Publications by authors named "Andrew M Harrison"

29 Publications

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A nationwide assessment of perceptions of research-intense academic careers among predoctoral MD and MD-PhD trainees.

J Clin Transl Sci 2020 Mar 4;4(4):307-316. Epub 2020 Mar 4.

American Physician Scientists Association (APSA), Westford, MA, USA.

Introduction: While previous studies have described career outcomes of physician-scientist trainees after graduation, trainee perceptions of research-intensive career pathways remain unclear. This study sought to identify the perceived interests, factors, and challenges associated with academic and research careers among predoctoral MD trainees, MD trainees with research-intense (>50%) career intentions (MD-RI), and MD-PhD trainees.

Methods: A 70-question survey was administered to 16,418 trainees at 32 academic medical centers from September 2012 to December 2014. MD vs. MD-RI (>50% research intentions) vs. MD-PhD trainee responses were compared by chi-square tests. Multivariate logistic regression analyses were performed to identify variables associated with academic and research career intentions.

Results: There were 4433 respondents (27% response rate), including 2625 MD (64%), 653 MD-RI (15%), and 856 MD-PhD (21%) trainees. MD-PhDs were most interested in pursuing academia (85.8%), followed by MD-RIs (57.3%) and MDs (31.2%). Translational research was the primary career intention for MD-PhD trainees (42.9%). Clinical duties were the primary career intention for MD-RIs (51.9%) and MDs (84.2%). While 39.8% of MD-PhD respondents identified opportunities for research as the most important career selection factor, only 12.9% of MD-RI and 0.5% of MD respondents shared this perspective. Interest in basic research, translational research, clinical research, education, and the ability to identify a mentor were each independently associated with academic career intentions by multivariate regression.

Conclusions: Predoctoral MD, MD-RI, and MD-PhD trainees are unique cohorts with different perceptions and interests toward academic and research careers. Understanding these differences may help to guide efforts to mentor the next generation of physician-scientists.
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http://dx.doi.org/10.1017/cts.2020.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681110PMC
March 2020

Febuxostat as a renoprotective agent for treatment of hyperuricaemia: a meta-analysis of randomised controlled trials.

Intern Med J 2021 May;51(5):752-762

Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.

Background: The objective of this meta-analysis of randomised controlled clinical trials (RCT) was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia.

Aims: Febuxostat is a xanthine oxidase inhibitor that decreases uric acid production. Recent studies suggested the renoprotective effect of febuxostat among hyperuricaemia patients. The aim of this study was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia.

Methods: We conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to July 2019 to identify RCT that examined the effects of febuxostat in adult patients with hyperuricaemia on serum creatinine, estimated glomerular filtration rate (eGFR), albuminuria, blood pressure parameters, major cardiovascular events, diarrhoea, joint pain, stroke and arrhythmia.

Results: Nine RCT with 2141 participants were included in this meta-analysis. Compared to placebo, the febuxostat group showed a higher eGFR at 6 months with a weighted mean difference (WMD) of 2.86 mL/min/1.73 m (P < 0.001), as well as the end of studies (eGFR WMD 2.69 mL/min/1.73 m , P < 0.001). There was also lower serum creatinine (SrCr WMD = -0.04 mg/dL, P < 0.001), reduction in systolic blood pressure (SBP WMD = -1.18 mmHg, P < 0.001) and diastolic blood pressure (DBP WMD = -1.14 mmHg, P = 0.04). There was no statistical difference between febuxostat and placebo in major cardiovascular events, diarrhoea, joint symptoms, stroke events and arrhythmia. Subgroup analysis among chronic kidney disease showed the febuxostat group had higher eGFR than the placebo group (eGFR WMD = 2.69 mL/min/1.73 m , P < 0.001).

Conclusion: Treating hyperuricaemia with febuxostat may slow the progression of chronic kidney disease irrespective of baseline renal function without significantly associated increased risks of major cardiovascular events, diarrhoea, joint symptoms, arrhythmia and stroke, compared to placebo.
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http://dx.doi.org/10.1111/imj.14814DOI Listing
May 2021

Rate of kidney function decline and factors predicting progression of kidney disease in type 2 diabetes mellitus patients with reduced kidney function: A nationwide retrospective cohort study.

Ther Apher Dial 2020 Dec 6;24(6):677-687. Epub 2020 Mar 6.

Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi.

