Snapshots of nascent RNA reveal cell- and stimulus-specific responses to acute kidney injury.

The current strategy to detect acute injury of kidney tubular cells relies on changes in serum levels of creatinine. Yet serum creatinine (sCr) is a marker of both functional and pathological processes and does not adequately assay tubular injury. In addition, sCr may require days to reach diagnostic thresholds, yet tubular cells respond with programs of damage and repair within minutes or hours. To detect acute responses to clinically relevant stimuli, we created mice expressing Rosa26-floxed-stop uracil phosphoribosyltransferase (Uprt) and inoculated 4-thiouracil (4-TU) to tag nascent RNA at selected time points. Cre-driven 4-TU-tagged RNA was isolated from intact kidneys and demonstrated that volume depletion and ischemia induced different genetic programs in collecting ducts and intercalated cells. Even lineage-related cell types expressed different genes in response to the 2 stressors. TU tagging also demonstrated the transient nature of the responses. Because we placed Uprt in the ubiquitously active Rosa26 locus, nascent RNAs from many cell types can be tagged in vivo and their roles interrogated under various conditions. In short, 4-TU labeling identifies stimulus-specific, cell-specific, and time-dependent acute responses that are otherwise difficult to detect with other technologies and are entirely obscured when sCr is the sole metric of kidney damage.

Left Ventricular Unloading Before Percutaneous Coronary Intervention is Associated With Improved Survival in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Systematic Review and Meta-Analysis.

BACKGROUND: Left ventricular unloading with Impella may improve survival outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS). However, the optimal timing to initiate left ventricular unloading has yet to be established. Therefore, we conducted a systematic review and meta-analysis to compare survival in patients with AMI-CS who were supported with Impella prior to PCI (pre-PCI) to those in whom support was initiated following PCI (post-PCI). METHODS: All studies that evaluated the impact of pre-PCI versus post-PCI Impella placement in patients with AMI-CS were included. Primary endpoints included in-hospital, 30-day, and 6-month survival rates. RESULTS: We identified five observational studies comparing outcomes in 432 patients with AMI-CS, of which 173 patients were treated with Impella pre-PCI and 259 patients post-PCI. Patients in the pre-PCI group had lower in-hospital mortality compared to patients in the post-PCI group (RR 0.62, 95% CI: 0.50-0.76, I2 = 0%). The lower mortality rate in the pre-PCI group remained evident at 30 days (HR 0.60, 95% CI: 0.47-0.78, I2 = 0%) and at 6 months (HR 0.66, 95% CI: 0.44-0.97, I2 = 0%). There was no difference in the risk of adverse events including reinfarction, stroke, major bleeding, acute ischemic limb, access site bleeding, and hemolysis. CONCLUSIONS: In this meta-analysis of studies evaluating survival among AMI-CS patients with left ventricular unloading initiated pre- versus post-PCI, Impella placement prior to PCI was associated with improved survival.

Characteristics, complications, and mortality of respiratory syncytial virus compared with influenza infections in hospitalized adult patients in Thailand.

INTRODUCTION: RSV is increasingly recognized in adults. An improved understanding of clinical manifestations and complications may facilitate diagnosis and management. METHODS: This was a retrospective study of hospitalized patients aged ≥ 18 years with RSV or influenza infection at Siriraj hospital, Thailand between January 2014 and December 2017. RESULTS: RSV and/or influenza were detected by RT-PCR in 570 (20.1%) of 2836 patients. After excluding patients coinfected with influenza A and B (n = 5), and with influenza and RSV (n = 3), 141 (5.0%) RSV and 421 (14.8%) influenza patients were analyzed. Over the study period, RSV circulated during the rainy season and peaked in September or October. Patients with RSV were older than patients with influenza and presented significantly less myalgia and fever, but more wheezing. Pneumonia was the most common complication, occurring in 110 (78.0%) of RSV cases and in 295 (70.1%) of influenza cases (p = 0.069). Cardiovascular complications were found in 30 (21.3%) RSV and 96 (22.8%) influenza (p = 0.707), and were reasons for admission in 15 (10.6%) RSV and 50 (11.9%) influenza. The in-hospital mortality rates for RSV (17; 12.1%) and influenza (60; 14.3%) were similar (p = 0.512). CONCLUSIONS: In Thailand, RSV is a less common cause of adult hospitalization than influenza, but pulmonary and cardiovascular complications, and mortality are similar. Clinical manifestations cannot reliably distinguish between RSV and influenza infection; laboratory-confirmed diagnosis is needed.