Publications by authors named "Felicity T Enders"

83 Publications

Chemical Characterization and Quantification of Circulating Intact PTH and PTH Fragments by High-Resolution Mass Spectrometry in Chronic Renal Failure.

Clin Chem 2021 Mar 6. Epub 2021 Mar 6.

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

Background: The precise concentrations of full-length parathyroid hormone (PTH1-84) and the identity and concentrations of PTH fragments in patients with various stages of chronic renal failure are unknown.

Methods: We developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to characterize and quantify PTH1-84 and PTH fragments in serum of 221 patients with progressive renal dysfunction. Following capture by matrix-bound amino-terminal or carboxyl-terminal region-specific antibodies and elution from matrix, PTH1-84 and PTH fragments were identified and quantitated using LC-HRMS. PTH was simultaneously measured using an intact PTH (iPTH) immunoassay.

Results: Full-length PTH1-84 and 8 PTH fragments (PTH28-84, 34-77, 34-84, 37-77, 37-84, 38-77, 38-84, and 45-84) were unequivocally identified and were shown to increase significantly when an eGFR declined to ≤17-23 mL/min/1.73m2. Serum concentrations of PTH1-84 were similar when measured by LC-HRMS following capture by amino-terminal or carboxyl-terminal immunocapture methods. In patients with an eGFR of <30 mL/min/1.73 m2, serum PTH concentrations measured using LC-HRMS were significantly lower than PTH measured using an iPTH immunoassay. PTH7-84 and oxidized forms of PTH1-84 were below the limit of detection (30 and 50 pg/mL, respectively).

Conclusions: LC-HRMS identifies circulating PTH1-84, carboxyl-terminal PTH fragments, and mid-region PTH fragments, in patients with progressive renal failure. Serum PTH1-84 and its fragments markedly rise when an eGFR decreases to ≤17-23 mL/min/1.73 m2. PTH concentrations measured using LC-HRMS tend to be lower than those measured using an iPTH immunoassay, particularly in severe chronic renal failure. Our data do not support the existence of circulating PTH7-84 and oxidized PTH1-84.
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http://dx.doi.org/10.1093/clinchem/hvab013DOI Listing
March 2021

Automated radiomic analysis of CT images to predict likelihood of spontaneous passage of symptomatic renal stones.

Emerg Radiol 2021 Mar 1. Epub 2021 Mar 1.

Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Purpose: To evaluate the ability of a semi-automated radiomic analysis software in predicting the likelihood of spontaneous passage of urinary stones compared with manual measurements.

Methods: Symptomatic patients visiting the emergency department with suspected stones in either kidney or ureters who underwent a CT scan were included. Patients were followed for up to 6 months for the outcome of a trial of passage. Maximum stone diameters in axial and coronal images were measured manually. Stone length, width, height, max diameter, volume, the mean and standard deviation of the Hounsfield units, and morphologic features were also measured using automated radiomic analysis software. Multivariate models were developed using these data to predict subsequent spontaneous stone passage, with results expressed as the area under a receiver operating curve (AUC).

Results: One hundred eighty-four patients (69 females) with a median age of 56 years were included. Spontaneous stone passage occurred in 114 patients (62%). Univariate analysis demonstrated an AUC of 0.83 and 0.82 for the maximum stone diameter determined manually in the axial and coronal planes, respectively. Multivariate models demonstrated an AUC of 0.82 for a model including manual measurement of maximum stone diameter in axial and coronal planes. The same AUC was found for a model including automatic measurement of maximum height and diameter of the stone. Further addition of morphological parameters measured automatically did not increase AUC beyond 0.83.

Conclusion: The semi-automated radiomic analysis of urinary stones shows similar accuracy compared with manual measurements for predicting urinary stone passage. Further studies are needed to predict clinical impacts of reporting the likelihood of urinary stone passage and improving inter-observer variation using automatic radiomic analysis software.
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http://dx.doi.org/10.1007/s10140-021-01915-4DOI Listing
March 2021

Subsequent urinary stone events are predicted by the magnitude of urinary oxalate excretion in enteric hyperoxaluria.

Nephrol Dial Transplant 2020 Dec 26. Epub 2020 Dec 26.

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

 : Data directly demonstrating the relationship between urinary oxalate (UOx) excretion and stone events in those with enteric hyperoxaluria (EH) are limited. Therefore, we assessed the relationship between UOx excretion and risk of kidney stone events in a retrospective population-based EH cohort. In all, 297 patients from Olmsted County, Minnesota were identified with EH based upon having a 24-h UOx ≥40 mg/24 h preceded by a diagnosis or procedure associated with malabsorption. Diagnostic codes and urologic procedures consistent with kidney stones during follow-up after baseline UOx were considered a new stone event. Logistic regression and accelerated failure time modeling were performed as a function of UOx excretion to predict the probability of new stone event and the annual rate of stone events, respectively, with adjustment for urine calcium and citrate. Mean ± standard deviation age was 51.4 ± 11.4 years and 68% were female. Median (interquartile range) UOx was 55.4 (46.6-73.0) mg/24 h and 81 patients had one or more stone event during a median follow-up time of 4.9 (2.8-7.8) years. Higher UOx was associated with a higher probability of developing a stone event (P < 0.01) and predicted an increased annual risk of kidney stones (P = 0.001). Estimates derived from these analyses suggest that a 20% decrease in UOx is associated with 25% reduction in the annual odds of a future stone event. Thus, these data demonstrate an association between baseline UOx and stone events in EH patients and highlight the potential benefit of strategies to reduce UOx in this patient group.

Background: Data directly demonstrating the relationship between urinary oxalate (UOx) excretion and stone events in those with enteric hyperoxaluria (EH) are limited.

Methods: We assessed the relationship between UOx excretion and risk of kidney stone events in a retrospective population-based EH cohort. In all, 297 patients from Olmsted County, Minnesota were identified with EH based upon having a 24-h UOx ≥40 mg/24 h preceded by a diagnosis or procedure associated with malabsorption. Diagnostic codes and urologic procedures consistent with kidney stones during follow-up after baseline UOx were considered a new stone event. Logistic regression and accelerated failure time modeling were performed as a function of UOx excretion to predict the probability of new stone event and the annual rate of stone events, respectively, with adjustment for urine calcium and citrate.

Results: Mean ± SD age was 51.4 ± 11.4 years and 68% were female. Median (interquartile range) UOx was 55.4 (46.6-73.0) mg/24 h and 81 patients had ≥1 stone event during a median follow-up time of 4.9 (2.8-7.8) years. Higher UOx was associated with a higher probability of developing a stone event (P < 0.01) and predicted an increased annual risk of kidney stones (P = 0.001). Estimates derived from these analyses suggest that a 20% decrease in UOx is associated with 25% reduction in the annual odds of a future stone event.

