A multi-trait GWAS identifies novel genes influencing albuminuria.

BACKGROUND: Albuminuria is common and associated with increased risks of end-stage kidney disease and cardiovascular diseases, yet its underlying mechanism remains obscure. Previous genome-wide association studies (GWAS) for albuminuria did not consider gene pleiotropy and primarily focused on European ancestry populations. This study adopted a multi-trait analysis of GWAS (MTAG) approach to jointly analyze two vital kidney traits, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) to identify and prioritize the genes associated with UACR. METHODS: Data from the Taiwan Biobank from 2012 to 2023 were analyzed. GWAS of UACR and eGFR were performed separately and the summary statistics from these GWAS were jointly analyzed using MTAG. The polygenic risk scores (PRS) of UACR were constructed for validation. The UACR-associated loci were further fine-mapped and prioritized based on their deleteriousness, eQTL associations, and relatedness to Mendelian kidney diseases. RESULTS: MTAG analysis of the UACR revealed 15 genetic loci, including 12 novel loci. The PRS for UACR was significantly associated with urinary albumin level (P < 0.001) and microalbuminuria (P = 0.001 ∼ 0.045). A list of priority genes was generated. Twelve genes with high priority included the albumin endocytic receptor gene LRP2 and ciliary genes  IFT172. CONCLUSIONS: The findings of this multi-trait GWAS suggest that primary cilia play a role in sensing mechanical stimuli, leading to albumin endocytosis. The priority list of genes warrants further translational investigation to reduce albuminuria.

Clinical utility of anal sphincter relaxation integral in water-perfused and solid-state high-resolution anorectal manometry.

BACKGROUND/PURPOSE: We investigated the diagnostic performance of the anal sphincter relaxation integral (ASRI) for infants with Hirschsprung's disease (HD). METHODS: We performed water-perfused high-resolution anorectal manometry (HRAM) in 18 infants (9 with HD), and solid-state HRAM in another 18 infants (4 with HD). We calculated the ASRI during the rectoanal inhibitory reflex (RAIR) maneuver at pressure cutoffs of <10 mmHg (ASRI 10) and <15 mmHg (ASRI 15). We investigated the diagnostic performance of the ASRI for HD in infants undergoing water-perfused and solid-state HRAM. RESULTS: HD infants who underwent either water-perfused or solid-state HRAM had significantly lower ASRI 10 and ASRI 15 values, compared with non-HD infants (P < 0.05 and P < 0.05, respectively). Using the water-perfused HRAM system, ASRI 10 and ASRI 15 values of <7 and <29 mmHg s.cm, respectively, exhibited good diagnostic performance for HD (88.89% and 88.89%, respectively). Receiver operating characteristic curve analysis indicated that ASRI 10 and ASRI 15 values of <5.5 and <20 mmHg s.cm, respectively, were optimal for the diagnosis of HD infants when using the solid-state HRAM system, with high diagnostic accuracies of 83.33% and 83.33%, respectively. CONCLUSION: ASRI may assist the diagnosis of HD infants using either water-perfused or solid-state HRAM. These systems require different catheter-specific ASRI cutoffs for the prediction of HD.

Phenotype, genotype, and clinical outcome of Taiwanese with congenital nephrotic syndrome.

