Joseph J. Larson

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (52)602.02 Total impact

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    ABSTRACT: Background: Even among ostensibly healthy adults, there is often mild pathology in the kidney. The detection of kidney microstructural variation and pathology by imaging and the clinical pattern associated with these structural findings is unclear. Study design: Cross-sectional (clinical-pathologic correlation). Setting & participants: Living kidney donors at Mayo Clinic (Minnesota and Arizona sites) and Cleveland Clinic 2000 to 2011. Predictors: Predonation kidney function, risk factors, and contrast computed tomographic scan of the kidneys. These scans were segmented for cortical volume and medullary volume, reviewed for parenchymal cysts, and scored for kidney surface roughness. Outcomes: Nephrosclerosis (glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis) and nephron size (glomerular volume, mean profile tubular area, and cortical volume per glomerulus) determined from an implantation biopsy of the kidney cortex at donation. Results: Among 1,520 living kidney donors, nephrosclerosis associated with increased kidney surface roughness, cysts, and smaller cortical to medullary volume ratio. Larger nephron size (nephron hypertrophy) associated with larger cortical volume. Nephron hypertrophy and larger cortical volume associated with higher systolic blood pressure, glomerular filtration rate, and urine albumin excretion; larger body mass index; higher serum uric acid level; and family history of end-stage renal disease. Both nephron hypertrophy and nephrosclerosis associated with older age and mild hypertension. The net effect of both nephron hypertrophy and nephrosclerosis associating with cortical volume was that nephron hypertrophy diminished volume loss with age-related nephrosclerosis and fully negated volume loss with mild hypertension-related nephrosclerosis. Limitations: Kidney donors are selected on health, restricting the spectrum of pathologic findings. Kidney biopsies in living donors are a small tissue sample leading to imprecise estimates of structural findings. Conclusions: Among apparently healthy adults, the microstructural findings of nephron hypertrophy and nephrosclerosis differ in their associations with kidney function, macrostructure, and risk factors.
    No preview · Article · Feb 2016 · American Journal of Kidney Diseases
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    ABSTRACT: Non-invasive tests to identify age and early disease-associated pathology within the kidney are needed. Specific populations of urinary extracellular vesicles (EVs) could potentially be used for such a diagnostic test. Random urine samples were obtained from age- and sex-stratified living kidney donors before kidney donation. A biopsy of the donor kidney was obtained at the time of transplantation to identify nephron hypertrophy (larger glomerular volume, cortex per glomerulus and mean profile tubular area) and nephrosclerosis (% fibrosis, % glomerulosclerosis and arteriosclerosis). Renal parenchymal-derived EVs in cell-free urine were quantified by digital flow cytometry. The relationship between these EV populations and structural pathology on the kidney biopsy was assessed. Clinical characteristics of the kidney donors (n=138, age range: 20-70 years, 50% women) were within the normative range. Overall, urine from women contained more EVs than that from men. The number of exosomes, juxtaglomerular cells and podocyte marker-positive EVs decreased (p<0.05) with increasing age. There were fewer total EVs as well as EVs positive for mesangial cell, parietal cell, descending limb of Henle's loop (simple squamous epithelium), collecting tubule-intercalated cell and monocyte chemoattractant protein-1 markers (p<0.05) in persons with nephron hypertrophy. The number of EVs positive for intercellular adhesion molecule-1, juxtaglomerular cell, podocyte, parietal cell, proximal tubular epithelial cell, distal tubular epithelial cell and collecting duct cells were fewer (p<0.05) in persons with nephrosclerosis. EVs carrying markers of cells from the renal pelvis epithelium did not associate with any indices of nephron hypertrophy or nephrosclerosis. Therefore, specific populations of EVs derived from cells of the glomerulus and nephron associate with underlying kidney structural changes. Further validation of these findings in other cohorts is needed to determine their clinical utility.
