The screening, diagnosis, and management of patients with autosomal dominant polycystic kidney disease: A national consensus statement from Taiwan.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage kidney disease (ESKD) worldwide. Guidelines for the diagnosis and management of ADPKD in Taiwan remains unavailable. In this consensus statement, we summarize updated information on clinical features of international and domestic patients with ADPKD, followed by suggestions for optimal diagnosis and care in Taiwan. Specifically, counselling for at-risk minors and reproductive issues can be important, including ethical dilemmas surrounding prenatal diagnosis and pre-implantation genetic diagnosis. Studies reveal that ADPKD typically remains asymptomatic until the fourth decade of life, with symptoms resulting from cystic expansion with visceral compression, or rupture. The diagnosis can be made based on a detailed family history, followed by imaging studies (ultrasound, computed tomography, or magnetic resonance imaging). Genetic testing is reserved for atypical cases mostly. Common tools for prognosis prediction include total kidney volume, Mayo classification and PROPKD/genetic score. Screening and management of complications such as hypertension, proteinuria, urological infections, intracranial aneurysms, are also crucial for improving outcome. We suggest that the optimal management strategies of patients with ADPKD include general medical care, dietary recommendations and ADPKD-specific treatments. Key points include rigorous blood pressure control, dietary sodium restriction and Tolvaptan use, whereas the evidence for somatostatin analogues and mammalian target of rapamycin (mTOR) inhibitors remains limited. In summary, we outline an individualized care plan emphasizing careful monitoring of disease progression and highlight the need for shared decision-making among these patients.

Machine-learning models are superior to severity scoring systems for the prediction of the mortality of critically ill patients in a tertiary medical center.

BACKGROUND: Intensive care unit (ICU) mortality prediction helps to guide therapeutic decision making for critically ill patients. Several scoring systems based on statistical techniques have been developed for this purpose. In this study, we developed a machine-learning model to predict patient mortality in the very early stage of ICU admission. METHODS: This study was performed with data from all patients admitted to the intensive care units of a tertiary medical center in Taiwan from 2009 to 2018. The patients' comorbidities, co-medications, vital signs, and laboratory data on the day of ICU admission were obtained from electronic medical records. We constructed random forest and extreme gradient boosting (XGBoost) models to predict ICU mortality, and compared their performance with that of traditional scoring systems. RESULTS: Data from 12,377 patients was allocated to training (n = 9901) and testing (n = 2476) datasets. The median patient age was 70.0 years; 9210 (74.41%) patients were under mechanical ventilation in the ICU. The areas under receiver operating characteristic curves for the random forest and XGBoost models (0.876 and 0.880, respectively) were larger than those for the Acute Physiology and Chronic Health Evaluation II score (0.738), Sequential Organ Failure Assessment score (0.747), and Simplified Acute Physiology Score II (0.743). The fraction of inspired oxygen on ICU admission was the most important predictive feature across all models. CONCLUSION: The XGBoost model most accurately predicted ICU mortality and was superior to traditional scoring systems. Our results highlight the utility of machine learning for ICU mortality prediction in the Asian population.

Systemic vascular resistance predicts high-output cardiac failure in patients with high-flow arteriovenous fistula.

