Racial Disparities in End-Stage Kidney Disease Outcomes among Asians and Native Hawaiians and Other Pacific Islanders across Geographic Residence.

INTRODUCTION: While Asian and Native Hawaiian and other Pacific Islander (NHOPI) patients have a high prevalence of kidney disease risk factors, there are sparse data examining their end-stage kidney disease (ESKD) outcomes. As Hawaii has high representation of Asian and NHOPI individuals, we compared their ESKD outcomes based on residence in the mainland USA versus Hawaii/Pacific Islands (PIs). MATERIALS AND METHODS: Using United States Renal Data System data, we examined the impact of geographic residence in the mainland versus Hawaii/PIs on race-mortality associations among incident ESKD patients transitioning to dialysis over January 1, 2000-December 31, 2016 using Cox regression. We examined likelihood of post-dialysis kidney transplantation using Cox models and cumulative incidence curves. RESULTS: Compared with White patients in the mainland, Asian and NHOPI patients in the mainland had lower mortality: adjusted HRs (95% CIs) 0.67 (0.66-0.67) and 0.72 (0.70-0.73), respectively. When examining Asian and NHOPI patients in Hawaii/PIs, survival benefit was attenuated in Asian and diminished to the null in NHOPI patients (ref: mainland White patients). Cumulative incidence curves comparing Asian, NHOPI, and White patients showed Asian and NHOPI patients in the mainland had the highest likelihood of transplantation, whereas NHOPI and Asian patients in Hawaii/PIs had the lowest likelihood. CONCLUSION: In the mainland, Asian and NHOPI patients had lower mortality versus White patients, whereas in Hawaii/PIs, this survival benefit was diminished in Asian and mitigated in NHOPI patients. NHOPI and Asian patients in Hawaii/PIs had less transplantation versus those in the mainland. Further research is needed to uncover factors contributing to differential ESKD outcomes among Asian and NHOPI patients across geographic residence.

MiR-125b Loss Activated HIF1α/pAKT Loop, Leading to Transarterial Chemoembolization Resistance in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Transarterial chemoembolization (TACE) is a standard locoregional therapy for patients with hepatocellular carcinoma (HCC) patients with a variable overall response in efficacy. We aimed to identify key molecular signatures and related pathways leading to HCC resistance to TACE, with the hope of developing effective approaches in preselecting patients with survival benefit from TACE. APPROACH AND RESULTS: Four independent HCC cohorts with 680 patients were used. MicroRNA (miRNA) transcriptome analysis in patients with HCC revealed a 41-miRNA signature related to HCC recurrence after adjuvant TACE, and miR-125b was the top reduced miRNA in patients with HCC recurrence. Consistently, patients with HCC with low miR-125b expression in tumor had significantly shorter time to recurrence following adjuvant TACE in two independent cohorts. Loss of miR-125b in HCC noticeably activated the hypoxia inducible factor 1 alpha subunit (HIF1α)/pAKT loop in vitro and in vivo. miR-125b directly attenuated HIF1α translation through binding to HIF1A internal ribosome entry site region and targeting YB-1, and blocked an autocrine HIF1α/platelet-derived growth factor ß (PDGFß)/pAKT/HIF1α loop of HIF1α translation by targeting the PDGFß receptor. The miR-125b-loss/HIF1α axis induced the expression of CD24 and erythropoietin (EPO) and enriched a TACE-resistant CD24-positive cancer stem cell population. Consistently, patients with high CD24 or EPO in HCC had poor prognosis following adjuvant TACE therapy. Additionally, in patients with HCC having TACE as their first-line therapy, high EPO in blood before TACE was also noticeably related to poor response to TACE. CONCLUSIONS: MiR-125b loss activated the HIF1α/pAKT loop, contributing to HCC resistance to TACE and the key nodes in this axis hold the potential in assisting patients with HCC to choose TACE therapy.

Can the Timed Up & Go Test and Montreal Cognitive Assessment predict outcomes in patients waitlisted for renal transplant?