    Full-text · Article · Feb 2016
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    ABSTRACT: Little is known in the United States (US) about the epidemiology of liver diseases that develop only during (are unique to) pregnancy. We investigated the incidence of liver diseases unique to pregnancy in Olmsted County, MN and long-term maternal and fetal outcomes. We identified 247 women with liver diseases unique to pregnancy from 1996 through 2010 using the Rochester Epidemiology Project database. The crude incidence rate was calculated by the number of liver disease cases divided by 35,101 pregnancies. Of pregnant women with liver diseases, 134 had preeclampsia with liver dysfunction, 72 had hemolysis-associated increased levels of liver enzymes and low-platelet (HELLP) syndrome, 26 had intrahepatic cholestasis of pregnancy, 14 had hyperemesis gravidarum with abnormal liver enzymes, and 1 had acute fatty liver of pregnancy. The crude incidence of liver diseases unique to pregnancy was 0.77%. Outcomes were worse among women with HELLP or preeclampsia than the other disorders-of women with HELLP, 70% had a premature delivery, 4% had abruptio placentae, 3% had acute kidney injury, and 3% had infant death. Of women with preeclampsia, 56.0% had a premature delivery, 4% had abruptio placentae, 3% had acute kidney injury, and 0.7% had infant death. After 7 median years of follow up (range, 0-18 years), 14% of the women developed recurrent liver disease unique to pregnancy; the proportions were highest in women with initial hyperemesis gravidarum (36%) or intrahepatic cholestasis of pregnancy (35%). Women with preeclampsia were more likely to develop subsequent hepatobiliary diseases. We found the incidence of liver disease unique to pregnancy in Olmsted County, MN to be lower than that reported from Europe or US tertiary referral centers. Maternal and fetal outcomes in Olmsted County were better than those reported from other studies, but fetal mortality was still high (0.7%-3.0%). Women with preeclampsia or HELLP are at higher risk for peri-partum complications and subsequent development of comorbidities. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Aug 2015 · Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association
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    ABSTRACT: Background Isotretinoin (13-cis retinoic acid) is a metabolite of vitamin A and has anti-inflammatory and immunoregulatory effects; however, a recent publication by DePaolo et al. demonstrated that in the presence of IL-15, retinoic acid can act as an adjuvant and promote inflammation against dietary proteins. Objective To evaluate the risk of overt and latent celiac disease (CD) among users of isotretinoin. Material and Methods Medical records of patients from 1995 to 2011 who had a mention of isotretinoin in their records (N = 8393) were searched for CD diagnosis using ICD-09CM codes. Isotretinoin exposure was compared across overt CD patients and their age- and gender-matched controls from the same pool. To evaluate the risk of latent CD with isotretinoin exposure, patients were overlapped with a community-based list of patients with waste serum samples that were tested for CD serology, excluding those with overt CD (2006–2011). Isotretinoin exposure was defined as the use of isotretinoin prior to CD diagnosis or serology. Results Of 8393 patients, 25 had a confirmed CD diagnosis. Compared to matched controls (N = 75), isotretinoin exposure was not significantly different between overt CD patients versus controls (36% versus 39%, respectively; P = 0.712). Likewise, latent CD defined as positive serology was not statistically different between isotretinoin exposed (N = 506) versus non-exposed (N = 571) groups (1.8% versus 1.4%, respectively; P = 0.474). Conclusions There was no association between isotretinoin use and risk of either overt or latent CD.
    Full-text · Article · Aug 2015 · PLoS ONE