BACKGROUND/PURPOSE: Congenital nephrotic syndrome (CNS) is one of the important causes of end-stage kidney disease in children. Studies on the genotype, phenotype, and clinical outcome in infants with CNS caused by genetic mutations are scarce. METHODS: We analyzed the genetic background, clinical manifestations, treatment response, and prognosis of pediatric patients with CNS in Taiwan. RESULTS: Fifteen infants with CNS were enrolled, and 11 patients of median age 21 (interquartile range 3∼44) days caused by genetic mutations from 10 unrelated families were included in the study. Of the eleven patients, 9 had extra-renal manifestations including microcephaly, facial dysmorphism, and skeletal anomalies. More than two-thirds of the patients had disease onset before 1 month of age. Diffuse meningeal sclerosis was the most common histological characteristic. Whole exome sequencing followed by direct Sanger sequence revealed mutations in OSGEP (R247Q), WT1 (R366H and R467Q), LAMB2 (Q1209∗ and c. 5432-5451 19 bp deletion), NUP93 (D302V), and LAGE3 (c.188+1G > A). Three of the variants were novel. Corticosteroids and/or immunosuppressants were administered in 2 patients, but both were refractory to treatment. During the mean 3.5 years of follow-up, all but two died of uremia and sepsis. The two survivors reached end-stage kidney disease and required peritoneal dialysis, and one of them underwent uneventful renal transplantation. CONCLUSIONS: The majority of patients with CNS in Taiwan were caused by OSGEP followed by WT1 mutation. R247Q is the hotspot mutation of OSGEP in Taiwan. CNS patients in Taiwan suffer from significant morbidity and mortality.

Pediatric glomerulopathy after COVID-19 vaccination: A case series and review of the literature.

BACKGROUND: Cases of glomerulopathy after COVID-19 vaccination have been reported in the adult population, while only a few cases have been reported in children and adolescents. For better understanding of this association in pediatric population, we aimed to describe clinical course of patients with glomerulopathy within 60 days of COVID-19 vaccination who were under followed up in the pediatric nephrology department of National Taiwan University Children's Hospital. METHODS: We reviewed the clinical characteristics, vaccine types, and outcomes of patients with newly diagnosed glomerular diseases or relapse of underlying glomerulopathy within 60 days after COVID-19 vaccination at our facility between January 2021 and July 2022. RESULTS: Thirteen pediatric patients were found to have newly diagnosed glomerular diseases or relapse from their underlying glomerulopathy after receiving their first, second, or third COVID-19 vaccines in our facility. Of the five pediatric patients with newly diagnosed glomerulopathy after vaccination, thin basement membrane nephropathy, idiopathic nephrotic syndrome, and hematuria have been identified. Seven patients had relapse episodes of underlying nephrotic syndrome and one patient with underlying isolated microscopic hematuria developed subnephrotic proteinuria after COVID-19 vaccination. All patients experienced remission or improvement with either immunosuppressive or conservative treatment during the follow-up period. CONCLUSIONS: This is the largest case series to date of pediatric glomerulopathy after COVID-19 vaccination. From our report, patients with either newly diagnosed or relapse of glomerulopathy after vaccination had good outcomes, and receiving vaccination to prevent COVID-19 infection or complications should be encouraged in pandemic era under close monitoring kidney manifestations.

Successful treatment of acute encephalitis and hepatitis in a child with COVID-19 infection.

We present the case of a 6-year-old Taiwanese boy with a fulminant course of COVID-19 manifesting as high fever, acute consciousness changes, and status epilepticus. Brain MRI showed restricted diffusion in the bilateral hemisphere. Electroencephalogram showed diffuse slow waves with few spikes. CSF study was clear without evidence of common pathogens. He received treatment with antiviral agents, corticosteroids, intravenous immunoglobulins, and anti-IL-6 monoclonal antibodies. However, progressive fulminant hepatitis, hyperammonaemia, and disseminated intravascular coagulopathy developed. Rescue therapy with hybrid continuous renal replacement therapy and plasma exchange were performed in the first 11 days. The patient improved and was extubated on the 11th day. After physical therapy, his neurological function improved significantly. The patient was discharged under rehabilitation after 1 month of hospitalization. Viral sequencing confirmed infection with the Omicron BA.2.3 variant, one of the dominant strains in Taiwan and Hong Kong. Whole-exome sequencing revealed heterozygous uncertain significance variants in TICAM-1, RNF 31, and mitochondrial MT-RNR1, which provide additional support for the fulminant course. To the best of our knowledge, this is the first reported case of COVID-19 in a child with a fulminant course of acute encephalitis and hepatitis who successfully recovered by hybrid continuous renal replacement therapy and plasma exchange.