Currently, the data on independent risk factors for the progression of kidney disease in type 2 diabetes mellitus (T2DM) patients with CKD are limited. This study aimed to investigate CKD progression in T2DM patients who have reduced kidney function with baseline estimated glomerular filtration rate (eGFRs) between 15 and 59 mL/min/1.73 m . This study was composed of a nationwide retrospective cohort of adult T2DM patients from 831 public hospitals in Thailand during the year 2015. T2DM patients with CKD stages 3 and 4 were followed up, until development of CKD stage 5, requirement of chronic dialysis, loss to follow-up, death, or 31 May 2018, whichever came first. Cox proportional hazard regression was utilized for analysis. A total of 8464 participants were included; 30.4% were male. The mean age was 69 ± 10 years. The mean eGFR was 45 ± 11 mL/min/1.73 m . The incidence of CKD stage 5 or the need for chronic dialysis was 16.4 per 1000 person-years. The annual rate of eGFR decline during a mean follow-up of 29 months was -2.3 mL/min/1.73 m ; 14.4% had a rapid decline in eGFR. The risk factors associated with progression to CKD stage 5 or the need for chronic dialysis were diabetes duration, systolic blood pressure, serum uric acid, albuminuria, and baseline eGFR. Conversely, older age and the use of renin-angiotensin aldosterone system blockade were associated with decreased risks for rapid CKD progression and incidence CKD stage 5 or dialysis. This study identifies multiple predictive risk factors that support a multifaceted approach to prevent progression of advanced CKD.
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http://dx.doi.org/10.1111/1744-9987.13480DOI Listing
December 2020

Clinical impact of intraoperative electronic health record downtime on surgical patients.

J Am Med Inform Assoc 2019 10;26(10):928-933

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Objective: Despite increased use of electronic health records (EHRs), the clinical impact of system downtime is unknown.

Materials And Methods: This retrospective matched cohort study evaluated the impact of EHR downtime episodes lasting more than 60 minutes over a 6-year study period. Patients age 18 years or older who underwent surgical procedures at least 60 minutes in duration with an inpatient stay exceeding 24 hours within the study period were eligible for inclusion. Out of 4115 patients exposed to 1 of 176 EHR downtime episodes, 4103 patients were matched to an unexposed cohort in a 1:1 ratio. Multivariable regression analysis, as well as trend analysis for effect of duration of downtime on outcomes, was performed.

Results: Downtime-exposed patients had operating room duration 1.1 times longer (p < .001) and postoperative length of stay 1.04 times longer (p = .007) compared to unexposed patients. The 30-day mortality rates were similar between these groups (odds ratio 1.26, p > .05). In trend analysis, there was no association between duration of downtime with respect to evaluated outcomes, postoperative length of stay, and 30-day mortality.

Conclusion: EHR downtime had no impact on 30-day mortality. Potential associations for increased postoperative length of stay and duration of time spent in the operating room were observed among downtime-exposed patients. No trend effect was observed with respect to duration of downtime and postoperative length of stay and 30-day mortality rates.
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http://dx.doi.org/10.1093/jamia/ocz029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647211PMC
October 2019

Elevated admission serum calcium phosphate product as an independent risk factor for acute kidney injury in hospitalized patients.

Hosp Pract (1995) 2019 Apr 21;47(2):73-79. Epub 2019 Jan 21.

a Division of Nephrology and Hypertension, Department of Medicine , Mayo Clinic , Rochester , MN , USA.

Background: Increased serum calcium-phosphate product (CaP) can result in acute kidney injury (AKI) due to tubular and interstitial calcium phosphate deposits. CaP of > 55 mg/dL is also associated with systemic calcification. However, the risk of AKI development among hospitalized patients with different admission calcium-phosphate product levels remains unclear.

Methods: All adult hospitalized patients who had both admission serum calcium and phosphate levels available from 2009 through 2013 were enrolled. Admission CaP was categorized based on its distribution into six groups (<22, 22- < 27, 27- < 32, 32- < 37, 37- < 42 and ≥42 mg/dL). The odds ratio (OR) of in-hospital mortality by admission CaP, using the CaP category of < 22 mg/dL as the reference group, was obtained by logistic regression analysis.

