Performance of American Gastroenterological Association Clinical Care Pathway for the risk stratification of patients with nonalcoholic fatty liver disease in the US population.

BACKGROUND AND AIMS: The American Gastroenterological Association (AGA) recently launched the Clinical Care Pathway for the Risk Stratification and Management of Patients with NAFLD to identify adults with significant fibrosis. We aimed to examine this pathway's performance in the US population. APPROACH AND RESULTS: Using the 2017-2018 National Health and Nutrition Examination Survey data, we identified participants aged ≥18 with available Fibrosis-4 (FIB-4) score and liver stiffness measurement (LSM) in the absence of other liver diseases. Based on the AGA clinical pathway, FIB-4 < 1.3 and LSM < 8 kilopascals (kPa) by vibration-controlled transient elastography (VCTE) are associated with low risk of significant fibrosis. Using these cutoffs, we examined the pathway performance using negative predictive value (NPV) and positive predictive value (PPV) and explored alternative risk-stratification strategies. There were 2322 participants with available data (projected to 94.2 million US adults). The NPV of LSM ≥ 8 kPa among those with FIB-4 < 1.3 was 90%, whereas the PPV among those with FIB-4 1.3-2.67 was 13%. As diabetes was a strong predictor of fibrosis, we propose a simple, alternative strategy to eliminate the indeterminate FIB-4 range and perform VCTE in those with FIB-4 ≥ 1.3 and diabetes. This strategy would decrease the number of VCTEs from 14.5 to 4.9 million and increase PPV from 13% to 33% without compromising the NPV among those who did not undergo VCTE. CONCLUSION: The implementation of the current AGA clinical pathway would lead to overutilization of VCTE. An alternative strategy using FIB-4 ≥ 1.3 and diabetes to select adults undergoing second-line testing will improve this pathway's performance and minimize unnecessary VCTEs.

Changing the face of academic medicine: an equity action plan for institutions.

In recent years, there have been concerted efforts to better recruit, support, and retain diverse faculty, staff, and trainees in academic medicine. However, many institutions lack comprehensive and strategic plans to provide support to retain and recruit individuals from historically underrepresented groups. In this article, we itemize specific mechanisms through which institutions can support diverse individuals with the goal of improving inclusion and belonging in the workforce to better reflect the diversity of the intended patient and research participant population.

Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design.

BACKGROUND & AIMS: The predicted risk and timeline to progression to liver-related outcomes in the population with NAFLD are not well-characterized. We aimed to examine the risk and time to progression to cirrhosis, hepatic decompensation and death in a contemporary population over a long follow-up period, to obtain information to guide endpoint selection and sample size calculations for clinical trials on NAFLD-related cirrhosis. METHODS: This is a retrospective study of prospectively collected data in a medical record linkage system, including all adults diagnosed with NAFLD between 1996-2016 by clinical, biochemical and radiological criteria in Olmsted County, Minnesota and followed until 2019. Liver-related outcomes and death were ascertained and validated by individual medical record review. Time and risk of progression from NAFLD to cirrhosis to decompensation and death were assessed using multistate modeling. RESULTS: A total of 5,123 individuals with NAFLD (median age 52 years, 53% women) were followed for a median of 6.4 (range 1-23) years. The risk of progression was as follows: from NAFLD to cirrhosis: 3% in 15 years; compensated cirrhosis to first decompensation: 33% in 4 years (8%/year); first decompensation to ≥2 decompensations: 48% in 2 years. Albumin, bilirubin, non-bleeding esophageal varices and diabetes were independent predictors of decompensation. Among the 575 deaths, 6% were liver related. Therapeutic trials in compensated cirrhosis would require enrolment of a minimum of 2,886 individuals followed for >2 years to detect at least a 15% relative decrease in liver-related endpoints. CONCLUSION: In this population-based cohort with 23 years of longitudinal follow-up, NAFLD was slowly progressive, with liver-related outcomes affecting only a small proportion of people. Large sample sizes and long follow-up are required to detect reductions in liver-related endpoints in clinical trials. LAY SUMMARY: For patients with compensated non-alcoholic steatohepatitis-related cirrhosis, the time spent in this state and the risk of progression to decompensation are not well-known in the population. We examined the clinical course of a large population-based cohort over 23 years of follow-up. We identified that adults with compensated cirrhosis spend a mean time of 4 years in this state and have a 10% per year risk of progression to decompensation or death. The risk of further progression is 3-fold higher in adults with cirrhosis and one decompensating event. These results are reflective of placebo arm risks in drug clinical trials and are essential in the estimation of adequate sample sizes.