Conclusions: These data demonstrate an association between baseline UOx and stone events in EH patients and highlight the potential benefit of strategies to reduce UOx in this patient group.
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http://dx.doi.org/10.1093/ndt/gfaa281DOI Listing
December 2020

Association of adverse childhood experiences with menopausal symptoms: Results from the Data Registry on Experiences of Aging, Menopause and Sexuality (DREAMS).

Maturitas 2021 Jan 14;143:209-215. Epub 2020 Oct 14.

Center for Women's Health, Mayo Clinic, 200 First St SW, Rochester, MN, USA; Division of General Internal Medicine, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, USA.

Objective: To examine the association of adverse childhood experiences (ACEs) with overall menopausal symptom burden in midlife women.

Study Design: This was a cross-sectional study of women between the ages of 40 and 65 years who were seen for specialty consultation in the Menopause and Women's Sexual Health Clinic, Mayo Clinic, Rochester, MN between May 1, 2015 and December 31, 2016.

Main Outcome Measures: Participants completed the ACE questionnaire to assess childhood abuse and neglect, the Menopause Rating Scale (MRS) to assess menopausal symptom burden, the Patient Health Questionnaire (PHQ-9) to assess depression, the Generalized Anxiety Disorder questionnaire (GAD-7) to assess anxiety, and provided information on current abuse (physical, sexual and verbal/emotional).

Results: Women meeting inclusion criteria (N = 1670) had a median age of 53.7 years (interquartile range: 49.1, 58.0). Of these women, 977 (58.5 %) reported any ACE and 288 (17.2 %) reported ≥4 ACEs. As menopausal symptoms increased in severity from the first to fourth quartile, the odds ratio of ACE 1-3 (vs. 0) increased from 1 to 2.50 (trend p < 0.01), and the odds ratio of ACE ≥ 4 (vs. 0) increased from 1 to 9.61 (trend p < 0.01), a pattern that was consistent across all menopausal symptom domains. The association between severe menopausal symptoms and higher childhood adversity (ACE score 1-3 or ≥4 vs. ACE = 0) remained significant after adjusting for age, partner status, education, employment, depression, anxiety, and hormone therapy use (OR 1.84 and 4.51, p < 0.01).

Conclusion: In this large cross-sectional study, there was a significant association between childhood adversity and self-reported menopausal symptoms that persisted even after adjustment for multiple confounders. These associations highlight the importance of screening women with bothersome menopausal symptoms for childhood adversity, and of offering appropriate management and counseling for the adverse experiences, when indicated.
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http://dx.doi.org/10.1016/j.maturitas.2020.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880696PMC
January 2021

Specific populations of urinary extracellular vesicles and proteins differentiate type 1 primary hyperoxaluria patients without and with nephrocalcinosis or kidney stones.

Orphanet J Rare Dis 2020 11 11;15(1):319. Epub 2020 Nov 11.

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

Background: Primary hyperoxaluria type 1 (PH1) is associated with nephrocalcinosis (NC) and calcium oxalate (CaOx) kidney stones (KS). Populations of urinary extracellular vesicles (EVs) can reflect kidney pathology. The aim of this study was to determine whether urinary EVs carrying specific biomarkers and proteins differ among PH1 patients with NC, KS or with neither disease process.

Methods: Mayo Clinic Rare Kidney Stone Consortium bio-banked cell-free urine from male and female PH1 patients without (n = 10) and with NC (n = 6) or KS (n = 9) and an eGFR > 40 mL/min/1.73 m were studied. Urinary EVs were quantified by digital flow cytometer and results expressed as EVs/ mg creatinine. Expressions of urinary proteins were measured by customized antibody array and results expressed as relative intensity. Data were analyzed by ANCOVA adjusting for sex, and biomarkers differences were considered statistically significant among groups at a false discovery rate threshold of Q < 0.20.

Results: Total EVs and EVs from different types of glomerular and renal tubular cells (11/13 markers) were significantly (Q < 0.20) altered among PH1 patients without NC and KS, patients with NC or patients with KS alone. Three cellular adhesion/inflammatory (ICAM-1, MCP-1, and tissue factor) markers carrying EVs were statistically (Q < 0.20) different between PH1 patients groups. Three renal injury (β2-microglobulin, laminin α5, and NGAL) marker-positive urinary EVs out of 5 marker assayed were statistically (Q < 0.20) different among PH1 patients without and with NC or KS. The number of immune/inflammatory cell-derived (8 different cell markers positive) EVs were statistically (Q < 0.20) different between PH1 patients groups. EV generation markers (ANO4 and HIP1) and renal calcium/phosphate regulation or calcifying matrixvesicles markers (klotho, PiT1/2) were also statistically (Q < 0.20) different between PH1 patients groups. Only 13 (CD14, CD40, CFVII, CRP, E-cadherin, EGFR, endoglin, fetuin A, MCP-1, neprilysin, OPN, OPGN, and PDGFRβ) out of 40 proteins were significantly (Q < 0.20) different between PH1 patients without and with NC or KS.

Conclusions: These results imply activation of distinct renal tubular and interstitial cell populations and processes associated with KS and NC, and suggest specific populations of urinary EVs and proteins are potential biomarkers to assess the pathogenic mechanisms between KS versus NC among PH1 patients.
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http://dx.doi.org/10.1186/s13023-020-01607-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659070PMC
November 2020

A single center randomized double blind controlled trial of pentoxifylline in acute pancreatitis: Challenges and opportunities.

Pancreatology 2020 Dec 3;20(8):1592-1597. Epub 2020 Oct 3.

Division of Gastroenterology and Hepatology (Drs Vege, Horibe, Chari [emeritus Member], and Loftus and Ms Clemens) and Division of Biomedical Statistics and Informatics (Dr Enders), Mayo Clinic, Rochester, MN, USA.

Objectives: Despite substantial morbidity and mortality associated with acute pancreatitis (AP), only one small randomized controlled drug trial (RCT) is available in the past few decades from the United States. Hence, we conducted a single-center, double-blind, placebo-controlled RCT of pentoxifylline in AP.

Methods: A total of 9 doses of oral pentoxifylline 400 mg or placebo tablet, three times daily, was administered within 72 h of diagnosis, using randomization blocks by pharmacy. Primary outcome was a composite outcome including any of the following: death, peripancreatic and/or pancreatic necrosis, infected pancreatic necrosis, persistent organ failure, persistent systemic inflammatory response syndrome, hospital stay longer than 4 days, need for intensive care, and need for intervention for necrosis.

Results: Between July 7, 2015, and April 4, 2017, we identified 685 patients with AP, 233 met eligibility criteria and 176 were approached for the study. Of these, 91 (51.7%) declined and finally 45 in pentoxifylline group and 38 in placebo group (83 total) were compared. There were no significant differences in primary outcome (27 [60.0%] vs 15 [39.5%]; P = .06). Pentoxifylline group was not associated with any benefit, but withlonger stay (42% vs. 21%; P = .04) and higher readmission rates (16 %vs 3%; P = .047).

