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1.
BMC Nephrol ; 25(1): 42, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38287343

ABSTRACT

BACKGROUND: Despite several clinical trials, the use of corticosteroid therapy for treating immunoglobulin A nephropathy (IgAN) remains controversial. We aimed to describe the use of corticosteroid therapy combined with supportive therapy in Norwegian patients with IgAN who had progressed to end-stage kidney disease. METHODS: We conducted a retrospective cohort study using data from the Norwegian Renal Registry. Overall, 143 patients with primary IgAN who progressed to end-stage kidney disease were divided into two groups: the corticosteroid group, who had been treated with corticosteroids and supportive therapy, and the non-corticosteroid group, which had underwent only supportive therapy. The kidney function, time to end-stage kidney disease, and adverse effects were described. The observation period lasted from the diagnostic kidney biopsy until the initiation of kidney replacement therapy. RESULTS: Of the 143 included patients, 103 underwent supportive therapy alone, and 40 were treated with corticosteroids. Most patients (94%) were treated with renin-angiotensin-system blockade, and all patients reached end-stage kidney disease after a median of 5 years (interquartile range; 2-9 years). Time from diagnosis until end-stage kidney disease was similar in the two study groups (p = 0.98). During 6 months of corticosteroid therapy, median eGFR declined from 21 (interquartile range; 13-46) mL/min/1.73 m2 to 20 (interquartile range; 12-40) mL/min/1.73 m2, and median proteinuria decreased from 5.5 g/24 h to 3.0 g/24 h. Most patients (87.5%) treated with corticosteroids reported adverse events. In our linear regression analysis investigating the time to ESKD, we found that age (ß = -0.079, p = 0.008) and proteinuria at diagnosis (ß = -0.50, p = 0.01) exhibited statistically significant associations with a delay in the progression to ESKD. CONCLUSIONS: In this cohort of Norwegian patients with IgAN, corticosteroid therapy did not affect the time from diagnosis until end-stage kidney disease among a cohort of patients who all reached end-stage kidney disease. The treatment was also associated with adverse effects.


Subject(s)
Glomerulonephritis, IGA , Kidney Failure, Chronic , Humans , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, IGA/epidemiology , Glomerulonephritis, IGA/complications , Retrospective Studies , Adrenal Cortex Hormones/therapeutic use , Kidney Failure, Chronic/complications , Proteinuria/drug therapy , Disease Progression , Glomerular Filtration Rate
2.
Kidney Int ; 105(4): 717-730, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38154557

ABSTRACT

Some patients diagnosed with benign IgA nephropathy (IgAN) develop a progressive clinical course, not predictable by known clinical or histopathological parameters. To assess if gene expression can differentiate between progressors and non-progressors with assumed benign IgAN, we tested microdissected glomeruli from archival kidney biopsy sections from adult patients with stable clinical remission (21 non-progressors) or from 15 patients that had undergone clinical progression within a 25-year time frame. Based on 1 240 differentially expressed genes from patients with suitable sequencing results, we identified eight IgAN progressor and nine non-progressor genes using a two-component classifier. These genes, including APOL5 and ZXDC, predicted disease progression with 88% accuracy, 75% sensitivity and 100% specificity on average 21.6 years before progressive disease was clinically documented. APOL lipoproteins are associated with inflammation, autophagy and kidney disease while ZXDC is a zinc-finger transcription factor modulating adaptive immunity. Ten genes from our transcriptomics data overlapped with an external genome wide association study dataset, although the gene set enrichment test was not statistically significant. We also identified 45 drug targets in the DrugBank database, including angiotensinogen, a target of sparsentan (dual antagonist of the endothelin type A receptor and the angiotensin II type 1 receptor) currently investigated for IgAN treatment. Two validation cohorts were used for substantiating key results, one by immunohistochemistry and the other by nCounter technology. Thus, glomerular mRNA sequencing from diagnostic kidney biopsies from patients with assumed benign IgAN can differentiate between future progressors and non-progressors at the time of diagnosis.