PURPOSE: Frail patients who undergo renal transplantation (RT) have more complications; however, little is known if these patients can sustain the wait to RT. We used the Timed Up and Go Test (TUGT) and Montreal Cognitive Assessment (MoCA) to determine outcomes of RT candidates. METHODS: In this retrospective study, 526 RT candidates underwent TUGT and MoCA (2015-2019) and were divided into "favorable" (transplanted or remained on the list) or "unfavorable" (not listed, removed from list, or died) outcome. Demographics, education, language, comorbidities, dialysis type, use of a walking device, TUGT, and MoCA were compared by outcome. RESULTS: Overall, 230 patients (43.7%) passed TUG, 268 (51%) passed MoCA, 133 (25.3%) passed both, and 161 (30.6%) failed both tests. Multivariate analysis demonstrated age ≥ 65 (OR 1.58, CI 1.03-2.43), cardiac disease (OR 3.09, CI 2.02-4.72), ≥36 months on dialysis (OR 1.80, CI 1.24-2.69), EPTS < 20% at time of MoCA (OR 0.26, CI 0.07-0.98), and failing TUGT (OR 2.14, CI 1.43-3.19) were associated with unfavorable outcome. Failing MoCA was not associated with outcome. CONCLUSIONS: MoCA test results were not associated with RT waitlist outcomes; however, passing the TUGT was associated with receiving RT or remaining on the list. Additional studies are needed to validate this and determine outcome after RT.

Transarterial Radioembolization for Hepatocellular Carcinoma with Major Vascular Invasion: A Nationwide Propensity Score-Matched Analysis with Target Trial Emulation.

PURPOSE: To examine National Cancer Database (NCDB) data to comparatively evaluate overall survival (OS) between patients undergoing transarterial radioembolization (TARE) and those undergoing systemic therapy for hepatocellular carcinoma with major vascular invasion (HCC-MVI). METHODS: One thousand five hundred fourteen patients with HCC-MVI undergoing first-line TARE or systemic therapy were identified from the NCDB. OS was compared using propensity score-matched Cox regression and landmark analysis. Efficacy was also compared within a target trial framework. RESULTS: TARE usage doubled between 2010 and 2015. Intervals before treatment were longer for TARE than for systemic therapy (mean [median], 66.5 [60] days vs 46.8 (35) days, respectively, P < .0001). In propensity-score-matched and landmark-time-adjusted analyses, TARE was found to be associated with a hazard ratio of 0.74 (95 % CI, 0.60-0.91; P = .005) and median OS of 7.1 months (95 % CI, 5.0-10.5) versus 4.9 months (95 % CI, 3.9-6.5) for systemically treated patients. In an emulated target trial involving 236 patients with unilobular HCC-MVI, a low number of comorbidities, creatinine levels <2.0 mg/dL, bilirubin levels <2.0 mg/dL, and international normalized ratio <1.7, TARE was found to be associated with a hazard ratio of 0.57 (95 % CI, 0.39-0.83; P = .004) and a median OS of 12.9 months (95 % CI, 7.6-19.2) versus 6.5 months (95 % CI, 3.6-11.1) for the systemic therapy arm. CONCLUSIONS: In propensity-score-matched analyses involving pragmatic and target trial HCC-MVI cohorts, TARE was found to be associated with significant survival benefits compared with systemic therapy. Although not a substitute for prospective trials, these findings suggest that the increasing use of TARE for HCC-MVI is accompanied by improved OS. Further trials of TARE in patients with HCC-MVI are needed, especially to compare with newer systemic therapies.

Factors and Survival Implications associated with biopsy of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the few cancers that can be diagnosed based on imaging findings alone. The factors associated with the decision to perform a biopsy and the clinical impact have not been previously studied. METHODS: We collected data of patients diagnosed with HCC between 2004 and 2015 from the National Cancer Database. We assessed associations between biopsy and survival with demographic and clinical factors. RESULTS: We included 160,507 patients. The median age was 62 (40-90), 74.1% were male and 74.9% were white. Over the 12-year period, 47.7% (76,524/160,517) underwent a biopsy. Factors associated with a biopsy were black race, older age, presence of metastatic disease, larger tumor size, and treatment at a community cancer center. Factors associated with increased mortality were older age, higher comorbidity index, larger tumor size, presence of metastatic disease, higher AFP and elevated bilirubin. There was a significant decreased use of biopsy over successive years (2007-2015). After adjusting for prognostic factors, biopsy had no significant impact on survival HR 1.01 (95%CI 1.00-1.03. p = 0.07). CONCLUSIONS: A significant number of patients underwent a biopsy. Performing a biopsy did not have a significant impact on survival.

