Clinical and genetic contributions to medical comorbidity in bipolar disorder: a study using electronic health records-linked biobank data.

Bipolar disorder is a chronic and complex polygenic disease with high rates of comorbidity. However, the independent contribution of either diagnosis or genetic risk of bipolar disorder to the medical comorbidity profile of individuals with the disease remains unresolved. Here, we conducted a multi-step phenome-wide association study (PheWAS) of bipolar disorder using phenomes derived from the electronic health records of participants enrolled in the Mayo Clinic Biobank and the Mayo Clinic Bipolar Disorder Biobank. First, we explored the conditions associated with a diagnosis of bipolar disorder by conducting a phenotype-based PheWAS followed by LASSO-penalized regression to account for correlations within the phenome. Then, we explored the conditions associated with bipolar disorder polygenic risk score (BD-PRS) using a PRS-based PheWAS with a sequential exclusion approach to account for the possibility that diagnosis, instead of genetic risk, may drive such associations. 53,386 participants (58.7% women) with a mean age at analysis of 67.8 years (SD = 15.6) were included. A bipolar disorder diagnosis (n = 1479) was associated with higher rates of psychiatric conditions, injuries and poisonings, endocrine/metabolic and neurological conditions, viral hepatitis C, and asthma. BD-PRS was associated with psychiatric comorbidities but, in contrast, had no positive associations with general medical conditions. While our findings warrant confirmation with longitudinal-prospective studies, the limited associations between bipolar disorder genetics and medical conditions suggest that shared environmental effects or environmental consequences of diagnosis may have a greater impact on the general medical comorbidity profile of individuals with bipolar disorder than its genetic risk.

Antidepressants that increase mitochondrial energetics may elevate risk of treatment-emergent mania.

Preclinical evidence suggests that antidepressants (ADs) may differentially influence mitochondrial energetics. This study was conducted to investigate the relationship between mitochondrial function and illness vulnerability in bipolar disorder (BD), specifically risk of treatment-emergent mania (TEM). Participants with BD already clinically phenotyped as TEM+ (n = 176) or TEM- (n = 516) were further classified whether the TEM associated AD, based on preclinical studies, increased (Mito+, n = 600) or decreased (Mito-, n = 289) mitochondrial electron transport chain (ETC) activity. Comparison of TEM+ rates between Mito+ and Mito- ADs was performed using generalized estimating equations to account for participants exposed to multiple ADs while adjusting for sex, age at time of enrollment into the biobank and BD type (BD-I/schizoaffective vs. BD-II). A total of 692 subjects (62.7% female, 91.4% White, mean age 43.0 ± 14.0 years) including 176 cases (25.3%) of TEM+ and 516 cases (74.7%) of TEM- with previous exposure to Mito+ and/or Mito- antidepressants were identified. Adjusting for age, sex and BD subtype, TEM+ was more frequent with antidepressants that increased (24.7%), versus decreased (13.5%) mitochondrial energetics (OR = 2.21; p = 0.000009). Our preliminary retrospective data suggests there may be merit in reconceptualizing AD classification, not solely based on monoaminergic conventional drug mechanism of action, but additionally based on mitochondrial energetics. Future prospective clinical studies on specific antidepressants and mitochondrial activity are encouraged. Recognizing pharmacogenomic investigation of drug response may extend or overlap to genomics of disease risk, future studies should investigate potential interactions between mitochondrial mechanisms of disease risk and drug response.

Phenotypic distinctions in depression and anxiety: a comparative analysis of comorbid and isolated cases.

BACKGROUND: Anxiety and depression are frequently comorbid yet phenotypically distinct. This study identifies differences in the clinically observable phenome across a wide variety of physical and mental disorders comparing patients with diagnoses of depression without anxiety, anxiety without depression, or both depression and anxiety. METHODS: Using electronic health records for 14 994 participants with depression and/or anxiety in the Mayo Clinic Biobank, a phenotype-based phenome-wide association study (Phe2WAS) was performed to test for differences between these groups across a broad range of clinical diagnoses observed in the electronic health record. Additional analyses were performed to determine the temporal sequencing of diagnoses. RESULTS: Compared to patients diagnosed only with anxiety, those diagnosed only with depression were more likely to have diagnoses of obesity (OR 1.75; p = 1 × 10-27), sleep apnea (OR 1.71; p = 1 × 10-22), and type II diabetes (OR 1.74; p = 9 × 10-18). Compared to those diagnosed only with depression, those diagnosed only with anxiety were more likely to have diagnoses of palpitations (OR 1.91; p = 2 × 10-25), benign skin neoplasms (OR 1.61; p = 2 × 10-17), and cardiac dysrhythmias (OR 1.45; p = 2 × 10-12). Patients with comorbid depression and anxiety were more likely to have diagnoses of other mental health disorders, substance use disorders, sleep problems, and gastroesophageal reflux relative to isolated depression. CONCLUSIONS: While depression and anxiety are closely related, this study suggests that phenotypic distinctions exist between depression and anxiety. Improving phenotypic characterization within the broad categories of depression and anxiety could improve the clinical assessment of depression and anxiety.

