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1.
Medicine (Baltimore) ; 103(4): e36952, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38277556

ABSTRACT

RATIONALE: This case report presents a challenging medical scenario involving a young adult male who exhibited an unusual combination of symptoms, including abrupt weight loss, declining renal function, proteinuria, and concurrent onset of diabetes mellitus. Remarkably, the patient had no previous medical history or family history of similar conditions, necessitating a comprehensive investigation. PATIENT CONCERNS: On March 10, 2021, a 25-year-old male sought medical attention due to the aforementioned symptoms. Initial assessments revealed stage 5 chronic kidney disease, with elevated blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as significant proteinuria. The only notable physical finding was obesity, and renal ultrasound showed normal-sized kidneys without cysts. DIAGNOSIS: A treatment plan was initiated to stabilize creatinine levels, including medications such as Glimepiride, Glyxambi, Bisoprolol, Amlodipine, and Valsartan. However, despite diligent medication management, proteinuria persisted, prompting further evaluation. A renal biopsy was performed on April 12th, 2023, leading to the diagnosis of glomerulocystic kidney disease with early-stage changes indicative of diabetic nephropathy. INTERVENTIONS: The patient continues to receive ongoing care and follow-up at our outpatient clinic to optimize therapeutic interventions and elucidate the underlying etiology of this complex clinical scenario. OUTCOMES: Ongoing investigations and therapeutic interventions are crucial to understand the underlying cause and optimize patient care in this intricate clinical scenario. LESSONS: This case underscores the complexity of diagnosing and managing a young adult presenting with concurrent renal dysfunction, proteinuria, and diabetes mellitus in the absence of prior underlying conditions. It highlights the importance of comprehensive evaluation and ongoing care in such challenging cases.


Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Kidney Failure, Chronic , Adult , Humans , Male , Diabetic Nephropathies/complications , Diabetic Nephropathies/diagnosis , Kidney/pathology , Kidney Failure, Chronic/therapy , Obesity/complications , Proteinuria/etiology
2.
Hypertens Res ; 47(5): 1103-1119, 2024 May.
Article in English | MEDLINE | ID: mdl-38228750

ABSTRACT

This comprehensive review offers a thorough exploration of recent advancements in our understanding of the intricate cardiovascular complications associated with Primary Aldosteronism (PA). PA encompasses a spectrum of conditions characterized by hypertension and excessive production of aldosterone operating independently of the renin-angiotensin system. Given its association with an elevated risk of cardiovascular and cerebrovascular complications, as well as a higher incidence of metabolic syndrome in comparison to individuals with essential hypertension (EH), an accurate diagnosis of PA is of paramount importance. This review delves into the intricate interplay between PA and cardiovascular health and focuses on the key pathophysiological mechanisms contributing to adverse cardiac outcomes. The impact of different treatment modalities on cardiovascular health is also examined, offering insights into potential therapeutic approaches. By highlighting the significance of recognizing PA as a significant contributor to cardiovascular morbidity, this review emphasizes the need for improved screening, early diagnosis, and tailored management strategies to both enhance patient care and mitigate the burden of cardiovascular diseases. The findings presented herein underscore the growing importance of PA in the context of cardiovascular medicine and emphasize the potential for translating these insights into targeted interventions to improve patient outcomes.


Subject(s)
Cardiovascular Diseases , Hyperaldosteronism , Humans , Cardiovascular Diseases/etiology , Hyperaldosteronism/complications , Hyperaldosteronism/diagnosis , Hyperaldosteronism/epidemiology , Hyperaldosteronism/therapy , Aldosterone/metabolism , Adrenalectomy
3.
Clin Kidney J ; 17(1): sfad292, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38186874