Tocilizumab for Severe and Critical COVID-19 Pneumonia in Queens, NYC.

New York City was hard hit by COVID-19. Elmhurst Hospital is a public hospital in Queens where more than 1500 patients were hospitalized with COVID. During the pandemic, various treatments were used with hopes of reducing the need for mechanical ventilation and death. METHODS: We retrospectively reviewed charts of patients admitted from March 25 to April 3 with severe or critical COVID-19 pneumonia who received tocilizumab compared with a similar cohort who did not. Analyses were performed to determine differences in outcomes. RESULTS: There was no observed difference in need for mechanical ventilation, length of stay, or mortality rate. In the tocilizumab-treated group, mechanical ventilation rate was 55%, and 49% of patients died. In the control group, 54% required mechanical ventilation and 46% died. Tocilizumab was overall well tolerated, although alanine aminotransferase elevation was more common in the tocilizumab-treated group. CONCLUSIONS: Tocilizumab failed to show short-term benefits in clinical outcomes in patients with hypoxic COVID pneumonia at our institution.

Serum metabolite profiles are associated with the presence of advanced liver fibrosis in Chinese patients with chronic hepatitis B viral infection.

BACKGROUND: Accurate and noninvasive diagnosis and staging of liver fibrosis are essential for effective clinical management of chronic liver disease (CLD). We aimed to identify serum metabolite markers that reliably predict the stage of fibrosis in CLD patients. METHODS: We quantitatively profiled serum metabolites of participants in 2 independent cohorts. Based on the metabolomics data from cohort 1 (504 HBV associated liver fibrosis patients and 502 normal controls, NC), we selected a panel of 4 predictive metabolite markers. Consequently, we constructed 3 machine learning models with the 4 metabolite markers using random forest (RF), to differentiate CLD patients from normal controls (NC), to differentiate cirrhosis patients from fibrosis patients, and to differentiate advanced fibrosis from early fibrosis, respectively. RESULTS: The panel of 4 metabolite markers consisted of taurocholate, tyrosine, valine, and linoelaidic acid. The RF models of the metabolite panel demonstrated the strongest stratification ability in cohort 1 to diagnose CLD patients from NC (area under the receiver operating characteristic curve (AUROC) = 0.997 and the precision-recall curve (AUPR) = 0.994), to differentiate fibrosis from cirrhosis (0.941, 0.870), and to stage liver fibrosis (0.918, 0.892). The diagnostic accuracy of the models was further validated in an independent cohort 2 consisting of 300 CLD patients with chronic HBV infection and 90 NC. The AUCs of the models were consistently higher than APRI, FIB-4, and AST/ALT ratio, with both greater sensitivity and specificity. CONCLUSIONS: Our study showed that this 4-metabolite panel has potential usefulness in clinical assessments of CLD progression in patients with chronic hepatitis B virus infection.

Risk factors for hepatocellular carcinoma (HCC) in the northeast of the United States: results of a case-control study.

PURPOSE: HCC incidence has been continuously rising in the US for the past 30 years. To understand the increase in HCC risk, we conducted a case-control study in Connecticut, New Jersey and part of New York City. METHODS: Through rapid case ascertainment and random digit dialing, we recruited 673 incident HCC patients and 1,166 controls. Information on demographic and anthropometric characteristics, lifestyle factors, medical and family cancer histories, were ascertained through telephone interviews using a structured questionnaire. Saliva specimens were collected for testing hepatitis C virus (HCV) antibodies. Unconditional logistic regression models were utilized to calculate odds ratio (OR) and 95% confidence interval (CI) to determine HCC associations with risk factors. RESULTS: The study confirmed that HCV infection and obesity were important risk factors for HCC, ORs 110 (95% CI 59.2-204) and 2.13 (95% CI 1.52-3.00), respectively. High BMI and HCV infection had synergy in association with elevated HCC risk. Patients both obese and infected with HCV had HCC detected on average nearly 10 years earlier than those with neither factor. Diabetes, cigarette smoking and heavy alcohol intake were all associated with increased risk of HCC, whereas aspirin and other NSAID use were associated with reduced risk. HCC cases tended to attain less education, with lower household incomes, unmarried, and to have had more sexual partners than the controls. CONCLUSIONS: Individuals at risk of HCC in the US comprise a unique population with low socioeconomic status and unhealthy lifestyle choices. Given the multifactorial nature, a comprehensive approach is needed in HCC prevention.