Subject(s)
Glomerulonephritis, IGA , Adult , Humans , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, IGA/genetics , Genome-Wide Association Study , Kidney Glomerulus/pathology , Gene Expression Profiling/methods , Gene Expression Regulation
3.
Clin Kidney J ; 16(12): 2514-2522, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38046027

ABSTRACT

Background: The establishment of the Oxford classification and newly developed prediction models have improved the prognostic information for immunoglobulin A nephropathy (IgAN). Considering new treatment options, optimizing prognostic information and improving existing prediction models are favorable. Methods: We used random forest survival analysis to select possible predictors of end-stage kidney disease among 37 candidate variables in a cohort of 232 patients with biopsy-proven IgAN retrieved from the Norwegian Kidney Biopsy Registry. The predictive value of variables with relative importance >5% was assessed using concordance statistics and the Akaike information criterion. Pearson's correlation coefficient was used to identify correlations between the selected variables. Results: The median follow-up period was 13.7 years. An isolated analysis of histological variables identified six variables with relative importance >5%: T %, segmental glomerular sclerosis without characteristics associated with other subtypes (not otherwise specified, NOS), normal glomeruli, global sclerotic glomeruli, segmental adherence and perihilar glomerular sclerosis. When histopathological and clinical variables were combined, estimated glomerular filtration rate (eGFR), proteinuria and serum albumin were added to the list. T % showed a better prognostic value than tubular atrophy/interstitial fibrosis (T) lesions with C-indices at 0.74 and 0.67 and was highly correlated with eGFR. Analysis of the subtypes of segmental glomerulosclerosis (S) lesions revealed that NOS and perihilar glomerular sclerosis were associated with adverse outcomes. Conclusions: Reporting T lesions as a continuous variable, normal glomeruli and subtypes of S lesions could provide clinicians with additional prognostic information and contribute to the improved performance of the Oxford classification and prognostic tools.

4.
Kidney Med ; 5(10): 100709, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37693652

ABSTRACT

Antiglomerular basement membrane (anti-GBM) disease is a rare, small-vessel vasculitis that affects the capillary beds of the kidneys and lungs. Although exceedingly rare, several case reports have described anti-GBM disease with a concurrent cancer diagnosis, suggesting a possible correlation between these 2 conditions. Herein, we describe the first known case to our knowledge of a woman in her early 60s with simultaneous anti-GBM disease and clear cell renal cell carcinoma, in which the tumor was thought to have been the substrate for anti-GBM disease. We believe that renal cell carcinoma may have contributed to the production of anti-GBM autoantibodies and, thus, anti-GBM disease. The concurrence of these 2 conditions complicated the treatment of the patient, who was hemodialysis-dependent at the time of hospital discharge. This report highlights the importance of considering anti-GBM disease as a potential diagnosis in patients with acute kidney failure, and how important it is to identify both clear cell renal cell carcinoma and anti-GBM disease at an early stage to improve outcomes.

5.
Nephrol Dial Transplant ; 38(5): 1183-1191, 2023 05 04.
Article in English | MEDLINE | ID: mdl-35904322

ABSTRACT

BACKGROUND: Recently, two immunoglobulin A (IgA) nephropathy-prediction tools were developed that combine clinical and histopathologic parameters. The International IgAN Prediction Tool predicts the risk for 50% declines in the estimated glomerular filtration rate or end-stage kidney disease up to 80 months after diagnosis. The IgA Nephropathy Clinical Decision Support System uses artificial neural networks to estimate the risk for end-stage kidney disease. We aimed to externally validate both prediction tools using a Norwegian cohort with a long-term follow-up. METHODS: We included 306 patients with biopsy-proven primary IgA nephropathy in this study. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford Classification. We used discrimination and calibration as principles for externally validating the prognostic models. RESULTS: The median patient follow-up was 17.1 years. A cumulative, dynamic, time-dependent receiver operating characteristic analysis showed area under the curve values ranging from 0.90 at 5 years to 0.83 at 20 years for the International IgAN Prediction Tool, while time-naive analysis showed an area under the curve value at 0.83 for the IgA Nephropathy Clinical Decision Support System. The International IgAN Prediction Tool was well calibrated, while the IgA Nephropathy Clinical Decision Support System tends to underestimate risk for patients at higher risk and overestimates risk in the lower risk categories. CONCLUSIONS: We have externally validated two prediction tools for IgA nephropathy. The International IgAN Prediction Tool performed well, while the IgA Nephropathy Clinical Decision Support System has some limitations.


