Uncomplicated epidural removal in a patient on a therapeutic heparin infusion: a case report.

BACKGROUND: Unanticipated postoperative thrombotic complications can occur in complex patients who receive preoperative epidurals. Therefore, it is imperative that we consider the risks and benefits of epidural management in the setting of therapeutic anticoagulation. We present a case of epidural catheter removal on a heparin infusion, due to the extreme risk of holding anticoagulation for any duration. CASE REPORT: A woman with hilar cholangiocarcinoma presented after uncomplicated hepatectomy, bile duct resection and hepaticojejunostomy, with a thoracic epidural for analgesia. On postoperative day 1, she developed a total portal vein thrombosis, requiring emergent open thrombectomy, transhepatic stenting and high-dose heparin infusion while the epidural was indwelling. The patient was deemed to have a profound risk of re-thrombosis if heparin were paused. Therefore, a multidisciplinary discussion between hepatobiliary surgery, critical care, neurosurgery, haematology, acute pain service and the patient's family ensued regarding epidural management. Options included catheter-directed thrombolytics to her stent while holding systemic anticoagulation, sterilely leaving the epidural catheter in place indefinitely, injecting prothrombotic agent into the epidural prior to removal, or removing the catheter without holding anticoagulation. Due to the risk of re-thrombosis in the portal vein and liver infarction, the heparin infusion was decreased to achieve the lowest therapeutic anti-Xa level, and the epidural was removed. The patient was continuously monitored in the intensive care unit without any adverse events. CONCLUSION: A multidisciplinary discussion is paramount to weigh the risk of epidural haematoma if a catheter is removed on therapeutic anticoagulation against catastrophic thrombosis if anticoagulation is paused.

Prolonged Blood Storage and Risk of Posttransfusion Acute Kidney Injury.

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.

Informed consent for invasive procedures in the emergency department.

BACKGROUND: Informed consent for procedures in the emergency department (ED) challenges practitioners to navigate complex ethical and medical ambiguities. A patient's altered mental status or emergent medical problem does not negate the importance of his or her participation in the decision-making process but, rather, necessitates a nuanced assessment of the situation to determine the appropriate level of participation. Given the complexities involved with informed consent for procedures in the ED, it is important to understand the experience of key stakeholders involved. METHODS: For this review, we searched Medline, the Cochrane database, and Clinicaltrials.gov for studies involving informed consent in the ED. Inclusion and exclusion criteria were designed to select for studies that included issues related to informed consent as primary outcomes. The following data was extracted from included studies: Title, authors, date of publication, study type, participant type (i.e. adult patient, pediatric patient, parent of pediatric patient, patient's family, or healthcare provider), number of participants, and primary outcomes measured. RESULTS: Fifteen articles were included for final review. Commonly addressed themes included medical education (7 of 15 studies), surrogate decision-making (5 of 15 studies), and patient understanding (4 of 15 studies). The least common theme addressed in the literature was community notification (1 of 15 studies). CONCLUSIONS: Studies of informed consent for procedures in the ED span many aspects of informed consent. The aim of the present narrative review is to summarize the work that has been done on informed consent for procedures in the ED.

Blood Pressure Management by Anesthesia Professionals: Evaluating Clinician Skill From Electronic Medical Records.

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.

An Algorithm for Classifying Patients Most Likely to Develop Severe Coronavirus Disease 2019 Illness.

OBJECTIVES: To develop an algorithm that predicts an individualized risk of severe coronavirus disease 2019 illness (i.e., ICU admission or death) upon testing positive for coronavirus disease 2019. DESIGN: A retrospective cohort study. SETTING: Cleveland Clinic Health System. PATIENTS: Those hospitalized with coronavirus disease 2019 between March 8, 2020, and July 13, 2020. INTERVENTIONS: A temporal coronavirus disease 2019 test positive cut point of June 1 was used to separate the development from validation cohorts. Fine and Gray competing risk regression modeling was performed. MEASUREMENTS AND MAIN RESULTS: The development set contained 4,520 patients who tested positive for coronavirus disease 2019 between March 8, 2020, and May 31, 2020. The validation set contained 3,150 patients who tested positive between June 1 and July 13. Approximately 9% of patients were admitted to the ICU or died of coronavirus disease 2019 within 2 weeks of testing positive. A prediction cut point of 15% was proposed. Those who exceed the cutoff have a 21% chance of future severe coronavirus disease 2019, whereas those who do not have a 96% chance of avoiding the severe coronavirus disease 2019. In addition, application of this decision rule identifies 89% of the population at the very low risk of severe coronavirus disease 2019 (< 4%). CONCLUSIONS: We have developed and internally validated an algorithm to assess whether someone is at high risk of admission to the ICU or dying from coronavirus disease 2019, should he or she test positive for coronavirus disease 2019. This risk should be a factor in determining resource allocation, protection from less safe working conditions, and prioritization for vaccination.