AIMS: Patients with high-flow arteriovenous (AV) access are at risk of developing high-output cardiac failure (HOCF) and subsequent hospitalization. However, diagnosing HOCF is challenging and often requires invasive procedures. The role of systemic vascular resistance (SVR) in diagnosing HOCF is underestimated, and its predictive value is limited. Our study aims to identify non-invasive risk factors for HOCF to facilitate early diagnosis and timely surgical interventions. METHODS AND RESULTS: We included 109 patients with high-flow AV access who underwent serial echocardiography. The retrospective cohort was divided into two groups based on their hospitalization due to HOCF. The two groups were matched for age and gender. After a mean follow-up of 25.1 months, 19 patients (17.4%) were hospitalized due to HOCF. The two groups had similar baseline characteristics. However, the HOCF group had a higher value of vascular access blood flow (Qa) (2168 ± 856 vs. 1828 ± 617 mL/min; P = 0.045). Echocardiographic analysis revealed that the HOCF group had more pronounced left ventricular diastolic dysfunction (E/e': 21.1 ± 7.3 vs. 16.2 ± 5.9; P = 0.002), more severe pulmonary hypertension (right ventricular systolic pressure: 41.4 ± 16.7 vs. 32.2 ± 12.8; P = 0.009), a higher Doppler-derived cardiac index (CI) (4.3 ± 0.8 vs. 3.7 ± 1.1; P = 0.031), and a lower Doppler-derived estimated SVR (eSVR) value (5.5 ± 0.3 vs. 6.9 ± 0.2; P = 0.002) than the non-HOCF group. Using multivariable Cox regression analysis, a low eSVR value (<6) emerged as an independent predictor of HOCF hospitalization with a hazard ratio of 9.084 (95% confidence interval, 2.33-35.39; P = 0.001). Receiver operating characteristic curve analysis indicated that CI/eSVR values more accurately predicted HOCF hospitalization [sensitivity: 94.7%, specificity: 51.0%, area under the curve (AUC): 0.75, P < 0.001] than the Qa/cardiac output ratio (AUC: 0.50, P = 0.955), Qa values ≥ 2000 mL/min (AUC: 0.60, P = 0.181), and Qa values indexed for height in metres (AUC: 0.65, P = 0.040). CONCLUSIONS: In patients with high-flow AV access, low eSVR values obtained through non-invasive Doppler echocardiography were associated with a high rate of HOCF hospitalizations. Therefore, routine eSVR screening in these patients might expedite the diagnosis of HOCF.

Granulocyte Colony-Stimulating Factor Improves Endothelial Progenitor Cell-Mediated Neovascularization in Mice with Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) have a higher prevalence of peripheral arterial disease (PAD), and endothelial progenitor cells (EPCs) play a pivotal role. We examined the impact of granulocyte colony-stimulating factor (G-CSF) on EPC function in response to tissue ischemia. Eight-week-old male C57BL/6J male mice were divided into sham operation and subtotal nephrectomy (SNx) groups, received hindlimb ischemic operation after seven weeks, then randomly received G-CSF or PBS intervention for four weeks with weekly follow-ups. SNx mice had significantly reduced limb reperfusion, decreased plasma EPC mobilization, and impaired angiogenesis in ischemic hindlimbs compared to the control group. However, G-CSF increased IL-10 and reversed these adverse changes. Additionally, ischemia-associated protein expressions, including IL-10, phospho-STAT3, VEGF, and phospho-eNOS, were significantly downregulated in the ischemic hindlimbs of SNx mice versus control, but these trends were reversed by G-CSF. Furthermore, in cultured EPCs, G-CSF significantly attenuated the decrease in EPC function initiated by indoxyl sulfate through IL-10. Overall, we discovered that G-CSF can improve EPC angiogenic function through a hypoxia/IL-10 signaling cascade and impede neovascular growth in response to ischemia of SNx mice. Our results highlight G-CSF's potential to restore angiogenesis in CKD patients with PAD via EPC-based methods.

Circulating Osteocalcin Fractions are Associated with Vascular Calcification and Mortality in Chronic Hemodialysis Patients.

BACKGROUND: Vascular calcification, a component of chronic kidney disease-mineral and bone disorder (CKD-MBD), is prevalent in patients with end-stage kidney disease (ESKD) and contributes to high mortality. However, the association between the blood level of total osteocalcin (OC) and vascular calcification and mortality remains inconclusive. We, therefore, investigated whether different OC fractions can serve as biomarkers of vascular calcification and mortality in the ESKD population. METHODS: This observational cohort study enrolled patients on maintenance hemodialysis. Plasma carboxylated OC (cOC), uncarboxylated OC (ucOC), and intact parathyroid hormone (PTH) were measured. The percentage of carboxylated OC (%cOC) was calculated as dividing cOC by total OC. The vascular calcification severity was defined by an aortic calcification grade. The patients were followed for three years and one month. RESULTS: A total of 184 patients were enrolled. In the multivariable logistic regression, plasma %cOC, but not cOC or ucOC, was independently associated with the severity of vascular calcification (OR 1.019, p = 0.036). A significant U-shaped correlation was found between plasma %cOC and PTH (p = 0.002). In the multivariable Cox regression, patients with higher plasma %cOC had a higher risk of mortality (quartiles Q4 versus Q1-Q3, HR 1.991 [95% CI: 1.036-3.824], p = 0.039). CONCLUSIONS: In patients undergoing chronic hemodialysis, plasma %cOC positively correlated with vascular calcification and exhibited a U-shaped correlation with PTH. Furthermore, a higher plasma %cOC was associated with increased mortality. These findings suggest that plasma %cOC may serve as a biomarker for CKD-MBD and a predictor of clinical outcomes in chronic hemodialysis patients.

