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Background Serum cystatin C level has been shown to have a stronger association with clinical outcomes than serum creatinine level. However, little is known about the combined association of cystatin C–based estimated glomerular filtration rate (eGFRcys) and albuminuria with clinical outcomes, particularly at levels lower than current chronic kidney disease (CKD) cutoffs. Study Design Prospective cohort. Setting & Participants 10,403 ARIC (Atherosclerosis Risk in Communities) Study participants followed up for a median of 10.2 years. Predictor eGFRcys, albuminuria. Outcomes Mortality, coronary heart disease (CHD), and heart failure, as well as a composite of any of these separate outcomes. Results Both decreased eGFRcys and albuminuria were associated independently with the composite outcome, as well as mortality, CHD, and heart failure. Although eGFRcys of 75-89 mL/min/1.73 m2 in the absence of albuminuria (albumin-creatinine ratio [ACR] <10 mg/g) or albuminuria with ACR of 10-29 mg/g with normal eGFRcys (90-104 mL/min/1.73 m2) was not associated significantly with any outcome compared with eGFRcys of 90-104 mL/min/1.73 m2 and ACR <10 mg/g, the risk of each outcome was significantly higher in those with both eGFRcys of 75-89 mL/min/1.73 m2 and ACR of 10-29 mg/g (for mortality, HR of 1.4 [95% CI, 1.1-2.0]; for CHD, HR of 1.9 [95% CI, 1.4-2.6]; for heart failure, HR of 1.8 [95% CI, 1.2-2.7]). Combining the 2 markers improved risk classification for all outcomes (P < 0.001), even in those without overt CKD. Limitations Only one measurement of cystatin C. Conclusions Mildly decreased eGFRcys and mild albuminuria independently contributed to the risk of mortality, CHD, and heart failure. Even minimally decreased eGFRcys (75-89 mL/min/1.73 m2) is associated with increased risk in the presence of mild albuminuria. Combining the 2 markers is useful for improved risk stratification even in those without clinical CKD.

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Melanoma is increasing in incidence and remains a major public health threat. Although the disease may be curable when identified early, advanced melanoma is characterized by widespread metastatic disease and a median survival of less than 10 months. In recent years, however, major advances in our understanding of the molecular nature of melanoma and the interaction of melanoma cells with the immune system have resulted in several new therapeutic strategies that are showing significant clinical benefit. Current therapeutic approaches include surgical resection of metastatic disease, chemotherapy, immunotherapy, and targeted therapy. Dacarbazine, interleukin-2, ipilimumab, and vemurafenib are now approved for the treatment of advanced melanoma. In addition, new combination chemotherapy regimens, monoclonal antibodies blocking the programmed death-1 (PD-1)/PD-ligand 1 pathway, and targeted therapy against CKIT, mitogen-activated protein/extracellular signal-regulated kinase (MEK), and other putative signaling pathways in melanoma are beginning to show promise in early-phase clinical trials. Further research on these modalities alone and in combination will likely be the focus of future clinical investigation and may impact the outcomes for patients with advanced melanoma.

SummaryBackground Estimated GFR by serum creatinine (eGFR creatinine ) is a pivotal measure of kidney function in clinical practice but can be affected by several non-GFR determinants, resulting in misclassification. Combining multiple kidney markers to predict risk is an area of substantial interest.Design, setting, participants, & measurements This study followed 9489 adults from visit 4 (1996-1998) of the Atherosclerosis Risk in Communities Study for a median of 11.2 years, and assessed joint association of eGFR creatinine , eGFR cystatin , and urinary albumin/creatinine ratio (ACR) with mortality, coronary heart disease, heart failure, AKI, and ESRD using Cox proportional hazards models. The predictive ability of ACR and eGFR cystatin beyond eGFR creatinine was also investigated.Results Lower eGFR creatinine and eGFR cystatin as well as elevated ACR were independently associated with risk for all outcomes. eGFR creatinine ,60 was not associated with risk of mortality, coronary heart disease, or heart failure if eGFR cystatin $60 with ACR ,30 mg/g compared with those with all three markers above CKD cutoffs (i.e., eGFR cystatin $60, eGFR creatinine $60, and ACR,30), whereas risk association with kidney outcomes remained: Hazard ratio (95% confidence interval), 0.96 (0.66, 1.39) for mortality, 0.85 (0.55, 1.31) for coronary heart disease, 0.99 (0.60, 1.63) for heart failure, 1.61 (0.92, 2.82) for AKI, and 3.53 (1.06, 11.68) for ESRD. Adding ACR to the fully adjusted model with eGFR creatinine or adding eGFR cystatin to both eGFR creatinine and ACR improved risk classification for all outcomes (P # 0.01).Conclusions eGFR cystatin can be a useful confirmatory marker in those with eGFR creatinine ,60 and whose ACR is ,30 mg/g. This approach improves risk classification, and provides reassurance to a large group of individuals with eGFR creatinine ,60.