ABSTRACT

Background: Immune checkpoint inhibitors (ICIs) have been associated with acute kidney injury (AKI). However, the occurrence rate of ICI-related AKI has not been systematically examined. Additionally, exposure to proton pump inhibitors (PPIs) and non-steroidal anti-inflammatory drugs (NSAIDs) were considered as risk factors for AKI, but with inconclusive results in ICI-related AKI. Our aim was to analyse the occurrence rate of all-cause AKI and ICI-related AKI and the occurrence rates of severe AKI and dialysis-requiring AKI, and to determine whether exposure to PPIs and NSAIDs poses a risk for all-cause and ICI-related AKI. Methods: This study population was adult ICI recipients. A systematic review was conducted by searching MEDLINE, Embase and PubMed through October 2023. We included prospective trials and observational studies that reported any of the following outcomes: the occurrence rate of all-cause or ICI-related AKI, the relationship between PPI or NSAID exposure and AKI development or the mortality rate in the AKI or non-AKI group. Proportional meta-analysis and pairwise meta-analysis were performed. The evidence certainty was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Results: A total of 120 studies comprising 46 417 patients were included. The occurrence rates of all-cause AKI were 7.4% (14.6% from retrospective studies and 1.2% from prospective clinical trials). The occurrence rate of ICI-related AKI was 3.2%. The use of PPIs was associated with an odds ratio (OR) of 1.77 [95% confidence interval (CI) 1.43-2.18] for all-cause AKI and an OR of 2.42 (95% CI 1.96-2.97) for ICI-related AKI. The use of NSAIDs was associated with an OR of 1.77 (95% CI 1.10-2.83) for all-cause AKI and an OR of 2.57 (95% CI 1.68-3.93) for ICI-related AKI. Conclusions: Our analysis revealed that approximately 1 in 13 adult ICI recipients may experience all-cause AKI, while 1 in 33 adult ICI recipients may experience ICI-related AKI. Exposure to PPIs and NSAIDs was associated with an increased OR risk for AKI in the current meta-analysis.

4.
J Formos Med Assoc ; 123 Suppl 2: S104-S113, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37173227

ABSTRACT

Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR) screening test from undergoing invasive subtyping procedures. We recommend that patients with a positive ARR test should undergo at least one confirmatory test to confirm or exclude the diagnosis of PA before directly proceeding to subtype studies, except for patients with significant PA phenotypes, including spontaneous hypokalemia, plasma aldosterone concentration >20 ng/dL plus plasma renin activity below a detectable level. Although a gold standard confirmatory test has not been identified, we recommend that saline infusion test and captopril challenge test, which were widely used in Taiwan. Patients with PA have been reported to have a higher prevalence of concurrent autonomous cortisol secretion (ACS). ACS is a biochemical condition of mild cortisol overproduction from adrenal lesions, but without the typical clinical features of overt Cushing's syndrome. Concurrent ACS may result in incorrect interpretation of adrenal venous sampling (AVS) and may lead to adrenal insufficiency after adrenalectomy. We recommend screening for ACS in patients with PA scheduled for AVS examinations as well as for adrenalectomy. We recommend the 1-mg overnight dexamethasone suppression test as screening method to detect ACS.


Subject(s)
Hyperaldosteronism , Hypertension , Humans , Aldosterone , Hyperaldosteronism/diagnosis , Renin , Hydrocortisone , Captopril
5.
Adv Mater ; 36(11): e2308243, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38102967

ABSTRACT

The development of facile, efficient synthesis method to construct low-cost and high-performance single-atom catalysts (SACs) for oxygen reduction reaction (ORR) is extremely important, yet still challenging. Herein, an atomically dispersed N, S co-doped carbon with abundant vacancy defects (NSC-vd) anchored Fe single atoms (SAs) is reported and a vacancy defects inductive effect is proposed for promoting electrocatalytic ORR. The optimized catalyst featured of stable Fe─N3 S1 active sites exhibits excellent ORR activity with high turnover frequency and mass activity. In situ Raman, attenuated total reflectance surface enhanced infrared absorption spectroscopy reveal the Fe─N3 S1 active sites exhibit different kinetic mechanisms in acidic and alkaline solutions. Operando X-ray absorption spectra reveal the ORR activity of Fe SAs/NSC-vd catalyst in different electrolyte is closely related to the coordination structure. Theoretical calculation reveals the upshifted d band center of Fe─N3 S1 active sites facilitates the adsorption of O2 and accelerates the kinetics process of *OH reduction. The abundant vacancy defects around the Fe─N3 S1 active sites balance the OOH* formation and *OH reduction, thus synergetically promoting the electrocatalytic ORR process.

