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  • Ovid Technologies (Wolters Kluwer Health)  (64)
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  • 1
    Online Resource
    Online Resource
    Multitarget Therapy for Maintenance Treatment of Lupus Nephritis
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Journal of the American Society of Nephrology Vol. 28, No. 12 ( 2017-12), p. 3671-3678
    Details
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 28, No. 12 ( 2017-12), p. 3671-3678
    Abstract: Our previous studies showed that multitarget therapy is superior in efficacy to intravenous cyclophosphamide as an induction treatment for lupus nephritis in Asian populations. We conducted an open label, multicenter study for 18 months as an extension of the prior induction therapy trial in 19 renal centers in China to assess the efficacy and safety of multitarget maintenance therapy in patients who had responded at 24 weeks during the induction phase. Patients who had undergone multitarget induction therapy continued to receive multitarget therapy (tacrolimus, 2–3 mg/d; mycophenolate mofetil, 0.50–0.75 g/d; prednisone, 10 mg/d), and patients who had received intravenous cyclophosphamide induction treatment received azathioprine (2 mg/kg per day) plus prednisone (10 mg/d). We assessed the renal relapse rate during maintenance therapy as the primary outcome. We recruited 116 patients in the multitarget group and 90 patients in the azathioprine group. The multitarget and azathioprine groups had similar cumulative renal relapse rates (5.47% versus 7.62%, respectively; adjusted hazard ratio, 0.82; 95% confidence interval, 0.25 to 2.67; P= 0.74), and serum creatinine levels and eGFR remained stable in both groups. The azathioprine group had more adverse events (44.4% versus 16.4% for multitarget therapy; P 〈 0.01), and the multitarget group had a lower withdrawal rate due to adverse events (1.7% versus 8.9% for azathioprine; P =0.02). In conclusion, multitarget therapy as a maintenance treatment for lupus nephritis resulted in a low renal relapse rate and fewer adverse events, suggesting that multitarget therapy is an effective and safe maintenance treatment for patients with lupus nephritis.
    Type of Medium: Online Resource
    ISSN: 1046-6673 , 1533-3450
    URL: Article
    DOI: 10.1681/ASN.2017030263
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2029124-3
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  • 2
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    Pathogenic Gene Spectrum and Clinical Implication in Chinese Patients with Lupus Nephritis
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Clinical Journal of the American Society of Nephrology Vol. 18, No. 7 ( 2023-7), p. 869-880
    Details
    In: Clinical Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 18, No. 7 ( 2023-7), p. 869-880
    Abstract: Lupus nephritis is a rare immunological disorder. Genetic factors are considered important in its causation. We aim to systematically investigate the rare pathogenic gene variants in patients with lupus nephritis. Methods Whole-exome sequencing was used to screen pathogenic gene variants in 1886 probands with lupus nephritis. Variants were interpreted on the basis of known pathogenic variants or the American College of Medical Genetics and Genomics guidelines and studied by functional analysis, including RNA sequencing, quantitative PCR, cytometric bead array, and Western blotting. Results Mendelian form of lupus nephritis was confirmed in 71 probands, involving 63 variants in 39 pathogenic genes. The detection yield was 4%. The pathogenic genes enriched in nuclear factor kappa-B (NF-κB), type I interferon, phosphatidylinositol-3-kinase/serine/threonine kinase Akt (PI3K/AKT), Ras GTPase/mitogen-activated protein kinase (RAS/MAPK), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. Clinical manifestation patterns were diverse among different signaling pathways. More than 50% of the pathogenic gene variants were reported to be associated with lupus or lupus nephritis for the first time. The identified pathogenic gene variants of lupus nephritis overlapped with those of autoinflammatory and immunodeficiency diseases. Inflammatory signatures, such as cytokine levels of IL-6, IL-8, IL-1 β , IFN α , IFN γ , and IP10 in serum and transcriptional levels of interferon-stimulated genes in blood, were significantly higher in patients with pathogenic gene variants compared with controls. The overall survival rate of patients with pathogenic gene variants was lower than those without pathogenic gene variants. Conclusions A small fraction of patients with lupus nephritis had identifiable pathogenic gene variants, primarily in NF-κB, type I interferon, PI3K/AKT, JAK/STAT, RAS/MAPK, and complement pathways.