Results: After excluding patients with end-stage renal disease, without serum creatinine measurement, and those who presented with AKI at the time of admission, a total of 9,864 patients were studied. In-hospital AKI occurred in 1,478 patients (15.0%). The incidence of AKI among patients with admission CaP < 22, 22 to < 27, 27 to < 32, 32 to < 37, 37 to < 42, and ≥42 mg/dL was 11.1%, 12.4%, 14.9%, 15.2%, 17.5%, and 19.9%, respectively. After adjusting for potential confounders, a CaP ≥37 mg/dL was associated with an increased risk of developing AKI with OR of 1.53 (CI 1.19-1.96) and 1.63 (CI 1.25-2.14) in patients with admission CaP 37- < 42 and ≥42, respectively. Subgroup analysis based on eGFR consistently demonstrated that CaP ≥37 mg/dL was associated with an increased risk of developing AKI in both chronic kidney disease (CKD) and non-CKD patients.

Conclusion: Elevated admission CaP was independently associated with an increased risk for in-hospital AKI.
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http://dx.doi.org/10.1080/21548331.2019.1568719DOI Listing
April 2019

Implementation of a New Guideline and Educational Sessions to Reduce Low-Value Continuous Pulse Oximetry Among Hospitalized Patients.

South Med J 2018 02;111(2):87-92

From the Departments of Internal Medicine, Medical Scientist Training Program, and Nursing Administration, Mayo Clinic, Jacksonville, Florida.

Objectives: The use of continuous pulse oximetry (CPOX) is ubiquitous among hospitalized patients, despite limited evidence that it improves clinical outcomes. The objective of this study was to reduce the use of CPOX among hospitalized patients in the nonintensive care unit and nonprogressive care unit settings.

Methods: This interventional trial included the creation a new local guideline for CPOX use and subsequent staff education. CPOX use, patient acuity, hospital length of stay, and code blue events were measured before and after the intervention.

Results: Postintervention there was a clinically significant and sustained decrease in CPOX use of 18% over 1 year. There were no significant changes postintervention in hospital length of stay or number of code blue events.

Conclusions: Development of a guideline for CPOX use and staff education successfully led to a decrease in CPOX use, without an increase in hospital length of stay or code blue events.
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http://dx.doi.org/10.14423/SMJ.0000000000000766DOI Listing
February 2018

Persistent acute kidney injury following transcatheter aortic valve replacement.

J Card Surg 2017 Sep 22;32(9):550-555. Epub 2017 Aug 22.

Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota.

Background: 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.

Methods: Adult patients undergoing TAVR at Mayo Clinic between January 1, 2008 and June 30, 2014 were enrolled. pAKI was defined as an increased serum creatinine at hospital discharge (≥0.3 mg/dL or ≥50% from baseline). Risk factors associated with pAKI were identified with multivariate logistic regression.

Results: A total of 386 patients met the inclusion criteria. Fifty patients (13%) had pAKI. Independent risk factors for pAKI on multivariate analysis included diabetes mellitus (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.29-4.66), prior percutaneous coronary intervention (PCI) (OR, 2.39; 95%CI, 1.24-4.80), intra-aortic balloon pump (IABP) use (OR, 8.14; 95%CI, 1.60-45.78), and blood transfusion (OR, 2.22; 95%CI, 1.15-4.27). Protective factors for pAKI included a higher baseline estimated glomerular filtration rate (eGFR) (OR, 0.83 per 10-mL/min/1.73 m increase in eGFR; 95%CI, 0.71-0.99). After adjusting for the Society of Thoracic Surgeons cardiac surgery risk score, pAKI occurrence remained significantly associated with increased 2-year mortality among hospital survivors (hazard ratio, 2.65; 95%CI, 1.51-4.41).

Conclusion: pAKI was significantly associated with higher mortality risk following TAVR. Baseline eGFR, diabetes mellitus, previous PCI, IABP, and blood transfusion were risk factors for post-procedural pAKI.
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http://dx.doi.org/10.1111/jocs.13200DOI Listing
September 2017

Medical Students Call for Single-Payer National Health Insurance.

Acad Med 2017 06;92(6):735

Year 7 student, Medical Scientist Training Program, Mayo Clinic, Rochester, Minnesota;

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http://dx.doi.org/10.1097/ACM.0000000000001699DOI Listing
June 2017

Comparison of methods of alert acknowledgement by critical care clinicians in the ICU setting.

PeerJ 2017 14;5:e3083. Epub 2017 Mar 14.

Department of Anesthesiology, Mayo Clinic , Rochester , MN , United States of America.

Background: Electronic Health Record (EHR)-based sepsis alert systems have failed to demonstrate improvements in clinically meaningful endpoints. However, the effect of implementation barriers on the success of new sepsis alert systems is rarely explored.

Objective: To test the hypothesis time to severe sepsis alert acknowledgement by critical care clinicians in the ICU setting would be reduced using an EHR-based alert acknowledgement system compared to a text paging-based system.

