Joseph J Larson

Mayo Clinic - Rochester, Rochester, MN, United States

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Publications (32)292.9 Total impact

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    ABSTRACT: 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.
    JAMA dermatology. 09/2014;
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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.
    Journal of Hepatology 04/2014; · 9.86 Impact Factor
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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.
    Liver Transplantation 02/2014; · 3.94 Impact Factor
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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.
    Mayo Clinic Proceedings 01/2014; · 5.79 Impact Factor
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    ABSTRACT: There is uncertainty about the efficacy and safety of treatment for hepatitis C virus (HCV) infection in patients with inflammatory bowel disease (IBD). IBD can become exacerbated during treatment with interferon (IFN) and serious adverse events, such as pancytopenia or hepatotoxicity, can be compounded by drug interactions. We investigated the risk of exacerbation of IBD during HCV therapy and the rate of adverse effects of concomitant therapy for HCV and IBD. We also evaluated the efficacy of HCV treatment in the IBD population. We conducted a retrospective review of all patients who underwent IFN-based treatment for HCV at the Mayo Clinic in Rochester, Minnesota from 2001 through 2012. Exacerbation of IBD was evaluated by clinical, endoscopic, and histologic parameters during antiviral therapy and the ensuing 12 months. Hematologic toxicity was assessed by levels of all 3 cell lineages at baseline and during therapy. Efficacy of antiviral treatment was assessed by serum levels of HCV RNA until 24 weeks after completion of therapy. We also conducted a detailed Medline database search and reviewed the literature on this topic. We identified 15 subjects with concomitant IBD (8 with ulcerative colitis and 7 with Crohn's disease). Only 1 patient experienced an exacerbation of the disease during therapy; symptoms were controlled with mesalamine enemas. Another patient developed a flare shortly after completing antiviral therapy; symptoms returned spontaneously to baseline 2 weeks later. All subjects experienced an anticipated degree of pancytopenia while on IFN-based therapy. The rate of sustained virologic response was 67 %. A concise review of available literature regarding the safety and efficacy of HCV treatment in IBD patients is also presented; although limited, the published data appears to support the safety of treatment with IFN in patients whose IBD is under control. In conjunction with data from the literature, our findings indicate that the efficacy and safety of HCV therapy with IFN and ribavirin for patients with IBD are comparable to those of subjects without IBD.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 07/2013; · 5.64 Impact Factor
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    ABSTRACT: The hospital at which liver transplantation (LT) is performed has a substantial impact on post-LT outcomes. Center-specific outcome data are closely monitored not only by the centers themselves but also by patients and government regulatory agencies. However, the true magnitude of this center effect, apart from the effects of the region and donor service area (DSA) as well as recipient and donor determinants of graft survival, has not been examined. We analyzed data submitted to the Organ Procurement and Transplantation Network for all adult (age ≥ 18 years) primary LT recipients (2005-2008). Using a mixed effects, proportional hazards regression analysis, we modeled graft failure within 1 year after LT on the basis of center (de-identified), region, DSA, and donor and recipient characteristics. At 115 unique centers, 14,654 recipients underwent transplantation. Rates of graft loss within a year varied from 5.9% for the lowest quartile of centers to 20.2% for the highest quartile. Gauged by a comparison of the 75th and 25th percentiles of the data, the magnitude of the center effect on graft survival (1.49-fold change) was similar to that of the recipient Model for End-Stage Liver Disease (MELD) score (1.47) and the donor risk index (DRI; 1.45). The center effect was similar across the DRI and MELD score quartiles and was not associated with a center's annual LT volume. After stratification by region and DSA, the magnitude of the center effect, though decreased, remained significant and substantial (1.30-fold interquartile difference). In conclusion, the LT center is a significant predictor of graft failure that is independent of region and DSA as well as donor and recipient characteristics. Liver Transpl, 2013. © 2013 AASLD.
