Background Perioperative acute kidney injury is common. However, it is unclear whether this merely represents a transient increase in creatinine or has prognostic value. Therefore, the long-term clinical importance of mild postoperative acute kidney injury remains unclear. This study assessed whether adults who do and do not experience mild kidney injury after noncardiac surgery are at similar risk for long-term renal injury. Methods This study is a retrospective cohort analysis of adults having noncardiac surgery at the Cleveland Clinic who had preoperative, postoperative, and long-term (1 to 2 yr after surgery) plasma creatinine measurements. The exposure (postoperative kidney injury) and outcome (long-term renal injury) were defined and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) initiative criteria. The primary analysis was for lack of association between postoperative kidney injury (stage I vs. no injury) and long-term renal injury. Results Among 15,621 patients analyzed, 3% had postoperative stage I kidney injury. Long-term renal outcomes were not similar in patients with and without postoperative stage I injury. Specifically, about 26% of patients with stage I postoperative kidney injury still had mild injury 1 to 2 yr later, and 11% had even more severe injury. A full third (37%) of patients with stage I kidney injury therefore had renal injury 1 to 2 yr after surgery. Patients with postoperative stage I injury had an estimated 2.4 times higher odds of having long-term renal dysfunction (KDIGO stage I, II, or III) compared with patients without postoperative kidney injury (odds ratio [95% CI] of 2.4 [2.0 to 3.0]) after adjustment for potential confounding factors. Conclusions In adults recovering from noncardiac surgery, even small postoperative increases in plasma creatinine, corresponding to stage I kidney injury, are associated with renal dysfunction 1 to 2 yr after surgery. Even mild postoperative renal injury should therefore be considered a clinically important perioperative outcome. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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Natural products (NPs) that exhibit anticancer activities are frequently not potent enough to be used clinically as therapeutics. Semi-synthesis and metabolic engineering are promising approaches for producing more efficacious derivatives of anticancer NPs (ACNPs), but each technique alone can be inefficient at obtaining specific ACNP derivatives that may be suspected to have enhanced anticancer activity. Here, we demonstrate that the methods of semi-synthesis and biocatalysis can be used as modules in succession and in different combinations to produce 6,8-dibromogenkwanin, a derivative of the ACNP apigenin. Further, we demonstrated that soybean seed coats can be used as a biocatalyst to convert brominated flavonoids into multiple derivatives. A strength of the combinatorial (bio)synthesis approach was that the order of the modules could be rearranged to increase the yield of the desired product. At lower treatment concentration (5 mM), 6,8-dibromogenkwanin exhibited enhanced antiproliferative activities against HT-29 colorectal adenocarcinoma cancer cells under normoxic and hypoxic conditions compared to its ACNP precursors, but not at higher concentrations. Dose-response analyses suggested that dibromogenkwanin had a distinct mode-of-action compared to apigenin. Thus, this proof-of-concept paper demonstrates combinatorial (bio)synthesis as an approach that can be used to produce novel chemistries for anticancer research.

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Background Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury. Methods The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria. Results The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units. Conclusions In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

BACKGROUND: Avoiding intraoperative hypotension might serve as a measure of clinician skill. We, therefore, estimated the range of hypotension in patients of nurse anesthetists, and whether observed differences were associated with a composite of serious complications. METHODS: First, we developed a multivariable model to predict the amount of hypotension, defined as minutes of mean arterial pressure (MAP) <65 mm Hg, for noncardiac surgical cases from baseline characteristics excluding nurse anesthetist. Second, we compared observed and predicted amounts of hypotension for each case and summarized “excess” amounts across providers. Third, we estimated the extent to which hypotension on an individual case level was independently associated with a composite of serious complications. Finally, we assessed the range of actual and excess minutes of MAP <65 mm Hg on a provider level, and the extent to which these pressure exposures were associated with complications. RESULTS: We considered 110,391 hours of anesthesia by 99 nurse anesthetists. A total of 69% of 25,702 included cases had at least 1 minute of MAP <65 mm Hg, with a median (quartiles) of 4 (0–15) minutes on the case level. We were unable to explain much variance of intraoperative hypotension from baseline patient characteristics. However, cases in the highest 2 quartiles (>10 and >24 min/case more than predicted) were an estimated 27% (95% confidence interval [CI], 1.1–1.4) and 31% (95% CI, 1.2–1.5) more likely to experience complications compared to those with 0 excess minutes (both P < .001). There was little variation of the average excess minutes <65 mm Hg across the nurse anesthetists, with median (quartiles) of 1.6 (1.2–1.9) min/h. There was no association in confounder-adjusted models on the nurse anesthetist level between average excess hypotension and complications, either for continuous exposure (P = .09) or as quintiles (P = .30). CONCLUSIONS: Hypotension is associated with complications on a case basis. But the average amount of hypotension for nurse anesthetists over hundreds of cases differed only slightly and was insufficient to explain meaningful differences in complications. Avoiding hypotension is a worthy clinical goal, but does not appear to be a useful metric of performance because the range of average amounts per clinician is not meaningfully associated with patient outcomes, at least among nurse anesthetists in 1 tertiary center.

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