Conclusions: We could not demonstrate superiority of pentoxifylline over placebo. Smaller sample size and inclusion of all types of severity might be the reasons for lack of efficacy. The challenges observed in the present study indicate that, in order to conduct a successful drug trial in AP, a multi center collaboration is essential.
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http://dx.doi.org/10.1016/j.pan.2020.09.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704646PMC
December 2020

Plasma Oxalate as a Predictor of Kidney Function Decline in a Primary Hyperoxaluria Cohort.

Int J Mol Sci 2020 May 20;21(10). Epub 2020 May 20.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.

This retrospective analysis investigated plasma oxalate (POx) as a potential predictor of end-stage kidney disease (ESKD) among primary hyperoxaluria (PH) patients. PH patients with type 1, 2, and 3, age 2 or older, were identified in the Rare Kidney Stone Consortium (RKSC) PH Registry. Since POx increased with falling estimated glomerular filtration rate (eGFR), patients were stratified by chronic kidney disease (CKD) subgroups (stages 1, 2, 3a, and 3b). POx values were categorized into quartiles for analysis. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of ESKD were estimated using the Cox proportional hazards model with a time-dependent covariate. There were 118 patients in the CKD1 group (nine ESKD events during follow-up), 135 in the CKD 2 (29 events), 72 in CKD3a (34 events), and 45 patients in CKD 3b (31 events). During follow-up, POx Q4 was a significant predictor of ESKD compared to Q1 across CKD2 (HR 14.2, 95% CI 1.8-115), 3a (HR 13.7, 95% CI 3.0-62), and 3b stages (HR 5.2, 95% CI 1.1-25), < 0.05 for all. Within each POx quartile, the ESKD rate was higher in Q4 compared to Q1-Q3. In conclusion, among patients with PH, higher POx concentration was a risk factor for ESKD, particularly in advanced CKD stages.
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http://dx.doi.org/10.3390/ijms21103608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279271PMC
May 2020

Urinary monocyte chemoattractant protein 1 associated with calcium oxalate crystallization in patients with primary hyperoxaluria.

BMC Nephrol 2020 04 15;21(1):133. Epub 2020 Apr 15.

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

Background: Patients with primary hyperoxaluria (PH) often develop kidney stones and chronic kidney disease. Noninvasive urine markers reflective of active kidney injury could be useful to gauge the effectiveness of ongoing treatments.

Methods: A panel of biomarkers that reflect different nephron sites and potential mechanisms of injury (clusterin, neutrophil gelatinase-associated lipocalin (NGAL), 8-isoprostane (8IP), monocyte-chemoattractant protein 1(MCP-1), liver-type fatty acid binding protein (L-FABP), heart-type fatty acid binding protein (H-FABP), and osteopontin (OPN)) were measured in 114 urine specimens from 30 PH patients over multiple visits. Generalized estimating equations were used to assess associations between biomarkers and 24 h urine excretions, calculated proximal tubular oxalate concentration (PTOx), and eGFR.

Results: Mean (±SD) age at first visit was 19.5 ± 16.6 years with an estimated glomerular filtration rate (eGFR) of 68.4 ± 21.0 ml/min/1.73m. After adjustment for age, sex, and eGFR, a higher urine MCP-1 concentration and MCP-1/creatinine ratio was positively associated with CaOx supersaturation (SS). Higher urine NGAL and NGAL/creatinine as well as OPN and OPN/creatinine were associated with higher eGFR. 8IP was negatively associated with PTOx and urinary Ox, but positively associated with CaOx SS.

Conclusion: In PH patients greater urine MCP-1 and 8IP excretion might reflect ongoing collecting tubule crystallization, while greater NGAL and OPN excretion may reflect preservation of kidney mass and function. CaOx crystals, rather than oxalate ion may mediate oxidative stress in hyperoxaluric conditions. Further studies are warranted to determine whether urine MCP-1 excretion predicts long term outcome or is altered in response to treatment.
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http://dx.doi.org/10.1186/s12882-020-01783-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161151PMC
April 2020

Translating innovation in biomedical research: Design and delivery of a competency-based regulatory science course.

J Clin Transl Sci 2020 Feb 23;4(1):8-15. Epub 2019 Dec 23.

Center for Clinical and Translational Science, Mayo Clinic, Rochester, MN, USA.

As the pace of biomedical innovation rapidly evolves, there is a need to train researchers to understand regulatory science challenges associated with clinical translation. We describe a pilot course aimed at addressing this need delivered jointly through the Mayo Clinic Center for Clinical and Translational Science and the Yale-Mayo Center for Excellence in Regulatory Science and Innovation. Course design was informed by the Association for Clinical and Translational Science's Regulatory Science Working Group's competencies. The course used didactic, case-, and problem-based learning sessions to expose students to regulatory science concepts. Course evaluation focused on student satisfaction and learning. A total of 25 students enrolled in the first two course deliveries. Students represented several disciplines and career stages, from predoctoral to faculty. Students reported learning "an incredible amount" (7/19, 36.8%) or "a lot" (9/19, 47.4%); this was reflected in individual coursework and their course evaluations. Qualitative feedback indicated that assignments that challenged them to apply the content to their own research were appreciated. The heterogeneity of students enrolled, coupled with assessments and course evaluations, supports the statement that there is a growing need and desire for regulatory science-focused curricula. Future research will determine the long-term impact.
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http://dx.doi.org/10.1017/cts.2019.432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103473PMC
February 2020

Clinical features of genetically confirmed patients with primary hyperoxaluria identified by clinical indication versus familial screening.

Kidney Int 2020 04 13;97(4):786-792. Epub 2019 Dec 13.

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

Primary hyperoxaluria is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage. Most patients with primary hyperoxaluria are diagnosed after clinical suspicion based on symptoms. Since some patients are detected by family screening following detection of an affected family member, we compared the clinical phenotype of these two groups. Patients with primary hyperoxaluria types 1, 2, and 3 enrolled in the Rare Kidney Stone Consortium Primary Hyperoxaluria Registry were retrospectively analyzed following capture of clinical and laboratory results in the Registry. Among 495 patients with primary hyperoxaluria, 47 were detected by family screening. After excluding 150 patients with end stage kidney disease at diagnosis, 300 clinical suspicion and 45 family screening individuals remained. Compared to patients with clinical suspicion, those identified by family screening had significantly fewer stones at diagnosis (mean 1.2 vs. 3.6), although initial symptoms occurred at a similar age (median age 6.1 vs. 7.6 years). Urinary oxalate did not differ between these groups. The estimated glomerular filtration rate at diagnosis and its decline over time were similar for the two groups. Altogether, five of 45 in family screening and 67 of 300 of clinical suspicion individuals developed end stage kidney disease at last follow-up. Thus, patients with primary hyperoxaluria identified through family screening have significant disease despite no outward clinical suspicion at diagnosis. Since promising novel treatments are emerging, genetic screening of family members is warranted because they are at significant risk for disease progression.
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http://dx.doi.org/10.1016/j.kint.2019.11.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175669PMC
April 2020

Risk Factors for Acute Kidney Injury in Hospitalized Non-Critically Ill Patients: A Population-Based Study.