Clinical course of light-chain smouldering multiple myeloma (idiopathic Bence Jones proteinuria): a retrospective cohort study.

BACKGROUND: Bence Jones proteinuria is a disorder that is defined by the excretion of monoclonal light-chain protein. About 15-20% of patients with multiple myeloma secrete monoclonal light chains only, without expression of the normal immunoglobulin heavy chain, which constitutes light-chain multiple myeloma. The definition, prevalence, and progression of these premalignant phases of light-chain multiple myeloma have not been fully characterised. We aimed to identify a subset of patients with idiopathic Bence Jones proteinuria who had a high risk of progression to light-chain multiple myeloma analogous to that seen in patients with smouldering multiple myeloma. METHODS: In this retrospective cohort study, we studied all patients seen at the Mayo Clinic (Rochester, MN, USA) within 30 days of diagnosis of idiopathic Bence Jones proteinuria between Jan 1, 1960, and June 30, 2004. Inclusion criteria were monoclonal light chain in the urine (≥0·2 g/24 h), absence of intact monoclonal immunoglobulin (M protein) in the serum, and no evidence of multiple myeloma, light-chain amyloidosis, or other related plasma-cell proliferative disorders. The primary endpoint was progression to symptomatic multiple myeloma or light-chain amyloidosis. We examined the cumulative probability of progression and the association of potential risk factors on progression rates to identify patients with a high risk of progression to multiple myeloma or light-chain amyloidosis. FINDINGS: We identified 101 patients with idiopathic Bence Jones proteinuria. During 901 total person-years of follow-up, 27 (27%) patients developed multiple myeloma and seven (7%) developed light-chain amyloidosis. The major risk factors for progression were amount of urinary excretion of M protein per 24 h, proportion of bone marrow plasma cells, presence of a markedly abnormal free-light-chain ratio (<0·01 or >100), and reduction of all three uninvolved immunoglobulins. Based on the risk of progression, monoclonal light-chain excretion of 0·5 g/24 h or greater or at least 10% bone marrow plasma cells, or both, in the absence of end-organ damage was used to define light-chain smouldering multiple myeloma. The cumulative probability of progression to active multiple myeloma or light-chain amyloidosis in patients with light-chain smouldering multiple myeloma was 27·8% (95% CI 14·2-39·2) at 5 years, 44·6% (27·9-57·4) at 10 years, and 56·5% (36·3-70·2) at 15 years. INTERPRETATION: Light-chain smouldering multiple myeloma as defined in this study is associated with a high risk of progression to symptomatic light-chain multiple myeloma, and this subset of patients needs careful observation and could benefit from clinical trials of early intervention. FUNDING: Jabbs Foundation (Birmingham, UK), US National Cancer Institute, and Henry J Predolin Foundation (Madison, WI, USA).

Effect of the pretransplant serum sodium concentration on outcomes following liver transplantation.

Hyponatremia is associated with an increased risk of mortality on the liver transplantation (LT) waiting list. Although the incorporation of the serum sodium (Na) level into the Model for End-Stage Liver Disease score may reduce wait-list mortality, concerns remain about a potential association between pre-LT hyponatremia and decreased post-LT survival. Furthermore, the relationship between pre-LT hypernatremia and post-LT survival remains unexplored. The purpose of this study was to investigate the impact of the entire spectrum of pre-LT serum Na levels on post-LT outcomes. We identified 19,537 patients from 2003 to 2010 for whom serum Na levels immediately before LT were available. The patients were divided into 3 groups [hyponatremic (Na ≤ 130 mEq/L), normonatremic (Na = 131-145 mEq/L), and hypernatremic (Na > 145 mEq/L)], and their post-LT outcomes were compared. There was no difference in in-hospital mortality or 90-day survival between patients with hyponatremia and patients with normonatremia. A fraction of the patients (2.4%) had hypernatremia, which was associated with increased in-hospital mortality (11.2% versus 4.2%, P < 0.001) and diminished 90-day survival (86.4% versus 94.0.%, P < 0.001). After adjustments for important clinical variables, the association of pre-LT hypernatremia with posttransplant mortality remained significant with a hazard ratio of 1.13 for each unit increase in the Na level > 145 mEq/L (P < 0.001). The duration of the hospitalization after LT was significantly longer for hypernatremic patients (P < 0.001). In conclusion, hyponatremia per se does not affect post-LT survival. Pre-LT hypernatremia is a highly significant risk factor for post-LT mortality.