Subject(s)
Glomerulonephritis, IGA , Kidney Failure, Chronic , Humans , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/pathology , Follow-Up Studies , Kidney Failure, Chronic/diagnosis , Prognosis , Glomerular Filtration Rate , Disease Progression
7.
Tidsskr Nor Laegeforen ; 142(16)2022 11 08.
Article in Norwegian | MEDLINE | ID: mdl-36345626

ABSTRACT

Immunoglobulin A (IgA) nephropathy is the most common form of primary glomerulonephritis globally and a frequent cause of severe kidney failure in young adults. Kidney biopsy is used to diagnose the condition. Despite it being identified more than fifty years ago, understanding of the disease's pathophysiology is limited, and there is currently no targeted treatment apart from supportive therapy. A number of clinical drug trials are now being undertaken, giving hope that effective treatment may become available in a few years. The patient care pathway usually starts in general practice, but assessment by a nephrologist is necessary for further diagnostics. In this clinical review article, we will describe the investigation, treatment and prognostic assessments for IgA nephropathy.


Subject(s)
Glomerulonephritis, IGA , Glomerulonephritis , Young Adult , Humans , Glomerulonephritis, IGA/therapy , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis/diagnosis , Kidney/metabolism
8.
BMC Nephrol ; 23(1): 26, 2022 01 11.
Article in English | MEDLINE | ID: mdl-35016634

ABSTRACT

BACKGROUND: The Oxford classification/MEST score is an established histopathologic scoring system for patients with IgA nephropathy (IgAN). The objective of this study was to derive a prognostic model for IgAN based on the MEST score and histopathologic features. METHODS: A total of 306 patients with biopsy-proven primary IgAN were included. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford classification. The study endpoint was end-stage renal disease (ESRD). Patients were subclassified into three risk models based on histologic features (Model A), a composite score calculated from the adjusted hazard ratio values (Model B), and on quartiles (Model C). RESULTS: The mean follow-up time was 16.5 years (range 0.2-28.1). In total, 61 (20%) patients reached ESRD during the study period. Univariate analysis of M, E, S, T and C lesions demonstrated that all types were associated with an increased risk of ESRD; however, a multivariate analysis revealed that only S, T and C lesions were associated with poor outcomes. Statistical analysis of 15-year data demonstrated that Models A and B were as predictive as the MEST score, with an area-under-the-curve at 0.85. The Harrel c index values were 0.81 and 0.80 for the MEST score and Models A and B, respectively. In the present cohort, adding C lesions to the MEST score did not improve the models prognostic value. CONCLUSIONS: Patients can be divided into risk classes based on their MEST scores. Histopathologic data provide valuable prognostic information at the time of diagnosis. Model B was the most suitable for clinical practice because it was the most user-friendly.


Subject(s)
Glomerulonephritis, IGA/pathology , Adult , Female , Follow-Up Studies , Glomerulonephritis, IGA/complications , Humans , Kidney Failure, Chronic/etiology , Male , Middle Aged , Prognosis , Time Factors
9.
Tidsskr Nor Laegeforen ; 141(16)2021 11 09.
Article in Norwegian | MEDLINE | ID: mdl-34758596