Mayo Clin Proc 2020 03 31;95(3):459-467. Epub 2020 Jan 31.

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

Objective: To develop and validate an acute kidney injury (AKI) risk prediction model for hospitalized non-critically ill patients.

Patients And Methods: We retrospectively identified all Olmsted County, Minnesota, residents admitted to non-intensive care unit (ICU) wards at Mayo Clinic Hospital, Rochester, Minnesota, in 2013 and 2014. The cohort was divided into development and validation sets by year. The primary outcome was hospital-acquired AKI defined by Kidney Disease: Improving Global Outcomes criteria. Cox regression was used to analyze mortality data. Comorbid risk factors for AKI were identified, and a multivariable model was developed and validated.

Results: The development and validation cohorts included 3816 and 3232 adults, respectively. Approximately 10% of patients in both cohorts had AKI, and patients with AKI had an increased risk of death (hazard ratio, 3.62; 95% CI, 2.97-4.43; P<.001). Significant univariate determinants of AKI were preexisting kidney disease, diabetes mellitus, hypertension, heart failure, vascular disease, coagulopathy, pulmonary disease, coronary artery disease, cancer, obesity, liver disease, and weight loss (all P<.05). The final multivariable model included increased baseline serum creatinine value, admission to a medical service, pulmonary disease, diabetes mellitus, kidney disease, cancer, hypertension, and vascular disease. The area under the receiver operating characteristic curves for the development and validation cohorts were 0.71 (95% CI, 0.69-0.75) and 0.75 (95% CI, 0.72-0.78), respectively.

Conclusion: Hospital-acquired AKI is common in non-ICU inpatients and is associated with worse outcomes. Patient data at admission can be used to identify increased risk; such patients may benefit from more intensive monitoring and earlier intervention and testing with emerging biomarkers.
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http://dx.doi.org/10.1016/j.mayocp.2019.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060836PMC
March 2020

Symptomatic and Radiographic Manifestations of Kidney Stone Recurrence and Their Prediction by Risk Factors: A Prospective Cohort Study.

J Am Soc Nephrol 2019 07 7;30(7):1251-1260. Epub 2019 Jun 7.

Divisions of Nephrology and Hypertension, and

Background: Meaningful interpretation of changes in radiographic kidney stone burden requires understanding how radiographic recurrence relates to symptomatic recurrence and how established risk factors predict these different manifestations of recurrence.

Methods: We recruited first-time symptomatic stone formers from the general community in Minnesota and Florida. Baseline and 5-year follow-up study visits included computed tomography scans, surveys, and medical record review. We noted symptomatic recurrence detected by clinical care (through chart review) or self-report, and radiographic recurrence of any new stone, stone growth, or stone passage (comparing baseline and follow-up scans). To assess the prediction of different manifestations of recurrence, we used the Recurrence of Kidney Stone (ROKS) score, which sums multiple baseline risk factors.

Results: Among 175 stone formers, 19% had symptomatic recurrence detected by clinical care and 25% detected by self-report; radiographic recurrence manifested as a new stone in 35%, stone growth in 24%, and stone passage in 27%. Among those with a baseline asymptomatic stone (54%), at 5 years, 51% had radiographic evidence of stone passage (accompanied by symptoms in only 52%). Imaging evidence of a new stone or stone passage more strongly associated with symptomatic recurrence detected by clinical care than by self-report. The ROKS score weakly predicted one manifestation-symptomatic recurrence resulting in clinical care (-statistic, 0.63; 95% confidence interval, 0.52 to 0.73)-but strongly predicted any manifestation of symptomatic or radiographic recurrence (5-year rate, 67%; -statistic, 0.79; 95% confidence interval, 0.72 to 0.86).

Conclusions: Recurrence after the first stone episode is both more common and more predictable when all manifestations of recurrence (symptomatic and radiographic) are considered.
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http://dx.doi.org/10.1681/ASN.2018121241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6622409PMC
July 2019

Effect of increasing doses of cystine-binding thiol drugs on cystine capacity in patients with cystinuria.

Urolithiasis 2019 Dec 13;47(6):549-555. Epub 2019 Apr 13.

Nephrology Division, NYU Langone Medical Center, New York, NY, USA.

Appropriate dosing of cystine-binding thiol drugs in the management of cystinuria has been based on clinical stone activity. When new stones form, the dose is increased. Currently, there is no method of measuring urinary drug levels to guide the titration of therapy. Increasing cystine capacity, a measure of cystine solubility, has been promoted as a method of judging the effects of therapy. In this study, we gave increasing doses of tiopronin or D-penicillamine, depending on the patients' own prescriptions, to ten patients with cystinuria and measured cystine excretion and cystine capacity. The doses were 0, 1, 2, 3 g per day, given in two divided doses, and administered in a random order. Going from 0 to 1 g/day led to an increase in cystine capacity from - 39.1 to 130.4 mg/L (P < 0.009) and decreased 24 h cystine excretion from 1003.9 to 834.8 mg/day (P = 0.039). Increasing the doses from 1 to 2 to 3 g/day had no consistent or significant effect to further increase cystine capacity or decrease cystine excretion. Whether doses higher than 1 g/day have additional clinical benefit is not clear from this study. Limiting doses might be associated with fewer adverse effects without sacrificing the benefit of higher doses if higher doses do not offer clinical importance. However, trials with stone activity as an outcome would be desirable.
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http://dx.doi.org/10.1007/s00240-019-01128-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790278PMC
December 2019

A matched cohort examination of publication rates among clinical subspecialty fellows enrolled in a translational science training program.

J Clin Transl Sci 2018 Oct;2(5):327-333

Department of Gastroenterology, Mayo Clinic, Rochester, MN, USA.

Purpose: This study examined the effectiveness of a formal postdoctoral education program designed to teach skills in clinical and translational science, using scholar publication rates as a measure of research productivity.

Method: Participants included 70 clinical fellows who were admitted to a master's or certificate training program in clinical and translational science from 1999 to 2015 and 70 matched control peers. The primary outcomes were the number of publications 5 years post-fellowship matriculation and time to publishing 15 peer-reviewed manuscripts post-matriculation.

Results: Clinical and translational science program graduates published significantly more peer-reviewed manuscripts at 5 years post-matriculation (median 8 vs 5, =0.041) and had a faster time to publication of 15 peer-reviewed manuscripts (matched hazard ratio = 2.91, =0.002). Additionally, program graduates' publications yielded a significantly higher average H-index (11 vs. 7, =0.013).

Conclusion: These findings support the effectiveness of formal training programs in clinical and translational science by increasing academic productivity.
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http://dx.doi.org/10.1017/cts.2018.336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390396PMC
October 2018

Narrow band imaging evaluation of duodenal villi in patients with and without celiac disease: A prospective study.