Racial/Ethnic Differences in Early Detection and Screening for Chronic Kidney Disease Among Adults in Hawaii: A 10-Year Population Health Study.

INTRODUCTION: Native Hawaiian and Asian American populations are the most understudied racial/ethnic groups in chronic kidney disease (CKD) research. The objective of our study was to describe sociodemographic and comorbidity risk factors of chronic kidney disease among 2,944 community-dwelling Native Hawaiian, Filipino, Chinese, Japanese, and non-Hispanic white participants who attended the National Kidney Foundation of Hawaii Kidney Early Detection Screening program during 2006-2017. METHODS: We used multivariable logistic regression models to examine the association between age, sex, race/ethnicity, and the major risk factors for CKD (diabetes, hypertension, cardiovascular disease, hypercholesterolemia, overweight and obesity, and smoking) with elevated urine albumin to creatinine ratio (ACR) among adults aged 18 or older in 5 racial/ethnic groups in Hawaii: Native Hawaiian, Filipino, Chinese, Japanese, and non-Hispanic white. RESULTS: In the age- and sex-adjusted model, Native Hawaiian participants were significantly more likely than non-Hispanic white participants to have an ACR of 30.0 mg/g or more (odds ratio [OR] = 1.50; 95% CI, 1.15-1.95; P = .003). In the model that adjusted for CKD risk factors, the difference between Native Hawaiian and non-Hispanic white participants became nonsignificant (OR = 1.27; 95% CI, 0.96-1.69; P = .09]). The higher prevalence of chronic conditions among Native Hawaiians partially explained their higher risk of having an elevated ACR. Filipinos had significantly higher odds than non-Hispanic whites of elevated ACR in the age- and sex-adjusted model (OR = 1.44; 95% CI, 1.14-1.84; P = .003) and after adjustment for CKD risk factors (OR = 1.36; 95% CI, 1.06-1.74; P = .01). CONCLUSION: Culturally targeted interventions are needed to improve health outcomes among Native Hawaiians and Asian Americans, particularly Filipinos, with CKD. Such interventions should focus on early kidney disease management so that disease progression can be delayed.

Should a homeless person become a deceased organ donor?

Efforts to increase deceased donation have included the use of US Public Health Service (PHS) high-risk donors. The homeless have high rates of medical and substance abuse issues that are often unrecognized. This study investigates whether the homeless should become suitable organ donors. We retrospectively reviewed 193 brain-dead prospective donors from Hawaii's organ procurement organization (OPO; 2013-2018) and compared two groups: homeless (n = 13) and non-homeless (n = 180) prospective donors. The homeless prospective donors were older (48.0 vs 40.7 years, P = .009) and had more substance abuse (30.8% vs 10%, P = .046), methamphetamine use (53.8% vs 12.2%, P = .001), cocaine use (23.1% vs 3.9%, P = .022), and urine with amphetamines (54.5% vs 17.9%, P = .049). The homeless prospective donors trended toward more PHS high-risk designation (50% vs 19%, P = .062). There was no difference in medical history, gender/race, hepatitis serologies, authorization for donation, and organs procured/transplanted between prospective donors. We have provided evidence that the homeless should become prospective organ donors; however, they have more high-risk behaviors and often have limited information. Larger studies from OPOs are needed to better characterize organ donation and track disease transmission in this population.

The prevalence and anatomy of parathyroid glands: a meta-analysis with implications for parathyroid surgery.

