Andrew M. Harrison

Bub1 kinase activity drives error correction and mitotic checkpoint control but not tumor suppression

Mice expressing a version of Bub1 that lacks kinase activity have increased chromosome segregation errors and aneuploidy but not increased susceptibility to tumors.

AKI after Transcatheter or Surgical Aortic Valve Replacement

Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement (SAVR) for patients with symptomatic severe aortic stenosis who are at high risk of perioperative mortality. Previous studies showed increased risk of postoperative AKI with TAVR, but it is unclear whether differences in patient risk profiles confounded the results. To conduct a propensity-matched study, we identified all adult patients undergoing isolated aortic valve replacement for aortic stenosis at Mayo Clinic Hospital in Rochester, Minnesota from January 1, 2008 to June 30, 2014. Using propensity score matching on the basis of clinical characteristics and preoperative variables, we compared the postoperative incidence of AKI, defined by Kidney Disease Improving Global Outcomes guidelines, and major adverse kidney events in patients treated with TAVR with that in patients treated with SAVR. Major adverse kidney events were the composite of in-hospital mortality, use of RRT, and persistent elevated serum creatinine ≥200% from baseline at hospital discharge. Of 1563 eligible patients, 195 matched pairs (390 patients) were created. In the matched cohort, baseline characteristics, including Society of Thoracic Surgeons risk score and eGFR, were comparable between the two groups. Furthermore, no significant differences existed between the TAVR and SAVR groups in postoperative AKI (24.1% versus 29.7%; P=0.21), major adverse kidney events (2.1% versus 1.5%; P=0.70), or mortality >6 months after surgery (6.0% versus 8.3%; P=0.51). Thus, TAVR did not affect postoperative AKI risk. Because it is less invasive than SAVR, TAVR may be preferred in high-risk individuals.

Rituximab for Non-Hodgkin's Lymphoma: A Story of Rapid Success in Translation

Translational stories range from straightforward to complex. In this commentary, the story of the rapid and successful translation of rituximab therapy for the treatment of non‐Hodgkins lymphoma (NHL) is examined. Development of this monoclonal antibody therapy began in the late 1980s. In 1994, rituximab received its first approval for the treatment of NHL by the United States Food and Drug Administration (FDA). Rituximab has since been approved for additional indications and has transformed medical practice. However, the social and political implications of these rapid successes are only beginning to become clear. In this commentary, key events in the rapid translation of rituximab from the bench to bedside are highlighted and placed into this historical framework. To accomplish this, the story of rituximab is divided into the following six topics, which we believe to be widely applicable to case studies of translation: (1) underlying disease, (2) key basic science, (3) key clinical studies in translation, (4) FDA approval process, (5) changes to medical practice, and (6) the social and political influences on translation.

The Effect of an Electronic Checklist on Critical Care Provider Workload, Errors, and Performance

Purpose: The strategy used to improve effective checklist use in intensive care unit (ICU) setting is essential for checklist success. This study aimed to test the hypothesis that an electronic checklist could reduce ICU provider workload, errors, and time to checklist completion, as compared to a paper checklist. Methods: This was a simulation-based study conducted at an academic tertiary hospital. All participants completed checklists for 6 ICU patients: 3 using an electronic checklist and 3 using an identical paper checklist. In both scenarios, participants had full access to the existing electronic medical record system. The outcomes measured were workload (defined using the National Aeronautics and Space Association task load index [NASA-TLX]), the number of checklist errors, and time to checklist completion. Two independent clinician reviewers, blinded to participant results, served as the reference standard for checklist error calculation. Results: Twenty-one ICU providers participated in this study. This resulted in the generation of 63 simulated electronic checklists and 63 simulated paper checklists. The median NASA-TLX score was 39 for the electronic checklist and 50 for the paper checklist (P = .005). The median number of checklist errors for the electronic checklist was 5, while the median number of checklist errors for the paper checklist was 8 (P = .003). The time to checklist completion was not significantly different between the 2 checklist formats (P = .76). Conclusion: The electronic checklist significantly reduced provider workload and errors without any measurable difference in the amount of time required for checklist completion. This demonstrates that electronic checklists are feasible and desirable in the ICU setting.