Study Design: In one arm of this simulation study, real alerts for patients in the medical ICU were delivered to critical care clinicians through the EHR. In the other arm, simulated alerts were delivered through text paging. The primary outcome was time to alert acknowledgement. The secondary outcomes were a structured, mixed quantitative/qualitative survey and informal group interview.

Results: The alert acknowledgement rate from the severe sepsis alert system was 3% ( = 148) and 51% ( = 156) from simulated severe sepsis alerts through traditional text paging. Time to alert acknowledgement from the severe sepsis alert system was median 274 min ( = 5) and median 2 min ( = 80) from text paging. The response rate from the EHR-based alert system was insufficient to compare primary measures. However, secondary measures revealed important barriers.

Conclusion: Alert fatigue, interruption, human error, and information overload are barriers to alert and simulation studies in the ICU setting.
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http://dx.doi.org/10.7717/peerj.3083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354075PMC
March 2017

Prognostic Importance of Low Admission Serum Creatinine Concentration for Mortality in Hospitalized Patients.

Am J Med 2017 May 18;130(5):545-554.e1. Epub 2016 Dec 18.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minn; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minn. Electronic address:

Objective: The study objective was to assess the association between low serum creatinine value at admission and in-hospital mortality in hospitalized patients.

Methods: This was a retrospective single-center cohort study conducted at a tertiary referral hospital. All hospitalized adult patients between 2011 and 2013 who had an admission creatinine value available were identified for inclusion in this study. Admission creatinine value was categorized into 7 groups: ≤0.4, 0.5 to 0.6, 0.7 to 0.8, 0.9 to 1.0, 1.1 to 1.2, 1.3 to 1.4, and ≥1.5 mg/dL. The primary outcome was in-hospital mortality. Logistic regression analysis was performed to obtain the odds ratio of in-hospital mortality for the various admission creatinine levels, using a creatinine value of 0.7 to 0.8 mg/dL as the reference group in the analysis of all patients and female patients and of 0.9 to 1.0 mg/dL in the analysis of male patients because it was associated with the lowest in-hospital mortality.

Results: Of 73,994 included patients, 973 (1.3%) died in the hospital. The association between different categories of admission creatinine value and in-hospital mortality assumed a U-shaped distribution, with both low and high creatinine values associated with higher in-hospital mortality. After adjustment for age, sex, ethnicity, principal diagnosis, and comorbid conditions, very low creatinine value (≤0.4 mg/dL) was significantly associated with increased mortality (odds ratio, 3.29; 95% confidence interval, 2.08-5.00), exceeding the risk related to a markedly increased creatinine value of ≥1.5 mg/dL (odds ratio, 2.56; 95% confidence interval, 2.07-3.17). The association remained significant in the subgroup analysis of male and female patients.

Conclusions: Low creatinine value at admission is independently associated with increased in-hospital mortality in hospitalized patients.
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http://dx.doi.org/10.1016/j.amjmed.2016.11.020DOI Listing
May 2017

Testing modes of computerized sepsis alert notification delivery systems.

BMC Med Inform Decis Mak 2016 12 9;16(1):156. Epub 2016 Dec 9.

Department of Anesthesiology, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA.

Background: The number of electronic health record (EHR)-based notifications continues to rise. One common method to deliver urgent and emergent notifications (alerts) is paging. Despite of wide presence of smartphones, the use of these devices for secure alerting remains a relatively new phenomenon.

Methods: We compared three methods of alert delivery (pagers, EHR-based notifications, and smartphones) to determine the best method of urgent alerting in the intensive care unit (ICU) setting. ICU clinicians received randomized automated sepsis alerts: pager, EHR-based notification, or a personal smartphone/tablet device. Time to notification acknowledgement, fatigue measurement, and user preferences (structured survey) were studied.

Results: Twenty three clinicians participated over the course of 3 months. A total of 48 randomized sepsis alerts were generated for 46 unique patients. Although all alerts were acknowledged, the primary outcome was confounded by technical failure of alert delivery in the smartphone/tablet arm. Median time to acknowledgment of urgent alerts was shorter by pager (102 mins) than EHR (169 mins). Secondary outcomes of fatigue measurement and user preference did not demonstrate significant differences between these notification delivery study arms.