Survival benefit of a third dose of the COVID-19 vaccine among hemodialysis patients: A prospective cohort study.

BACKGROUND: Hemodialysis (HD) patients are particularly vulnerable to severe coronavirus disease 2019 (COVID-19) due to their immunocompromised state and comorbid conditions. Timely vaccination could be the most effective strategy to reduce morbidity and mortality. However, data on the survival benefit of the COVID-19 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and death among HD patients are limited, especially during the Omicron-dominant period. METHODS: In this prospective hospital-based cohort study, we identified HD patients from July 1, 2021, to April 29, 2022. The patients were divided into fully vaccinated and partially vaccinated groups. We compared the humoral response, risk of developing SARS-CoV-2 infection, and all-cause mortality between the two groups. RESULTS: Among the 440 HD patients included, 152 patients were fully vaccinated, and 288 patients were partially vaccinated. Patients in the fully vaccinated group exhibited higher anti-spike protein receptor-binding domain (S protein RBD) antibody levels and lower risks of all-cause mortality (adjusted hazard ratio, 0.35; 95% confidence interval, 0.17-0.73; p = 0.005) than the partially vaccinated group. However, the risk for SARS-CoV-2 infection did not significantly differ between the two groups. Irrespective of the number of vaccinations, the risk of all-cause mortality was lower in patients with anti-S protein RBD antibody levels in the higher tertile. CONCLUSION: A third dose of the COVID-19 vaccine was associated with a decreased risk of all-cause mortality among HD patients during the Omicron-dominant period. A higher post-vaccination anti-S protein RBD antibody level was also associated with a lower risk of mortality.

Key pathological features characterize minimal change disease-like IgA nephropathy.

AIMS: A subset of IgA nephropathy (IgAN) patients exhibiting minimal change disease (MCD) like features present with nephrotic-range proteinuria and warrants immunosuppressive therapy (IST). However, the diagnosis of MCD-like IgAN varied by reports. We aimed to identify the key pathological features of MCD-like IgAN. METHODS: In this cohort, 228 patients had biopsy-proven IgAN from 2009 to 2021, of which 44 without segmental sclerosis were enrolled. Patients were classified into segmental (< 50% glomerular capillary loop involvement) or global (> 50%) foot process effacement (FPE) groups. We further stratified them according to the usage of immunosuppressant therapy after biopsy. Clinical manifestations, treatment response, and renal outcome were compared. RESULTS: 26 cases (59.1%) were classified as segmental FPE group and 18 cases (40.9%) as global FPE group. The global FPE group had more severe proteinuria (11.48 [2.60, 15.29] vs. 0.97 [0.14, 1.67] g/g, p = 0.001) and had a higher proportion of complete remission (81.8% vs. 20%, p = 0.018). In the global FPE group, patients without IST experienced more rapid downward eGFR change than the IST-treated population (-0.38 [-1.24, 0.06] vs. 1.26 [-0.17, 3.20]mL/min/1.73 m2/month, p = 0.004). CONCLUSIONS: The absence of segmental sclerosis and the presence of global FPE are valuable pathological features that assist in identifying MCD-like IgAN.

