***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract Background Inflammation signaled by Janus kinases ( JAKs ) promotes progression of diabetic kidney disease ( DKD ) . Baricitinib is an oral , reversible , selective inhibitor of JAK1 and JAK2 . This study tested the efficacy of baricitinib versus placebo on albuminuria in adults with Type 2 diabetes at high risk for progressive DKD . Methods In this Phase 2 , double-blind , dose-ranging study , participants were r and omized 1:1:1:1:1 to receive placebo or baricitinib ( 0.75 mg daily ; 0.75 mg twice daily ; 1.5 mg daily ; or 4 mg daily ) , for 24 weeks followed by 4–8 weeks of washout . Results Participants ( N = 129 ) were 63±9.1 ( mean±st and ard deviation ) years of age , 27.1 % ( 35/129 ) women and 11.6 % ( 15/129 ) African-American race . Baseline hemoglobin A1c ( HbA1c ) was 7.3±1 % and estimated glomerular filtration rate was 45.0±12.1 mL/min/1.73 m2 with first morning urine albumin – creatinine ratio ( UACR ) of 820 ( 407–1632 ) ( median ; interquartile range ) mg/g . Baricitinib , 4 mg daily , decreased morning UACR by 41 % at Week 24 compared with placebo ( ratio to baseline 0.59 , 95 % confidence interval 0.38–0.93 , P = 0.022 ) . UACR was decreased at Weeks 12 and 24 and after 4–8 weeks of washout . Baricitinib 4 mg decreased inflammatory biomarkers over 24 weeks ( urine C – X – C motif chemokine 10 and urine C – C motif lig and 2 , plasma soluble tumor necrosis factor receptors 1 and 2 , intercellular adhesion molecule 1 and serum amyloid A ) . The only adverse event rate that differed between groups was anemia at 32.0 % ( 8/25 ) for baricitinib 4 mg daily versus 3.7 % ( 1/27 ) for placebo . Conclusions Baricitinib decreased albuminuria in participants with Type 2 diabetes and DKD . Further research is required to determine if baricitinib reduces DKD progression OBJECTIVE Renal dysfunction is a key risk factor for all-cause mortality in patients with type 2 diabetes ( T2D ) . Circulating tumor necrosis factor receptor 1 ( TNFR1 ) was recently suggested as a strong biomarker for end-stage renal failure in T2D . However , its relevance regarding all-cause death has yet to be conclusively established . We aim ed to assess the prognostic value of serum TNFR1  concentration for all-cause death in T2D and diabetic kidney disease ( DKD ) from the SURDIAGENE ( Survie , Diabete de type 2 et Genetique ) study . RESEARCH DESIGN AND METHODS A total of 522 T2D patients with DKD ( estimated glomerular filtration rate [ eGFR ] < 60 and /or urinary albumin-to-creatinine ratio [ uACR ] > 30 mg/mmol ) were followed for a median duration of 48 months , and 196 deaths occurred . RESULTS Incidence rate ( 95 % CI ) for death increased as quartiles of TNFR1 concentration increased ( first quartile : 4.7 % patient-years [ 3.0–6.3 % ] ; second quartile : 7.7 % [ 5.4–10.0 % ] ; third quartile : 9.3 % [ 6.7–11.9 % ] ; fourth quartile : 15.9 % [ 12.2–19.5 % ] ) . In multivariate analysis taking age , diabetes duration , HbA1c , uACR , and eGFR into account , compared with the first quartile , patients from the fourth quartile had an adjusted hazard ratio for death of 2.98 ( 95 % CI 1.70–5.23 ) . The integrated discrimination improvement index was statistically significant when adding TNFR1 concentration to the UK Prospect i ve Diabetes Study outcome equation ( P = 0.031 ) . CONCLUSIONS TNFR1 is a strong prognostic factor for all-cause mortality in T2D with renal dysfunction , and its clinical utility is suggested in addition to established risk factors for all-cause mortality Background We aim ed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)‐α ( TNFR1 and TNFR2 ) and cardiovascular outcomes in patients with stable coronary heart disease . Methods and Results CLARICOR ( Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease ) is a r and omized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease . The primary outcome was a composite of nonfatal acute myocardial infa rct ion , unstable angina pectoris , cerebrovascular disease , and all‐cause mortality . Patients were followed up for 10 years ; discovery sample , those assigned placebo ( 1204 events in n=1998 ) ; and replication sample , those assigned clarithromycin ( 1220 events in n=1979 ) . We used Cox regression adjusted for C‐reactive protein level , established cardiovascular risk factors , kidney function , and cardiovascular drugs . After adjustments , higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample ( hazard ratio per SD increase , 1.13 ; 95 % confidence interval , 1.05–1.22 ; P=0.001 for TNFR1 ; hazard ratio , 1.16 ; 95 % confidence interval , 1.08–1.24 ; P<0.001 for TNFR2 ) . The associations were similar in the replication sample . The associations with the composite outcome were mainly driven by acute myocardial infa rct ion , cardiovascular mortality , and noncardiovascular mortality . The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly ( < 1 % ) . Conclusions Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease . Yet , the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited . Clinical Trial Registration URL : https://www . clinical trials.gov . Unique identifier : NCT00121550 Abstract Cardiovascular disease ( CVD ) is the main public health problem in