Excellent quality of life after liver transplantation for patients with perihilar cholangiocarcinoma who have undergone neoadjuvant chemoradiation.

Patients with perihilar cholangiocarcinoma (CCA) undergoing neoadjuvant chemoradiation followed by liver transplantation (LT) have excellent survival. However, little is known about their quality of life (QOL). We assessed the QOL of these patients and compared it to the QOL of patients who underwent transplantation for other liver diseases. From 1993 to 2010, 129 CCA patients underwent LT, and 93 (72%) were alive as of November 2010. All recipients were sent a previously validated QOL questionnaire composed of disease-specific QOL metrics (liver disease symptoms, Karnofsky score, health perception, and index of well-being) and generic QOL metrics [Short Form 36 (SF-36) and European Quality of Life (EuroQol)]. These recipients were compared to 110 transplant recipients with other liver diseases (excluding hepatitis C). Among the recipients with CCA, the response rate was 85% (n = 79). Patients with CCA did significantly better on liver disease symptoms (3.3 versus 3.2, P = 0.05), the Karnofsky score (90.8 versus 86.6, P = 0.03), the SF-36 Physical Functioning domain (52.0 versus 46.3, P < 0.001), and the EuroQol Mobility category (10% versus 33%, P = 0.001), and they rated their overall health better in comparison with non-CCA patients (85.9 versus 80.7, P = 0.02). CCA patients scored consistently higher on all other domains, albeit without significant differences. The observed differences in QOL remained unchanged when adjustments were made for demographic factors, including the level of education. In conclusion, patients who underwent neoadjuvant chemoradiation followed by LT for perihilar CCA reported excellent QOL that was equal to or better than that of recipients with other liver diseases. These results are important in light of the continued debate about the feasibility of this aggressive treatment in patients with perihilar CCA.

Immunoglobulin m monoclonal gammopathy of undetermined significance and smoldering Waldenström macroglobulinemia.

Monoclonal gammopathy of undetermined significance of the immunoglobulin M class was diagnosed in 213 patients at the Mayo Clinic, 29 (14%) of whom developed lymphoma, Waldenström macroglobulinemia, or a related disorder over 1567 person-years of follow-up. The cumulative probability of progression was 10% at 5 years, 18% at 10 years, and 24% at 15 years, or approximately 1.5% per year. The concentration of serum monoclonal protein at diagnosis and the initial serum albumin value were the only independent predictors of progression with multivariate analysis. By contrast, during 285 person-years of follow-up, 34 (71%) of 48 patients with smoldering Waldenström macroglobulinemia (SWM) progressed to Waldenström macroglobulinemia (WM), which required therapy, along with amyloid light chain (AL) amyloidosis (1) and lymphoma (1). The cumulative probability of progression was 6% at 1 year, 39% at 3 years, 59% at 5 years, and 65% at 10 years. The percentage of lymphoplasmacytic cells in the bone marrow, size of the serum monoclonal (M) spike, and hemoglobin value were significant independent risk factors for progression.

A clinical deterioration prediction tool for internal medicine patients.

Many early warning models for hospitalized patients use variables measured on admission to the hospital ward; few have been rigorously derived and validated. The objective was to create and validate a clinical deterioration prediction tool using routinely collected clinical and nursing measurements. Multivariate regression analysis was used to determine clinical variables statistically associated with clinical deterioration; subsequently, the model tool was retrospectively validated using a different cohort of medical inpatients. The Braden Scale (P = .01; odds ratio [OR] = 0.91; confidence interval [CI] = 0.84-0.98), respiratory rate (P < .01; OR = 1.08; CI = 1.04-1.13), oxygen saturation (P < .01; OR = 0.97; CI = 0.96-0.99), and shock index (P < .01; OR = 2.37; CI = 1.14-3.98) were predictive of clinical deterioration 2-12 hours in the future. When applied to the validation cohort, the tool demonstrated fair concordance with actual outcomes. This tool created using routinely collected clinical measurements can serve as a very early warning system for hospitalized medical patients.