Ethnic Differences in Analgesic Efficacy and Safety of Liposomal Bupivacaine Among Asian and Caucasian Surgical Patients: A Retrospective Matched-Cohort Analysis.

BACKGROUND: Extended-release local anesthetics allow for prolonged analgesia after a single administration. Although Asians demonstrate different pain thresholds than Caucasians, whether they have different postoperative local anesthetic analgesic effects has not been elucidated. OBJECTIVE: We aimed to compare the postoperative analgesic efficacy of liposomal bupivacaine on Asian and Caucasian adults, and the incidence of local anesthetic systemic toxicity (LAST) syndrome. METHODS: We conducted a retrospective, assessor-blinded cohort study of adult patients who received liposomal bupivacaine for surgery between 2012 and 2018. Asians and Caucasians were matched in a 1:1 ratio by clinical characteristics and surgery type. The primary outcome was pain management, defined as average pain score and opioid consumption during the initial 72 postoperative hours. The secondary outcome was the incidence of LAST syndrome. Reviewers were blinded to the ethnicity of the patient. RESULTS: After 1:1 propensity score matching, 130 Asians and 129 Caucasians were analyzed. All confounding variables were balanced, except for higher body mass index in the Asian group. Pain scores were lower (adjusted mean difference of -0.50 [97.5% CI, -0.98, -0.01]; superiority p = 0.011) and opioid consumption was not greater (geometric means ratio, 0.61 [97.5% CI, 0.36, 1.04]; non-inferiority p ＜ 0.001) in Asian patients compared to Caucasian patients. Only one Caucasian patient was judged as having a potential case of LAST syndrome. The length of hospital stay and the incidence of additional complications were not different between the groups. CONCLUSION: Asian adults receiving liposomal bupivacaine as part of multimodal perioperative analgesia demonstrated lower pain scores compared to matching Caucasians, despite not having greater opioid consumption.

Mild Acute Kidney Injury after Noncardiac Surgery Is Associated with Long-term Renal Dysfunction: A Retrospective Cohort Study.

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.

Combining semi-synthesis with plant and microbial biocatalysis: new frontiers in producing a chemical arsenal against cancer.

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 µM), 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.

Arabidopsis MATE45 antagonizes local abscisic acid signaling to mediate development and abiotic stress responses.

Anthocyanins provide ideal visual markers for the identification of mutations that disrupt molecular responses to abiotic stress. We screened Arabidopsis mutants of ABC (ATP-Binding Cassette) and MATE (Multidrug And Toxic compound Extrusion) transporter genes under nutritional stress and identified four genes (ABCG25,ABCG9,ABCG5, and MATE45) required for normal anthocyanin pigmentation. ABCG25 was previously demonstrated to encode a vascular-localized cellular exporter of abscisic acid (ABA). Our results show that MATE45 encodes an aerial meristem- and a vascular-localized transporter associated with the trans-Golgi, and that it plays an important role in controlling the levels and distribution of ABA in growing aerial meristems and non-meristematic tissues. MATE45 promoter-GUS reporter fusions revealed the activity localized to the leaf and influorescence meristems and the vasculature. Loss-of-function mate45 mutants exhibited accelerated rates of aerial organ initiation suggesting at least partial functional conservation with the maize ortholog bige1. The aba2-1 mutant, which is deficient in ABA biosynthesis, exhibited a number of phenotypes that were rescued in the mate45-1 aba2-1 double mutant. mate45 exhibited enhanced the seed dormancy, and germination was hypersensitive to ABA. Enhanced frequency of leaf primordia growth in mate45 seedlings grown in nutrient imbalance stress was ABA-dependent. The ABA signaling reporter construct pRD29B::GUS revealed elevated levels of ABA signaling in the true leaf primordia of mate45 seedlings grown under nutritional stress, and gradually reduced signaling in surrounding cotyledon and hypocotyl tissues concomitant with reduced expressions of ABCG25. Our results suggest a role of MATE45 in reducing meristematic ABA and in maintaining ABA distribution in adjacent non-meristematic tissues.