Conclusions: Technical failure of secure smartphone/tablet alert delivery presents a barrier to testing the optimal method of urgent alert delivery in the ICU setting. Results from fatigue evaluation and user preferences for alert delivery methods were similar in all arms. Further investigation is thus necessary to understand human and technical barriers to implementation of commonplace modern technology in the hospital setting.
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http://dx.doi.org/10.1186/s12911-016-0396-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5148853PMC
December 2016

Transapical versus transfemoral approach and risk of acute kidney injury following transcatheter aortic valve replacement: a propensity-adjusted analysis.

Ren Fail 2017 Nov 21;39(1):13-18. Epub 2016 Oct 21.

a Department of Internal Medicine, Division of Nephrology and Hypertension , Mayo Clinic , Rochester , MN , USA.

Background: The aim of this study was to compare the incidence of post-procedural acute kidney injury (AKI) and other renal outcomes in patients undergoing transapical (TA) and transfemoral (TF) approaches for transcatheter aortic valve replacement (TAVR).

Methods: All consecutive adult patients undergoing TAVR for aortic stenosis from 1 January 2008 to 30 June 2014 at a tertiary referral hospital were included. AKI was defined based on Kidney Disease Improving Global Outcomes (KDIGO) criteria. Logistic regression adjustment, propensity score stratification, and propensity matching were performed to assess the independent association between procedural approach and AKI.

Results: Of 366 included patients, 171 (47%) underwent TAVR via a TA approach. AKI occurrence in this group was significantly higher compared to the TF group (38% vs. 18%, p < .01). The TA approach remained significantly associated with increased risk of AKI after logistic regression (OR 3.20; CI 1.68-4.36) and propensity score adjustment: OR 2.83 (CI 1.66-4.80) for stratification and 3.82 (CI 2.04-7.44) for matching. Nonetheless, there was no statistically significant difference among the TA and TF groups with respect to major adverse kidney events (MAKE) or estimated glomerular filtration rate (eGFR) at six months post-procedure.

Conclusion: In a cohort of patients undergoing TAVR for aortic stenosis, a TA approach significantly increases the AKI risk compared with a TF approach. However, the TAVR approach did not affect severe renal outcomes or long-term renal function.
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http://dx.doi.org/10.1080/0886022X.2016.1244072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014512PMC
November 2017

Development and Implementation of Sepsis Alert Systems.

Clin Chest Med 2016 06 20;37(2):219-29. Epub 2016 Feb 20.

Department of Anesthesiology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA. Electronic address:

Development and implementation of sepsis alert systems is challenging, particularly outside the monitored intensive care unit (ICU) setting. Barriers to wider use of sepsis alerts include evolving clinical definitions of sepsis, information overload, and alert fatigue, due to suboptimal alert performance. Outside the ICU, barriers include differences in health care delivery models, charting behaviors, and availability of electronic data. Current evidence does not support routine use of sepsis alert systems in clinical practice. Continuous improvement in the afferent and efferent aspects will help translate theoretic advantages into measurable patient benefit.
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http://dx.doi.org/10.1016/j.ccm.2016.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884325PMC
June 2016

Temporal trends in the utilization of vasopressors in intensive care units: an epidemiologic study.

BMC Pharmacol Toxicol 2016 05 7;17(1):19. Epub 2016 May 7.

Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Background: The choice of vasopressor use in the intensive care unit (ICU) depends primarily on provider preference. This study aims to describe the rate of vasopressor utilization and the trends of each vasoactive agent usage in the ICU over the span of 7 years in a tertiary referral center.

Methods: All adult ICU admissions, including medical, cardiac, and surgical ICUs from January 1st, 2007 through December 31st, 2013 were included in this study. Vasopressor use was defined as the continuous intravenous administration of epinephrine, norepinephrine, phenylephrine, dopamine, or vasopressin within a given ICU day. The vasopressor utilization index (VUI) was defined as the proportion of ICU days on each vasoactive agent divided by the total ICU days with vasopressor usage.

Results: During the study period, 72,005 ICU admissions and 272,271 ICU days were screened. Vasopressors were used in 19,575 ICU admissions (27 %) and 59,811 ICU days (22 %). Vasopressin was used in 24,496 (41 %), epinephrine in 23,229 (39 %), norepinephrine in 20,648 (34 %), dopamine in 9449 (16 %), and phenylephrine in 7508 (13 %) ICU days. The VUInorepinephrine increased from 0.24 in 2007 to 0.46 in 2013 and VUIphenylephrine decreased from 0.20 in 2007 to 0.08 in 2013 (p < 0.001 both). For epinephrine, dopamine, and vasopressin VUI did not change over the course of study.