Incidence of monoclonal gammopathy of undetermined significance and estimation of duration before first clinical recognition.

OBJECTIVES: To determine the incidence of monoclonal gammopathy of undetermined significance (MGUS) in the general population and to estimate the duration of occult MGUS before first diagnosis. METHODS: To estimate incidence we used innovative methods to exploit the Olmsted County, Minnesota, MGUS prevalence data, along with follow-up from a large cohort of patients with clinically detected MGUS. The prevalence cohort consisted of 21,463 persons systematically screened for the presence or absence of MGUS. The clinical cohort consisted of 7472 patients with MGUS diagnosed at Mayo Clinic from January 1, 1990, to May 13, 2010. The incidence of MGUS was estimated using the prevalence estimates, the rate of MGUS progression, and the death rates from MGUS using Markov chain methods. RESULTS: We estimate that the annual incidence of MGUS in men is 120 per 100,000 population at the age of 50 years and increases to 530 per 100,000 population at the age of 90 years. The rates for women are 60 per 100,000 population at the age of 50 years and 370 per 100,000 population at the age of 90 years. We estimate that 56% of women 70 years of age diagnosed as having MGUS have had the condition for more than 10 years, including 28% for more than 20 years. Corresponding values for men are 55% and 31%, respectively. At 60 years of age, the proportion of prevalent cases that are clinically recognized is 13%. This rate increases to 33% at the age of 80 years. CONCLUSION: In addition to an accumulation of cases, the age-related increase in prevalence of MGUS is related to a true increase in incidence with age. When first clinically recognized, MGUS has likely been present in an undetected state for a median duration of more than 10 years.

Progression in smoldering Waldenstrom macroglobulinemia: long-term results.

The purpose of this study was to define the risk of progression and survival of patients with smoldering Waldenström macroglobulinemia (SWM). SWM is defined clinically as having a serum monoclonal IgM protein≥3 g/dL and/or≥10% bone marrow lymphoplasmacytic infiltration but no evidence of end-organ damage (anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly). We searched a computerized database and reviewed the medical records of all patients at Mayo Clinic who fulfilled the criteria of SWM between 1974 and 1995. During 285 cumulative person-years of follow-up of the 48 patients with SWM (median, 15.4 years), 34 (71%) progressed to symptomatic Waldenström macroglobulinemia (WM) requiring treatment, one to primary amyloidosis, and one to lymphoma (total, 75%). The cumulative probability of progression to symptomatic WM, amyloidosis, or lymphoma was 6% at 1 year, 39% at 3 years, 59% at 5 years, and 68% at 10 years. The major risk factors for progression were percentage of lymphoplasmacytic cells in the bone marrow, size of the serum M-spike, and the hemoglobin value. Patients with SWM should be followed and not treated until symptomatic WM develops. Treatment on a clinical trial for those at greatest risk of progression should be considered.

Long-term biological variation of serum protein electrophoresis M-spike, urine M-spike, and monoclonal serum free light chain quantification: implications for monitoring monoclonal gammopathies.

BACKGROUND: We analyzed serial data in patients with clinically stable monoclonal gammopathy to determine the total variation of serum M-spikes [measured with serum protein electrophoresis (SPEP)], urine M-spikes [measured with urine protein electrophoresis (UPEP)], and monoclonal serum free light chain (FLC) concentrations measured with immunoassay. METHODS: Patients to be studied were identified by (a) no treatment during the study interval, (b) no change in diagnosis and <5 g/L change in serum M-spike over the course of observation; (c) performance of all 3 tests (SPEP, UPEP, FLC immunoassay) in at least 3 serial samples that were obtained 9 months to 5 years apart; (d) serum M-spike ≥10 g/L, urine M-spike ≥200 mg/24 h, or clonal FLC ≥100 mg/L. The total CV was calculated for each method. RESULTS: Among the cohort of 158 patients, 90 had measurable serum M-spikes, 25 had urine M-spikes, and 52 had measurable serum FLC abnormalities. The CVs were calculated for serial SPEP M-spikes (8.1%), UPEP M-spikes (35.8%), and serum FLC concentrations (28.4%). Combining these CVs and the interassay analytical CVs, we calculated the biological CV for the serum M-spike (7.8%), urine M-spike (35.5%), and serum FLC concentration (27.8%). CONCLUSIONS: The variations in urine M-spike and serum FLC measurements during patient monitoring are similar and are larger than those for serum M-spikes. In addition, in this group of stable patients, a measurable serum FLC concentration was available twice as often as a measurable urine M-spike.