  • No preview · Article · Apr 2015 · Gastroenterology

  • No preview · Article · Apr 2015 · Gastroenterology
  • Disha Khemani · Joseph J. Larson · Michael D. Leise

    No preview · Article · Apr 2015 · Gastroenterology

  • No preview · Article · Apr 2015 · Gastroenterology

  • No preview · Article · Mar 2015 · Alimentary Pharmacology & Therapeutics
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    ABSTRACT: Chronic kidney disease (CKD) is an important comorbidity after liver transplantation (LT); however, reliable tools with which to evaluate these patients are limited. In this work, we examine the extent to which the addition of serum cystatin C improves glomerular filtration rate (GFR) estimation and mortality prediction, in comparison to various GFR-estimating equations. The GFR was measured in LT recipients by iothalamate clearance. Concurrent serum cystatin C was assayed in banked serum samples. Performance of GFR-estimating equations with and without cystatin C, including the modification of diet in renal disease and CKD-epidemiology collaboration formulas was assessed. The proportional hazards regression analysis was performed to determine the association between serum cystatin C and mortality. A total of 586 iothalamate results were obtained in 401 patients after a mean of 4 years after LT. When compared to measured GFR, the formula with both creatinine and cystatin C, namely, CKD-epidemiology cr-cys, outperformed those with either marker alone. Performance of creatinine-based models was similar to one another. Serum cystatin C, by itself or as a part of an estimated GFR, was a significant predictor of mortality. Serum cystatin C has an important role in enhancing accuracy of GFR estimation and predicting mortality in LT recipients.
    No preview · Article · Jan 2015 · Transplantation
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    ABSTRACT: Chemotherapy of patients with inactive hepatitis B virus (HBV) infection can lead to viral reactivation and flares of hepatitis. We investigated the proportions of patients screened for HBV infection before chemotherapy over time and outcomes of screened patients. In a retrospective study, we collected data from a pharmacy database on patients who underwent cytotoxic chemotherapy for solid or hematologic malignancies at the Mayo Clinic in Rochester, Minnesota, from January 1, 2006 through September 30, 2011. Laboratory data were collected from electronic medical records. Screening was identified based on tests for HB surface antigen, for any reason at any time before chemotherapy. Of 8005 patients undergoing chemotherapy, 1279 (16%) were screened for HBV infection before chemotherapy, including 668/1805 patients with hematologic malignancies (37%). The proportion of patients screened for HBV increased from 14.3% in 2006-2008 to 17.7% in 2009-2011 (P<.01). This trend was attributed mostly to an increase the proportion of patients with hematologic malignancies, from 32.7% in 2006-2008 to 40.6% in 2009-2011 (P<.01). Of 13 patients who tested positive for HBV, 5 did not receive prophylactic antiviral therapy; HBV infection was reactivated in 2 of these patients. None the 8 patients who received an antiviral agent before chemotherapy experienced HBV reactivation. Of 58 unscreened patients who had increases in levels of alanine aminotransferase (>300 U/L), only 1 appeared to have an undiagnosed HBV infection. Only a small percentage of patients receiving chemotherapy are screened for HBV infection. However, a larger proportion was screened during 2009-2011 than 2006-2008, especially of patients with hematologic malignancies. Strategies are needed to ensure that patients receiving chemotherapy are protected from the consequences of undiagnosed HBV infection. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Nov 2014 · Clinical Gastroenterology and Hepatology
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    Preview · Article · Sep 2014 · Journal of Hepatology