World J Gastrointest Endosc 2019 Feb;11(2):145-154

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States.

Background: Duodenal biopsies are commonly obtained during esophagogastroduodenoscopy (EGD) but are very often histopathologically normal. Therefore, a more strategic method for evaluating the duodenal mucosa and avoiding unnecessary biopsies is needed.

Aim: To examine the clinical utility of narrow band imaging (NBI) for evaluating duodenal villous morphology.

Methods: We performed a prospective cohort study of adult patients at Mayo Clinic Rochester from 2013-2014 who were referred for EGD with duodenal biopsies. A staff endoscopist scored, in real-time, the NBI-based appearance of duodenal villi into one of three categories (normal, partial villous atrophy, or complete villous atrophy), captured ≥ 2 representative duodenal NBI images, and obtained mucosal biopsies therein. Images were then scored by an advanced endoscopist and gastroenterology fellow, and biopsies (gold standard) by a pathologist, in a masked fashion using the same three-category classification. Performing endoscopist, advanced endoscopist, and fellow NBI scores were compared to histopathology to calculate performance characteristics [sensitivity, specificity, positive and negative, negative predictive value (NPV), and accuracy]. Inter-rater agreement was assessed with Cohen's kappa.

Results: 112 patients were included. The most common referring indications were dyspepsia (47%), nausea (23%), and suspected celiac disease (14%). Duodenal histopathology scores were: 84% normal, 11% partial atrophy, and 5% complete atrophy. Performing endoscopist NBI scores were 79% normal, 14% partial atrophy, and 6% complete atrophy compared to 91%, 5%, and 4% and 70%, 24%, and 6% for advanced endoscopist and fellow, respectively. NBI performed favorably for all raters, with a notably high (92%-100%) NPV. NBI score agreement was best between performing endoscopist and fellow (κ = 0.65).

Conclusion: NBI facilitates accurate, non-invasive evaluation of duodenal villi. Its high NPV renders it especially useful for foregoing biopsies of histopathologically normal duodenal mucosa.
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http://dx.doi.org/10.4253/wjge.v11.i2.145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379743PMC
February 2019

The Importance of Statistical Competencies for Medical Research Learners.

J Stat Educ 2018 21;26(2):137-142. Epub 2018 Aug 21.

Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN.

It is very important for medical professionals and medical researchers to be literate in statistics. However, we have found that the degree of literacy that is required should not be identical for every statistical competency or even for every learner. We first begin by describing why the development, teaching, and assessment of statistical competencies for medical professionals and medical researchers are critical tasks. We next review our three substantial efforts at developing a comprehensive list of statistical competencies that can be used as a guide for what medical research learners should know about statistics, for curricular development, and for assessment of statistical education. We then summarize the origin and the inclusion of the statistical competency items. We follow this with a description of potential uses and applications of the statistical competencies to improve targeted learning for medical research learners. Finally, we discuss implications of the statistical competencies for undergraduate statistics education.
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http://dx.doi.org/10.1080/10691898.2018.1484674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322685PMC
August 2018

Predictors of Symptomatic Kidney Stone Recurrence After the First and Subsequent Episodes.

Mayo Clin Proc 2019 02 4;94(2):202-210. Epub 2018 Dec 4.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Division of Epidemiology, Mayo Clinic, Rochester, MN. Electronic address:

Objective: To predict symptomatic recurrence among community stone formers with one or more previous stone episodes.

Patients And Methods: A random sample of incident symptomatic kidney stone formers in Olmsted County, Minnesota, was followed for all symptomatic stone episodes resulting in clinical care from January 1, 1984, through January 31, 2017. Clinical and radiographic characteristics at each stone episode predictive of subsequent episodes were identified.

Results: There were 3364 incident kidney stone formers with 4951 episodes. The stone recurrence rates per 100 person-years were 3.4 (95% CI, 3.2-3.7) after the first episode, 7.1 (95% CI, 6.4-7.9) after the second episode, 12.1 (95% CI, 10.3-13.9) after the third episode, and 17.6 (95% CI, 15.1-20.0) after the fourth or higher episode (P<.001 for trend). A parsimonious model identified the following independent risk factors for recurrence: younger age; male sex; higher body mass index; family history of stones; pregnancy; incident asymptomatic stone on imaging before the first episode; suspected stone episode before the first episode; history of a brushite, struvite, or uric acid stone; no history of calcium oxalate monohydrate stone; kidney pelvic or lower pole stone on imaging; no ureterovesical junction stone on imaging; number of kidney stones on imaging; and diameter of the largest kidney stone on imaging. The model had a C-index corrected for optimism of 0.681 and was used to develop a prediction tool. The risk of recurrence in 5 years ranged from 0.9% to 94%, depending on risk factors, number of past episodes, and years since the last episode.

Conclusion: The revised Recurrence Of Kidney Stone tool predicts the risk of symptomatic recurrence by using readily available clinical characteristics of stone formers.
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http://dx.doi.org/10.1016/j.mayocp.2018.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390834PMC
February 2019

Humidity as a non-pharmaceutical intervention for influenza A.

PLoS One 2018 25;13(9):e0204337. Epub 2018 Sep 25.

Center for Clinical and Translational Science, Mayo Clinic, Rochester, Minnesota, United States of America.

Influenza is a global problem infecting 5-10% of adults and 20-30% of children annually. Non-pharmaceutical interventions (NPIs) are attractive approaches to complement vaccination in the prevention and reduction of influenza. Strong cyclical reduction of absolute humidity has been associated with influenza outbreaks in temperate climates. This study tested the hypothesis that raising absolute humidity above seasonal lows would impact influenza virus survival and transmission in a key source of influenza virus distribution, a community school. Air samples and objects handled by students (e.g. blocks and markers) were collected from preschool classrooms. All samples were processed and PCR used to determine the presence of influenza virus and its amount. Additionally samples were tested for their ability to infect cells in cultures. We observed a significant reduction (p < 0.05) in the total number of influenza A virus positive samples (air and fomite) and viral genome copies upon humidification as compared to control rooms. This suggests the future potential of artificial humidification as a possible strategy to control influenza outbreaks in temperate climates. There were 2.3 times as many ILI cases in the control rooms compared to the humidified rooms, and whether there is a causal relationship, and its direction between the number of cases and levels of influenza virus in the rooms is not known. Additional research is required, but this is the first prospective study suggesting that exogenous humidification could serve as a scalable NPI for influenza or other viral outbreaks.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204337PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155525PMC
March 2019

Combined Celiac Ganglia and Plexus Neurolysis Shortens Survival, Without Benefit, vs Plexus Neurolysis Alone.

Clin Gastroenterol Hepatol 2019 03 12;17(4):728-738.e9. Epub 2018 Sep 12.

Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota.

Background & Aims: Pancreatic cancer produces debilitating pain that opioids often ineffectively manage. The suboptimal efficacy of celiac plexus neurolysis (CPN) might result from brief contact of the injectate with celiac ganglia. We compared the effects of endoscopic ultrasound-guided celiac ganglia neurolysis (CGN) vs the effects of CPN on pain, quality of life (QOL), and survival.