Incidence, prevalence, and survival of chronic pancreatitis: a population-based study.

OBJECTIVES: Population-based data on chronic pancreatitis (CP) in the United States are scarce. We determined incidence, prevalence, and survival of CP in Olmsted County, MN. METHODS: Using Mayo Clinic Rochester's Medical Diagnostic Index followed by a detailed chart review, we identified 106 incident CP cases from 1977 to 2006 (89 clinical cases, 17 diagnosed only at autopsy); CP was defined by previously published Mayo Clinic criteria. We calculated age- and sex-adjusted incidence (for each decade) and prevalence rate (1 January 2006) per 100,000 population (adjusted to 2000 US White population). We compared the observed survival rate for patients with expected survival for age- and sex-matched Minnesota White population. RESULTS: Median age at diagnosis of CP was 58 years, 56% were male, and 51% had alcoholic CP. The overall (clinical cases or diagnosed only at autopsy) age- and sex-adjusted incidence was 4.05/100,000 person-years (95% confidence interval (CI) 3.27-4.83). The incidence rate for clinical cases increased significantly from 2.94/100,000 during 1977-1986 to 4.35/100,000 person-years during 1997-2006 (P<0.05) because of an increase in the incidence of alcoholic CP. There were 51 prevalent CP cases on 1 January 2006 (57% male, 53% alcoholic). The age- and sex-adjusted prevalence rate per 100,000 population was 41.76 (95% CI 30.21-53.32). At last follow-up, 50 patients were alive. Survival among CP patients was significantly lower than age- and sex-specific expected survival in Minnesota White population (P<0.001). CONCLUSIONS: Incidence and prevalence of CP are low, and ∼50% are alcohol related. The incidence of CP cases diagnosed during life is increasing. Survival of CP patients is lower than in the Minnesota White population.

A revised model for end-stage liver disease optimizes prediction of mortality among patients awaiting liver transplantation.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Cirrhosis is present in most patients with hepatitis B and hepatocellular carcinoma.

BACKGROUND & AIMS: There are few data available about the prevalence or effects of cirrhosis in patients with hepatocellular carcinoma (HCC) from viral hepatitis. We compared patients with HCC and hepatitis B virus (HBV) or hepatitis C virus (HCV) infections to determine the proportions of cirrhosis in each group, virologic and tumor characteristics, and overall survival. METHODS: This analysis included patients with HBV (n = 64) or HCV (n = 118) infection who were diagnosed with HCC at the Mayo Clinic in Rochester, Minnesota from 1994-2008; groups were matched for age and sex. The diagnosis of cirrhosis was based on histology and, if histologic information was insufficient or unavailable, clinical indicators that included ascites or varices, thrombocytopenia or splenomegaly, and radiographic configuration of cirrhosis. Virologic characteristics, tumor stage, and patient survival were also assessed. RESULTS: The prevalence of histologic cirrhosis was 88% among patients with HBV infection and 93% among those with HCV infection (P = .46). When the most inclusive criteria for cirrhosis were applied, cirrhosis was present in 94% of patients with HBV and 97% with HCV (P = .24). Among HCV patients, 5.2% were negative for HCV RNA after antiviral treatment; 63.4% of HBV patients had HBV DNA <2000 IU/mL with or without treatment. Patients with HBV tended to have less surveillance and more advanced stages of HCC, without differences in survival from those with HCV infection (P = .75). CONCLUSIONS: Most patients with HCC and chronic viral hepatitis had evidence of cirrhosis, including those with HBV infection and those without active viral replication.

Serum sodium, renal function, and survival of patients with end-stage liver disease.