    Type of Medium: Online Resource
    ISSN: 1555-9041 , 1555-905X
    URL: Article
    DOI: 10.2215/CJN.0000000000000185
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2216582-4
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  • 3
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    XueBiJing Injection Versus Placebo for Critically Ill Patients With Severe Community-Acquired Pneumonia: A Randomized Controlled Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Critical Care Medicine Vol. 47, No. 9 ( 2019-09), p. e735-e743
    Details
    In: Critical Care Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. 9 ( 2019-09), p. e735-e743
    Abstract: To investigate whether XueBiJing injection improves clinical outcomes in critically ill patients with severe community-acquired pneumonia. Design: Prospective, randomized, controlled study. Setting: Thirty-three hospitals in China. Patients: A total of 710 adults 18–75 years old with severe community-acquired pneumonia. Interventions: Participants in the XueBiJing group received XueBiJing, 100 mL, q12 hours, and the control group received a visually indistinguishable placebo. Measurements and Main Results: The primary outcome was 8-day improvement in the pneumonia severity index risk rating. Secondary outcomes were 28-day mortality rate, duration of mechanical ventilation and total duration of ICU stay. Improvement in the pneumonia severity index risk rating, from a previously defined endpoint, occurred in 203 (60.78%) participants receiving XueBiJing and in 158 (46.33%) participants receiving placebo (between-group difference [95% CI], 14.4% [6.9–21.8%] ; p 〈 0.001). Fifty-three (15.87%) XueBiJing recipients and 84 (24.63%) placebo recipients (8.8% [2.4–15.2%]; p = 0.006) died within 28 days. XueBiJing administration also decreased the mechanical ventilation time and the total ICU stay duration. The median mechanical ventilation time was 11.0 versus 16.5 days for the XueBiJing and placebo groups, respectively ( p = 0.012). The total duration of ICU stay was 12 days for XueBiJing recipients versus 16 days for placebo recipients ( p = 0.004). A total of 256 patients experienced adverse events (119 [35.63%] vs 137 [40.18%] in the XueBiJing and placebo groups, respectively [ p = 0.235]). Conclusions: In critically ill patients with severe community-acquired pneumonia, XueBiJing injection led to a statistically significant improvement in the primary endpoint of the pneumonia severity index as well a significant improvement in the secondary clinical outcomes of mortality, duration of mechanical ventilation and duration of ICU stay.
    Type of Medium: Online Resource
    ISSN: 0090-3493
    URL: Article
    DOI: 10.1097/CCM.0000000000003842
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2034247-0
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  • 4
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    Online Resource
    Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Chinese Medical Journal Vol. 136, No. 10 ( 2023-05-20), p. 1207-1215
    Details
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 136, No. 10 ( 2023-05-20), p. 1207-1215
    Abstract: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. Methods: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. Results: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). Conclusion: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. Trial registration: ClinicalTrials.gov, NCT04563936.
    Type of Medium: Online Resource
    ISSN: 0366-6999 , 2542-5641
    URL: Article
    DOI: 10.1097/CM9.0000000000002638
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2108782-9
    SSG: 6,25
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  • 5
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    Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights Into Cardiovascular Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 145, No. 5 ( 2022-02), p. 357-370
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 145, No. 5 ( 2022-02), p. 357-370
    Abstract: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10 -11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P =3.27×10 -30 ) and MMP-3 (β=-0.60±0.05, P =1.67×10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P =1.34×10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.121.055117
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1466401-X
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  • 6
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    Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Stroke Vol. 51, No. 12 ( 2020-12), p. 3504-3513
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 12 ( 2020-12), p. 3504-3513
    Abstract: Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. Methods: In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. Results: Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P =0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P =0.23, P interaction =0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively ( P =NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P =0.001). Conclusions: In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171). Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03354429.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.120.032239
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467823-8
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  • 7
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    Randomized Comparisons of Double-Dose Clopidogrel or Adjunctive Cilostazol Versus Standard Dual Antiplatelet in Patients With High Posttreatment Platelet Reactivity : Results of the CREATIVE Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Circulation Vol. 137, No. 21 ( 2018-05-22), p. 2231-2245
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 137, No. 21 ( 2018-05-22), p. 2231-2245
    Abstract: Patients undergoing percutaneous coronary intervention react differently to antiplatelet drugs. Those with low responsiveness to clopidogrel have a higher risk of cardiac ischemic events. The goal of this study is to conduct a head-to-head comparison of the safety and effectiveness of intensified antiplatelet therapies (either double-dose clopidogrel [DOUBLE] or adjunctive cilostazol [TRIPLE] ) and conventional strategy (STANDARD) in patients after percutaneous coronary intervention. Methods: In this single-center, randomized, controlled trial, we used thromboelastography, a platelet function test, to select 1078 patients undergoing percutaneous coronary intervention at high thrombotic risk and compared the intensified antiplatelet therapies with standard antiplatelet therapy. The primary outcome was the incidence of major adverse cardiac and cerebrovascular events at 18 months after percutaneous coronary intervention, defined as a composite of all-cause death, myocardial infarction, target vessel revascularization, or