6.
Nutrients ; 14(19)2022 Oct 07.
Article in English | MEDLINE | ID: mdl-36235814

ABSTRACT

BACKGROUND: Folate is a water-soluble vitamin and is essential for maintaining cell functions. Dialysis removes folate, and folate deficiency is reported in patients with end-stage kidney disease (ESKD). However, there is no consensus as to the appropriate dosage of folate supplements and their advantages and disadvantages for patients with ESKD. METHODS: This study was based on the electronic medical records of the Chang Gung Research Database (CGRD) of the Chang Gung Medical Foundation. We included patients who were diagnosed with ESKD, initiated hemodialysis, and were given folic acid supplements at any point from 1 January 2001 to 31 December 2019. The patients were divided into weekly and daily folic acid supplementation groups. We reduced the effects of confounding through the inverse probability of treatment weighting based on the propensity score. RESULTS: We identified 2081 and 954 newly diagnosed patients with ESKD, who received daily and weekly folic acid supplements. The mean follow-up time was 5.8 years, and the event rates of arteriovenous access thrombosis were 17.0% and 23.6% in the daily and weekly folic acid supplementation groups (sub-distribution hazard ratio = 0.69, 95% confidence interval = 0.61 to 0.77), respectively. Neither group significantly differed in the occurrence of other clinical events, such as major cardiovascular cardiac events (e.g., myocardial infarction and ischemic stroke), all-cause mortality, cardiovascular death, infection death, malignancy, and adverse effects. CONCLUSION: a daily 5 mg folic acid supplementation might result in a lower event rate of arteriovenous access thrombosis in patients with ESKD than weekly folic acid supplementation. Further prospective studies are warranted to explore the preventive effect of folate on thrombosis.


Subject(s)
Kidney Failure, Chronic , Thrombosis , Cohort Studies , Dietary Supplements , Folic Acid , Humans , Kidney Failure, Chronic/drug therapy , Renal Dialysis , Thrombosis/chemically induced , Vitamins , Water
7.
J Clin Immunol ; 42(8): 1730-1741, 2022 11.
Article in English | MEDLINE | ID: mdl-35947322

ABSTRACT

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are a predisposing factor for pulmonary alveolar proteinosis (PAP) and Cryptococcus gattii cryptococcosis. This study aimed to investigate clinical manifestations in anti-GM-CSF Ab-positive patients with C. gattii cryptococcosis and analyze the properties of anti-GM-CSF Abs derived from these patients and patients with PAP. METHODS: Thirty-nine patients diagnosed with cryptococcosis (caused by C. neoformans or C. gattii) and 6 with PAP were enrolled in the present study. Clinical information was obtained from medical records. Blood samples were collected for analysis of autoantibody properties. We also explored the National Health Insurance Research Database (NHIRD) of Taiwan to investigate the epidemiology of cryptococcosis and PAP. RESULTS: High titers of neutralizing anti-GM-CSF Abs were identified in 15 patients with cryptococcosis (15/39, 38.5%). Most anti-GM-CSF Ab-positive cryptococcosis cases had central nervous system (CNS) involvement (14/15, 93.3%). Eleven out of 14 (78.6%) anti-GM-CSF Ab-positive CNS cryptococcosis patients were confirmed to be infected with C. gattii, and PAP did not occur synchronously or metachronously in a single patient from our cohort. Exploration of an association between HLA and anti-GM-CSF Ab positivity or differential properties of autoantibodies from cryptococcosis patients and PAP yielded no significant results. CONCLUSION: Anti-GM-CSF Abs can cause two diseases, C. gattii cryptococcosis and PAP, which seldom occur in the same subject. Current biological evidence regarding the properties of anti-GM-CSF Abs cannot provide clues regarding decisive mechanisms. Further analysis, including more extensive cohort studies and investigations into detailed properties, is mandatory to better understand the pathogenesis of anti-GM-CSF Abs.