Prediction of the risk of developing end-stage renal diseases in newly diagnosed type 2 diabetes mellitus using artificial intelligence algorithms.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) imposes a great burden on healthcare systems, and these patients experience higher long-term risks for developing end-stage renal disease (ESRD). Managing diabetic nephropathy becomes more challenging when kidney function starts declining. Therefore, developing predictive models for the risk of developing ESRD in newly diagnosed T2DM patients may be helpful in clinical settings. METHODS: We established machine learning models constructed from a subset of clinical features collected from 53,477 newly diagnosed T2DM patients from January 2008 to December 2018 and then selected the best model. The cohort was divided, with 70% and 30% of patients randomly assigned to the training and testing sets, respectively. RESULTS: The discriminative ability of our machine learning models, including logistic regression, extra tree classifier, random forest, gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and light gradient boosting machine were evaluated across the cohort. XGBoost yielded the highest area under the receiver operating characteristic curve (AUC) of 0.953, followed by extra tree and GBDT, with AUC values of 0.952 and 0.938 on the testing dataset. The SHapley Additive explanation summary plot in the XGBoost model illustrated that the top five important features included baseline serum creatinine, mean serum creatine within 1 year before the diagnosis of T2DM, high-sensitivity C-reactive protein, spot urine protein-to-creatinine ratio and female gender. CONCLUSIONS: Because our machine learning prediction models were based on routinely collected clinical features, they can be used as risk assessment tools for developing ESRD. By identifying high-risk patients, intervention strategies may be provided at an early stage.

Associations of the Serum Total Carbon Dioxide Level with Long-Term Clinical Outcomes in Sepsis Survivors.

INTRODUCTION: Sepsis is characterized by a dysregulated host response to infection that leads to multiple organ dysfunction and often complicated with metabolic acidosis. However, the associations between serum total carbon dioxide level (TCO2) and long-term clinical outcomes in sepsis survivors remains unknown. METHODS: A total of 7212 sepsis survivors aged ≥ 20 years who were discharged from January  1, 2008 to December 31, 2018 were included in our analyses. The sepsis survivors were further divided into high TCO2 (≥ 18 mmol/L) and low TCO2 (< 18 mmol/L) groups, comprising 5023 and 2189 patients, respectively. The following outcomes of interest were included: all-cause mortality, myocardial infarction, ischemic stroke, hospitalization for heart failure, ventricular arrhythmia, and end-stage renal disease (ESRD). RESULTS: After propensity score matching, the low TCO2 group was at higher risks of all-cause mortality (hazard ratio [HR] 1.28, 95% confidence interval [95% CI] 1.18-1.39), myocardial infarction (HR 1.83, 95% CI 1.39-2.43), and ESRD (HR 1.38, 95% CI 1.16-1.64) than the high TCO2 group. The results remained similar after considering death as a competing risk. CONCLUSION: Patients discharged from hospitalization for sepsis have higher risks of worse long-term clinical outcomes. Physicians may need to pay more attention to sepsis survivors whose TCO2 was low.

Di-(2-ethylhexyl) Phthalate Limits the Lipid-Lowering Effects of Simvastatin by Promoting Protein Degradation of Low-Density Lipoprotein Receptor: Role of PPARγ-PCSK9 and LXRα-IDOL Signaling Pathways.

Dialysis prevents death from uremia in patients with end-stage renal disease (ESRD). Nevertheless, during hemodialysis, circulating levels of di-(2-ethylhexyl) phthalate (DEHP) are increased due to phthalates leaching from medical tubes. Statins are an effective therapy for reducing the risks associated with cardiovascular diseases in patients with chronic kidney disease; however, the mechanism by which statins fail to reduce cardiovascular events in hemodialysis ESRD patients remains unclear. In this study, we investigated whether DEHP and its metabolites interfere with the lipid-lowering effect of statins in hepatocytes. In Huh7 cells, treatment with DEHP and its metabolites abolished the simvastatin-conferred lipid-lowering effect. Mechanistically, DEHP down-regulated the expression of low-density lipoprotein receptor (LDLR) and led to a decrease in LDL binding, which was mediated by the activation of the PPARγ-PCSK9 and LXRα-IDOL signaling pathways. Additionally, the NOX-ROS-TRPA1 pathway is involved in the DEHP-mediated inhibition of LDLR expression and LDL binding activity. Blockage of this pathway abrogated the DEHP-mediated inhibition in the LDLR expression and LDL binding of simvastatin. Collectively, DEHP induces the activation of the NOX-ROS-TRPA1 pathway, which in turn activates PPARγ-PCSK9- and LXRα-IDOL-dependent signaling, and, ultimately, diminishes the statin-mediated lipid-lowering effect in hepatocytes.

