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Highlights In a national cohort of over 10,273 patients with COVID-19, more than 60% of all cases in South Korea reported no symptoms at the time of diagnosis. Our findings suggest that symptom-based screening alone may fail to control transmission during the infected but asymptomatic stage. Expanding criteria for contact tracing and testing should be urgently considered.

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Although diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease eventually requiring chronic kidney replacement therapy, the prevalence of DKD has failed to decline over the past 30 years. In order to reduce disease prevalence, extensive research has been ongoing to improve prediction of DKD onset and progression. Although the most commonly used markers of DKD are albuminuria and estimated glomerular filtration rate, their limitations have encouraged researchers to search for novel biomarkers that could improve risk stratification. Considering that DKD is a complex disease process that involves several pathophysiologic mechanisms such as hyperglycemia induced inflammation, oxidative stress, tubular damage, eventually leading to kidney damage and fibrosis, many novel biomarkers that capture one specific mechanism of the disease have been developed. Moreover, the increasing use of high-throughput omic approaches to analyze biological samples that include proteomics, metabolomics, and transcriptomics has emerged as a strong tool in biomarker discovery. This review will first describe recent advances in the understanding of the pathophysiology of DKD, and second, describe the current clinical biomarkers for DKD, as well as the current status of multiple potential novel biomarkers with respect to protein biomarkers, proteomics, metabolomics, and transcriptomics.

Background Muscle wasting is prevalent in cancer patients, and early recognition of this phenomenon is important for risk stratification. Recent studies have suggested that the creatinine–cystatin C ratio may correlate with muscle mass in several patient populations. The association between creatinine–cystatin C ratio and survival was assessed in cancer patients. Methods A total of 3060 patients who were evaluated for serum creatinine and cystatin C levels at the time of cancer diagnosis were included. The primary outcome was 6‐month mortality. The 1‐year mortality, and length of intensive care unit (ICU) and hospital stay were also evaluated. Results The mean age was 61.6 ± 13.5 years, and 1409 patients (46.0%) were female. The median creatinine and cystatin C levels were 0.9 (interquartile range [IQR], 0.6–1.3) mg/dL and 1.0 (IQR, 0.8–1.5) mg/L, respectively, with a creatinine–cystatin C ratio range of 0.12–12.54. In the Cox proportional hazards analysis, an increase in the creatinine–cystatin C ratio was associated with a significant decrease in the 6‐month mortality (per 1 creatinine–cystatin C ratio, hazard ratio [HR] 0.35; 95% confidence interval [CI], 0.28–0.44). When stratified into quartiles, the risk of 6‐month mortality was significantly lower in the highest quartile (HR 0.30; 95% CI, 0.24–0.37) than in the lowest quartile. Analysis of 1‐year mortality outcomes revealed similar findings. These associations were independent of confounding factors. The highest quartile was also associated with shorter lengths of ICU and hospital stay (both P < 0.001). Conclusions The creatinine–cystatin C ratio at the time of cancer diagnosis significantly associates with survival and hospitalization in cancer patients.

Background Increased body mass index (BMI) has been associated with higher risk of severe coronavirus disease 2019 (COVID-19) infections. However, whether obesity is a risk factor for contracting COVID-19 has been hardly investigated so far. Methods We examined the association between BMI level and the risk of COVID-19 infection in a nationwide case-control study comprised of 3,788 case patients confirmed with COVID-19 between January 24 and April 9, 2020 and 15,152 controls matched by age and sex, who were aged 20 years or more and underwent National Health Insurance Service (NHIS) health examinations between 2015−2017, using data from the Korean NHIS with linkage to the Korea Centers for Disease Control and Prevention data. Our primary exposure of interest was BMI level categorized into four groups; &18.5 (underweight), 18.5-22.9 (normal weight), 23-24.9 (overweight), and ≥25 kg/m 2 (obese). Results Of the entire 18,940 study population, 11,755 (62.1%) were women, and the mean (SD) age of the study participants was 53.7 (13.8) years. In multivariable logistic regression models adjusted for sociodemographic, comorbidity, laboratory and medication data, there was a graded association between higher BMI levels and higher risk of COVID-19 infection; compared to normal weight individuals, the adjusted ORs in the overweight and obese individuals were 1.13 (95% CI, 1.03-1.25) and 1.26 (95% CI, 1.15-1.39), respectively. This association was robust across age and sex subgroups. Conclusions Higher BMI levels were associated with higher risk of contracting COVID-19.

Atrial fibrillation (AF) is the most common arrhythmia. Gain-of-function mutations in KCNQ1, the pore-forming α-subunit of the slow delayed rectifier K current (IKs) channel, have been associated with AF. The purpose of this study was functional assessment of a mutation in KCNQ1 identified in a family with persistent AF and sinus bradycardia. We investigated whether this KCNQ1 missense mutation could form the genetic basis for AF and bradycardia simultaneously in this family. Sanger sequencing in a family with hereditary persistent AF identified a novel KCNQ1 variant (V241F) in a highly conserved region of S4 domain. The proband and her son developed bradycardia and persistent AF in an age-dependent fashion. The other son was a mutation carrier but he showed sinus bradycardia and not AF. Whole-cell patch clamp electrophysiology showed that V241F mutation in KCNQ1 shifted the activation curve to the left and dramatically slowed deactivation, leading to a constitutively open-like phenotype. Computer modeling showed that V241F would slow pacemaker activity. Also, simulations of atrial excitation predicted that V241F results in extreme shortening of action potential duration, possibly resulting in AF. Our study indicates that V241F might cause sinus bradycardia by increasing IKs. Additionally, V241F likely shortens atrial refractoriness to promote a substrate for reentry. KCNQ1 mutations have previously been described in AF, yet this is the first time a mutation in KCNQ1 is associated with age-dependent bradycardia and persistent AF. This finding further supports the hypothesis that sinus node dysfunction contributes to the development of AF.

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