PURPOSE: The anatomy of parathyroid glands (PTG) is highly variable in the population. The aim of this study was to conduct a systematic analysis on the prevalence and location of PTG in healthy and hyperparathyroidism (HPT) patients. METHODS: An extensive search of the major electronic databases was conducted to identify all studies that reported relevant data on the number of PTG per patient and location of PTG. The data was extracted from the eligible studies and pooled into a meta-analysis. RESULTS: The overall analysis of 26 studies (n = 7005 patients; n = 23,519 PTG) on the number of PTG showed that 81.4% (95% CI 65.4-85.8) of patients have four PTG. A total of 15.9% of PTG are present in ectopic locations, with 11.6% (95% CI 5.1-19.1) in the neck and 4.3% (95% CI 0.7-9.9) in mediastinum. The subgroup analysis of ectopic PTG showed that 51.7% of ectopic PTG in the neck are localized in retroesophageal/paraesophageal space or in the thyroid gland. No significant differences were observed between the healthy and HPT patients and cadaveric and intraoperative studies. CONCLUSIONS: Knowledge regarding the prevalence, location, and anatomy of PTG is essential for surgeons planning for and carrying out parathyroidectomies, as any unidentified PTG, either supernumerary or in ectopic location, can result in unsuccessful treatment and need for reoperation.

Effect of Concomitant Positive Hepatitis B Surface Antigen on the Risk of Liver Metastasis: A Retrospective Clinical Study of 4033 Consecutive Cases of Newly Diagnosed Colorectal Cancer.

Background: The aim of this study was to evaluate the effect of chronic hepatitis B infection on the risk of synchronous colorectal liver metastasis (synCRLM). Methods: A total of 4033 consecutive patients with newly diagnosed colorectal cancer (CRC) with hepatitis B testing were enrolled. The prevalence of synCRLM was compared between hepatitis B surface antigen (HBsAg)-positive and -negative patients; significant predictors for synCRLM were analyzed by logistic regression analysis; Fibrosis-4 Index for Liver Fibrosis (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), and hepatitis B e antigen (HBeAg) status were compared between patients with or without synCRLM. Results: The prevalence of synCRLM was significantly higher in the HBsAg+ patients than that in the HBsAg- patients (15.57% vs 8.60%; P < .001, χ2 test). A logistic regression analysis indicated that HBsAg+ showed the highest hazard ratio (2.317 [95% confidence interval, 1.406-3.820]) for synCRLM. Both FIB-4 and APRI were significantly higher in those with HBsAg positivity but no synCRLM compared to those with HBsAg positivity and synCRLM (FIB-4: 1.23 [0.92-1.88] vs 1.09 [0.74-1.51], P = .045; APRI: 0.23 [0.227-0.387] vs 0.18 [0.171-0.309], P = .023, Mann-Whitney test; all shown as median [25th-75th percentile]); HBeAg positivity was detected in 26.32% of those with positive HBsAg and synCRLM compared to 18.45% of those with positive HBsAg but no synCRLM; the difference was not statistically significant. Conclusions: Concomitant chronic HBV infection significantly increases the risk of CRLM, and for HBsAg+ CRC patients, elevated FIB-4/APRI may be antimetastatic. Further study is needed to determine whether active HBV replication is prometastatic.

PET/CT with 18F Fluorocholine as an Imaging Biomarker for Chronic Liver Disease: A Preliminary Radiopathologic Correspondence Study in Patients with Liver Cancer.

Purpose To determine the relationship between hepatic uptake at preoperative fluorine 18 (18F) fluorocholine combined positron emission tomography (PET) and computed tomography (CT) and the histopathologic features of chronic liver disease in patients with Child-Pugh class A or B disease who are undergoing hepatic resection for liver cancer. Materials and Methods Forty-eight patients with resectable liver tumors underwent preoperative 18F fluorocholine PET/CT. Mean liver standardized uptake value (SUVmean) measurements were obtained from PET images, while histologic indexes of inflammation and fibrosis were applied to nontumor liver tissue from resection specimens. Effects of histopathologic features on liver SUVmean were examined with analysis of variance. Results Liver SUVmean ranged from 4.3 to 11.6, correlating significantly with Knodell histologic activity index (ρ = -0.81, P < .001) and several clinical indexes of liver disease severity. Liver SUVmean also differed significantly across groups stratified by necroinflammatory severity and Metavir fibrosis stage (P < . 001). The area under the receiver operating characteristic curve for 18F fluorocholine PET/CT detecting Metavir fibrosis stage F1 or higher was 0.89 ± 0.05, with an odds-ratio of 3.03 (95% confidence interval: 1.59, 5.88) and sensitivity and specificity of 82% and 93%, respectively. Conclusion Correlations found in patients undergoing hepatic resection for liver cancer between liver 18F fluorocholine uptake and histopathologic indexes of liver fibrosis and inflammation support the use of 18F fluorocholine PET/CT as a potential imaging biomarker for chronic liver disease. © RSNA, 2018.