An eighth note.

Venous stenosis is the most common cause of arteriovenous fistula (AVF) failure in hemodialysis patients. For patients with AVF stenosis, the pressure over the antecedent part of the AVF stenotic lesion will increase if arterial inflow is sufficient. We report a chronic hemodialysis patient who received an angiographic examination for the juxta-anastomosis stenosis of his AVF. A unique feature of a collateral venous branch antecedent to the stenotic lesion was noted, resembling a musical sign as the "eighth note." After percutaneous transluminal angioplasty, the eighth note attenuated markedly at once. Of note, the eighth note sign is not seen frequently, and thus we postulate that the formation of an eighth note sign on the radiocephalic fistula should fulfill the following requirements, including a sufficient arterial inflow, an adjacent collateral branch close enough to the arteriovenous anastomosis, a severe juxta-anastomotic stenotic lesion, and an intact ulnar venous drainage system.

Plasma Galectin-9 Is a Useful Biomarker for Predicting Renal Function in Patients Undergoing Native Kidney Biopsy.

CONTEXT.­: Galectin-9 reduces tissue damage in certain immune-mediated glomerular diseases. However, its role in structural and functional renal changes in patients with varying types of chronic kidney disease (CKD) is less clear. OBJECTIVE.­: To investigate the association between plasma galectin-9 levels, proteinuria, tubulointerstitial lesions, and renal function in different CKD stages. DESIGN.­: We measured plasma galectin-9 levels in 243 patients undergoing renal biopsy for determining the CKD etiology. mRNA and protein expression levels of intrarenal galectin-9 were assessed by quantitative real-time polymerase chain reaction and immunostaining. Relationships between plasma galectin-9, clinical characteristics, and tubulointerstitial damage were analyzed with logistic regression. We investigated galectin-9 expression patterns in vitro in murine J774 macrophages treated with differing stimuli. RESULTS.­: To analyze the relationship between galectin-9 and clinical features, we divided the patients into 2 groups according to median plasma galectin-9 levels. The high galectin-9 group tended to be older and to have decreased renal function, higher proteinuria, and greater interstitial fibrosis. After multivariable adjustment, elevated plasma galectin-9 levels were independently associated with stage 3b or higher CKD. An analysis of gene expression in the tubulointerstitial compartment in the biopsy samples showed a significant positive correlation between intrarenal galectin-9 mRNA expression and plasma galectin-9 levels. Immunohistochemistry confirmed increased galectin-9 expression in the renal interstitium of patients with advanced CKD, and most galectin-9-positive cells were macrophages, as determined by double-immunofluorescence staining. In vitro experiments showed that galectin-9 expression in macrophages was significantly increased after interferon-γ stimulation. CONCLUSIONS.­: Our findings suggest that plasma galectin-9 is a good biomarker for diagnosing advanced CKD.

Astrocytic aryl hydrocarbon receptor mediates chronic kidney disease-associated mental disorders involving GLT1 hypofunction and neuronal activity enhancement in the mouse brain.