The genetic contribution to the comorbidity of depression and anxiety: a multi-site electronic health records study of almost 178 000 people.

BACKGROUND: Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation. METHODS: Diagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry. RESULTS: In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18-1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05-1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06-1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11-1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02-1.09), showing a genetic risk gradient across the conditions and the comorbidity. CONCLUSIONS: This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.

Poor Relationship Between Fractionated Exhaled Nitric Oxide and Disease Activity in Eosinophilic Esophagitis.

Current eosinophilic esophagitis care requires monitoring with repeat endoscopy and biopsy, which has significant cost, risk, and inconvenience for patients. Fractionated exhaled nitric oxide testing (FeNO) is a standardized non-invasive test with proven utility in evaluation of asthma. Elevated FeNO has reported use in other eosinophilic inflammatory conditions; however, its use in eosinophilic esophagitis has not been fully evaluated. To assess the utility of FeNO in predicting severity of eosinophilic esophagitis activity. Fifty patients received fractionated exhaled nitric oxide testing within 1 week of endoscopic evaluation with biopsy for determination of peak eosinophil counts. Presence of furrows was also evaluated with respect to FeNO levels. Spearman correlation was calculated between FeNO and peak eosinophil counts (PEC) with subgroup analysis performed based on PPI use. Spearman correlation was performed on the change in FeNO and PEC on the patients receiving repeat testing. FeNO was poorly correlated to PEC (Spearman correlation 0.22). With a cut-off FeNO value of > 40 ppb, specificity of FeNO for detecting presence of ≥ 15 eos/hpf was 0.94 and sensitivity was 0.16. FeNO showed weak relationship to presence of furrows. Within the subgroup of patients not taking PPI, the spearman correlation was 0.21. Delta- FeNO versus Delta-PEC had spearman correlation of 0.72 for patients receiving repeat testing. FeNO likely has limited clinical utility for predicting severity of esophageal eosinophilia. In patients with FeNO levels > 40 ppb, specificity of testing was high, but very few patients reached this FeNO level.

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

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.

Pouchitis Is a Common Complication in Patients With Familial Adenomatous Polyposis Following Ileal Pouch-Anal Anastomosis.

BACKGROUND & AIMS: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical procedure most commonly selected for patients with familial adenomatous polyposis (FAP) or ulcerative colitis that is refractive to medical treatment. Pouchitis is the most common complication in patients with ulcerative colitis after IPAA, but is thought to rarely occur in patients with FAP. We investigated the frequency of pouchitis and other pouch-related complications in patients with FAP after IPAA. METHODS: We performed a retrospective cohort study of all patients with FAP who underwent IPAA at a single tertiary institution from 1992 through 2015 (n = 113). Patients were identified using International Classification of Diseases-9 diagnostic and current procedural terminology codes. We obtained relevant demographic and clinical data from patients' electronic medical records. The frequencies of pouchitis and pouch-related complications were determined. RESULTS: Twenty-five patients (22.1%) developed pouchitis (mean time to pouchitis, 4.1 years) and 88 did not (77.9%). Patients with pouchitis showed a trend toward developing late (>90 days after IPAA) pouch-related complications (56.0% of patients with pouchitis developed late complications, compared with 36.4% without). In patients who developed pouchitis, the disease course was acute in 72.0% and chronic in 28.0%. Of those treated, 69.6% responded to antibiotics, 13.0% became dependent on antibiotics, and 13.0% developed antibiotic resistance. CONCLUSIONS: Pouchitis is more prevalent in patients with FAP than previously believed. Although pouchitis seems to occur later in patients with FAP than in patients with ulcerative colitis, and have a milder course, it should be considered a common complication among patients with FAP following IPAA.