Subject(s)
Cryptococcosis , Pulmonary Alveolar Proteinosis , Humans , Autoantibodies , Cryptococcosis/diagnosis , Cryptococcosis/epidemiology , Pulmonary Alveolar Proteinosis/diagnosis , Pulmonary Alveolar Proteinosis/etiology , Granulocyte-Macrophage Colony-Stimulating Factor/immunology
8.
J Exp Med ; 219(9)2022 09 05.
Article in English | MEDLINE | ID: mdl-35833912

ABSTRACT

Anti-interferon (IFN)-γ autoantibodies (AIGAs) are a pathogenic factor in late-onset immunodeficiency with disseminated mycobacterial and other opportunistic infections. AIGAs block IFN-γ function, but their effects on IFN-γ signaling are unknown. Using a single-cell capture method, we isolated 19 IFN-γ-reactive monoclonal antibodies (mAbs) from patients with AIGAs. All displayed high-affinity (KD < 10-9 M) binding to IFN-γ, but only eight neutralized IFN-γ-STAT1 signaling and HLA-DR expression. Signal blockade and binding affinity were correlated and attributed to somatic hypermutations. Cross-competition assays identified three nonoverlapping binding sites (I-III) for AIGAs on IFN-γ. We found that site I mAb neutralized IFN-γ by blocking its binding to IFN-γR1. Site II and III mAbs bound the receptor-bound IFN-γ on the cell surface, abolishing IFN-γR1-IFN-γR2 heterodimerization and preventing downstream signaling. Site III mAbs mediated antibody-dependent cellular cytotoxicity, probably through antibody-IFN-γ complexes on cells. Pathogenic AIGAs underlie mycobacterial infections by the dual blockade of IFN-γ signaling and by eliminating IFN-γ-responsive cells.


Subject(s)
Mycobacterium Infections , Receptors, Interferon , Antibodies, Monoclonal , Autoantibodies , Electric Impedance , Humans , Interferon-gamma , Mycobacterium Infections/genetics , Mycobacterium Infections/microbiology , Receptors, Interferon/genetics
9.
Nephrol Dial Transplant ; 37(11): 2093-2101, 2022 10 19.
Article in English | MEDLINE | ID: mdl-35512604

ABSTRACT

BACKGROUND: The extent of interstitial fibrosis in the kidney not only correlates with renal function at the time of biopsy but also predicts future renal outcome. However, its assessment by pathologists lacks good agreement. The aim of this study is to construct a machine learning-based model that enables automatic and reliable assessment of interstitial fibrosis in human kidney biopsies. METHODS: Validated cortex, glomerulus and tubule segmentation algorithms were incorporated into a single model to assess the extent of interstitial fibrosis. The model performances were compared with expert renal pathologists and correlated with patients' renal functional data. RESULTS: Compared with human raters, the model had the best agreement [intraclass correlation coefficient (ICC) 0.90] to the reference in 50 test cases. The model also had a low mean bias and the narrowest 95% limits of agreement. The model was robust against colour variation on images obtained at different times, through different scanners, or from outside institutions with excellent ICCs of 0.92-0.97. The model showed significantly better test-retest reliability (ICC 0.98) than humans (ICC 0.76-0.94) and the amount of interstitial fibrosis inferred by the model strongly correlated with 405 patients' serum creatinine (r = 0.65-0.67) and estimated glomerular filtration rate (r = -0.74 to -0.76). CONCLUSIONS: This study demonstrated that a trained machine learning-based model can faithfully simulate the whole process of interstitial fibrosis assessment, which traditionally can only be carried out by renal pathologists. Our data suggested that such a model may provide more reliable results, thus enabling precision medicine.


Subject(s)
Kidney , Machine Learning , Humans , Creatinine , Fibrosis , Reproducibility of Results , Kidney/pathology , Biopsy
10.
Biomed J ; 45(4): 675-685, 2022 08.
Article in English | MEDLINE | ID: mdl-34506971

ABSTRACT

BACKGROUND: Classification of glomerular diseases and identification of glomerular lesions require careful morphological examination by experienced nephropathologists, which is labor-intensive, time-consuming, and prone to interobserver variability. In this regard, recent advance in machine learning-based image analysis is promising. METHODS: We combined Mask Region-based Convolutional Neural Networks (Mask R-CNN) with an additional classification step to build a glomerulus detection model using human kidney biopsy samples. A Long Short-Term Memory (LSTM) recurrent neural network was applied for glomerular disease classification, and another two-stage model using ResNeXt-101 was constructed for glomerular lesion identification in cases of lupus nephritis. RESULTS: The detection model showed state-of-the-art performance on variedly stained slides with F1 scores up to 0.944. The disease classification model showed good accuracies up to 0.940 on recognizing different glomerular diseases based on H&E whole slide images. The lesion identification model demonstrated high discriminating power with area under the receiver operating characteristic curve up to 0.947 for various glomerular lesions. Models showed good generalization on external testing datasets. CONCLUSION: This study is the first-of-its-kind showing how each step of kidney biopsy interpretation carried out by nephropathologists can be captured and simulated by machine learning models. The models were integrated into a whole slide image viewing and annotating platform to enable nephropathologists to review, correct, and confirm the inference results. Further improvement on model performances and incorporating inputs from immunofluorescence, electron microscopy, and clinical data might realize actual clinical use.