    Liver Transplantation 06/2013; · 3.94 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: According to the National Center for Health Statistics (NCHS), "chronic liver disease and cirrhosis" is the 12 (th) -leading cause of death in the United States (US). However, this single descriptor might not adequately enumerate all deaths from liver disease. The aim of our study was to update data on liver mortality in the US. METHODS: Mortality data were obtained from the Rochester Epidemiology Project (REP; 1999-2008) and the National Death Registry (1979-2008). Liver-specific mortality values were calculated. In contrast to the narrow NCHS definition, updated liver-related causes of death included other specific liver diagnoses (e.g. hepatorenal syndrome), viral hepatitis, and hepatobiliary cancers. RESULTS: The REP database contained information on 261 liver-related deaths, with an age- and sex-adjusted death rate of 27.0/100,000 persons (95% confidence interval, 23.7-30.3). Of these, only 71 deaths (27.2%) would have been captured by the NCHS definition. Of cases for which viral hepatitis or hepatobiliary cancer was the cause of death, 96.9% and 94.3% had liver-related immediate causes of death, respectively. In analysis of data from the National Death registry (2008), use of the updated definition increased liver mortality by more than 2-fold (from 11.7 to 25.7 deaths/100,000, respectively). Using NCHS definitions, liver-related deaths decreased from 18.9/100,000 in 1979 to 11.7/100,000 in 2008-a reduction of 38%. However, using the updated estimate, liver-related deaths persons were essentially unchanged from 1979 (25.8/100,000) to 2008 (25.7/100,000). Mortality burden was systematically underestimated among non-whites and persons of Hispanic ethnicity. CONCLUSION: Based on analyses of the REP and National Death databases, liver-related mortality has been underestimated over the past 2 decades in the US.
    Gastroenterology 04/2013; · 12.82 Impact Factor
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    ABSTRACT: BACKGROUND: Primary biliary cirrhosis is a cholestatic liver disease characterized by immune-mediated destruction of bile ducts. Its pathogenesis is largely unknown, although complex interactions between environment and genetic predisposition are proposed. AIMS: Identify disease risk factors using a detailed patient questionnaire and compare study findings to 3 published reports. METHODS: Questionnaire data were prospectively collected from 522 cases and 616 controls of the Mayo Clinic Primary Biliary Cirrhosis Genetic Epidemiology Registry. Case and control responses were compared using logistic regression, adjusting for recruitment age, sex, and education level. RESULTS: Cases reported ever regularly smoking cigarettes more frequently than controls (P<0.001). History of urinary tract infection was similar between groups; however, cases reported multiple urinary tract infections more commonly than controls (P<0.001). Frequency of other autoimmune disease was higher in cases than controls (P<0.001). As well, prevalence of primary biliary cirrhosis among first-degree relatives was higher in case families than control families (P<0.001). CONCLUSIONS: Our study confirms prior reported risk factors associated with disease risk. Given the potential importance of gene and environment interactions, further examination of environmental risk factors considering genetic background may provide new insight into primary biliary cirrhosis pathogenesis.
    Digestive and Liver Disease 03/2013; · 3.16 Impact Factor
  • Archives of internal medicine 09/2012; · 11.46 Impact Factor
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    ABSTRACT: Smaller studies have evaluated SLC6A4 5-HTTLPR and GNβ3 825C>T polymorphisms in IBS, and interactions between 5-HTT LPR with life events have been reported in the psychiatric literature, but gene-environment studies in IBS are lacking. The purpose of this study was to assess the association of two polymorphisms with IBS and age of onset, and whether there are gene-environment interactions with IBS. Outpatients with IBS and controls completed a validated questionnaire and provided blood for DNA. Comparisons of genotype/allele frequencies between cases and controls were performed with logistic regression. Linear regression was used to evaluate the association between the variants and age of onset. Environmental variables tested included abuse, parental alcohol abuse, parental psychiatric disorders, and gastrointestinal infections. Genotyping was performed in 385 cases and 262 controls with median age of 50 years (range, 18.0-70.0) and 498 (77 %) females. The IBS subtype distribution among cases was: 102 (26 %) D-IBS, 40 (10 %) C-IBS, 125 (32 %) M-IBS, 118 (31 %) other. No association was observed between IBS or age of onset and both variants. Significant interactions were observed between GI infection and the GNβ3 825T allele. For those reporting gastrointestinal infection, the OR for IBS was 3.9 (95 % CI 1.2-12.7) whereas the OR was 0.86 (95 % CI 0.65-1.13) for those without prior infection. There was a significant interaction between the GNβ3 polymorphism and infection in the development of IBS, suggesting that its etiology is the result of a combination of specific genetic and environmental risk factors.
    Digestive Diseases and Sciences 08/2012; 57(10):2650-7. · 2.26 Impact Factor