Conclusion: Vasopressors were used in about one fourth of ICU admissions and about one-fifth of ICU days. Although vasopressin is the most commonly used vasopressor, the use of norepinephrine found to have an increasing trajectory.
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http://dx.doi.org/10.1186/s40360-016-0063-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859949PMC
May 2016

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

Clin Kidney J 2016 Feb 9;9(1):51-6. Epub 2015 Sep 9.

Division of Nephrology and Hypertension, Department of Medicine , Mayo Clinic , Rochester, MA , USA.

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.
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http://dx.doi.org/10.1093/ckj/sfv086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720187PMC
February 2016

The comparison of the commonly used surrogates for baseline renal function in acute kidney injury diagnosis and staging.

BMC Nephrol 2016 Jan 9;17. Epub 2016 Jan 9.

Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Background: Baseline serum creatinine (SCr) level is frequently not measured in clinical practice. The aim of this study was to investigate the effect of various methods of baseline SCr determination measurement on accuracy of acute kidney injury (AKI) diagnosis in critically ill patients.

Methods: This was a retrospective cohort study. All adult intensive care unit (ICU) patients admitted at a tertiary referral hospital from January 1, 2011 through December 31, 2011, with at least one measured SCr value during ICU stay, were included in this study. The baseline SCr was considered either an admission SCr (SCrADM) or an estimated SCr, using MDRD formula, based on an assumed glomerular filtration rate (GFR) of 75 ml/min/1.73 m(2) (SCrGFR-75). Determination of AKI was based on the KDIGO SCr criterion. Propensity score to predict the likelihood of missing SCr was used to generate a simulated cohort of 3566 patients with baseline outpatient SCr, who had similar characteristics with patients whose outpatient SCr was not available.

Results: Of 7772 patients, 3504 (45.1 %) did not have baseline outpatient SCr. Among patients without baseline outpatient SCr, AKI was detected in 571 (16.3 %) using the SCrADM and 997 (28.4 %) using SCrGFR-75 (p < .001). Compared with non-AKI patients, patients who met AKI only by SCrADM, but not SCrGFR-75, were significantly associated with 60-day mortality (OR 2.90; 95 % CI 1.66-4.87), whereas patients who met AKI only by SCrGFR-75, but not SCrADM, had a non-significant increase in 60-day mortality risk (OR 1.33; 95 % CI 0.94-1.88). In a simulated cohort of patients with baseline outpatient SCr, SCrGFR-75 yielded a higher sensitivity (77.2 vs. 50.5 %) and lower specificity (87.8 vs. 94.8 %) for the AKI diagnosis in comparison with SCrADM.

Conclusions: When baseline outpatient SCr was not available, using SCrGFR-75 as surrogate for baseline SCr was found to be more sensitive but less specific for AKI diagnosis compared with using SCrADM. This resulted in higher incidence of AKI with larger likelihood of false-positive cases.
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http://dx.doi.org/10.1186/s12882-016-0220-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707008PMC
January 2016

Systematic Review of the Use of Phytochemicals for Management of Pain in Cancer Therapy.

Biomed Res Int 2015 20;2015:506327. Epub 2015 Oct 20.

Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA.

Pain in cancer therapy is a common condition and there is a need for new options in therapeutic management. While phytochemicals have been proposed as one pain management solution, knowledge of their utility is limited. The objective of this study was to perform a systematic review of the biomedical literature for the use of phytochemicals for management of cancer therapy pain in human subjects. Of an initial database search of 1,603 abstracts, 32 full-text articles were eligible for further assessment. Only 7 of these articles met all inclusion criteria for this systematic review. The average relative risk of phytochemical versus control was 1.03 [95% CI 0.59 to 2.06]. In other words (although not statistically significant), patients treated with phytochemicals were slightly more likely than patients treated with control to obtain successful management of pain in cancer therapy. We identified a lack of quality research literature on this subject and thus were unable to demonstrate a clear therapeutic benefit for either general or specific use of phytochemicals in the management of cancer pain. This lack of data is especially apparent for psychotropic phytochemicals, such as the Cannabis plant (marijuana). Additional implications of our findings are also explored.
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http://dx.doi.org/10.1155/2015/506327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630373PMC
August 2016

AKI after Transcatheter or Surgical Aortic Valve Replacement.

J Am Soc Nephrol 2016 06 20;27(6):1854-60. Epub 2015 Oct 20.

Division of Nephrology and Hypertension, Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine,

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.
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http://dx.doi.org/10.1681/ASN.2015050577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884118PMC
June 2016

Sodium Correction Practice and Clinical Outcomes in Profound Hyponatremia.