stroke. Bleeding Academic Research Consortium defined bleeding complications (types 1, 2, 3, or 5) were the safety end points. Results: The primary end point occurred in 52 patients (14.4%) in the STANDARD group, 38 patients (10.6%) in the DOUBLE group, and 30 patients (8.5%) in the TRIPLE group (hazard ratio, 0.720; 95% confidence interval, 0.474–1.094, DOUBLE versus STANDARD; hazard ratio, 0.550; 95% confidence interval, 0.349–0.866, TRIPLE versus STANDARD). No significant difference in the rates of major bleeding (Bleeding Academic Research Consortium grade≥3) was found in the DOUBLE group (3.34% versus 1.93% in STANDARD, P =0.133) and the TRIPLE group (2.53% versus 1.93% in STANDARD, P =0.240). The rate of Bleeding Academic Research Consortium–defined minor bleeding increased in the DOUBLE group (27.4% versus 20.3% in STANDARD, P =0.031), but not in the TRIPLE group (23.6% versus 20.3% in STANDARD, P =0.146). Conclusions: In patients with low responsiveness to clopidogrel, as measured by thromboelastography, the intensified antiplatelet strategies with adjunctive use of cilostazol significantly improved the clinical outcomes without increasing the risk of major bleeding. Decreased trend of negative outcomes could be observed in patients with double dosage of clopidogrel, but the difference was not significant. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01779401.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.117.030190
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1466401-X
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  • 8
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    Clinical Implications of a New DDX58 Pathogenic Variant That Causes Lupus Nephritis due to RIG-I Hyperactivation
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Journal of the American Society of Nephrology Vol. 34, No. 2 ( 2023-02), p. 258-272
    Details
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 2 ( 2023-02), p. 258-272
    Abstract: Lupus nephritis (LN) is the major cause of death among systemic lupus erythematosus patients, with heterogeneous phenotypes and different responses to therapy. Identifying genetic causes and finding potential therapeutic targets of LN is a major unmet clinical need. We identified a novel DDX58 pathogenic variant, R109C, that leads to RIG-I hyperactivation and type I IFN signaling upregulation by disrupting RIG-I autoinhibition, causing LN, which may respond to a JAK inhibitor. Genetic testing of families with multiple cases of LN that identifies this variant may lead to targeted therapy. Background Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus, with heterogeneous phenotypes and different responses to therapy. Identifying genetic causes of LN can facilitate more individual treatment strategies. Methods We performed whole-exome sequencing in a cohort of Chinese patients with LN and identified variants of a disease-causing gene. Extensive biochemical, immunologic, and functional analyses assessed the effect of the variant on type I IFN signaling. We further investigated the effectiveness of targeted therapy using single-cell RNA sequencing. Results We identified a novel DDX58 pathogenic variant, R109C, in five unrelated families with LN. The DDX58 R109C variant is a gain-of-function mutation, elevating type I IFN signaling due to reduced autoinhibition, which leads to RIG-I hyperactivation, increased RIG-I K63 ubiquitination, and MAVS aggregation. Transcriptome analysis revealed an increased IFN signature in patient monocytes. Initiation of JAK inhibitor therapy (baricitinib 2 mg/d) effectively suppressed the IFN signal in one patient. Conclusions A novel DDX58 R109C variant that can cause LN connects IFNopathy and LN, suggesting targeted therapy on the basis of pathogenicity.
    Type of Medium: Online Resource
    ISSN: 1046-6673 , 1533-3450
    URL: Article
    DOI: 10.1681/ASN.2022040477
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2029124-3
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  • 9
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    Body mass index combined with waist circumference can predict moderate chronic kidney disease : A retrospective study
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Medicine Vol. 100, No. 12 ( 2021-03-26), p. e25017-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 12 ( 2021-03-26), p. e25017-
    Abstract: Overweight and obesity may be associated with poor clinical outcome, including chronic kidney disease (CKD). However, whether body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC) are related to CKD is yet to be elucidated. A total of 7593 adults were divided into 4 groups based on the estimated glomerular filtration rate (eGFR) quartile. The eGFR was calculated with the CKD Epidemiology Collaboration. Multiple linear regression analyzed the association between eGFR and WHR, BMI, and WC. Logistic regression analysis determined whether the CKD patients were associated with WHR, BMI, and WC after adjusting for other variables. The mean age of the cohort was 72.34 ± 7.30 years. Multiple linear regression analysis showed that WC ( P  = .006) was associated with eGFR, although adjusted by lifestyle factor and biochemical indicators. The individuals in the underweight, overweight, and obese groups had significantly lower eGFR value than those in the healthy weight group in moderate CKD. The eGFR in the overweight group with WHR ≤0.894 was higher than in the healthy weight group with WHR 〉 0.894 group ( P  = .036). Overweight with WHR ≤0.894 group had a longer WC with a pronounced increase in the hip circumference. Logistic regression analysis showed that the WC (OR = 1.362, P   〈  .001) and BMI (OR = 1.227, P  = .031) were independent risk factors for moderate CKD patients. Each standard deviation (SD) of high BMI and WC level was associated with 23.0% and 17.3% higher odds of moderate CKD (OR = 1.230, P  = .017 and OR = 1.173, P  = .021, respectively). WC is an independent risk factor for eGFR. Combined BMI and WC are important factors that would predict moderate CKD patients.
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    URL: Article
    DOI: 10.1097/MD.0000000000025017
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2049818-4
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  • 10
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    1934 TREATMENT OF UPPER URINARY CALCULI WITH MPCNL A SINGLE-CENTER EXPERIENCE OF 19 YEARS
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Journal of Urology Vol. 187, No. 4S ( 2012-04)
    Details
    In: Journal of Urology, Ovid Technologies (Wolters Kluwer Health), Vol. 187, No. 4S ( 2012-04)
    Type of Medium: Online Resource
    ISSN: 0022-5347 , 1527-3792
    URL: Article
    DOI: 10.1016/j.juro.2012.02.2092
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
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