Atypical hemolytic uremic syndrome: Consensus of diagnosis and treatment in Taiwan.

Atypical hemolytic uremic syndrome (aHUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, is a rare but life-threatening systemic disorder caused by the dysregulation of the complement pathway. Current advances in molecular analysis and pathogenesis have facilitated the establishment of diagnosis and development of effective complement blockade. Based on this recent consensus, we provide suggestions regarding the diagnosis and management of aHUS in Taiwan. The diagnosis of aHUS is made by the presence of TMA with normal ADAMTS13 activity without known secondary causes. Although only 60% of patients with aHUS have mutations in genes involving the compliment and coagulation systems, molecular analysis is suggestive for helping establish diagnosis, clarifying the underlying pathophysiology, guiding the treatment decision-making, predicting the prognosis, and deciding renal transplantation. Complement blockade, anti-C5 monoclonal antibody, is the first-line therapy for patients with aHUS. Plasma therapy should be considered for removing autoantibody in patients with atypical HUS caused by anti-CFH or complement inhibitor is unavailable.

Autoantibodies to Oxidatively Modified Peptide: Potential Clinical Application in Coronary Artery Disease.

Coronary artery disease (CAD) is a global health issue. Lipid peroxidation produces various by-products that associate with CAD, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA). The autoantibodies against HNE and MDA-modified peptides may be useful in the diagnosis of CAD. This study included 41 healthy controls (HCs) and 159 CAD patients with stenosis rates of <30%, 30−70%, and >70%. The plasma level of autoantibodies against four different unmodified and HNE-modified peptides were measured in this study, including CFAH1211−1230, HPT78−108, IGKC2−19, and THRB328−345. Furthermore, feature ranking, feature selection, and machine learning models have been utilized to exploit the diagnostic performance. Also, we combined autoantibodies against MDA and HNE-modified peptides to improve the models' performance. The eXtreme Gradient Boosting (XGBoost) model received a sensitivity of 78.6% and a specificity of 90.4%. Our study demonstrated the combination of autoantibodies against oxidative modification may improve the model performance.

Using anti-malondialdehyde-modified peptide adduct autoantibodies in serum of taiwanese women to diagnose primary Sjogren's syndrome.

BACKGROUND: Sjogren's syndrome (SS) is a systemic autoimmune disease featured with a dry mouth and dry eyes. Several autoantibodies, including anti-SSA, anti-SSB, antinuclear antibodies can be detected in patients with SS. Oxidation-specific epitopes (OSEs) can be formed from malondialdehyde (MDA)-modified protein adducts and trigger chronic inflammation. In this study, our purposes were used serum levels of anti-MDA-modified peptide adducts autoantibodies to evaluate predictive performance by machine learning algorithms in primary Sjögren's syndrome (pSS) and assess the association between pSS and healthy controls. METHODS: Three novel MDA-modified peptide adducts, including immunoglobulin (Ig) gamma heavy chain 1 (IGHG1)102-131, complement factor H (CFAH)1045-1062, and Ig heavy constant alpha 1 (IGHA1)307-327 were identified and validated. Serum levels of protein, MDA-modified protein adducts, MDA, and autoantibodies recognizing unmodified peptides and MDA-modified peptide adducts were measured. Statistically significance in correlations and odds ratios (ORs) were estimated. RESULTS: The random forest classifier utilized autoantibodies combination composed of IgM anti-IGHG1102-131, IgM anti-IGHG1102-131 MDA and IgM anti-IGHA1307-327 achieved predictive performance as an accuracy of 88.0%, a sensitivity of 93.7%, and a specificity of 84.4% which may be as potential diagnostic biomarkers to differentiate patients with pSS from rheumatoid arthritis (RA), and secondary SS in RA and HCs. CONCLUSIONS: Our findings imply that low levels of IgA anti-IGHG1102-131 MDA (OR = 2.646), IgA anti-IGHG1102-131 (OR = 2.408), IgA anti-CFAH1045-1062 (OR = 2.571), and IgA anti-IGHA1307-327 (OR = 2.905) may denote developing risks of pSS, respectively.