Methods: We performed a randomized, double-blind trial of patients with unresectable pancreatic ductal adenocarcinoma and abdominal pain; 60 patients (age 66.4±11.6 years; male 66%) received CPN and 50 patients (age 66.8±10.0 years; male 56%) received CGN. Primary outcomes included pain control and QOL at week 12 and survival (overall median and 12 months). Secondary outcomes included morphine response, performance status, secondary neurolytic effects, and adverse events.

Results: Rates of pain response at 12 weeks were 46.2% for CGN and 40.4% for CPN (P = .84). There was no significant difference in improvement of QOL between the techniques. The median survival time was significantly shorter for patients receiving CGN (5.59 months) compared to (10.46 months) (hazard ratio for CGN, 1.49; 95% CI, 1.02-2.19; P = .042), particularly for patients with non-metastatic disease (hazard ratio for CGN, 2.95; 95% CI, 1.61-5.45; P < .001). Rates of survival at 12 months were 42% for patients who underwent CPN vs 26% for patients who underwent CGN. The number of adverse events did not differ between techniques.

Conclusion: In a prospective study of patients with unresectable pancreatic ductal adenocarcinoma and abdominal pain, we found CGN to reduce median survival time without improving pain, QOL, or adverse events, compared to CPN. The role of CGN must be therefore be reassessed. Clinicaltrials.gov no: NCT01615653.
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http://dx.doi.org/10.1016/j.cgh.2018.08.040DOI Listing
March 2019

An Academic Medical Center's Learners' Perceptions of Health Disparities.

PRiMER 2018 13;2:19. Epub 2018 Sep 13.

Mayo Clinic, Department of Health Sciences Research, Division of Biostatistics.

Introduction: Lack of health equity ultimately leads to unequal treatment of diverse patients and contributes to the growing disparities seen in national health. Academic medical centers should consider providing health care providers and biomedical researchers training on how to identify and address health disparities.

Methods: The authors led an introductory health disparities course for graduate students and research and clinical fellows at an academic medical center in the Midwest. We compared pre/postcourse assessments to determine changes in learners' perceptions and knowledge of health disparities using an unpaired analysis to permit inclusion of responses provided only at baseline.

Results: Sixty-two learners completed preassessment, with 56 completing the postassessment (90%). In the postcourse assessment, learners reported an increase in knowledge of disparities and had changes in their perceptions of health disparities linked to treatment of different patient groups based on demographic characteristics. There was a statistically significant difference in learners' perceptions of how patients are treated based on gender identity (=0.02) and sexual orientation (=0.04).

Conclusions: The results detail how an academic medical center can provide training on health disparities for diverse learners. This study underscores the influence of health disparities from the perspective of learners who conduct biomedical research and patient care. This course serves a model for introductory-level health disparities courses.
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http://dx.doi.org/10.22454/PRiMER.2018.867250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426136PMC
September 2018

Risk of ESRD and Mortality in Kidney and Bladder Stone Formers.

Am J Kidney Dis 2018 12 23;72(6):790-797. Epub 2018 Aug 23.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. Electronic address:

Rationale & Objectives: Kidney stones have been associated with increased risk for end-stage renal disease (ESRD). However, it is unclear whether there is also an increased risk for mortality and if these risks are uniform across clinically distinct categories of stone formers.

Study Design: Historical matched-cohort study.

Setting & Participants: Stone formers in Olmsted County, MN, between 1984 and 2012 identified using International Classification of Diseases, Ninth Revision codes. Age- and sex-matched individuals who had no codes for stones were the comparison group.

Predictor: Stone formers were placed into 5 mutually exclusive categories after review of medical charts: incident symptomatic kidney, recurrent symptomatic kidney, asymptomatic kidney, bladder only, and miscoded (no stone).

Outcomes: ESRD, mortality, cardiovascular mortality, and cancer mortality.

Analytical Approach: Cox proportional hazards models with adjustment for baseline comorbid conditions.

Results: Overall, 65 of 6,984 (0.93%) stone formers and 102 of 28,044 (0.36%) non-stone formers developed ESRD over a mean follow-up of 12.0 years. After adjusting for baseline hypertension, diabetes mellitus, dyslipidemia, gout, obesity, and chronic kidney disease, risk for ESRD was higher in recurrent symptomatic kidney (HR, 2.34; 95% CI, 1.08-5.07), asymptomatic kidney (HR, 3.94; 95% CI, 1.65-9.43), and miscoded (HR, 6.18; 95% CI, 2.25-16.93) stone formers, but not in incident symptomatic kidney or bladder stone formers. The adjusted risk for all-cause mortality was higher in asymptomatic kidney (HR, 1.40; 95% CI, 1.18-1.67) and bladder (HR, 1.37; 95% CI, 1.12-1.69) stone formers. Chart review of asymptomatic and miscoded stone formers suggested increased risk for adverse outcomes related to diagnoses including urinary tract infection, cancer, and musculoskeletal or gastrointestinal pain.

Conclusions: The higher risk for ESRD in recurrent symptomatic compared with incident symptomatic kidney stone formers suggests that stone events are associated with kidney injury. The clinical indication for imaging in asymptomatic stone formers, the correct diagnosis in miscoded stone formers, and the cause of a bladder outlet obstruction in bladder stone formers may explain the higher risk for ESRD or death in these groups.
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http://dx.doi.org/10.1053/j.ajkd.2018.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252145PMC
December 2018

Detection and Characterization of Renal Stones by Using Photon-Counting-based CT.

Radiology 2018 11 7;289(2):436-442. Epub 2018 Aug 7.

From the Department of Radiology (R.P.M., J.G.F., A.F., S.L., T.J.V., M.L.W., C.H.M.) and Department of Biomedical Statistics and Informatics (F.T.E.), Mayo Clinic, 200 1st St SW, Rochester, MN 55905; Siemens Healthcare-Imaging and Therapy Systems, Malvern, Pa (A.F.H.); Siemens Healthcare, Forchheim, Germany (R.G.); and CAMP, Technical University of Munich, Garching (Munich), Germany (R.G.).