Quantifying the impact of chronic conditions on a diagnosis of major depressive disorder in adults: a cohort study using linked electronic medical records.

BACKGROUND: Major depressive disorder (MDD) is often comorbid with other chronic mental and physical health conditions. Although the literature widely acknowledges the association of many chronic conditions with the risk of MDD, the relative importance of these conditions on MDD risk in the presence of other conditions is not well investigated. In this study, we aimed to quantify the relative contribution of selected chronic conditions to identify the conditions most influential to MDD risk in adults and identify differences by age. METHODS: This study used electronic health record (EHR) data on patients empanelled with primary care at Mayo Clinic in June 2013. A validated EHR-based algorithm was applied to identify newly diagnosed MDD patients between 2000 and 2013. Non-MDD controls were matched 1:1 to MDD cases on birth year (±2 years), sex, and outpatient clinic visits in the same year of MDD case diagnosis. Twenty-four chronic conditions defined by Chronic Conditions Data Warehouse were ascertained in both cases and controls using diagnosis codes within 5 years of index dates (diagnosis dates for cases, and the first clinic visit dates for matched controls). For each age group (45 years or younger, between 46 and 60, and over 60 years), conditional logistic regression models were used to test the association between each condition and subsequent MDD risk, adjusting for educational attainment and obesity. The relative influence of these conditions on the risk of MDD was quantified using gradient boosting machine models. RESULTS: A total of 11,375 incident MDD cases were identified between 2000 and 2013. Most chronic conditions (except for eye conditions) were associated with risk of MDD, with different association patterns observed depending on age. Among 24 chronic conditions, the greatest relative contribution was observed for diabetes mellitus for subjects aged ≤ 60 years and rheumatoid arthritis/osteoarthritis for those over 60 years. CONCLUSIONS: Our results suggest that specific chronic conditions such as diabetes mellitus and rheumatoid arthritis/osteoarthritis may have greater influence than others on the risk of MDD.

Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.

Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviours and although strides have been made using genome-wide association studies to identify risk variants, most variants identified have been for nicotine consumption, rather than TUD. Here we leveraged four US biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records) in 653,790 individuals (495,005 European, 114,420 African American and 44,365 Latin American) and data from UK Biobank (ncombined = 898,680). We identified 88 independent risk loci; integration with functional genomic tools uncovered 461 potential risk genes, primarily expressed in the brain. TUD was genetically correlated with smoking and psychiatric traits from traditionally ascertained cohorts, externalizing behaviours in children and hundreds of medical outcomes, including HIV infection, heart disease and pain. This work furthers our biological understanding of TUD and establishes electronic health records as a source of phenotypic information for studying the genetics of TUD.

Pharmacotherapy exposure as a marker of disease complexity in bipolar disorder: Associations with clinical & genetic risk factors.

Individuals with bipolar disorder (BD) require chronic pharmacotherapy, typically including medication switches or polypharmacy due to persisting symptoms or intolerable side effects. Here, we quantified pharmacotherapy exposure (PE) of Mayo Clinic BD Biobank participants using the number of cross-sectional (at enrollment) and lifetime BD-specific medications and medication classes, to understand the relationship between PE and markers of disease severity or treatment failure, psychiatric comorbidities, and polygenic risk scores (PRS) for six major psychiatric disorders. Being female (p < 0.05), older (p < 0.01), having history of suicide attempts (p < 0.0001), and comorbid attention-deficit/hyperactivity disorder (p < 0.05) or generalized anxiety disorder (p < 0.05) were uniformly associated with higher PE. Lifetime exposure to unique medication classes among participants with BD-I was significantly lower than for those with schizoaffective disorder (estimate = -2.1, p < 0.0001) while significantly higher than for those with BD-II (estimate = 0.5, p < 0.01). Further, higher PRS for schizophrenia (SCZ) and anxiety resulted in greater lifetime medication counts (p < 0.01), both driven by antipsychotic (p < 0.001) and anxiolytic use (p < 0.05). Our results provide initial evidence of the utility of PE as a measure of disease complexity or treatment resistance, and that PE may be predicted by higher genetic risk for SCZ and anxiety.

Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous health outcomes.

Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviors, and although strides have been made using genome-wide association studies (GWAS) to identify risk variants, the majority of variants identified have been for nicotine consumption, rather than TUD. We leveraged five biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records, EHR) in 898,680 individuals (739,895 European, 114,420 African American, 44,365 Latin American). We identified 88 independent risk loci; integration with functional genomic tools uncovered 461 potential risk genes, primarily expressed in the brain. TUD was genetically correlated with smoking and psychiatric traits from traditionally ascertained cohorts, externalizing behaviors in children, and hundreds of medical outcomes, including HIV infection, heart disease, and pain. This work furthers our biological understanding of TUD and establishes EHR as a source of phenotypic information for studying the genetics of TUD.

Quantification of diet quality utilizing the rapid eating assessment for participants-shortened version in bipolar disorder: Implications for prospective depression and cardiometabolic studies.

OBJECTIVES: Recognizing bipolar disorder as a multi-system metabolic condition driven, in part, by binge eating behavior and atypical depressive symptoms, this study aimed to quantify diet quality and evaluate clinical correlates in a bipolar disorder cohort. METHODS: Participants from the Mayo Clinic Bipolar Disorder Biobank (n = 734) completed the Rapid Eating Assessment for Participants - Shortened version (REAP-S) to determine diet quality. The average REAP-S score for a U.S. omnivorous diet is 32 (range 13 to 39) with higher scores indicating healthier diet. Demographic variables were collected in a standardized clinical questionnaire. Depressive symptoms were assessed by the Bipolar Inventory of Symptoms Scale. Cardiometabolic variables were retrieved from the electronic health record. Associations between continuous variables and REAP-S scores (total, 'healthy foods' and 'avoidance of unhealthy foods') were assessed using linear regression. RESULTS: Overall, our sample had a mean REAP-S score of 27.6 (4.9), suggestive of a lower diet quality than the average general population in the US. There was a significant inverse relationship between mean REAP-S lower scores with increased BMI, waist circumference, disordered eating and depression. All these associations were significantly stronger in female participants. LIMITATIONS: EHR cross-sectional data. CONCLUSIONS: Our data suggest unhealthy diet quality in bipolar disorder is associated with depression, obesity and cardiometabolic abnormalities. Additional work is encouraged to prospectively track mood and diet quality to further understand the bidirectional relationship and clarify if dietary interventions can positively impact mood. Further delineating potential sex differences in diet quality and depression may provide greater appreciation of modifiable risk factors for future cardiometabolic burden.

Interferon Chemokine Score and Other Cytokine Measures Track With Changes in Disease Activity in Patients With Juvenile and Adult Dermatomyositis.

OBJECTIVE: Our aim was to identify cytokines and chemokines in patients with adult dermatomyositis (DM) and juvenile dermatomyositis (JDM) that predict changes in disease activity. METHODS: Multiplexed immunoassays (Meso Scale Discovery) enabled simultaneous measurement of interferon (IFN)-regulated chemokines and other pro- and anti-inflammatory cytokines specific to differentiation of specific T-cell and innate pathways. Cytokine scores were computed for IFNCK (IP-10, MCP-1), Th1 (IFNÉ£, TNFα, and IL2), Th2 (IL4, IL10, IL12, and IL 13), Th17 (IL6, IL17, IL1ß), macrophage (MIP-1α, MIP-1ß, IL8), and regulatory (IL10, TNFα) factors. Spearman correlation and mixed models were used to examine whether cytokines at a previous visit predict change in disease activity at the next visit. RESULTS: The study included 36 patients (16 DM and 20 JDM) with at least two visits (87 patient intervals between two visits). Mean age (SD) at inclusion was 56.9 (18.4) years for DM and 10.8 (6.6) years in JDM, 67% of patients were female, 89% Caucasian. The mean (SD) physician global, muscle and extra-muscular disease activity Visual Analog Scale scores at inclusion were 41 (26), 36 (30), and 34 (21) mm, respectively. The change in IFN score from one visit to the next was associated with the change in physician global (P = 0.010) and extramuscular (P < 0.001) disease activity scores. Preliminary results revealed significant correlations of previous IFNCK score and IL-6 with subsequent disease activity measures, but after adjustment for multiple visits per patient, these associations did not reach statistical significance. CONCLUSION: There is a potential relationship between IFNCK and other cytokine scores seen in adult and juvenile DM with future disease states.

Association of Asthma with Rheumatoid Arthritis: A Population-Based Case-Control Study.