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    ABSTRACT: Importance Isotretinoin is the standard treatment for refractory severe nodulocystic acne. A true association between prior isotretinoin use and development of inflammatory bowel disease (IBD) is uncertain. Addressing the reality of this association is important in decision making for both the clinician and the patient when isotretinoin treatment is indicated.Objective To assess the risk of IBD mainly in patients with acne with and without isotretinoin exposure.Design, Setting, and Participants In this retrospective, single-center study, the electronic medical records of patients who were primarily seeking acne treatment were reviewed for isotretinoin exposure. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to search for IBD diagnosis. participants included 1078 patients from 1995 to 2011, with isotretinoin referenced in their medical records, and who had ongoing local medical care defined as having had a serum sample collected between 2006 to 2011 for any reason while an Olmsted County, Minnesota, resident at the time of serum sample collection.Exposures The exposed group included the patients with confirmed prior isotretinoin exposure (n = 576), and the nonexposed group were defined as patients who never received isotretinoin or received it after the diagnosis of IBD (n = 502).Main Outcomes and Measures Risk of IBD among isotretinoin-exposed vs nonexposed patients.Results Both groups were comparable by race, prior systemic antibiotic use, and systemic tetracycline use. Inflammatory bowel disease developed less frequently in the isotretinoin-exposed group vs the nonexposed group (0.9% vs 2.6%; P = .03; unadjusted odds ratio [OR], 0.33; 95% CI, 0.12-0.93; P = .04). The negative association between isotretinoin exposure and IBD remained after adjusting for sex (OR, 0.28; 95% CI, 0.10-0.80; P = .02) and for sex and nonacne indication (OR, 0.28; 95% CI, 0.10-0.79; P = .02).Conclusions and Relevance Our study did not show an increased risk of IBD with prior isotretinoin use. If anything, the risk seemed to be decreased. Although these results may be due to chance given the small number of IBD cases, the anti-inflammatory and immune-modulating effects of isotretinoin may be worth exploring.
    No preview · Article · Sep 2014 · JAMA Dermatology
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    ABSTRACT: Hyponatremia is associated with an increased risk of mortality on the liver transplant (LTx) waiting list. Though incorporation of the serum sodium into the MELD score may reduce wait list mortality, concerns remain about a potential association between pre-LTx hyponatremia and decreased post-LTx survival. Furthermore, the relationship between pre-LTx hypernatremia and post-LTx survival remains unexplored. The purpose of this study was to investigate the impact of the entire spectrum pre-LTx serum sodium (Na) on post-LTx outcomes. We identified 19,537patients with serum Na that was available immediately before LTx from 2003-20010. Patients were divided into three groups including hyponatremic (Na ≤ 130 mEq/L), normonatremic (Na=131-145mEq/L) and hypernatremic (Na >145 mEq/L) groups and their post-LTx outcomes compared. There was no difference in in-hospital mortality or 90-day survival between patients with hyponatremia and normonatremia. A fraction (2.4%) of patients had hypernatremia, which was associated with increased in-hospital death (11.2% vs. 4.2%, p<0.001) and diminished 90 day survival (86.4% vs. 94.0.%, p<0.001). After adjusting for important clinical variables, the association of preLTx hypernatremia with post-transplant mortality remained significant with a HR=1.13 for each unit increase in sodium >145mEq/L (p<0.001). Length of hospitalization after LTx was significantly longer in hypernatremic patients (p < 0.001). In conclusion, hyponatremia per se does not affect post-LTx survival. Pre-LTx hypernatremia is a highly significant risk factor for post-LTx mortality. Liver Transpl , 2014. © 2014 AASLD.
    No preview · Article · Jun 2014 · Liver Transplantation