patients with chronic kidney disease ( CKD ) ; however , there is no established biomarker for predicting CVD morbidity and mortality in CKD . The aim of this study was to evaluate the role of circulating tumor necrosis factor receptors ( cTNFRs ) in predicting CVD risk in CKD patients . We prospect ively recruited 984 patients with CKD from 11 centers between 2006 and 2012 . The levels of cTNFR1 and cTNFR2  were determined by performing an enzyme-linked immunosorbent assay . During the mean follow-up period of 4 years , 36 patients experienced a CVD event . The median serum concentrations of cTNFR1 and cTNFR2 were 2703.4 ( 225.6–13,057.7 ) and 5661.0 ( 634.9–30,599.6 ) pg/mL , respectively , and the cTNFR1 level was closely correlated with the cTNFR2 level ( r = 0.86 , P < .0001 ) . The urinary protein-to-creatinine ratio ( UPCR ) and estimated glomerular filtration rate ( eGFR ) were significantly correlated with the cTNFR2 level ( r = 0.21 for UPCR , r = −0.67 for eGFR ; P < .001 for all ) . Similar correlations were observed for serum cTNFR1 ( r = 0.21 for UPCR , r = −0.75 for eGFR ; P < .001 for all ) . In the Cox proportional hazard analyses , cTNFR1 ( hazard ratio [ HR ] 2.506 , 95 % confidence interval [ CI ] 1.186–5.295 , P = .016 ) and cTNFR2 ( HR 4.156 , 95 % CI 1.913–9.030 , P < .001 ) predicted CVD risk even after adjustment for clinical covariates , such as UPCR , eGFR , and high-sensitivity C-reactive protein . cTNFR1 and 2 are associated with CVD and other risk factors in CKD , independently of eGFR and UPCR . Furthermore , cTNFRs could be relevant predictors of CVD in CKD patients BACKGROUND Several studies have demonstrated that levels of circulating inflammatory markers such as tumour necrosis factorα ( TNFα ) , are associated with early progression of diabetic nephropathy ( DN ) . The aim of this study was to investigate whether there is an association between circulating TNFα receptor and disease progression in patients with advanced type 2 DN and severe proteinuria . METHODS Between 2006 and 2011 , we measured levels of circulating soluble TNFα receptor 1 ( TNFR1 ) and soluble TNFα receptor 2 ( TNFR2 ) at baseline and 4 and 12 months in 101 patients included in a multicenter r and omized controlled trial to compare the effect of optimal doses of renin-angiotensin system blockers in monotherapy or in combination ( dual blockade ) to slow progression of established type 2 DN . The primary composite endpoint was a > 50 % increase in baseline serum creatinine , end-stage renal disease , or death . RESULTS The median follow-up was 32 months ( IQR , 18 - 48 ) , during which time 28 patients ( 22.7 % ) achieved the primary endpoint . The TNFR1 level , but not the TNFR2 level , was correlated with other inflammatory markers . Cox regression analysis showed that the highest TNFR1 levels ( HR , 2.60 ; 95%CI , 1.11 - 86.34 ) and baseline proteinuria ( HR 1.32 ; 95%CI 1.15 - 1.52 ) were associated with the primary endpoint . The mixed model analysis revealed that TNFR1 and the TNFR2 levels did not change after starting treatment with renin-angiotensin system blockers . CONCLUSIONS Our results show that the highest levels of TNFR1 are independently associated with progression of renal disease and death in type 2 DN . The renin angiotensin blockers have no effect on these inflammatory markers Aims /hypothesisMultiplex proteomics could improve underst and ing and risk prediction of major adverse cardiovascular events ( MACE ) in type 2 diabetes . This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes . Methods We combined data from six prospect i ve epidemiological studies of 30–77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay . Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE . We used gradient-boosted machine learning and lasso regularised Cox regression in a r and om 75 % training sub sample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25 % test sub sample . Results Of 1211 adults with type 2 diabetes ( 32 % women ) , 211 experienced a MACE over a mean ( ±SD ) of 6.4 ± 2.3 years . We replicated associations ( < 5 % false discovery rate ) between risk of MACE and eight proteins : matrix metalloproteinase (MMP)-12 , IL-27 subunit α ( IL-27a ) , kidney injury molecule (KIM)-1 , fibroblast growth factor (FGF)-23 , protein S100-A12 , TNF receptor (TNFR)-1 , TNFR-2 and TNF-related apoptosis-inducing lig and receptor (TRAIL-R)2 . Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 ( 95 % CI 0.682 , 0.689 ) to 0.748 ( 95 % CI 0.746 , 0.751 ) . A sparse model of 20 added proteins achieved a C statistic of 0.747 ( 95 % CI 0.653 , 0.842 ) in the test sample . Conclusions /interpretationWe identified eight protein biomarkers , four of which are novel , for risk of MACE in community residents with type 2 diabetes , and found improved risk prediction by combining multiplex proteomics with an 
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The subgroup analyses and sensitivity analyses further illustrated these results of renal outcome and its robustness .
Circulating TNFR-1 and TNFR-2 are independently associated with higher risk of renal disease progression , CVD events , and mortality in patients with diabetes and might contribute to the clinical risk assessment in the future