Subject(s)
Deep Learning , Humans , Image Processing, Computer-Assisted/methods , Machine Learning , Neural Networks, Computer , ROC Curve
11.
J Clin Med ; 10(21)2021 Nov 04.
Article in English | MEDLINE | ID: mdl-34768682

ABSTRACT

The adverse impact of Coronavirus disease 2019 (COVID-19) on kidney function has been reported since the global pandemic. The burden of COVID-19 on kidney transplant recipients, however, has not been systematically analyzed. A systematic review and meta-analysis with a random-effect model was conducted to explore the rate of mortality, intensive care unit admission, invasive mechanical ventilation, acute kidney injury, kidney replacement therapy and graft loss in the adult kidney transplant population with COVID-19. Sensitivity analysis, subgroup analysis and meta-regression were also performed. Results: we demonstrated a pooled mortality rate of 21% (95% CI: 19-23%), an intensive care unit admission rate of 26% (95% CI: 22-31%), an invasive ventilation rate among those who required intensive care unit care of 72% (95% CI: 62-81%), an acute kidney injury rate of 44% (95% CI: 39-49%), a kidney replacement therapy rate of 12% (95% CI: 9-15%), and a graft loss rate of 8% (95% CI: 5-15%) in kidney transplant recipients with COVID-19. The meta-regression indicated that advancing age is associated with higher mortality; every increase in age by 10 years was associated with an increased mortality rate of 3.7%. Regional differences in outcome were also detected. Further studies focused on treatments and risk factor identification are needed.

12.
Int J Mol Sci ; 22(12)2021 Jun 11.
Article in English | MEDLINE | ID: mdl-34208103

ABSTRACT

TAFRO syndrome is an extremely rare form of idiopathic MCD, characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis on bone marrow biopsy, and organomegaly. Like idiopathic MCD, renal involvement is also a common presentation in patients with TAFRO syndrome. Furthermore, membranoproliferative glomerulonephritis (MPGN)-like injury and thrombotic microangiopathy (TMA) are the most reported histopathologic findings of renal biopsy. Several molecular mechanisms have been previously postulated in order to explain the TAFRO syndrome symptoms, including abnormal production of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), etc. The role of these cytokines in renal injury, however, is not well understood. The aim of this review article is to summarize the latest knowledge of molecular mechanisms behind the TAFRO syndrome and their potential role in renal damage.


Subject(s)
Castleman Disease/complications , Castleman Disease/therapy , Kidney/pathology , Thrombotic Microangiopathies/complications , Thrombotic Microangiopathies/therapy , Animals , Castleman Disease/physiopathology , Humans , Thrombotic Microangiopathies/physiopathology
13.
J Clin Endocrinol Metab ; 106(6): 1594-1605, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33677489

ABSTRACT

CONTEXT: Fenofibrate provides limited cardiovascular (CV) benefits in the general population; however, little is known about its benefit among advanced chronic kidney disease (CKD) patients. OBJECTIVE: This study compared outcomes among advanced CKD patients treated with fenofibrate, statins, a combination of both, and none of these. METHODS: This national cohort study was based on Taiwan's National Health Insurance Research Database. Patients younger than 20 years with advanced CKD were identified and further divided into 4 groups according to treatment. The inverse probability of treatment weighting was used to balance baseline characteristics. Patients received fenofibrate, statins, a combination of fenofibrate and statins, or none of these in the 3 months preceding the advanced CKD date. Main outcome measures included all-cause mortality, CV death, and incidence of permanent dialysis. RESULTS: The fenofibrate and statin groups exhibited a lower risk of CV death (fenofibrate vs nonuser: hazard ratio [HR]: 0.84; 95% CI, 0.75-0.94; statins vs nonuser: HR: 0.94; 95% CI, 0.90-0.97) compared with the nonuser group. The fenofibrate group further exhibited the lowest incidence of permanent dialysis (fenofibrate vs nonuser: subdistribution HR [SHR]: 0.78; 95% CI, 0.77-0.80; statins vs fenofibrate: SHR: 1.27; 95% CI, 1.26-1.29; combination vs fenofibrate: SHR: 1.15; 95% CI, 1.13-1.17). Furthermore, the combined administration of fenofibrate and high-intensity statins exhibited a lower risk of major adverse cardiac and cerebrovascular events. CONCLUSION: For patients with advanced CKD, continuing fenofibrate may provide a protective effect on CV outcomes equal to that of statins, and it may further delay the need for permanent dialysis. The combination of fenofibrate and high-intensity statins may have additional benefits.