  • No preview · Article · May 2014 · Gastroenterology
  • Amanda M. Lynn · Joseph J. Larson · Michael D. Leise

    No preview · Article · May 2014 · Gastroenterology
  • Amanda M. Lynn · Joseph J. Larson · Michael D. Leise

    No preview · Article · May 2014 · Gastroenterology
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    ABSTRACT: Objective To examine the effectiveness and tolerability of triple therapy with pegylated interferon (p-IFN), ribavirin (RBV), and telaprevir in patients with chronic hepatitis C receiving treatment in an academic practice setting and in a more clinically diverse population compared with patients receiving treatment in phase 3 trials. Patients and Methods A prospective database of all patients with viral hepatitis undergoing antiviral therapy from January 1, 2006, to July 1, 2012, was queried to identify treatment-naive and -experienced patients with chronic hepatitis C receiving dual and triple therapies. On-treatment response categories included rapid virologic response, extended rapid virologic response, early virologic response, and sustained virologic response. These patients were compared with matched controls, namely, patients who underwent dual therapy with p-IFN and RBV. Matching was performed for age, cirrhosis status, and prior treatment. Results There were 55 patients who received triple therapy and met the eligibility criteria, consisting of treatment-naive (n=35) and -experienced patients (n=20: those with relapse, 9; those with nonresponse, 9; and those who terminated the treatment early, 2). Rapid virologic response was achieved in 41% of the patients, extended rapid virologic response in 41%, and early virologic response in 75%. Sustained virologic response was observed in 51% (18/35) of treatment-naive patients, 67% (6/9) of the patients with prior nonresponse, and 56% (5/9) of those with prior relapse. Corresponding results after dual therapy were 37% (23/62), 11% (2/18), and 27% (3/11), respectively. The mean decrease in the hemoglobin level at weeks 4, 8, and 24 of triple therapy was 2.8, 3.8, and 3.2 mg/dL compared with 2.4, 2.6, and 2.4 mg/dL with dual therapy (to convert mg/dL to mmol/L, multiply values by 0.0259). Conclusion Telaprevir-based triple therapy in clinical practice is considerably more effective than dual therapy with p-IFN and RBV despite the significant degree of anemia that complicated therapy, requiring RBV dose reduction and erythropoietin support.
    No preview · Article · May 2014 · Mayo Clinic Proceedings
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    ABSTRACT: Background The etiology of irritable bowel syndrome (IBS) is not been fully elucidated, but childhood trauma may disturb the brain–gut axis and therefore be important. Thus, we conducted a family based case–control study of IBS cases and their relatives with the aims to (i) determine the frequency of childhood trauma among IBS cases and controls as well as their relatives, and (ii) assess childhood trauma among IBS cases with affected relatives (familial IBS).Methods Outpatients with IBS, matched controls, and their first-degree relatives completed a self-report version of Bremner' Early Trauma Inventory. Percent of cases and controls with a family history were compared and odds ratios were computed using chi-squared test; recurrence risks to relatives were computed using logistic regression and generalized estimating equations.Key ResultsData were collected from 409 cases, 415 controls, 825 case relatives, and 921 control relatives. IBS cases had a median age of 50 and 83% were women. Of IBS cases, 74% had experienced any general trauma compared to 59% among controls, yielding an odds ratio of 1.56 (95% CI: 1.13–2.15, p < 0.008). There were no statistical differences between IBS relatives and control relatives with regards to lifetime trauma.Conclusions & InferencesIBS is associated with childhood trauma, and these traumas often occur prior to onset of IBS symptoms. This provides further insight into how traumatic childhood events are associated with development of adult IBS.
    Full-text · Article · May 2014 · Neurogastroenterology and Motility
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    ABSTRACT: The accuracy of creatinine-based estimated GFR (eGFR) in assessing the prevalence of chronic kidney disease (CKD) and associated mortality after liver transplantation (LTx) is unknown. Using measured GFR (mGFR) by iothalamate clearance, we determined the prevalence of the entire spectrum of renal dysfunction and the impact of CKD on mortality after LTx. A database that prospectively tracks all LTx recipients at this academic transplant program from 1985 to 2012 was queried to identify all adult primary LTx recipients. Our post-LTx protocol incorporates GFR measurement by iothalamate clearance at regular intervals. A multistate model was used to assess the prevalence of CKD, kidney transplant and death after LTx. Time-dependent Cox regression analysis was performed to evaluate the impact of mGFR and eGFR changes on survival. A total of 1,211 transplant recipients were included. At the time of LTx, the median age was 54 years, 60% were male and 86% were Caucasian. At 25 years after LTx, 54% of patients died, 9% underwent kidney transplantation, whereas 7%, 21% and 18% had mGFR >60, 59-30 and <30 ml/min/1.73m(2) respectively. The risk of death increased when mGFR decreased below 30 ml/min/1.73m(2): HR=2.67 (95% CI=1. 80-3.96) for GFR=29-15 ml/min/1.73m(2) and HR=5.47(95% CI=3.10-9.65) for GFR<15 ml/min/1.73m(2). Compared to mGFR, eGFR underestimated mortality risk in LTx recipients with an eGFR of 30-90 ml/min/1.73m(2). An overwhelming majority of LTx recipients develop CKD. The risk of death increases exponentially when GFR<30 ml/min/1.73m(2). Creatinine-based eGFR underestimates the mortality risk in a large proportion of patients.
    No preview · Article · Apr 2014 · Journal of Hepatology