Chronic kidney disease (CKD)-associated mental disorders have been attributed to the excessive accumulation of hemodialysis-resistant indoxyl-3-sulfate (I3S) in the brain. I3S not only induces oxidative stress but is also a potent endogenous agonist of the aryl hydrocarbon receptor (AhR). Here, we investigated the role of AhR in CKD-induced brain disorders using a 5/6 nephrectomy-induced CKD mouse model, which showed increased I3S concentration in both blood and brain, anxiety and impaired novelty recognition, and AhR activation in the anterior cortex. GFAP+ reactive astrocytes were increased accompanied with the reduction of glutamate transporter 1 (GLT1) on perineuronal astrocytic processes (PAPs) in the anterior cingulate cortex (ACC) in CKD mice, and these alterations were attenuated in both neural lineage-specific and astrocyte-specific Ahr conditional knockout mice (nAhrCKO and aAhrCKO). By using chronic I3S treatment in primary astrocytes and glia-neuron (GN) mix cultures to mimic the CKD brain microenvironment, we also found significant reduction of GLT1 expression and activity in an AhR-dependent manner. Chronic I3S treatment induced AhR-dependent pro-oxidant Nox1 and AhR-independent anti-oxidant HO-1 expressions. Notably, AhR mediates chronic I3S-induced neuronal activity enhancement and synaptotoxicity in GN mix, not neuron-enriched cortical culture. In CKD mice, neuronal activity enhancement was observed in ACC and hippocampal CA1, and these responses were abrogated by both nAhrCKO and aAhrCKO. Finally, intranasal AhR antagonist CH-223191 administration significantly ameliorated the GLT1/PAPs reduction, increase in c-Fos+ neurons, and memory impairment in the CKD mice. Thus, astrocytic AhR plays a crucial role in the CKD-induced disturbance of neuron-astrocyte interaction and mental disorders.

Echocardiographic features of left ventricular dysfunction and outcomes in chronic kidney disease.

OBJECTIVE: Heart failure (HF) imposes a substantial burden and the prevalence of HF is high in patients with chronic kidney disease (CKD). HF results in multiple hospital admissions, but whether HF subtypes worsen long-term outcomes and renal function in patients with CKD remains inconclusive. METHODS: The study comprised 10 904 patients with CKD aged ≥20 years who underwent echocardiography between 1 January 2011 and 31 December 2018. The patients were stratified into four groups: non-HF, HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF). The primary end points were all-cause mortality, major adverse cardiovascular events (MACEs) and adverse renal outcomes. RESULTS: In inverse probability of treatment weighting-adjusted method, the risk of all-cause mortality and MACEs relative to the non-HF group was greatest in the HFrEF group (HR 3.18 (95% CI 2.57 to 3.93) and HR 3.83 (95% CI 3.20 to 4.59)), followed by the HFmrEF (HR 2.75 (95% CI 2.22 to 3.42) and HR 3.08 (95% CI 2.57 to 3.69)) and HFpEF (HR 1.85 (95% CI 1.59 to 2.15) and HR 2.43 (95% CI 2.16 to 2.73) groups. In addition, the HFrEF group had the greatest risks of end-stage renal disease (HR 2.58 (95% CI 1.94 to 3.44)) compared with other groups. CONCLUSIONS: HF is associated with subsequent worse clinical outcomes, which may be more pronounced in patients with HFrEF, followed by those with HFmrEF and those with HFpEF relative to non-HF group.

UMOD Mutations in Chronic Kidney Disease in Taiwan.

UMOD is the first identified and the most commonly mutated gene that causes autosomal dominant tubulointerstitial kidney disease (ADTKD). Recent studies have shown that ADTKD-UMOD is a relatively common cause of chronic kidney disease (CKD). However, the status of ADTKD-UMOD in Taiwan remains unknown. In this study, we identified three heterozygous UMOD missense variants, c.121T > C (p.Cys41Arg), c.179G > A (p.Gly60Asp), and c.817G > T (p.Val273Phe), in a total of 221 selected CKD families (1.36%). Two of these missense variants, p.Cys41Arg and p.Gly60Asp, have not been reported previously. In vitro studies showed that both uromodulin variants have defects in cell membrane trafficking and excretion to the culture medium. The structure model predicted altered disulfide bond formation in both variants, but only p.Gly60Asp was predicted to cause protein destabilization. Our findings extend the mutation spectrum and indicate that the ADTKD-UMOD contributed to a small but significant cause of CKD in the Taiwanese population.

Functioning tailor-made 3D-printed vascular graft for hemodialysis.

