A putative "chemokine switch" that regulates systemic acute inflammation in humans.

Systemic inflammation is complex and likely drives clinical outcomes in critical illness such as that which ensues following severe injury. We obtained time course data on multiple inflammatory mediators in the blood of blunt trauma patients. Using dynamic network analyses, we inferred a novel control architecture for systemic inflammation: a three-way switch comprising the chemokines MCP-1/CCL2, MIG/CXCL9, and IP-10/CXCL10. To test this hypothesis, we created a logical model comprising this putative architecture. This model predicted key qualitative features of systemic inflammation in patient sub-groups, as well as the different patterns of hospital discharge of moderately vs. severely injured patients. Thus, a rational transition from data to data-driven models to mechanistic models suggests a novel, chemokine-based mechanism for control of acute inflammation in humans and points to the potential utility of this workflow in defining novel features in other complex diseases.

Risk factors for acute kidney injury after pharmacomechanical thrombolysis for acute deep vein thrombosis.

BACKGROUND: Pharmacomechanical thrombolysis (PMT) is an established treatment for selected patients with acute deep vein thrombosis (DVT). Despite significant clinical success, hemolysis can lead to acute kidney injury (AKI) with unknown longer term implications. Our aim was to characterize the rate of AKI after PMT and identify those patients at the greatest risk. METHODS: A retrospective medical record review of patients with acute DVT who had undergone PMT in our institution from 2007 to 2018 was performed. The baseline demographics, comorbidities, preoperative clinical characteristics, procedural details, postoperative hospital course, and follow-up data were reviewed. The primary outcome was postoperative AKI (≥1.5 times preoperative creatinine), and longer term renal impairment. Logistic regression modeling was used to identify associated factors. RESULTS: A total of 137 patients (mean age, 47 ± 16.6 years; 49.6% male) who had undergone PMT for treatment of acute DVT were identified (85.4% AngioJet system; Boston Scientific Corp, Marlborough, Mass). Of the 137 patients, 30 (21.9%) had developed AKI in the periprocedural period, 1 of whom had required hemodialysis in the perioperative period. The patients who had developed AKI had had significantly greater rates of preoperative coronary artery disease (23.1% vs 4.7%; P = .002), diabetes mellitus (19.2% vs 6.6%; P = .045), dyslipidemia (42.3% vs 17.9%; P = .008), and hypertension (53.6% vs 29.3%; P = .018). No significant difference was found in preoperative creatinine (0.99 vs 0.92 mg/dL; P = .65) or glomerular filtration rate (GFR; 96.9 vs 91.8 mL/min; P = .52) between the two groups. Multivariate analysis demonstrated bilateral DVT (odds ratio [OR], 4.35; 95% confidence interval [CI], 1.47-12.86; P = .008), single-session PMT (OR, 3.05; 95% CI, 1.02-9.11; P = .046), and female sex (OR, 2.85; 95% CI, 1.01-8.04; P = .048) were significant predictors of AKI. Of the 30 patients, 10 had had normal renal function at discharge and 15 and 25 patients had had normal renal function at the first and subsequent clinical follow-up visits, respectively. The remaining five patients (3.6%) had progressed to moderate (GFR, <60 mL/min) or severe (GFR, <30 mL/min) renal insufficiency, with one requiring long-term hemodialysis. CONCLUSIONS: The use of PMT for treatment of acute DVT conferred a risk of AKI that will progress to chronic renal failure in a small fraction of affected patients. Patients with bilateral extensive DVTs have a greater risk of AKI; thus, longer priming with a thrombolytic drip before PMT should be preferred for this population.