BACKGROUND & AIMS: Serum creatinine, a component of the model for end-stage liver disease (MELD), is an important prognostic indicator in patients with end-stage liver disease (ESLD). In addition, serum sodium has recently been recognized as an important predictor of mortality in patients with ESLD. We investigate the role of serum creatinine and sodium, and glomerular filtration rate (GFR) as determinants of survival in patients with ESLD. METHODS: A prospective database was utilized to identify all adults listed for primary liver transplantation (LTx) at the Mayo Clinic, Rochester, between 1990 and 1999. GFR was measured by iothalamate clearance. RESULTS: Among 837 patients listed for LTx, 660 had complete data including measured GFR. There was a significant association between GFR and survival after adjustment for MELD, with a linear rise in the risk of death as GFR decreased between 60 and 20ml/min/1.73m(2). Multivariable models showed that GFR is superior to creatinine in predicting mortality - a model consisting of total bilirubin (hazard ratio (HR)=2.17, p<0.01), INR (HR=3.26, p<0.01) and GFR (HR=0.42, p<0.01) was superior to MELD (chi-square 65.6 vs. 59.4, c-statistic 0.792 vs. 0.780). Serum sodium did not contribute to survival prediction when accurately measured GFR data were available. CONCLUSIONS: Serum concentrations of creatinine and sodium in patients with end-stage liver disease reflect a reduction in renal function, the underlying event that decreases survival.

Impact of pretransplant hyponatremia on outcome following liver transplantation.

UNLABELLED: Hyponatremia is associated with reduced survival in patients with cirrhosis awaiting orthotopic liver transplantation (OLT). However, data are sparse regarding the impact of hyponatremia on outcome following OLT. We investigated the effect of hyponatremia at the time of OLT on mortality and morbidity following the procedure. The study included 2,175 primary OLT recipients between 1990 and 2000. Serum sodium concentrations obtained immediately prior to OLT were correlated with subsequent survival using proportional hazards analysis. Morbidity associated with hyponatremia was assessed, including length of hospitalization, length of intensive care unit (ICU) admission, and occurrence of central pontine myelinolysis (CPM). Out of 2,175 subjects, 1,495 (68.7%) had normal serum sodium (>135 mEq/L) at OLT, whereas mild hyponatremia (125-134 mEq/L) was present in 615 (28.3%) and severe hyponatremia (<125 mEq/L) in 65 (3.0%). Serum sodium had no impact on survival up to 90 days after OLT (multivariate hazard ratio = 1.00, P = 0.99). Patients with severe hyponatremia tended to have a longer stay in the ICU (median = 4.5 days) and hospital (17.0 days) compared to normonatremic recipients (median ICU stay = 3.0 days, hospital stay = 14.0 days; P = 0.02 and 0.08, respectively). There were 10 subjects that developed CPM, with an overall incidence of 0.5%. Although infrequent, the incidence of CPM did correlate with serum sodium levels (P < 0.01). CONCLUSION: Pre-OLT serum sodium does not have a statistically significant impact on survival following OLT. The incidence of CPM correlates with hyponatremia, although its overall incidence is low. Incorporation of serum sodium in organ allocation may not adversely affect the overall post-OLT outcome.

The MMPI-2: a contemporary normative study of midwestern family medicine outpatients.

For more than 60 years it has been known that profiles from the Minnesota Multiphasic Personality Inventory (MMPI), obtained from medical patients, are elevated when scores are plotted using general population norms. These elevations have been most apparent on the neurotic triad (NTd), the first 3 clinical scales on the MMPI profile. More than 45 years have passed since a nonreferred, normative sample of MMPIs was established from 50,000 consecutive medical outpatients. We present comparable but contemporary normative data for the revised MMPI (MMPI-2) based on a nonreferred sample of 1,243 family medicine outpatients (590 women; 653 men). As true for the original MMPI, contemporary medical outpatients have profiles that are significantly different, clinically and statistically, from the general population norms for the MMPI-2. This is particularly evident in elevations on the NTd. New normative tables of uniform medical T (UMT) scores were developed following the procedures used to create the uniform T scores for the MMPI-2. Measures of internal consistency are reported; test-retest reliability was established over a mean of 3.7 weeks, and results characterizing the stability of the validity and clinical scales are presented.

Hyponatremia and mortality among patients on the liver-transplant waiting list.