Mayo Clin Proc 2015 Oct;90(10):1348-55

Multidisciplinary Epidemiology and Translational Research in Intensive Care, Mayo Clinic, Rochester, MN; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.

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.
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http://dx.doi.org/10.1016/j.mayocp.2015.07.014DOI Listing
October 2015

Automated Sepsis Detection, Alert, and Clinical Decision Support: Act on It or Silence the Alarm?

Crit Care Med 2015 Aug;43(8):1776-7

Medical Scientist Training Program, Mayo Graduate School, Mayo Clinic, Rochester, MN Department of Anesthesiology, Mayo Clinic, Rochester, MN Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1097/CCM.0000000000001099DOI Listing
August 2015

Improving the Accuracy of Cardiovascular Component of the Sequential Organ Failure Assessment Score.

Crit Care Med 2015 Jul;43(7):1449-57

1Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN. 2Department of Anesthesiology, Multidisciplinary Epidemiology and Translational Research in Intensive Care (METRIC), Mayo Clinic, Rochester, MN. 3Mayo School of Graduate Medical Education, Medical Scientist Training Program, Mayo Clinic, Rochester, MN. 4Department of Anesthesiology, Mayo Clinic, Rochester, MN.

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.
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http://dx.doi.org/10.1097/CCM.0000000000000929DOI Listing
July 2015

Agreement between whole blood and plasma sodium measurements in profound hyponatremia.

Clin Biochem 2015 May 13;48(7-8):525-8. Epub 2015 Mar 13.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

Objectives: We compared two different methods of whole blood sodium measurement to plasma sodium measurement using samples in the profoundly hyponatremic range (Na < 120 mmol/L).

Design And Methods: Whole blood pools with a range of low sodium values were generated using combinations and dilutions of pooled electrolyte-balanced lithium heparin samples submitted for arterial blood gas analysis. Each pool was analyzed five times on a Radiometer 827 blood gas analyzer and iSTAT analyzer. Pools were centrifuged to produce plasma, which was analyzed five times on a Roche Cobas c501 chemistry analyzer. An additional 40 fresh (analyzed on day of collection) excess lithium heparin arterial blood gas samples from 36 patients were analyzed on the Radiometer 827, iSTAT, and Cobas c501 as described above. The setting was a tertiary referral center. Blood samples were collected from a combination of patients in the intensive care unit, operating theaters and emergency room.

Results: All methods demonstrated excellent precision, even in the profoundly hyponatremic measurement range (Na < 120 mmol/L using a plasma reference method). However, agreement between the methods varied with the degree of hyponatremia. In the profoundly hyponatremic range, Radiometer whole blood sodium values were nearly identical to plasma reference sodium, while iSTAT whole blood sodium showed a consistent positive bias relative to plasma sodium in this range.

Conclusion: If whole blood direct sodium measurements are compared with plasma sodium in profoundly hyponatremic patients consideration should be given to the use of Radiometer blood gas analyzers over iSTAT since the latter shows a positive bias relative to a plasma comparative method.
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http://dx.doi.org/10.1016/j.clinbiochem.2015.03.001DOI Listing
May 2015

Developing the surveillance algorithm for detection of failure to recognize and treat severe sepsis.

Mayo Clin Proc 2015 Feb 6;90(2):166-75. Epub 2015 Jan 6.

Multidisciplinary Epidemiology and Translational Research in Intensive Care, Mayo Clinic, Rochester MN; Department of Anesthesiology, Mayo Clinic, Rochester MN. Electronic address:

Objective: To develop and test an automated surveillance algorithm (sepsis "sniffer") for the detection of severe sepsis and monitoring failure to recognize and treat severe sepsis in a timely manner.

Patients And Methods: We conducted an observational diagnostic performance study using independent derivation and validation cohorts from an electronic medical record database of the medical intensive care unit (ICU) of a tertiary referral center. All patients aged 18 years and older who were admitted to the medical ICU from January 1 through March 31, 2013 (N=587), were included. The criterion standard for severe sepsis/septic shock was manual review by 2 trained reviewers with a third superreviewer for cases of interobserver disagreement. Critical appraisal of false-positive and false-negative alerts, along with recursive data partitioning, was performed for algorithm optimization.