Purpose To compare a research photon-counting-detector (PCD) CT scanner to a dual-source, dual-energy CT scanner for the detection and characterization of renal stones in human participants with known stones. Materials and Methods Thirty study participants (median age, 61 years; 10 women) underwent a clinical renal stone characterization scan by using dual-energy CT and a subsequent research PCD CT scan by using the same radiation dose (as represented by volumetric CT dose index). Two radiologists were tasked with detection of stones, which were later characterized as uric acid or non-uric acid by using a commercial dual-energy CT analysis package. Stone size and contrast-to-noise ratio were additionally calculated. McNemar odds ratios and Cohen k were calculated separately for all stones and small stones (≤3 mm). Results One-hundred sixty renal stones (91 stones that were ≤ 3 mm in axial length) were visually detected. Compared with 1-mm-thick routine images from dual-energy CT, the odds of detecting a stone at PCD CT were 1.29 (95% confidence interval: 0.48, 3.45) for all stones. Stone segmentation and characterization were successful at PCD CT in 70.0% (112 of 160) of stones versus 54.4% (87 of 160) at dual-energy CT, and was superior for stones 3 mm or smaller at PCD CT (45 vs 25 stones, respectively; P = .002). Stone characterization agreement between scanners for stones of all sizes was substantial (k = 0.65). Conclusion Photon-counting-detector CT is similar to dual-energy CT for helping to detect renal stones and is better able to help characterize small renal stones. © RSNA, 2018.
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http://dx.doi.org/10.1148/radiol.2018180126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204218PMC
November 2018

The Changing Incidence and Presentation of Urinary Stones Over 3 Decades.

Mayo Clin Proc 2018 03 14;93(3):291-299. Epub 2018 Feb 14.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Division of Epidemiology, Mayo Clinic, Rochester, MN. Electronic address:

Objective: To evaluate trends in the incidence of kidney stones and characteristics associated with changes in the incidence rate over 3 decades.

Patients And Methods: Adult stone formers in Olmsted County, Minnesota, from January 1, 1984, to December 31, 2012, were validated and characterized by age, sex, stone composition, and imaging modality. The incidence of kidney stones per 100,000 person-years was estimated. Characteristics associated with changes in the incidence rate over time were assessed using Poisson regression models.

Results: There were 3224 confirmed symptomatic (stone seen), 606 suspected symptomatic (no stone seen), and 617 incidental asymptomatic kidney stone formers. The incidence of confirmed symptomatic kidney stones increased from the year 1984 to 2012 in both men (145 to 299/100,000 person-years; incidence rate ratio per 5 years, 1.14, P<.001) and women (51 to 217/100,000 person-years; incidence rate ratio per 5 years, 1.29, P<.001). Overall, the incidence of suspected symptomatic kidney stones did not change, but that of asymptomatic kidney stones increased. Utilization of computed tomography for confirmed symptomatic stones increased from 1.8% in 1984 to 77% in 2012; there was a corresponding higher increased incidence of symptomatic small stones (≤3 mm) than of larger stones (>3 mm). Confirmed symptomatic kidney stones with documented spontaneous passage also increased. The incidence of kidney stones with unknown composition increased more than that of stones with known composition.

Conclusion: The incidence of both symptomatic and asymptomatic kidney stones has increased dramatically. The increased utilization of computed tomography during this period may have improved stone detection and contributed to the increased kidney stone incidence.
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http://dx.doi.org/10.1016/j.mayocp.2017.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849397PMC
March 2018

Risk of Pancreatic Cancer in Patients With Pancreatic Cysts and Family History of Pancreatic Cancer.

Clin Gastroenterol Hepatol 2018 07 7;16(7):1123-1130.e1. Epub 2018 Feb 7.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background & Aims: A diagnosis of pancreatic cancer in a first-degree relative increases an individuals' risk of this cancer. However, it is not clear whether this cancer risk increases in individuals with pancreatic cystic lesions who have a first-degree relative with pancreatic cancer. The Fukuoka criteria are used to estimate risk of pancreatic cancer for patients with pancreatic cystic lesions: individuals with cysts with high risk or worrisome features (Fukuoka positive) have a higher risk of pancreatic cancer than individuals without these features (Fukuoka negative). We aimed to compare the risk of pancreatic cancer and surgery based on presence or absence of pancreatic cystic lesions and a first-degree relative with pancreatic cancer.

Methods: We performed a retrospective study of patients seen at the Mayo Clinic in Rochester, Minnesota, from January 1, 2000, through December 31, 2012. We identified individuals with: pancreatic cystic lesions and first-degree relative with pancreatic cancer (group 1, n = 269), individuals with pancreatic cystic lesions but no first-degree relative with pancreatic cancer (group 2, n = 1195), and individuals without pancreatic cystic lesions but with a first-degree relative with pancreatic cancer (group 3, n = 720). We compared, among groups, as well among patients with cysts classified according to Fukuoka criteria, proportions of individuals who developed pancreatic cancer or underwent pancreatic surgery within a 5-year period.

Results: A significantly higher proportion of individuals in group 1 developed pancreatic cancer during the 5-year period than in group 3 (6.64% vs 1.69%; P = .03); there was no significant difference between the percentage of individuals in group 1 vs group 2 who developed pancreatic cancer (6.64% vs 4.05%; P = .41). There was no significant difference in pancreatic cancer development among individuals with Fukuoka-positive cysts with vs without a family history of pancreatic cancer (P = .39). There was no significant difference in the proportion of patients in group 1 vs group 2 who underwent pancreatic surgery for their pancreatic cyst over the 5-year period (14.37% vs 11.80%; P = .59). Among patients with Fukuoka-negative cysts, a significantly higher proportion underwent surgery in group 1 than in group 2 (10.90% vs 5.90%; P = .03). However, among patients with Fukuoka-positive cysts, there was no difference in proportions of patients who underwent surgery between groups 1 and 2 (P = .66).

Conclusions: In a retrospective study of patients with pancreatic cysts and/or cancer, we found that a family history of pancreatic cancer does not affect 5-year risk of pancreatic cancer in patients with pancreatic cystic lesions. Despite this, among patients with Fukuoka-negative cysts, a higher proportion of those with a family history of pancreatic cancer undergo surgery than patients without family history of pancreatic cancer.
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http://dx.doi.org/10.1016/j.cgh.2018.01.049DOI Listing
July 2018

Incidence and cost analysis of hospital admission and 30-day readmission among patients with cirrhosis.

Hepatol Commun 2018 02 18;2(2):188-198. Epub 2018 Jan 18.

Division of Gastroenterology and Hepatology Rochester MN.

We examined risks for first hospitalization and the rate, risk factors, costs, and 1-year outcome of 30-day readmission among patients admitted for complications of cirrhosis. Data were retrospectively analyzed for adult patients with cirrhosis residing in Minnesota, Iowa, or Wisconsin and admitted from 2010 through 2013 at both campuses of the Mayo Clinic Hospital in Rochester, MN. Readmission was captured at the two hospitals as well as at community hospitals in the tristate area within the Mayo Clinic Health System. The incidence of hospitalization for complications of cirrhosis was 100/100,000 population, with increasing age and male sex being the strongest risks for hospitalization. For the 2,048 hospitalized study patients, the overall 30-day readmission rate was 32%; 498 (24.3%) patients were readmitted to Mayo Clinic hospitals and 157 (7.7%) to community hospitals, mainly for complications of portal hypertension (52%) and infections (30%). Readmission could not be predicted accurately. There were 146 deaths during readmission and an additional 105 deaths up to 1 year of follow-up (50.4% total mortality). Annual postindex hospitalization costs for those with a 30-day readmission were substantially higher ($73,252) than those readmitted beyond 30 days ($62,053) or those not readmitted ($5,719). At 1-year follow-up, only 20.4% of patients readmitted within 30 days were at home. In conclusion, patients with cirrhosis have high rates of hospitalization, especially among men over 65 years, and of unscheduled 30-day readmission. Readmission cannot be accurately predicted. Postindex hospitalization costs are high; nationally, the annual costs are estimated to be more than $4.45 billion. Only 20% of patients readmitted within 30 days are home at 1 year. ( 2018;2:188-198).
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http://dx.doi.org/10.1002/hep4.1137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796328PMC
February 2018

Statistical competencies for medical research learners: What is fundamental?