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    ABSTRACT: The epidemiology of biliary tract cancers has changed in the United States in the past several decades. The aim of this study is to evaluate biliary tract cancers with regard to the incidence rates, etiology, treatment, and survival in Olmsted County between 1976 and 2008. Community residents over 20 years of age with a newly diagnosed biliary tract cancers were identified using the Rochester Epidemiology Project. Clinical information, including tumor stage, treatment, and survival status was abstracted from the medical records. The incidence rate was calculated considering the entire population of Olmsted County to be at risk and adjusted by age and sex according to US Census 2000 population. Temporal trends of patient survival with biliary tract cancers were assessed. A total of 116 subjects met the study criteria. The age-sex-adjusted incidence rate of intrahepatic cholangiocarcinoma (ICC) increased from 0.3 to 2.1 (P=0.02) but one of gall bladder (GB) cancer decreased from 4.0 to 2.2 (P=0.04) per 100,000 person-years between 1976 and 2008 (P<0.01). Overall incidence rates of remaining biliary tract cancers have not changed. Overall 59% of patients presented with stage 3 or 4 cancers and a median survival was 6.3 months. Survival in patients with biliary tract cancer has minimally improved from median survival of 4.2-7.7 months between 1976 and 2008 (P=0.05). In Olmsted County, the incidence of ICC and GB cancer has increased and decreased, respectively. The prognosis remains poor in community residents diagnosed with biliary tract cancers.
    The American Journal of Gastroenterology 07/2012; 107(8):1256-62. · 7.55 Impact Factor
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    ABSTRACT: Adherence to a gluten-free diet is the only effective treatment for celiac disease. It has been recommended that patients be followed up, make regular visits to the clinic, and undergo serologic analysis for markers of celiac disease, although a follow-up procedure has not been standardized. We determined how many patients with celiac disease are actually followed up. We collected data on 122 patients with biopsy-proven celiac disease, diagnosed between 1996 and 2006 in Olmsted County, Minnesota (70% women; median age, 42 y), for whom complete medical records and verification of residency were available. We determined the frequency at which patients received follow-up examinations, from 6 months to 5 years after diagnosis. The Kaplan-Meier method was used to estimate event rates at 1 and 5 years. Patients were classified according to categories of follow-up procedures recommended by the American Gastroenterological Association (AGA). We estimated that by 1 and 5 years after diagnosis with celiac disease, 41.0% and 88.7% of the patients had follow-up visits, 33.6% and 79.8% were assessed for compliance with a gluten-free diet, 3.3% and 15.8% met with a registered dietitian, 2.5% and 18.1% had an additional intestinal biopsy, and 22.1% and 65.6% received serologic testing for markers of celiac disease, respectively. Among 113 patients (93%) who were followed up for more than 4 years, only 35% received follow-up analyses that were consistent with AGA recommendations. Patients with celiac disease are not followed up consistently. Follow-up examinations often are inadequate and do not follow AGA recommendations. Improving follow-up strategies for patients with celiac disease could improve management of this disease.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 05/2012; 10(8):893-899.e1. · 5.64 Impact Factor
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    ABSTRACT: Survival of patients with hepatocellular carcinoma (HCC) is determined by the extent of the tumor and the underlying liver function. We aimed to develop a survival model for HCC based on objective parameters including the Model for Endstage Liver Disease (MELD) as a gauge of liver dysfunction. This analysis is based on 477 patients with HCC seen at Mayo Clinic Rochester between 1994 and 2008 (derivation cohort) and 904 patients at the Korean National Cancer Center between 2000 and 2003 (validation cohort). Multivariate proportional hazards models and corresponding risk score were created based on baseline demographic, clinical, and tumor characteristics. Internal and external validation of the model was performed. Discrimination and calibration of this new model were compared against existing models including Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), and Japan Integrated Staging (JIS) scores. The majority of the patients had viral hepatitis as the underlying liver disease (100% in the derivation cohort and 85% in the validation cohort). The survival model incorporated MELD, age, number of tumor nodules, size of the largest nodule, vascular invasion, metastasis, serum albumin, and alpha-fetoprotein. In cross-validation, the coefficients remained largely unchanged between iterations. Observed survival in the validation cohort matched closely with what was predicted by the model. The concordance (c)-statistic for this model (0.77) was superior to that for BCLC (0.71), CLIP (0.70), or JIS (0.70). The score was able to further classify patient survival within each stage of the BCLC classification. CONCLUSION: A new model to predict survival of HCC patients based on objective parameters provides refined prognostication and supplements the BCLC classification.