ABSTRACT

BACKGROUND: Systemic lupus erythematosus and anti-phospholipid syndrome may cause severe haematological complications despite few other symptoms of disease. CASE PRESENTATION: A previously healthy woman in her late twenties was admitted to hospital with chest pain and dyspnoea. CT of the thorax revealed bilateral pulmonary embolism and urine sampling showed haematuria and proteinuria. A few days after hospital admission, she developed transfusion-requiring anaemia. The investigation revealed a positive direct antiglobulin test, presence of anti-nuclear antibodies, lupus anticoagulant, anti-cardiolipin and anti-glycoprotein antibodies. INTERPRETATION: Pulmonary embolism in a young, previously healthy woman may be caused by different predisposing conditions. Systemic lupus erythematosus with accompanying anti-phospholipid syndrome was the diagnosis in this case. Severe autoimmune haemolytic disease may occur as a secondary phenomenon to systemic lupus erythematosus, and the condition must not be overlooked.


Subject(s)
Antiphospholipid Syndrome , Lupus Erythematosus, Systemic , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Dyspnea/etiology , Female , Humans , Lupus Coagulation Inhibitor , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Proteinuria/etiology
10.
Clin Pract ; 11(3): 459-466, 2021 Jul 22.
Article in English | MEDLINE | ID: mdl-34449553

ABSTRACT

Although rare, acute myelogenous leukemia (AML) can include extramedullary manifestations, sometimes presenting as a solid tumor called a myeloid sarcoma. Myeloid sarcoma can be the cause of the initial presenting complaint before AML diagnosis, or may be detected as a sign of disease-relapse after treatment. Here, we report a case in which the initial presentation included abdominal discomfort and signs of kidney failure. Further investigation revealed signs of unilateral hydronephrosis. Due to a diagnostic delay, the patient was diagnosed with AML with extramedullary manifestation only after the development of full-blown leukemia. Biopsy of the compressive tumor confirmed an extramedullary myeloid sarcoma, and [18F]-FDG-PET/CT proved useful for patient diagnosis and follow-up. This case report illustrates the importance of thorough examination and diagnosis, as a serious underlying disease with a rare cause can debut with an unusual presentation.

11.
Clin Pract ; 9(4): 1184, 2019 Nov 05.
Article in English | MEDLINE | ID: mdl-31929868

ABSTRACT

Waldenström's macroglobulinemia (WM), characterized with monoclonal immunoglobulins of type M and lymphoplasmacytic lymphoma, is a rare clonal Bcell disorder. WM usually present as an indolent lymphoma, and renal involvement is, in contrast to multiple myeloma, very rarely seen. We present a patient presenting with severe nephritis and nephrotic range proteinuria of more than 9 g/day as initial manifestations of WM. Furthermore, we discuss diagnostic and therapeutic approaches for this rare manifestation of the disease, in the light of recent research and treatment recommendations.

12.
Nephrol Dial Transplant ; 32(11): 1841-1850, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-29106593

ABSTRACT

BACKGROUND: Patients with immunoglobulin A nephropathy (IgAN) who present with mild to moderate proteinuria and normal renal function are assumed to have excellent short-term renal prognosis, but the long-term prognosis is uncertain. METHODS: Patients were selected from the Norwegian Kidney Biopsy Registry based on the following criteria: diagnostic renal biopsy performed in the period 1988-99, with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and proteinuria <1 g/24 h at the time of biopsy. Patients were invited for a nephrological examination with a review of medical history and investigation of blood pressure, urinary findings and eGFR. RESULTS: A total of 145 patients attended the examination, performed by the first author, after a median of 22 (interquartile range 19-25) years after diagnosis. At the examination, 27 patients (18.6%) had a ≥50% decrease in GFR, of whom 4 (2.8%) had developed end-stage renal disease (ESRD). The mean duration from renal biopsy to ≥ 50% decrease in GFR was 17.3 ± 5.1 years in our cohort. Clinical remission was observed in 42 (29.0%) patients. Renal biopsies were re-examined utilizing the Oxford classification criteria. Mesangial hypercellularity was found in 12.3%, endocapillary proliferation was detected in 10.7% and segmental glomerulosclerosis was observed in 23.8%. All biopsies were scored as T0 (tubular atrophy in < 25% of the cortical area). None of the clinical or histopathological variables recorded at the time of biopsy could identify patients with progressive disease. Cumulative risks of ≥50% decrease in eGFR were 2.1% after 10 years, 4.1% after 15 years, 13.9% after 20 years and 24.7% after 25 years. CONCLUSIONS: We have shown that 18.6% of patients with assumed benign IgAN had progressive disease after a median duration of 22 years and that these patients could not be predicted at the time of biopsy. Our study demonstrates that an extended follow-up period is needed when assessing prognosis in this group of patients.