Surgical anatomy of the external branch of the superior laryngeal nerve: a systematic review and meta-analysis.

PURPOSE: To provide a comprehensive evidence-based assessment of the anatomical characteristics of the external branch of the superior laryngeal nerve (EBSLN). MATERIALS AND METHODS: A thorough systematic search was performed on the major electronic databases PubMed, EMBASE, Cochrane library, and ScienceDirect to identify eligible studies. Data were extracted and pooled into a meta-analysis. The primary outcomes were the EBSLN identification rate (total number of EBSLN identified divided by the total number of dissected hemilarynges) and the prevalence of various EBSLN types. RESULTS: A total of 56 studies (n = 13,444 hemilarynges) were included. The overall pooled EBSLN identification rate was 89.24% (95% CI 85.49-92.49). This rate was higher for cadaveric (95.00%; 95% CI 89.73-99.35) compared to that reported in intraoperative studies (86.99%; 95% CI 82.37-91.01). Significantly higher identification rates were reported for studies in which intraoperative nerve monitoring was used (95.90%; 95% CI 94.30-97.25) compared to those which only relied on direct visual identification of the EBSLN (76.56%; 95% CI 69.34-83.08). Overall, Cernea type IIa (nerves crossing the superior thyroid artery less than 1 cm above the upper edge of the superior thyroid pole) and Friedman type 1 (nerves running their entire course superficial to the inferior pharyngeal constrictor) were the most prevalent (41.84%; 95% CI 33.28-48.08 and 50%; 95% CI 29.90-65.62, respectively). The combined prevalence of Cernea IIa and IIb (nerves crossing the superior thyroid artery below the upper edge of the superior thyroid pole) was higher in intraoperative studies compared to that in cadaveric studies (64.3% vs 49.4%). The EBSLN coursed medial to the superior thyroid artery in 70.98% (95% CI 55.14-84.68) of all cases. CONCLUSION: The use of intraoperative nerve monitoring improves EBSLN identification rates. In light of the highly variable anatomical patterns displayed by the EBSLN, thorough pre-operative knowledge of its anatomy can be crucial in minimizing incidences of its iatrogenic injury.

Evaluation of quantitative miRNA expression platforms in the microRNA quality control (miRQC) study.

MicroRNAs are important negative regulators of protein-coding gene expression and have been studied intensively over the past years. Several measurement platforms have been developed to determine relative miRNA abundance in biological samples using different technologies such as small RNA sequencing, reverse transcription-quantitative PCR (RT-qPCR) and (microarray) hybridization. In this study, we systematically compared 12 commercially available platforms for analysis of microRNA expression. We measured an identical set of 20 standardized positive and negative control samples, including human universal reference RNA, human brain RNA and titrations thereof, human serum samples and synthetic spikes from microRNA family members with varying homology. We developed robust quality metrics to objectively assess platform performance in terms of reproducibility, sensitivity, accuracy, specificity and concordance of differential expression. The results indicate that each method has its strengths and weaknesses, which help to guide informed selection of a quantitative microRNA gene expression platform for particular study goals.

Insights from Screening a Racially and Ethnically Diverse Population for Chronic Kidney Disease.

BACKGROUND: The value of chronic kidney disease (CKD) screening in the general population remains unclear but may be beneficial in populations with high disease prevalence. We examined risk factors for albuminuria among participants in a state-wide CKD screening program in Hawaii. METHODS: The National Kidney Foundation of Hawaii Kidney Early Detection Screening (NKFH-KEDS) program held 19 CKD screening events from 2006 to 2012. Participants rotated through 5 stations during which sociodemographic, blood glucose, urine albumin-to-creatinine ratio (ACR), and spot urine albumin data were collected. Multivariate logistic regression analyses (adjusted for age, sex, race/ethnicity, body mass index [BMI]) were used to identify clinical predictors of abnormal ACR (≥30 µg/mg) and abnormal spot urine albumin (>20 mg/L) levels. RESULTS: Among 1,190 NKFH-KEDS participants who met eligibility criteria, 13 and 49% had abnormal ACR and urine albumin levels, respectively. In multivariate logistic regression analyses, participants of older age (>65 years), Asian and Pacific Islander race/ethnicity, BMI ≥30 kg/m2, and with hypertension had higher risk of abnormal ACR. Being of older age; Asian, Pacific Islander, and Mixed race/ethnicity; and having diabetes was associated with higher risk of abnormal urine albumin levels in adjusted analyses. CONCLUSIONS: NKFH-KEDS participants of older age; Asian and Pacific Islander race/ethnicity; and with obesity, hypertension, and diabetes had higher risk of kidney damage defined by elevated ACR and urine albumin levels. Further studies are needed to determine whether targeted screening programs can result in timely identification of CKD and implementation of interventions that reduce cardiovascular disease, death, and progression to end-stage renal disease.