BACKGROUND: The two ends of arteriovenous graft (AVG) are anastomosed to the upper limb vessels by surgery for hemodialysis therapy. However, the size of upper limb vessels varies to a large extent among different individuals. METHODS: According to the shape and size of neck vessels quantified from the preoperative computed tomography angiographic scan, the ethylene-vinyl acetate (EVA)-based AVG was produced in H-shape by the three-dimensional (3D) printer and then sterilized. This study investigated the function of this novel 3D-printed AVG in vitro and in vivo. RESULTS: This 3D-printed AVG can be implanted in the rabbit's common carotid artery and common jugular vein with ease and functions in vivo. The surgical procedure was quick, and no suture was required. The blood loss was minimal, and no hematoma was noted at least 1 week after the surgery. The blood flow velocity within the implanted AVG was 14.9 ± 3.7 cm/s. Additionally, the in vitro characterization experiments demonstrated that this EVA-based biomaterial is biocompatible and possesses a superior recovery property than ePTFE after hemodialysis needle cannulation. CONCLUSIONS: Through the 3D printing technology, the EVA-based AVG can be tailor-made to fit the specific vessel size. This kind of 3D-printed AVG is functioning in vivo, and our results realize personalized vascular implants. Further large-animal studies are warranted to examine the long-term patency.

Decoy Receptor 3 Suppresses T-Cell Priming and Promotes Apoptosis of Effector T-Cells in Acute Cell-Mediated Rejection: The Role of Reverse Signaling.

Background: Decoy receptor 3 (DcR3) belongs to the tumor necrosis factor (TNF) receptor superfamily and neutralizes TNF ligands, including FasL and TRAIL, to prevent T activation during T-cell priming. However, the cellular mechanisms underlying acute cell-mediated rejection (ACMR) remain unknown. Methods: We generated DcR3 transgenic (Tg) mice and mice with high DcR3 expression (HDE) to study both in vivo and in vitro. FasR RNA knockdown in immortalized CD4+CD8+ T-cells was used to survey the role of DcR3 on FasR/Fas-associated protein with death domain (FADD)/caspase 8 pathway and its cross-link to TNF receptor-associated factor 1 (TNFR1)-associated death domain protein (TRADD) in suppressing TNFR1. TNF/TRADD knockout mice were used to show the importance of TNF adaptor protein. Results: DcR3.Fc suppressed C57BL/6 female T-cell activation and transformation into CD4+CD69+, CD4+CD44+, and CD4+CD25+Foxp3+ when compared with isotype IgG1 and its co-treatment with FasL/TRAIL after exposing to bone marrow-derived dendritic cells (BMDCs) that carried alloantigen with male H-Y and minor antigenic determinant. Interleukin-17 and interferon-γ productions by BMDC-activated T-cells were lowered after co-treating with DcR3.Fc. DcR3.Fc induced effector T-cells (Teffs) and was susceptible to FasR-mediated apoptosis through the FADD/TRADD/caspase 8 pathway. After exposing to DcR3.Fc, TRADD was silenced, likely turning down the inflammatory response. The systemic effects of DcR3 Tg mice and HDE phenotype induced by the promoter of cytomegalovirus not only attenuated ACMR severity but also ameliorated the high serum creatinine and blood urea nitrogen levels even with high T-cell exposure frequencies. Besides this, DcR3 has minor biological effects on both MHC-matched and MHC-mismatched models. Conclusions: High DcR3 doses protect renal tubular epithelial cells from acute T-cell attack during the T-cell priming stage via interfering with TNF ligand-mediated reverse signaling and possibly promoting Teff apoptosis through FasR upregulation. Our findings supported that the decoy receptor is involved in T-cell modulation in kidney transplant rejection.

2022 Taiwan lipid guidelines for primary prevention.

Elevated circulating low-density lipoprotein cholesterol (LDL-C) is a major risk factor of atherosclerotic cardiovascular disease (ASCVD). Early control of LDL-C to prevent ASCVD later in life is important. The Taiwan Society of Lipids and Atherosclerosis in association with the other seven societies developed this new lipid guideline focusing on subjects without clinically significant ASCVD. In this guideline for primary prevention, the recommended LDL-C target is based on risk stratification. A healthy lifestyle with recommendations for foods, dietary supplements and alcohol drinking are described. The pharmacological therapies for LDL-C reduction are recommended. The aim of this guideline is to decrease the risk of ASCVD through adequate control of dyslipidemia in Taiwan.