Subject(s)
Glomerulonephritis, IGA/pathology , Glomerulosclerosis, Focal Segmental/pathology , Adult , Biomarkers/urine , Biopsy , Disease Progression , Female , Follow-Up Studies , Glomerular Filtration Rate , Glomerulonephritis, IGA/physiopathology , Glomerulonephritis, IGA/therapy , Glomerulonephritis, IGA/urine , Glomerulosclerosis, Focal Segmental/physiopathology , Glomerulosclerosis, Focal Segmental/therapy , Glomerulosclerosis, Focal Segmental/urine , Humans , Kidney/pathology , Kidney/physiopathology , Kidney Failure, Chronic/pathology , Male , Prognosis , Proteinuria/pathology , Treatment Outcome
13.
Am J Nephrol ; 41(3): 210-9, 2015.
Article in English | MEDLINE | ID: mdl-25872002

ABSTRACT

BACKGROUND: Predicting outcome in individual patients with IgA nephropathy (IgAN) is difficult but important. For this purpose, the absolute renal risk (ARR) model has been developed in a French cohort to calculate the risk of end-stage renal disease (ESRD) and death. ARR (0-3) is scored in individual IgAN patients based on the presence of proteinuria ≥1 g/24 h, hypertension, and severe histopathological lesions (1 point per risk factor). We have validated the ARR model in a Norwegian cohort of IgAN patients and tested whether adding data on initial estimated glomerular filtration rate (eGFR) and age improved prediction. METHODS: IgAN patients diagnosed between 1988 and 2012 were identified in the Norwegian Kidney Biopsy Registry, and endpoints were identified by record linkage with the Norwegian Renal Registry (ESRD) and the Population Registry (deaths). RESULTS: We identified 1,134 IgAN patients. The mean duration of follow-up was 10.2 years (range 0.0 to 25.7 years). Two hundred and fifty one patients developed ESRD and there were 69 pre-ESRD deaths. The ARR model significantly stratified the IgAN cohort according to risk of ESRD/death. The inclusion of eGFR and age significantly improved the ARR prognostic model; in the receiver operator characteristics (ROC) analysis, area under the curve (AUC) at 10-years of follow-up increased from 0.79 to 0.89, p < 0.001. CONCLUSIONS: ARR is a suitable prognostic model for stratifying IgAN patients according to the risk of ESRD or death. Including initial eGFR and age in the model substantially improved its accuracy in our nationwide cohort.


Subject(s)
Disease Progression , Glomerular Filtration Rate , Glomerulonephritis, IGA/mortality , Glomerulonephritis, IGA/physiopathology , Kidney Failure, Chronic/epidemiology , Kidney/pathology , Adult , Age Factors , Aged , Female , Follow-Up Studies , Glomerulonephritis, IGA/blood , Glomerulonephritis, IGA/pathology , Humans , Hypertension/epidemiology , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/pathology , Male , Middle Aged , Norway , Prognosis , Proteinuria/blood , Risk Factors , Time Factors
14.
Nephrol Dial Transplant ; 30 Suppl 1: i67-75, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25694535