    Hepatology 02/2012; 56(2):614-21. · 12.00 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is related to risk factors of coronary artery disease, such as dyslipidemia, diabetes, and metabolic syndrome, which are closely linked with visceral adiposity. The aim of this study was to investigate whether NAFLD was associated with coronary artery calcification (CAC), which is used as a surrogate marker for coronary atherosclerosis independent of computed tomography (CT)-measured visceral adiposity. Out of 5,648 subjects who visited one of our health screening centers between 2003 and 2008, we enrolled 4,023 subjects (mean age, 56.9 ± 9.4 years; 60.7% males) without known liver disease or a history of ischemic heart disease. CAC score was evaluated using the Agatston method. On univariate analysis, the presence of CAC (score >0) was significantly associated with age, sex, body mass index, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, triglycerides, and increased risk of diabetes, hypertension, smoking, and NAFLD. Increasing CAC scores (0, <10, 10-100, ≥ 100) were associated with higher prevalence of NAFLD (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.61-2.10; P<0.001). Multivariable ordinal regression analysis was adjusted for traditional risk factors, and CT-measured visceral adipose tissue area in a subgroup of subjects showed that the increased CAC scores were significantly associated with the presence of NAFLD (OR, 1.28, 95% CI, 1.04-1.59; P = 0.023) independent of visceral adiposity. CONCLUSION: Patients with NAFLD are at increased risk for coronary atherosclerosis independent of classical coronary risk factors, including visceral adiposity. These data suggest that NAFLD might be an independent risk factor for coronary artery disease.
    Hepatology 01/2012; 56(2):605-13. · 12.00 Impact Factor
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    ABSTRACT: To analyze longitudinal trends in the incidence, etiology, and treatment of hepatocellular carcinoma (HCC) in community residents in Olmsted County, Minnesota, and their survival. Olmsted County residents 20 years or older with HCC newly diagnosed from January 1, 1976, through December 31, 2008, were identified using a community-wide medical record linkage system (Rochester Epidemiology Project). The incidence rate of HCC was calculated by age and sex according to the 2000 US Census population. Temporal trends of HCC etiology, treatment, and patient survival were assessed. The age- and sex-adjusted incidence rate for HCC in Olmsted County was 3.5 per 100,000 person-years for the first era (1976-1990), 3.8 per 100,000 for the second era (1991-2000), and 6.9 per 100,000 for the third era (2001-2008). Alcohol use was the most common risk factor in the first and second eras and chronic hepatitis C virus in the third. The proportion attributed to nonalcoholic fatty liver disease was small (5/47 [10.6%] in the third era). Because the proportion of patients receiving curative treatment increased over time, survival also improved, with a median survival time of 3, 6, and 9 months in the first, second, and third eras, respectively (P=.01). In this midwestern US community, the incidence of HCC has increased, primarily due to hepatitis C virus. Although there was a demonstrable improvement in the outcome of HCC in community residents over time, the overall prognosis remains poor.
    Mayo Clinic Proceedings 01/2012; 87(1):9-16. · 5.79 Impact Factor
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    ABSTRACT: The Model for End Stage Liver Disease (MELD) was originally developed based on data from patients who underwent the transjugular intrahepatic portosystemic shunt procedure. An updated MELD based on data from patients awaiting liver transplantation should improve mortality prediction and allocation efficiency. Wait-list data from adult primary liver transplantation candidates from the Organ Procurement and Transplantation Network were divided into a model derivation set (2005-2006; n=14,214) and validation set (2007-2008; n=13,945). Cox regression analysis was used to derive and validate an optimized model that updated coefficients and upper and lower bounds for MELD components and included serum levels of sodium. Main outcomes measure was ability to predict 90-day mortality of patients on the liver transplantation wait list. Optimized MELD score updated coefficients and implemented new upper and lower bounds for creatinine (0.8 and 3.0 mg/dL, respectively) and international normalized ratio (1 and 3, respectively). Serum sodium concentrations significantly predicted mortality, even after adjusting for the updated MELD model. The final model, based on updated fit of the 4 variables (ie, bilirubin, creatinine, international normalized ratio, and sodium) had a modest yet statistically significant gain in discrimination (concordance: 0.878 vs 0.865; P<.01) in the validation dataset. Utilization of the new score could affect up to 12% of patients (based on changed score for 459 of 3981 transplants in the validation set). Modification of MELD score to update coefficients, change upper and lower bounds, and incorporate serum sodium levels improved wait-list mortality prediction and should increase efficiency of allocation of donated livers.
    Gastroenterology 02/2011; 140(7):1952-60. · 12.82 Impact Factor
  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor
  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor
  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor
  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor

Publication Stats

201 Citations
292.90 Total Impact Points

Institutions

  • 2009–2013
    • Mayo Clinic - Rochester
      • • Department of Gastroenterology and Hepatology
      • • Department of Hospital Internal Medicine
      Rochester, MN, United States
    • Mayo Foundation for Medical Education and Research
      • Division of Gastroenterology and Hepatology
      Rochester, MI, United States