Validation of Computerized Automatic Calculation of the Sequential Organ Failure Assessment Score

Purpose. To validate the use of a computer program for the automatic calculation of the sequential organ failure assessment (SOFA) score, as compared to the gold standard of manual chart review. Materials and Methods. Adult admissions (age > 18 years) to the medical ICU with a length of stay greater than 24 hours were studied in the setting of an academic tertiary referral center. A retrospective cross-sectional analysis was performed using a derivation cohort to compare automatic calculation of the SOFA score to the gold standard of manual chart review. After critical appraisal of sources of disagreement, another analysis was performed using an independent validation cohort. Then, a prospective observational analysis was performed using an implementation of this computer program in AWARE Dashboard, which is an existing real-time patient EMR system for use in the ICU. Results. Good agreement between the manual and automatic SOFA calculations was observed for both the derivation (N=94) and validation (N=268) cohorts: 0.02 ± 2.33 and 0.29 ± 1.75 points, respectively. These results were validated in AWARE (N=60). Conclusion. This EMR-based automatic tool accurately calculates SOFA scores and can facilitate ICU decisions without the need for manual data collection. This tool can also be employed in a real-time electronic environment.

Admission hyperuricemia increases the risk of acute kidney injury in hospitalized patients(.).

Background The association between elevated admission serum uric acid (SUA) and risk of in-hospital acute kidney injury (AKI) is limited. The aim of this study was to assess the risk of developing AKI in all hospitalized patients with various admission SUA levels. Methods This is a single-center retrospective study conducted at a tertiary referral hospital. All hospitalized adult patients who had admission SUA available from January 2011 through December 2013 were analyzed in this study. Admission SUA was categorized based on its distribution into six groups (<3.4, 3.4–4.5, 4.5–5.8, 5.8–7.6, 7.6–9.4 and >9.4 mg/dL). The primary outcome was in-hospital AKI occurring after hospital admission. Logistic regression analysis was performed to obtain the odds ratio (OR) of AKI of various admission SUA levels using the most common SUA level range (5.8–7.6 mg/dL) as the reference group. Results Of 1435 patients enrolled, AKI occurred in 263 patients (18%). The incidence of AKI and need for dialysis was increased in patients with higher admission SUA levels. After adjusting for potential confounders, SUA >9.4 mg/dL was associated with an increased risk of developing AKI, with ORs of 1.79 [95% confidence interval (CI) 1.13–2.82]. Conversely, admission SUA <3.4 and 3.4–4.5 mg/dL were associated with a decreased risk of developing AKI, with ORs of 0.38 (95% CI 0.17–0.75) and 0.50 (95% CI 0.28–0.87), respectively. Conclusions Elevated admission SUA was associated with an increased risk for in-hospital AKI.

Sodium Correction Practice and Clinical Outcomes in Profound Hyponatremia

OBJECTIVES To assess the epidemiology of nonoptimal hyponatremia correction and to identify associated morbidity and in-hospital mortality. PATIENTS AND METHODS An electronic medical record search identified all patients admitted with profound hyponatremia (sodium <120 mmol/L) from January 1, 2008, through December 31, 2012. Patients were classified as having optimally or nonoptimally corrected hyponatremia at 24 hours after admission. Optimal correction was defined as sodium correction in 24 hours of 6 through 10 mmol/L. We investigated the association between sodium correction and demographic and outcome variables, including occurrence of osmotic demyelination syndrome (ODS). Baseline characteristics by correction outcome categories were compared using the Kruskal-Wallis test for continuous variables and the χ(2) test for categorical variables. Odds ratios for in-hospital mortality between groups were assessed using logistic regression. Adjusted differences in hospital length of stay (LOS) and intensive care unit (ICU) LOS were assessed using the Dunnett 2-tailed t test. RESULTS A total of 412 patients satisfied inclusion criteria of whom 174 (42.2%) were admitted to the ICU. A total of 211 (51.2%) had optimal correction of their hyponatremia at 24 hours, 87 (21.1%) had undercorrected hyponatremia, and 114 (27.9%) had overcorrected hyponatremia. Both patient factors and treatment factors were associated with nonoptimal correction. There was a single case of ODS. Overcorrection was not associated with in-hospital mortality or ICU LOS. When adjusted for patient factors, undercorrection of profound hyponatremia was associated with an increase in hospital LOS (9.3 days; 95% CI, 1.9-16.7 days). CONCLUSION Nonoptimal correction of profound hyponatremia is common. Fortunately, nonoptimal correction is associated with serious morbidity only infrequently.