Subject(s)
Cardiovascular Diseases/prevention & control , Fenofibrate/therapeutic use , Kidney Failure, Chronic/prevention & control , Renal Insufficiency, Chronic/drug therapy , Adult , Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/pathology , Cohort Studies , Disease Progression , Female , Heart Disease Risk Factors , Humans , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Male , Middle Aged , Renal Dialysis/statistics & numerical data , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/pathology , Retrospective Studies , Risk Factors , Taiwan/epidemiology , Young Adult
14.
J Formos Med Assoc ; 120(1 Pt 1): 121-129, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32855034

ABSTRACT

BACKGROUND: To update information about the internationally accepted standards and clinical recommendations for the detection and diagnosis of primary aldosteronism (PA). METHODS: The Taiwan Society of Aldosteronism (TSA) Task Force reviewed the latest literature and reached a consensus after group meetings. The nine critical issues were recognized to provide updated information and internationally acceptable protocols. RESULTS: When screening for PA by using the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR), withdrawal or adjustment of antihypertensive medication is not always necessary on the first patient visit. Hypokalemia should be corrected before ARR screening. In spontaneous hypokalemia, plasma renin below detection levels, and PAC higher than 20 ng/dL (550 pmol/L), further confirmatory testing is unnecessary for PA diagnosis. Direct renin concentration (DRC) could be used for PA diagnosis if PRA is unavailable. Although additional confirmatory tests are suggested, the result of a single test is still reliable. For patient safety, discontinuation or adjustment of antihypertensive medications is indicated before adrenal venous sampling (AVS). ACTH could be beneficial for successful adrenal vein cannulation but is not necessary for determining lateralization in AVS. Simultaneous technique is preferred for AVS. Adrenal NP-59 scintigraphy integrated with SPECT/CT could guide PA management. CONCLUSION: With introduction of these new concepts to the clinicians, we expect better identification, management and treatment of PA patients.


Subject(s)
Hyperaldosteronism , Adrenal Glands , Aldosterone , Humans , Hyperaldosteronism/diagnosis , Hypertension , Renin , Taiwan
15.
Nutrients ; 12(11)2020 Oct 31.
Article in English | MEDLINE | ID: mdl-33142717

ABSTRACT

BACKGROUND: Previous studies have demonstrated that dietary therapy can delay the initiation of dialysis, but little research has investigated whether patients with very poor renal function would benefit from a dietary therapy. METHODS: This study was performed by using the Chang Gung Research Database (CGRD), which is based on the largest medical system in Taiwan. Patients with estimated glomerular filtration rates (eGFR) < 15 mL/min/1.73 m2 between 2001 and 2015 with more than 3 months of low-protein diet supplemented with ketoanalogues (sLPD) were extracted (Ketosteril group). We then assigned five patients without any sLPD to match one patient of the Ketosteril group (comparison group). Both groups were followed up for 1 year for the initiation of dialysis and rates of major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: The Ketosteril group (n = 547), compared with the comparison group (n = 2735), exhibited a lower incidence of new-onset dialysis (40.2% vs. 44.4%, subdistribution hazard ratio (SHR): 0.80, 95% confidence interval (CI): 0.70-0.91) and MACCEs (3.7% vs. 5.9%, HR: 0.61, 95% CI: 0.38-0.97). The beneficial effect of an sLPD did not differ in patients with a baseline eGFR < 5 mL/min/1.73 m2. CONCLUSION: Even among patients with extremely low eGFR, sLPD treatment can safely delay the need for dialysis.