AF detection in patients with CS is improved with prolonged rhythm monitoring and is better with ILR compared to wearable devices. AF was more common in older patients. The clinical significance of these findings is unknown at this point.

ObjectiveProlonged QT interval predisposes to ventricular arrhythmias and sudden cardiac death. However, the association between QT interval and mortality by the level of pre-existing kidney function has not been investigated.MethodsWe followed 6565 participants from the National Health and Nutrition Examination Survey III for a median of 13.3 years. Sample divided according to corrected QT (QTc) interval was as follows: normal (QTc <450 ms for men and <460 ms for women) or prolonged. It was further categorised as follows: (1) no chronic kidney disease (CKD), that is, albumin to creatinine ratio (ACR) <30 mg/g and estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2; (2) CKD by eGFR only (eGFR <60 mL/min/1.73 m2, ACR <30 mg/g); (3) CKD by ACR only (ACR >30 mg/g, eGFR >60 mL/min/1.73 m2) and (4) CKD by both. Cox proportional hazards models were used.ResultsCKD group had prolonged QTc than those without CKD (20.5%vs12.9%, p<0.0001). Both prolonged QTc and CKD are independently associated with increased risk of mortality. When combined, risk of mortality is higher in those with CKD by eGFR with prolonged QTc than normal QTc (HR 2.6 (1.7–3.9) and 3.1 (1.7–5.4) vs 1.4 (1.1–1.7) and 1.7 (1.3–2.1) for all-cause and CV mortality). There is no significant difference in risk in those with CKD by ACR when QTc is prolonged. There is significant improvement in risk prediction for all-cause and CV mortality when QTc is added to CKD beyond established CV risk factors (net reclassification index p<0.00001).ConclusionA screening ECG in those with CKD may help in finer risk stratification and may be considered.

Background Until recently, circulating micro-RNAs (miRNAs) have attracted major interest as novel biomarkers for the early diagnosis of coronary artery disease (CAD). This review article summarizes the available evidence on the correlation of micro-RNAs with both the clinical and subclinical coronary artery disease and highlights the necessity for exploring miRNAs as a potential diagnostic and prognostic biomarker of early CAD in an adult population. Methods A systematic literature analysis and retrieval online systems Public/Publisher MEDLINE/ Excerpta Medica Database /Medical Literature Analysis and Retrieval System Online,(PUBMED/EMBASE/MEDLINE) search were conducted for relevant information. Search was limited to the articles published in English language and conducted on humans, January 2000 onwards. We excluded studies of heart surgery, coronary artery bypass grafting (CABG), angioplasty and heart transplant. Eighteen studies met the inclusion criteria. Results Seven out of 18 studies were multivariate, i.e. adjusted for age, gender, body mass index (BMI), smoking, hypertension, diabetes, and blood lipid profiles, while the remaining twelve studies were univariate analysis. Different sources of miRNAs were used, i.e. plasma/serum, microparticles, whole blood, platelets, blood mononuclear intimal and endothelial progenitor cells were investigated. Fourteen out of 18 studies showed up-regulation of different miRNA in CAD patients and in vulnerable plaque disease. Four out of 18 studies showed both the up-regulation and down-regulation of miRNA in the population, while only three studies showed down-regulation of miRNA. Various sources and types of miRNA were used in each study. Conclusion This review gives an extensive overview of up-regulation and down-regulation of miRNA in CAD and non-CAD patients. The pattern of miRNA regulation with respect to CAD/non-CAD study subjects varies across individual studies and different parameters, which could be the possible reason for this aberrancy. We suggest further trials be conducted in future for highlighting the role of miRNA in CAD, which may improve both the diagnostic and therapeutic approaches to stratifying CAD burden in the general population.