Improving the accuracy of cardiovascular component of the sequential organ failure assessment score

Objectives:The Sequential Organ Failure Assessment score is an attractive risk prediction model because of its simplicity and graded assessment of morbidity and mortality. Due to changes in clinical practice over time, the cardiovascular component of the Sequential Organ Failure Assessment score no longer accurately reflects current clinical practice. To address this limitation, we developed and validated a modified cardiovascular component of the Sequential Organ Failure Assessment score that takes into account all vasoactive agents used in current clinical practice, uses shock index as a substitute for mean arterial pressure, and incorporates serum lactate as a biomarker for shock states. Design:Retrospective cohort. Setting:Mayo Clinic, Rochester, MN. Patients:Adult patients admitted to one of six ICUs. Interventions:None. Measurements and Main Results:Score performance was assessed via area under the receiver operator characteristic curve. A total of 16,386 ICU admissions were included: 9,204 in the derivation cohort and 7,182 in the validation cohort. area under the receiver operator characteristic curve was significantly higher for modified cardiovascular component of the Sequential Organ Failure Assessment score than for cardiovascular component of the Sequential Organ Failure Assessment for in-ICU mortality (0.801 vs 0.718; difference = 0.083; p < 0.001), in-hospital mortality (0.783 vs 0.651; difference = 0.132; p < 0.001), and 28-day mortality (0.737 vs 0.655; difference = 0.082; p < 0.001). When modified cardiovascular component of the Sequential Organ Failure Assessment score was added to the remaining Sequential Organ Failure Assessment components, the modified Sequential Organ Failure Assessment score again outperformed the existing Sequential Organ Failure Assessment score: in-ICU mortality (0.836 vs 0.822; difference = 0.014; p < 0.001), in-hospital mortality (0.799 vs 0.784; difference = 0.015; p < 0.001), and 28-day mortality (0.798 vs 0.783; difference = 0.015; p < 0.001). Similar results were seen in the validation cohort. Conclusions:The modified cardiovascular component of the Sequential Organ Failure Assessment score outperforms the existing cardiovascular component of the Sequential Organ Failure Assessment score in predicting patient outcomes and improves the overall performance of the Sequential Organ Failure Assessment model. This score is easily calculated, includes serum lactate as a biomarker for shock states, and incorporates all vasopressors used in current clinical practice.

Persistent acute kidney injury following transcatheter aortic valve replacement

Acute kidney injury (AKI) and its severity after transcatheter aortic valve replacement (TAVR) have been associated with worse outcomes. Studies have shown that AKI duration (transient or persistent) affects outcomes independently of AKI severity. This study was undertaken to determine the association, risk factors, and outcomes associated with persistent AKI (pAKI) after TAVR.

Lessons learned from an unusual case of inflammatory breast cancer.

Inflammatory breast cancer (IBC) is a rare breast malignancy that is associated with poor long-term outcomes despite aggressive surgical and chemotherapeutic interventions. We recently treated a 56-year-old woman with right-sided IBC and biopsy-proven cutaneous metastases to her back and left breast. She underwent chemotherapy, bilateral modified radical mastectomy, and radiation therapy. One year after diagnosis, she is currently disease-free based on positron-emission tomography (PET) imaging and repeat skin biopsies. To provide insight into the management of IBC, we present this interesting case with a reflection on important lessons to be learned.