BACKGROUND: TH1 and TH2 cells have counterregulatory relationships. However, the relationship between asthma, a TH2-predominant condition, and risk of systemic inflammatory diseases such as rheumatoid arthritis (RA), a TH1 condition, is poorly understood. OBJECTIVE: We aimed to determine whether asthma was associated with increased risks of incident RA among adults. METHODS: We conducted a retrospective population-based case-control study that examined existing incident RA cases and controls matched by age, sex, and registration year from the general population in Olmsted County, Minnesota, between January 2002 and December 2007. We performed comprehensive medical record reviews to ascertain asthma status using predetermined asthma criteria. The frequency of a history of asthma before the index date was compared between cases and controls. Logistic regression models were used to adjust for confounding factors. RESULTS: We enrolled 221 RA cases and 218 controls. Of the 221 RA cases, 156 (70.6%) were females, 207 (93.7%) were white, the median age at the index date was 52.5 years, and 53 (24.0%) had a history of asthma. Controls had similar characteristics except that 35 of 218 controls (16.1%) had a history of asthma. After adjustment for sex, age, smoking, body mass index, socioeconomic status, and comorbidity, asthma was significantly associated with increased risks of RA (adjusted odds ratio, 1.74; 95% CI, 1.05-2.90; P = .03). CONCLUSIONS: Despite the counterregulatory relationship between TH1 and TH2 cells, patients with asthma had a significantly higher risk of developing RA than healthy individuals.

Improving Quality of Life in Patients at Risk for Post-Intensive Care Syndrome.

OBJECTIVE: To improve quality of life (QOL) in patients at risk for post-intensive care syndrome (PICS). PATIENTS AND METHODS: We conducted a mixed-method, prospective, observational, pre-post interventional study in an adult medical and mixed medical/surgical/transplant intensive care unit (ICU) at a tertiary academic hospital. Preintervention included patients admitted from October 1 through October 31, 2016, and postintervention included patients admitted from January 15 through February 14, 2017. First, a multidisciplinary team of stakeholders identified barriers associated with decreased QOL in patients at risk for PICS. Next, interventions were designed and implemented. The effect of interventions was assessed using a mixed-method analysis. The qualitative analysis used a modified grounded theory approach. The quantitative analysis included assessment of preexisting symptoms and risk factors associated with PICS. The 36-Item Short-Form Health Status Survey (SF-36), which surveys physical and mental composite scores, was used to assess QOL. RESULTS: Barriers identified were lack of awareness and understanding of PICS. Interventions included educational videos, paper and online education and treatment materials, and online and in-person support groups for education and treatment. After interventions, the qualitative analysis found that patients who participated in the interventions after hospital discharge showed improved QOL, whereas education during hospitalization alone was not effective. The quantitative analysis did not find improvement in QOL, as defined by SF-36 physical or mental composite scores. CONCLUSION: Interventions targeted to patients after hospitalization may offer subjective improvement in QOL for those at risk for PICS.

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

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. (Hepatology Communications 2018;2:188-198).

Preoperative Clostridium difficile Infection Does Not Affect Pouch Outcomes in Patients with Ulcerative Colitis Who Undergo Ileal Pouch-anal Anastomosis.

BACKGROUND: The operation of choice for patients with chronic ulcerative colitis (CUC) is restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Pouchitis is the most common complication after IPAA. The incidence of Clostridium difficile infection (CDI) is higher in CUC patients than the general population and can lead to significant disease flares and higher rates of colectomy. We sought to determine the risk of pouchitis in patients with precolectomy CDI and 90-day postoperative IPAA complications. METHODS: A retrospective case-control study was conducted on patients with CUC who underwent an IPAA between January 1, 2000 and January 10, 2015. The study cohort was comprised of patients diagnosed with CDI within 90 days before colectomy; patients with CUC without CDI comprised the control cohort. The primary outcome measure was the frequency of pouchitis after IPAA. Secondary outcomes included time to pouchitis, 90-day postoperative pouch morbidity: surgical site infection, hemorrhage, anastomotic leak, fistula formation, pouchitis treatment and response, and pouch failure requiring end-ileostomy or fecal diversion. Univariate and multivariable analysis was used to determine differences between CDI and non-CDI groups. RESULTS: Forty-eight case patients and 154 control patients were included. Patients with preoperative CDI were younger (P = 0.010), had higher rates of medically refractory disease (P = 0.002), and had greater use of biologic therapy (P = 0.046). The rate of pouchitis was 50.0% (n = 24) and 46.8% (n = 72) (P = 0.694) among patients with and without preoperative CDI, respectively. Patients with preoperative CDI who developed pouchitis post-IPAA were more likely to require medical management with an anti-TNFα (P = 0.042) and surgical management with end/diverting ileostomy (P = 0.042). Preoperative CDI was associated with higher rates of postoperative IPAA anastamotic or pouch strictures (P = 0.018). Multivariable analysis revealed primary sclerosing cholangitis (PSC) as the only variable associated with increased risk for pouchitis (OR 10.59; 95% CI, 3.07-51.08; P < 0.001). CONCLUSIONS: Preoperative CDI does not seem to be associated with an increased risk of pouchitis in patients with CUC.