Results: An algorithm based on criteria for suspicion of infection, systemic inflammatory response syndrome, organ hypoperfusion and dysfunction, and shock had a sensitivity of 80% and a specificity of 96% when applied to the validation cohort. In order, low systolic blood pressure, systemic inflammatory response syndrome positivity, and suspicion of infection were determined through recursive data partitioning to be of greatest predictive value. Lastly, 117 alert-positive patients (68% of the 171 patients with severe sepsis) had a delay in recognition and treatment, defined as no lactate and central venous pressure measurement within 2 hours of the alert.

Conclusion: The optimized sniffer accurately identified patients with severe sepsis that bedside clinicians failed to recognize and treat in a timely manner.
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http://dx.doi.org/10.1016/j.mayocp.2014.11.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571011PMC
February 2015

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

J Intensive Care Med 2016 Mar 12;31(3):205-12. Epub 2014 Nov 12.

Multidisciplinary Epidemiology and Translational Research in Intensive Care (METRIC), Mayo Clinic, Rochester, MN, USA Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA

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.
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http://dx.doi.org/10.1177/0885066614558015DOI Listing
March 2016

Rituximab for non-Hodgkin's lymphoma: a story of rapid success in translation.

Clin Transl Sci 2014 Feb 3;7(1):82-6. Epub 2013 Oct 3.

Medical Scientist Training Program, Mayo Clinic, Rochester, Minnesota, USA.

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-Hodgkin's 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.
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http://dx.doi.org/10.1111/cts.12111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264563PMC
February 2014

Validation of computerized automatic calculation of the sequential organ failure assessment score.

Crit Care Res Pract 2013 9;2013:975672. Epub 2013 Jul 9.

Medical Scientist Training Program, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA ; Multidisciplinary Epidemiology and Translational Research in Intensive Care (METRIC), Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA.

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.
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http://dx.doi.org/10.1155/2013/975672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722890PMC
August 2013

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

J Cell Biol 2012 Dec 3;199(6):931-49. Epub 2012 Dec 3.

Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA.

The mitotic checkpoint protein Bub1 is essential for embryogenesis and survival of proliferating cells, and bidirectional deviations from its normal level of expression cause chromosome missegregation, aneuploidy, and cancer predisposition in mice. To provide insight into the physiological significance of this critical mitotic regulator at a modular level, we generated Bub1 mutant mice that lack kinase activity using a knockin gene-targeting approach that preserves normal protein abundance. In this paper, we uncover that Bub1 kinase activity integrates attachment error correction and mitotic checkpoint signaling by controlling the localization and activity of Aurora B kinase through phosphorylation of histone H2A at threonine 121. Strikingly, despite substantial chromosome segregation errors and aneuploidization, mice deficient for Bub1 kinase activity do not exhibit increased susceptibility to spontaneous or carcinogen-induced tumorigenesis. These findings provide a unique example of a modular mitotic activity orchestrating two distinct networks that safeguard against whole chromosome instability and reveal the differential importance of distinct aneuploidy-causing Bub1 defects in tumor suppression.
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http://dx.doi.org/10.1083/jcb.201205115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518220PMC
December 2012

Microtubule-depolymerizing kinesin KLP10A restricts the length of the acentrosomal meiotic spindle in Drosophila females.

Genetics 2012 Oct 3;192(2):431-40. Epub 2012 Aug 3.

Waksman Institute, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA.

During cell division, a bipolar array of microtubules forms the spindle through which the forces required for chromosome segregation are transmitted. Interestingly, the spindle as a whole is stable enough to support these forces even though it is composed of dynamic microtubules, which are constantly undergoing periods of growth and shrinkage. Indeed, the regulation of microtubule dynamics is essential to the integrity and function of the spindle. We show here that a member of an important class of microtubule-depolymerizing kinesins, KLP10A, is required for the proper organization of the acentrosomal meiotic spindle in Drosophila melanogaster oocytes. In the absence of KLP10A, microtubule length is not controlled, resulting in extraordinarily long and disorganized spindles. In addition, the interactions between chromosomes and spindle microtubules are disturbed and can result in the loss of contact. These results indicate that the regulation of microtubule dynamics through KLP10A plays a critical role in restricting the length and maintaining bipolarity of the acentrosomal meiotic spindle and in promoting the contacts that the chromosomes make with microtubules required for meiosis I segregation.
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http://dx.doi.org/10.1534/genetics.112.143503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3454874PMC
October 2012

Lessons learned from an unusual case of inflammatory breast cancer.

J Surg Educ 2012 May-Jun;69(3):350-4

Mayo Medical School, Mayo Clinic, Rochester, Minnesota 55905, USA.

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.
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http://dx.doi.org/10.1016/j.jsurg.2011.10.016DOI Listing
August 2012