Subject(s)
Amino Acids, Essential/administration & dosage , Diet, Protein-Restricted/methods , Dietary Supplements , Glomerular Filtration Rate , Renal Insufficiency, Chronic/therapy , Aged , Disease Progression , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Renal Dialysis/statistics & numerical data , Renal Insufficiency, Chronic/physiopathology , Retrospective Studies , Taiwan , Treatment Outcome
16.
Adv Mater ; 32(52): e2005713, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33206426

ABSTRACT

Directed self-assembly of block copolymers is a key enabler for nanofabrication of devices with sub-10 nm feature sizes, allowing patterning far below the resolution limit of conventional photolithography. Among all the process steps involved in block copolymer self-assembly, solvent annealing plays a dominant role in determining the film morphology and pattern quality, yet the interplay of the multiple parameters during solvent annealing, including the initial thickness, swelling, time, and solvent ratio, makes it difficult to predict and control the resultant self-assembled pattern. Here, machine learning tools are applied to analyze the solvent annealing process and predict the effect of process parameters on morphology and defectivity. Two neural networks are constructed and trained, yielding accurate prediction of the final morphology in agreement with experimental data. A ridge regression model is constructed to identify the critical parameters that determine the quality of line/space patterns. These results illustrate the potential of machine learning to inform nanomanufacturing processes.

17.
J Exp Med ; 217(12)2020 12 07.
Article in English | MEDLINE | ID: mdl-32880631

ABSTRACT

Talaromyces marneffei causes life-threatening opportunistic infections, mainly in Southeast Asia and South China. T. marneffei mainly infects patients with human immunodeficiency virus (HIV) but also infects individuals without known immunosuppression. Here we investigated the involvement of anti-IFN-γ autoantibodies in severe T. marneffei infections in HIV-negative patients. We enrolled 58 HIV-negative adults with severe T. marneffei infections who were otherwise healthy. We found a high prevalence of neutralizing anti-IFN-γ autoantibodies (94.8%) in this cohort. The presence of anti-IFN-γ autoantibodies was strongly associated with HLA-DRB1*16:02 and -DQB1*05:02 alleles in these patients. We demonstrated that adult-onset acquired immunodeficiency due to autoantibodies against IFN-γ is the major cause of severe T. marneffei infections in HIV-negative patients in regions where this fungus is endemic. The high prevalence of anti-IFN-γ autoantibody-associated HLA class II DRB1*16:02 and DQB1*05:02 alleles may account for severe T. marneffei infections in Southeast Asia. Our findings clarify the pathogenesis of T. marneffei infection and pave the way for developing novel treatments.


Subject(s)
Autoantibodies/immunology , Interferon-gamma/immunology , Mycoses/immunology , Mycoses/microbiology , Talaromyces/physiology , Adult , Aged , Alleles , Autoantibodies/blood , Case-Control Studies , Female , HLA-DRB1 Chains/immunology , Humans , Male , Middle Aged , Mycoses/blood , Young Adult
18.
Sci Rep ; 10(1): 8066, 2020 05 15.
Article in English | MEDLINE | ID: mdl-32415125

ABSTRACT

To date, few studies have been conducted to pairwise compare the prognosis of peritoneal dialysis (PD), unplanned PD, and unplanned hemodialysis (HD). We analyzed longitudinal data from Taiwan's National Health Insurance Research Database. We included 45,165 patients whose initial dialytic modality was PD or unplanned HD between January 1, 2001 and December 31, 2013. We divided the patients into three groups according to their initial dialytic modalities. The primary outcomes were all-cause mortality and death from infection during 1-year follow up. The risks of all-cause mortality and infection death were higher in the unplanned PD group than in the planned PD group (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.28-1.60; HR 1.54, 95% CI 1.32-1.80). Likewise, the risks of all-cause mortality and infection death were higher in the unplanned HD group (HR 1.64, 95% CI 1.48-1.82; HR 1.85, 95% CI 1.61-2.13). Furthermore, the risks of all-cause mortality and infection death were also higher in the unplanned HD group than in the unplanned PD group (HR 1.15, 95% CI 1.07-1.23; HR 1.20, 95% CI 1.09-1.32). In conclusion, our study demonstrates that patients whose initial modality was planned PD or unplanned PD may have better clinical outcomes than those whose initial modality was unplanned HD.