A Coronary Artery Disease Monitoring Model Built from Clinical Data and Alpha-1-Antichymotrypsin.

Coronary artery disease (CAD) is one of the most common subtypes of cardiovascular disease. The progression of CAD initiates from the plaque of atherosclerosis and coronary artery stenosis, and eventually turns into acute myocardial infarction (AMI) or stable CAD. Alpha-1-antichymotrypsin (AACT) has been highly associated with cardiac events. In this study, we proposed incorporating clinical data on AACT levels to establish a model for estimating the severity of CAD. Thirty-six healthy controls (HCs) and 162 CAD patients with stenosis rates of <30%, 30−70%, and >70% were included in this study. Plasma concentration of AACT was determined by enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve analysis and associations were conducted. Further, five machine learning models, including decision tree, random forest, support vector machine, XGBoost, and lightGBM were implemented. The lightGBM model obtained a sensitivity of 81.4%, a specificity of 67.3%, and an area under the curve (AUC) of 0.822 for identifying CAD patients with a stenosis rate of <30% versus >30%. In this study, we provided a demonstration of a monitoring model with clinical data and AACT.

Machine Learning in Prediction of Bladder Cancer on Clinical Laboratory Data.

Bladder cancer has been increasing globally. Urinary cytology is considered a major screening method for bladder cancer, but it has poor sensitivity. This study aimed to utilize clinical laboratory data and machine learning methods to build predictive models of bladder cancer. A total of 1336 patients with cystitis, bladder cancer, kidney cancer, uterus cancer, and prostate cancer were enrolled in this study. Two-step feature selection combined with WEKA and forward selection was performed. Furthermore, five machine learning models, including decision tree, random forest, support vector machine, extreme gradient boosting (XGBoost), and light gradient boosting machine (GBM) were applied. Features, including calcium, alkaline phosphatase (ALP), albumin, urine ketone, urine occult blood, creatinine, alanine aminotransferase (ALT), and diabetes were selected. The lightGBM model obtained an accuracy of 84.8% to 86.9%, a sensitivity 84% to 87.8%, a specificity of 82.9% to 86.7%, and an area under the curve (AUC) of 0.88 to 0.92 in discriminating bladder cancer from cystitis and other cancers. Our study provides a demonstration of utilizing clinical laboratory data to predict bladder cancer.

Identifying young adults at high risk of cardiometabolic disease using cluster analysis and the Framingham 30-yr risk score.

BACKGROUND AND AIMS: Current strategies to reduce cardiovascular disease (CVD) risk in young adults are largely limited to those at extremes of risk. In cohort studies we have shown cluster analysis identified a large sub-group of adolescents with multiple risk factors. This study examined if individuals classified at 'high-risk' by cluster analysis could also be identified by their Framingham risk scores. METHODS AND RESULTS: Raine Study data at 17- (n = 1048) and 20-years (n = 1120) identified high- and low-risk groups by cluster analysis using continuous measures of systolic BP, BMI, triglycerides and insulin resistance. We assessed:- CVD risk at 20-years using the Framingham 30 yr-risk-score in the high- and low-risk clusters, and cluster stability from adolescence to adulthood. Cluster analysis at 17- and 20-years identified a high-risk group comprising, 17.9% and 21.3%, respectively of the cohort. In contrast, only 1.2% and 3.4%, respectively, met the metabolic syndrome criteria, all of whom were within the high-risk cluster. Compared with the low-risk cluster, Framingham scores of the high-risk cluster were elevated in males (9.4%; 99%CI 8.3, 10.6 vs 6.0%; 99%CI 5.7, 6.2) and females (4.9%; 99%CI 4.4, 5.4 vs 3.2%; 99%CI 3.0, 3.3) (both P < 0.0001). A score >8 for males and >4 for females identified those at high CVD risk with 99% confidence. CONCLUSION: Cluster analysis using multiple risk factors identified ∼20% of young adults at high CVD risk. Application of our Framingham 30 yr-risk cut-offs to individuals allows identification of more young people with multiple risk factors for CVD than conventional metabolic syndrome criteria.

