recurrence in the latest follow-up. ALPPS for hepatocellular carcinoma with liver cirrhosis cases, more likely to happen AKI. More strict patient screening criteria, early RRT may improve the prognosis.

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.

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.