Subject(s)
Cardiovascular Diseases/mortality , Infections/mortality , Kidney Failure, Chronic/mortality , Renal Dialysis/adverse effects , Aged , Cardiovascular Diseases/etiology , Cardiovascular Diseases/pathology , Female , Follow-Up Studies , Humans , Infections/etiology , Infections/pathology , Kidney Failure, Chronic/therapy , Longitudinal Studies , Male , Prognosis , Prospective Studies , Taiwan
19.
BMC Anesthesiol ; 19(1): 73, 2019 05 15.
Article in English | MEDLINE | ID: mdl-31092199

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is often used in critical patients with severe myocardial failure. However, the mortality rate of patients on ECMO is often high. Recent studies have suggested that endothelial activation with subsequent vascular barrier breakdown is a critical pathogenic mechanism of organ damage and is related to the outcome of critical illness. This study aimed to determine whether endothelial biomarkers can be served as prognostic factors for the outcome of patients on ECMO. METHODS: This prospective study enrolled 23 critically ill patients on veno-arterial ECMO in the intensive care units of a tertiary care hospital between March 2014 and February 2015. Serum samples were tested for thrombomodulin, angiopoietin (Ang)-1, Ang-2, and vascular endothelial growth factor (VEGF). Demographic, clinical, and laboratory data were also collected. RESULTS: The overall mortality rate was 56.5%. The combination of Ang-2 at the time of ECMO support (day 0) and VEGF at day 2 had the ability to discriminate mortality (area under receiver operating characteristic curve [AUROC], 0.854; 95% confidence interval: 0.645-0.965). CONCLUSIONS: In this study, we found that the combination of Ang-2 at day 0 and VEGF at day 2 was a modest model for mortality discrimination in this group of patients.


Subject(s)
Endothelium, Vascular/metabolism , Extracorporeal Membrane Oxygenation/methods , Shock, Cardiogenic/blood , Shock, Cardiogenic/diagnosis , Vascular Endothelial Growth Factor A/blood , Vesicular Transport Proteins/blood , Adult , Aged , Biomarkers/blood , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Shock, Cardiogenic/mortality
20.
J Formos Med Assoc ; 118(10): 1408-1415, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31133523

ABSTRACT

BACKGROUND/PURPOSE: A reliable noninvasive prognostic factor of ANCA-associated vasculitis (AAV) is still lacking, but little research has focused on the value of MPO-ANCA titers in patients with active vasculitis. This study explored the prognostic significance of MPO-ANCA titer in active AAV patients. METHODS: Ninety-seven inpatients diagnosed with MPO-ANCA associated vasculitis at Linkou Chang Gung Memorial hospital and Keelung Chang Gung Memorial hospital from January 2005 to December 2016 were enrolled. Serum ANCA titers and basic characteristics of these patients at diagnosis were collected completely Medical records since AAV diagnosis were reviewed to evaluate two years renal and patient outcome. RESULTS: The patients were divided into the two groups according to the median ANCA titers, the more than four times of the normal cut-off value group (high titer group) and the less ANCA titer group (low titer group). The high titer group had significant poor initial renal function (eGFR 16.7 vs 40.7 mL/min/1.73 m2, P = 0.006), and significantly lower two-year renal survival (Log rank P < 0.001). Whereas patient survival (Log rank P = 0.894) was not different The Cox regression models revealed that baseline Birmingham Vasculitis Activity Score, eGFR and a 4-fold increase in ANCA titer were associated with the requirement of permanent dialysis. In the subgroup analysis, the ANCA titer was still an important risk factor for renal outcomes (P = 0.036) in patients with better initial renal function (eGFR≧15 mL/min). CONCLUSION: This study demonstrated that higher MPO-ANCA titers at diagnosis was associated with poor initial renal function and 2-year renal outcomes.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/blood , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Antibodies, Antineutrophil Cytoplasmic/blood , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/therapy , Adult , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/enzymology , Biomarkers/blood , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Peroxidase/immunology , Prognosis , Proportional Hazards Models , Renal Dialysis , Retrospective Studies , Severity of Illness Index , Survival Rate
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