J Clin Transl Sci 2017 Jun 9;1(3):146-152. Epub 2017 May 9.

Department of Medicine, Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Introduction: It is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.

Methods: We surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'

Results: There were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).

Conclusion: We have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature.
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http://dx.doi.org/10.1017/cts.2016.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647667PMC
June 2017

Plasma oxalate in relation to eGFR in patients with primary hyperoxaluria, enteric hyperoxaluria and urinary stone disease.

Clin Biochem 2017 Dec 29;50(18):1014-1019. Epub 2017 Jul 29.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States. Electronic address:

Background: Since plasma oxalate (POx) concentrations increase at lower glomerular filtration rate (GFR) levels, even among those without enteric (EH) or primary hyperoxaluria (PH), the appropriate thresholds for considering a disorder of oxalate metabolism are poorly defined. The current study was completed to establish relationships between POx, GFR, and urine oxalate excretion (UOx) among patients with PH, EH, and routine urinary stone disease (USD).

Methods: The most recent POx measurement on all Mayo Clinic patients between 2005 and 2015 were electronically pulled from the Lab Information System together with the closest serum creatinine within 14days and 24h urine study within 60days. After exclusion of patients not in steady state at the time of blood draw, 270 patients were available for study. Records were reviewed for clinical diagnoses to categorize patients as PH, EH, or USD. Waste plasma for Pox was also obtained from controls without USD undergoing clinical GFR testing.

Results: In all 3 groups POx increased as eGFR fell. For any given eGFR, POx was highest in the PH group and lowest in the USD and control groups (p<0.0001). POx was also influenced by UOx excretion (reflecting total body oxalate burden, absorption from diet and endogenous production). Generalized estimating equations of POx vs eGFR revealed higher average POx levels in PH compared to EH,USD or control, and for EH compared to USD or control. GEE prediction models were created that use POx, UOx, age, and serum creatinine to estimate the probability of a PH diagnosis.

Conclusions: New models were developed to help interpret POx when considering PH in clinical practice even when it was not previously suspected and/or eGFR is reduced.
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http://dx.doi.org/10.1016/j.clinbiochem.2017.07.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705406PMC
December 2017

Nonrelaxing Pelvic Floor Dysfunction Is an Underestimated Complication of Ileal Pouch-Anal Anastomosis.

Clin Gastroenterol Hepatol 2017 Aug 1;15(8):1242-1247. Epub 2017 Mar 1.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background & Aims: Nonrelaxing pelvic floor dysfunction (N-RPFD), or dyssynergic defecation, is the paradoxical contraction and/or impaired relaxation of pelvic floor and anal muscles during defecation. Few studies have evaluated this disorder in patients with an ileal pouch-anal anastomosis (IPAA). We investigated the frequency of N-RPFD in patients with and without chronic pouchitis following IPAA and the effectiveness of biofeedback therapy within this population.

Methods: We conducted a retrospective study of all patients with an IPAA who underwent anorectal manometry between January 2000 and March 2015 (n = 111). N-RPFD was diagnosed in patients with symptoms consistent with a pouch evacuation disorder and 1 or more of the following abnormal tests: anorectal manometry, balloon expulsion test, barium or magnetic resonance defecography, or external anal sphincter electromyography. Patients who completed biofeedback therapy were identified and assessed to determine symptomatic response.

Results: Of the 111 patients evaluated, 83 (74.8%) met criteria for N-RPFD. A significantly higher proportion of patients with chronic pouchitis were diagnosed with N-RPFD than patients without chronic pouchitis (83.3% vs 62.2%, respectively; P = .012). Most patients diagnosed with N-RPFD had abnormal results from the balloon expulsion test (78.3%); 53.0% of patients diagnosed with N-RPFD had abnormal findings from external anal sphincter electromyography, 25.3% had abnormal defecography findings, and 20.5% had abnormal findings from anorectal manometry. Twenty-two patients completed biofeedback therapy: 15 patients (68.2%) had mild-moderate improvement and 5 patients (22.7%) had significant improvement of symptoms.

Conclusions: N-RPFD occurs in almost 75% of patients with an IPAA, especially in patients with chronic pouchitis. Biofeedback seems to be an effective therapy for patients with an IPAA and N-RPFD, but further studies are needed for validation.
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http://dx.doi.org/10.1016/j.cgh.2017.02.024DOI Listing
August 2017

Assessment of multi-modality evaluations of obscure gastrointestinal bleeding.

World J Gastroenterol 2017 Jan;23(4):614-621

Ryan Law, Jithinraj E Varayil, Louis M WongKeeSong, Jeffrey Alexander, Elizabeth Rajan, Stephanie Hansel, Brenda Becker, David H Bruining, Nayantara Coelho-Prabhu, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States.

Aim: To determine the frequency of bleeding source detection in patients with obscure gastrointestinal bleeding (OGIB) who underwent double balloon enteroscopy (DBE) after pre-procedure imaging [multiphase computed tomography enterography (MPCTE), video capsule endoscopy (VCE), or both] and assess the impact of imaging on DBE diagnostic yield.

Methods: Retrospective cohort study using a prospectively maintained database of all adult patients presenting with OGIB who underwent DBE from September 1, 2002 to June 30, 2013 at a single tertiary center.

Results: Four hundred and ninety five patients (52% females; median age 68 years) underwent DBE for OGIB. AVCE and/or MPCTE performed within 1 year prior to DBE (in 441 patients) increased the diagnostic yield of DBE (67.1% with preceding imaging 59.5% without). Using DBE as the gold standard, VCE and MPCTE had a diagnostic yield of 72.7% and 32.5% respectively. There were no increased odds of finding a bleeding site at DBE compared to VCE (OR = 1.3, = 0.150). There were increased odds of finding a bleeding site at DBE compared to MPCTE (OR = 5.9, < 0.001). In inpatients with overt OGIB, diagnostic yield of DBE was not affected by preceding imaging.

Conclusion: DBE is a safe and well-tolerated procedure for the diagnosis and treatment of OGIB, with a diagnostic yield that may be increased after obtaining a preceding VCE or MPCTE. However, inpatients with active ongoing bleeding may benefit from proceeding directly to antegrade DBE.
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http://dx.doi.org/10.3748/wjg.v23.i4.614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292334PMC
January 2017