Peptide-based electrochemical sensor with nanogold enhancement for detecting rheumatoid arthritis.

Rheumatoid arthritis (RA), an autoimmune and chronic inflammatory disorder, is an incurable disease. We developed a peptide-based electrochemical sensor using electrochemical impedance spectroscopy that can be used to detect autoantibodies for RA diagnostics. We first validated that the developed peptide showed high sensitivity and could compliment the current gold standard method of an anti-cyclic citrullinated peptide antibody (anti-CCP) ELISA. The developed peptide can be modified on the nanogold surface of the working electrode of sensing chips through the method of a self-assembling monolayer. The sensing process was first optimized using a positive control cohort and a healthy control cohort. Subsequently, 10 clinically confirmed samples from RA patients and five healthy control samples were used to find the threshold value of the impedance between RA and healthy subjects. Furthermore, 10 clinically confirmed samples but with low values of anti-CCP autoantibodies were used to evaluate the sensitivity of the present method compared to the conventional method. The proposed method showed better sensitivity than the current conventional anti-CCP ELISA method.

A novel deep intronic variant strongly associates with Alkaptonuria.

Alkaptonuria is a rare autosomal recessive inherited disorder of tyrosine metabolism, which causes ochronosis, arthropathy, cardiac valvular calcification, and urolithiasis. The epidemiology of alkaptonuria in East Asia is not clear. In this study, patients diagnosed with alkaptonuria from January 2010 to June 2020 were reviewed. Their clinical and molecular features were further compared with those of patients from other countries. Three patients were found to have alkaptonuria. Mutation analyses of the homogentisate 1,2-dioxygenase gene (HGD) showed four novel variants c.16-2063 A > C, p.(Thr196Ile), p.(Gly344AspfsTer25), and p.(Gly362Arg) in six mutated alleles (83.3%). RNA sequencing revealed that c.16-2063 A > C activates a cryptic exon, causing protein truncation p.(Tyr5_Ile6insValTer17). A literature search identified another 6 patients with alkaptonuria in East Asia; including our cases, 13 of the 18 mutated alleles have not been reported elsewhere in the world. Alkaptonuria is rare in Taiwan and East Asia, with HGD variants being mostly novel and private.

Bolus transit of upper esophageal sphincter on high-resolution impedance manometry study correlate with the laryngopharyngeal reflux symptoms.

Laryngopharyngeal reflux symptom is a troublesome upper esophageal problem, and reflux symptom index (RSI) is commonly applied for the assessment of clinical severity. We investigated the relationship between the upper esophageal sphincter impedance integral (UESII) and RSI scores in this study. Totally 158 subjects with high-resolution esophageal impedance manometry (HRIM) with RSI questionnaire assessment were recruited. There are 57 (36.08%), 74 (46.84%), 21 (13.29%), and 6 (3.79%) patients were categorized as normal, ineffective esophageal motility disorder, absent contractility, and achalasia by HRIM examination, respectively. Subjects with RSI > 13 were noted to have lower UESII than others with RSI ≦ 13 (7363.14 ± 1085.58 vs. 11,833.75 ± 918.77 Ω s cm; P < 0.005). The ROC analysis yielded a UESII cutoff of < 2900 Ω s cm for the best prediction of subjects with RSI > 13 (P = 0.002). Both female gender and UESII cutoff of < 2900 Ω s cm were significant predictors of RSI > 13 in logistic regression analysis (OR = 3.84 and 2.83; P = 0.001 and 0.01; respectively). Lower UESII on HRIM study, indicating poor bolus transit of UES during saline swallows, is significantly associated with prominent laryngopharyngeal reflux symptoms scored by RSI score.