BACKGROUND: Under the current liver-transplantation policy, donor organs are offered to patients with the highest risk of death. METHODS: Using data derived from all adult candidates for primary liver transplantation who were registered with the Organ Procurement and Transplantation Network in 2005 and 2006, we developed and validated a multivariable survival model to predict mortality at 90 days after registration. The predictor variable was the Model for End-Stage Liver Disease (MELD) score with and without the addition of the serum sodium concentration. The MELD score (on a scale of 6 to 40, with higher values indicating more severe disease) is calculated on the basis of the serum bilirubin and creatinine concentrations and the international normalized ratio for the prothrombin time. RESULTS: In 2005, there were 6769 registrants, including 1781 who underwent liver transplantation and 422 who died within 90 days after registration on the waiting list. Both the MELD score and the serum sodium concentration were significantly associated with mortality (hazard ratio for death, 1.21 per MELD point and 1.05 per 1-unit decrease in the serum sodium concentration for values between 125 and 140 mmol per liter; P<0.001 for both variables). Furthermore, a significant interaction was found between the MELD score and the serum sodium concentration, indicating that the effect of the serum sodium concentration was greater in patients with a low MELD score. When applied to the data from 2006, when 477 patients died within 3 months after registration on the waiting list, the combination of the MELD score and the serum sodium concentration was considerably higher than the MELD score alone in 32 patients who died (7%). Thus, assignment of priority according to the MELD score combined with the serum sodium concentration might have resulted in transplantation and prevented death. CONCLUSIONS: This population-wide study shows that the MELD score and the serum sodium concentration are important predictors of survival among candidates for liver transplantation.

Serum aminotransferase activity and mortality risk in a United States community.

UNLABELLED: Serum aminotransferase [such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] is commonly used as an indicator of liver disease. The aim of the study was to determine the degree to which aminotransferase results are associated with increased mortality at the population level. All adult residents of Olmsted County, Minnesota, who had a health care encounter at Mayo Clinic, Rochester, in 1995 were identified and their AST or ALT results extracted from a laboratory database. These subjects were followed forward from January 1995 to April 2006 and their survival determined. To exclude patients with abnormal results because of a terminal illness, deaths within the first 2 years were excluded. The main outcome measure was survival. Standardized mortality ratios (SMRs) were calculated, based on Minnesota White death rates. During 1995, AST was measured at least once in 18,401 community residents, of whom 2,350 (13%) had results greater than the upper limit of normal (ULN). Of 6,823 subjects who had their ALT measured, 911 (13%) had results higher than ULN. Abnormal AST was associated with a significantly increased SMR (1.32 for 1-2x ULN and 1.78 for >2x ULN). SMR was also higher for abnormal ALT (SMR = 1.21 for 1-2x ULN and 1.51 for >2x ULN). In contrast, normal AST or ALT was associated with a risk of death lower than expected (SMR 0.95 for AST, 0.61 for ALT). CONCLUSION: Serum levels of AST and ALT obtained in a routine medical care setting are associated with future mortality in community residents.

Deaths on the liver transplant waiting list: an analysis of competing risks.

The usual method of estimating survival probabilities, namely the Kaplan-Meier method, is suboptimal in the analysis of deaths on the transplant waiting list. Death, transplantation, and withdrawal from list must all be considered. In this analysis, we applied the competing risk analysis method, which allows evaluating these end points individually and simultaneously, to compare the risk of waiting list death across era, blood types, liver disease diagnosis, and severity (Model for End-stage Liver Disease; MELD). Of 861 patients registered on the waiting list at Mayo Clinic Rochester between 1990 and 1999, 657 (76%) patients underwent transplantation, 82 (10%) died while waiting, 41 (5%) withdrew from the list, and 81 (9%) patients were still waiting as of February 2002. The risk of death at 3 years was 10% by the competing risk analysis. During the study period, the median time to transplantation increased from 45 to 517 days. In univariate analyses, there was no significant difference in the risk of death by era of listing (P = .25) or blood type (P = .31), whereas the risk of death was significantly higher in patients with alcohol-induced liver disease and those with higher MELD score (P < .01). A multivariable analysis showed that after adjusting for MELD, blood type, and diagnosis, patients listed in the latter era had higher mortality. In conclusion, the competing risk analysis method is useful in estimating the risk of death among patients awaiting liver transplantation.