Gene Expression Profiling in Blood and Affected Muscle Tissues Reveals Differential Activation Pathways in Patients with New-onset Juvenile and Adult Dermatomyositis.

OBJECTIVE: To identify shared and differential molecular pathways in blood and affected muscle between adult dermatomyositis (DM) and juvenile DM, and their association with clinical disease activity measures. METHODS: Gene expression of transcription factors and cytokines involved in differentiation and effector function of T cell subsets, regulatory T cells and follicular Th cells, were analyzed in the blood from 21 newly diagnosed adult and 26 juvenile DM subjects and in 15 muscle specimens (7 adult and 8 juvenile DM) using a custom RT2 Profiler PCR Array. Disease activity was determined and measured by established disease activity tools. RESULTS: The most prominent finding was the higher blood expression of Th17-related cytokines [retinoic acid-related orphan receptor-γ, interferon regulatory factor 4, interleukin (IL)-23A, IL-6, IL-17F, and IL-21] in juvenile DM at baseline. In contrast, adult patients with DM showed increased blood levels of STAT3 and BCL6 compared with juvenile DM. In muscle, GATA3, IL-13, and STAT5B were found at higher levels in juvenile patients with DM compared with adult DM. Among 25 patients (11 adult and 14 juvenile DM) who had blood samples at baseline and at 6 months, increased expression of IL-1ß, STAT3, STAT6, STAT5B, and BCL6 was associated with an improvement in global extramuscular disease activity. CONCLUSION: We observed differences in gene expression profiling in blood and muscle between new-onset adult and juvenile DM. Cytokine expression in the blood of juvenile patients with new-onset DM was dominated by Th17-related cytokines compared with adult patients with DM. This may reflect the activation of different Th pathways between muscle and blood.

Ethnicity, Socioeconomic Status, and Health Disparities in a Mixed Rural-Urban US Community-Olmsted County, Minnesota.

OBJECTIVE: To characterize health disparities in common chronic diseases among adults by socioeconomic status (SES) and ethnicity in a mixed rural-urban community of the United States. PATIENTS AND METHODS: We conducted a cross-sectional study to assess the association of the prevalence of the 5 most burdensome chronic diseases in adults with SES and ethnicity and their interaction. The Rochester Epidemiology Project medical records linkage system was used to identify the prevalence of coronary heart disease, asthma, diabetes, hypertension, and mood disorder using International Classification of Diseases, Ninth Revision codes recorded from January 1, 2005, through December 31, 2009, among all adult residents of Olmsted County, Minnesota, on April 1, 2009. For SES measurements, an individual HOUsing-based index of SocioEconomic Status (HOUSES) derived from real property data was used. Logistic regression models were used to examine the association of the prevalence of chronic diseases with ethnicity and HOUSES score and their interaction. RESULTS: We identified 88,010 eligible adults with HOUSES scores available, of whom 48,086 (54.6%) were female and 80,699 (91.7%) were non-Hispanic white; the median (interquartile range) age was 45 years (30-58 years). Overall and in the subgroup of non-Hispanic whites, SES measured by HOUSES was inversely associated with the prevalence of all 5 chronic diseases independent of age, sex, and ethnicity (P<.001). While an association of ethnicity with disease prevalence was observed for all the chronic diseases, SES modified the effect of ethnicity for clinically less overt conditions (interaction P<.05 for each condition [diabetes, hypertension, and mood disorder]) but not for coronary heart disease, a clinically more overt condition. CONCLUSION: In a mixed rural-urban setting with a predominantly non-Hispanic white population, health disparities in chronic diseases still exist across SES. The extent to which SES modifies the effect of ethnicity on the risk of chronic diseases may depend on the nature of the disease.