ABSTRACT

BACKGROUND: Glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies (ANCA) is associated with increased mortality and a high risk of end-stage renal disease (ESRD). Here, we investigated whether the prognosis has improved over the last 25 years. METHODS: Patients were identified in the Norwegian Kidney Biopsy Registry. We included all patients with pauci-immune crescentic glomerulonephritis and a positive ANCA test from 1988 to 2012. Deaths and ESRD in the cohort were identified through record linkage with the Norwegian Population Registry (deaths) and the Norwegian Renal Registry (ESRD). Outcomes of patients diagnosed in 1988-2002 were compared with outcomes of patients diagnosed in 2003-12. RESULTS: A cohort of 455 patients with ANCA-associated glomerulonephritis was identified. The mean follow-up was 6.0 years (range, 0.0-23.4). During the study period, 165 (36%) patients died and 124 (27%) progressed to ESRD. Compared with patients diagnosed in 1988-2002, those diagnosed in 2003-12 had higher mean initial estimated glomerular filtration rates (37 versus 27 mL/min/1.73 m(2)) and lower risk of ESRD (1-year risk: 13 versus 19%; 10-year risk: 26 versus 37%). The composite endpoint, ESRD or death within 0-1 year after diagnosis, was reduced from 34 to 25%. In patients over 60 years old, 1-year mortality fell from 33 to 20%. CONCLUSIONS: In Norwegian patients with ANCA-associated glomerulonephritis, prognosis was significantly better in 2003-12 compared with 1988-2002. This improvement was probably partly due to a shorter diagnostic delay, and better therapeutic management in older patients.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Glomerulonephritis/diagnosis , Adult , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/mortality , Antibodies, Antineutrophil Cytoplasmic/blood , Female , Glomerulonephritis/etiology , Glomerulonephritis/mortality , Humans , Male , Middle Aged , Norway , Prognosis , Survival Rate , Young Adult
15.
Am J Kidney Dis ; 62(5): 883-90, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23796906

ABSTRACT

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis globally. Few studies have investigated mortality in patients with IgAN compared with the age- and sex-adjusted general population. STUDY DESIGN: Cohort study with record linkage between the Norwegian Kidney Biopsy Registry, Norwegian Cause of Death Registry, and Norwegian Renal Registry. SETTING & PARTICIPANTS: 633 patients diagnosed with IgAN in 1988-2004. PREDICTOR: Estimated glomerular filtration rate (eGFR), age, and sex. OUTCOMES: Deaths and causes of death before and after the onset of end-stage renal disease through 2008. RESULTS: Mean follow-up was 11.8 (range, 0-20.8) years. During the observation period, the observed number of deaths was 80 and the expected number was 42.1, resulting in a standardized mortality ratio (SMR) of 1.9 (95% CI, 1.5-2.4). Risk stratification based on initial eGFR showed that SMR was 1.0 (95% CI, 0.6-1.6) if eGFR was ≥60 mL/min/1.73 m(2), 1.9 (95% CI, 1.3-2.8) if eGFR was 30-60 mL/min/1.73 m(2), and 3.6 (95% CI, 2.6-5.0) in patients with eGFR <30 mL/min/1.73 m(2). Renal replacement therapy (RRT) was initiated in 146 patients and 35 of the 80 deaths occurred after the start of RRT. The age- and sex-adjusted SMR was not increased significantly in the pre-RRT period (1.3; 95% CI, 1.0-1.7), but was increased after initiation of RRT (4.9; 95% CI, 3.5-7.0). The most common cause of death was cardiovascular disease, accounting for 45% of all deaths. LIMITATIONS: Treatment during follow-up is not known. CONCLUSIONS: Mortality in patients with IgAN was twice the expected rate, but not significantly increased before RRT. The risk of end-stage renal disease was substantially higher than risk of death.


Subject(s)
Glomerulonephritis, IGA/epidemiology , Glomerulonephritis, IGA/mortality , Registries , Adult , Aged , Cohort Studies , Female , Follow-Up Studies , Glomerular Filtration Rate/physiology , Glomerulonephritis, IGA/physiopathology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Norway/epidemiology , Renal Replacement Therapy , Retrospective Studies , Survival Rate
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