Profiling of serum bile acids in a healthy Chinese population using UPLC-MS/MS.

Bile acids (BAs) are a group of important physiological agents for cholesterol metabolism, intestinal nutrient absorption, and biliary secretion of lipids, toxic metabolites, and xenobiotics. Extensive research in the last two decades has unveiled new functions of BAs as signaling molecules and metabolic regulators that modulate hepatic lipid, glucose, and energy homeostasis through the activation of nuclear receptors and G-protein-coupled receptor signaling in gut-liver metabolic axis involving host-gut microbial co-metabolism. Therefore, investigation of serum BA profiles, in healthy human male and female subjects with a wide range of age and body mass index (BMI), will provide important baseline information on the BA physiology as well as metabolic homeostasis among human subjects that are regulated by two sets of genome, host genome, and symbiotic microbiome. Previous reports on age- or gender-related changes on BA profiles in animals and human showed inconsistent results, and the information acquired from various studies was highly fragmentary. Here we profiled the serum BAs in a large population of healthy participants (n = 502) and examined the impact of age, gender, and BMI on serum BA concentrations and compositions using a targeted metabonomics approach with ultraperformance liquid chromatography triple-quadrupole mass spectrometry. We found that the BA profiles were dependent on gender, age, and BMI among study subjects. The total BAs were significantly higher in males than in females (p < 0.05) and higher in obese females than in lean females (p < 0.05). The difference in BA profiles between male and female subjects was decreased at age of 50-70 years, while the difference in BA profiles between lean and obese increased for subjects aged 50-70 years. The study provides a comprehensive understanding of the BA profiles in healthy subjects and highlights the need to take into account age, gender, and BMI differences when investigating pathophysiological changes of BAs resulting from gastrointestinal diseases.

Distinct Plasma Bile Acid Profiles of Biliary Atresia and Neonatal Hepatitis Syndrome.

Biliary atresia (BA) is a severe chronic cholestasis disorder of infants that leads to death if not treated on time. Neonatal hepatitis syndrome (NHS) is another leading cause of neonatal cholestasis confounding the diagnosis of BA. Recent studies indicate that altered bile acid metabolism is closely associated with liver injury and cholestasis. In this study, we systematically measured the bile acid metabolome in plasma of BA, NHS, and healthy controls. Liver bile acids were also measured using biopsy samples from 48 BA and 16 NHS infants undergoing operative cholangiography as well as 5 normal adjacent nontumor liver tissues taken from hepatoblastoma patients as controls. Both BA and NHS samples had significantly elevated bile acid levels in plasma compared to normal controls. BA patients showed a distinct bile acid profile characterized by the higher taurochenodeoxycholic acid (TCDCA) level and lower chenodeoxycholic acid (CDCA) level than those in NHS patients. The ratio of TCDCA to CDCA in plasma was significantly higher in BA compared to healthy infants (p < 0.001) or NHS (p < 0.001). The area under receiver operating characteristic curve for TCDCA/CDCA to differentiate BA from NHS was 0.923 (95% CI: 0.862-0.984). These findings were supported by significantly altered expression levels of bile acid transporters and nuclear receptors in liver including farnesoid X receptor (FXR), small heterodimer partner (SHP), bile salt export pump (BSEP), and multidrug resistant protein 3 (MDR3) in BA compared to NHS. Taken together, the plasma bile acid profiles are distinct in BA, NHS, and normal infants, as characterized by the ratio of TCDCA/CDCA differentially distributed among the three groups of infants.

Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD. METHODS AND FINDINGS: English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies. CONCLUSION: The presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors' Summary.