Aldosterone Excess Induced Mitochondria Decrease and Dysfunction via Mineralocorticoid Receptor and Oxidative Stress In Vitro and In Vivo.

Aldosterone excess plays a major role in the progression of cardiac dysfunction and remodeling in clinical diseases such as primary aldosteronism and heart failure. However, the effect of aldosterone excess on cardiac mitochondria is unclear. In this study, we investigated the effect of aldosterone excess on cardiac mitochondrial dysfunction and its mechanisms in vitro and in vivo. We used H9c2 cardiomyocytes to investigate the effect and mechanism of aldosterone excess on cardiac mitochondria, and further investigated them in an aldosterone-infused ICR mice model. The results of the cell study showed that aldosterone excess decreased mitochondrial DNA, COX IV and SOD2 protein expressions, and mitochondria ATP production. These effects were abolished or attenuated by treatment with a mineralocorticoid receptor (MR) antagonist and antioxidant. With regard to the signal transduction pathway, aldosterone suppressed cardiac mitochondria through an MR/MAPK/p38/reactive oxygen species pathway. In the mouse model, aldosterone infusion decreased the amount of cardiac mitochondrial DNA and COX IV protein, and the effects were also attenuated by treatment with an MR antagonist and antioxidant. In conclusion, aldosterone excess induced a decrease in mitochondria and mitochondrial dysfunction via MRs and oxidative stress in vitro and in vivo.

The Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers on Clinical Outcomes of Acute Kidney Disease Patients: A Systematic Review and Meta-Analysis.

Background: Acute kidney injury (AKI) may increase the risk of chronic kidney disease (CKD), development of end-stage renal disease (ESRD), and mortality. However, the impact of exposure to angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (ACEi/ARB) in patients experiencing AKI/acute kidney disease (AKD) is still unclear. Methods: In this systematic review, we searched all relevant studies from PubMed, Embase, Cochrane, Medline, Collaboration Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, and ClinicalTrials.gov until July 21, 2020. We evaluated whether the exposure to ACEi/ARB after AKI onset alters recovery paths of AKD and impacts risks of all-cause mortality, recurrent AKI, or incident CKD. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. Results: A total of seven articles, involving 70,801 patients, were included in this meta-analysis. The overall patient mortality rate in this meta-analysis was 28.4%. Among AKI patients, all-cause mortality was lower in ACEi/ARB users than in ACEi/ARB nonusers (log odds ratio (OR) -0.37, 95% confidence interval (CI): -0.42--0.32, p < 0.01). The risk of recurrent adverse kidney events after AKI was lower in ACEi/ARB users than in nonusers (logOR -0.25, 95% CI: -0.33--0.18, p < 0.01). The risk of hyperkalemia was higher in ACEi/ARB users than in nonusers (logOR 0.43, 95% CI: 0.27-0.59, p < 0.01). Patients with continued use of ACEi/ARB after AKI also had lower mortality risk than those prior ACEi/ARB users but who did not resume ACEi/ARB during AKD (logOR -0.36, 95% CI: -0.4--0.31, p < 0.01). Conclusions: Exposure to ACEi/ARB after AKI is associated with lower risks of all-cause mortality, recurrent AKI, and progression to incident CKD. Patients with AKI may have a survival benefit by continued use of ACEi/ARB; however, a higher incidence of hyperkalemia associated with ACEi/ARB usage among these patients deserves close clinical monitoring.

Rapid Trio Exome Sequencing for Autosomal Recessive Renal Tubular Dysgenesis in Recurrent Oligohydramnios.

Oligohydramnios is not a rare prenatal finding. However, recurrent oligohydramnios is uncommon, and genetic etiology should be taken into consideration. We present two families with recurrent fetal oligohydramnios that did not respond to amnioinfusion. Rapid trio-whole-exome sequencing (WES) revealed mutations in the AGT gene in both families within 1 week. The first family had a compound heterozygous mutation with c.856 + 1G > T and c.857-619_1269 + 243delinsTTGCCTTGC changes. The second family had homozygous c.857-619_1269 + 243delinsTTGCCTTGC mutations. AGT gene mutation may lead to autosomal recessive renal tubular dysgenesis, a rare and lethal disorder that can result in early neonatal death. Both the alleles identified are known alleles associated with pathogenicity. Our findings suggest that trio-WES analysis may help rapidly identify causative etiologies that can inform prompt counseling and decision-making prenatally.

Comparison of cystatin C-based and creatinine-based glomerular filtration rate in the prediction of postoperative residual hypertension in aldosterone-producing adenoma patients after adrenalectomy.

Renal function is associated with postoperative residual hypertension in aldosterone-producing adenoma(APA) patients. Cystatin C-based glomerular filtration rate (GFR) can more accurately estimate renal function than creatinine-based methods. However, which renal function estimation method can more accurately predict postoperative hypertension in APA patients is still unknown. We recruited 180 APA patients who underwent adrenalectomy. Preoperative creatinine and cystatin C-based GFRs were calculated. Residual hypertension was defined as persistent hypertension > 140/90 mmHg or requiring anti-hypertensive medications 1 year after surgery. Sixty-five(36.1%) of the 180 APA patients had residual hypertension. Multivariate logistic regression and receiver operating characteristic (ROC) curve analysis showed a combination of creatinine and cystatin method CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine-cystatin GFR was significantly associated with residual postoperative hypertension and had the largest area under the ROC curve, which was statistically larger than that of Cockcroft-Gault creatinine-based GFR. In both net reclassification index and integrated discrimination index models, CKD-EPI creatinine-cystatin GFR significantly improved the discriminatory power of CG-GFR. Among these renal function estimations used in the presented study, creatinine-cystatin combined GFR was a precise method to predict residual postoperative hypertension in APA patients received adrenalectomy. These finding may help identify those patients with higher risk of residual hypertension after operation.

Clinical Assay for the Early Detection of Colorectal Cancer Using Mass Spectrometric Wheat Germ Agglutinin Multiple Reaction Monitoring.

Colorectal cancer (CRC) is currently the third leading cause of cancer-related mortality in the world. U.S. Food and Drug Administration-approved circulating tumor markers, including carcinoembryonic antigen, carbohydrate antigen (CA) 19-9 and CA125 were used as prognostic biomarkers of CRC that attributed to low sensitivity in diagnosis of CRC. Therefore, our purpose is to develop a novel strategy for novel clinical biomarkers for early CRC diagnosis. We used mass spectrometry (MS) methods such as nanoLC-MS/MS, targeted LC-MS/MS, and stable isotope-labeled multiple reaction monitoring (MRM) MS coupled to test machine learning algorithms and logistic regression to analyze plasma samples from patients with early-stage CRC, late-stage CRC, and healthy controls (HCs). On the basis of our methods, 356 peptides were identified, 6 differential expressed peptides were verified, and finally three peptides corresponding wheat germ agglutinin (WGA)-captured proteins were semi-quantitated in 286 plasma samples (80 HCs and 206 CRCs). The novel peptide biomarkers combination of PF454-62, ITIH4429-438, and APOE198-207 achieved sensitivity 84.5%, specificity 97.5% and an AUC of 0.96 in CRC diagnosis. In conclusion, our study demonstrated that WGA-captured plasma PF454-62, ITIH4429-438, and APOE198-207 levels in combination may serve as highly effective early diagnostic biomarkers for patients with CRC.