Baseline Clinical Factors Are Associated With Risk of Complications in Crohn's Disease: Appraisal of the American Gastroenterological Association Clinical Care Pathway.

INTRODUCTION: The American Gastroenterological Association (AGA) has compiled risk factors that may be predictive of disease complications in Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate the performance of the AGA risk factors for risk stratification in UC and CD. METHODS: We included participants of 2 cohorts: the Ocean State Crohn's and Colitis Area Registry cohort and the Mayo Clinic cohort. Baseline clinical risk factors were extracted according to the AGA pathway. Our primary end point was defined as follows: (i) any inflammatory bowel disease related-hospitalization, (ii) any inflammatory bowel disease-related bowel surgery, or (iii) any progression of disease. We analyzed the association of the number of AGA risk factors with our end point. Statistical multivariable modeling was performed with Cox proportional hazards model. RESULTS: A total of 412 patients with CD were included. Comparing ≥3 risk factors with 0-1 risk factor, we found a significantly increased risk of complications in both the Ocean State Crohn's and Colitis Area Registry cohort (hazard ratio [HR] 2.75, 95% confidence interval 1.71-4.41) and Mayo Clinic cohort (HR 2.07, 95% confidence interval 1.11-3.84). Diagnosis at younger age (HR 2.07), perianal disease (HR 1.99), and B2/B3 behavior (HR 1.92) were significantly associated with disease complications. We did not observe a consistent association between number of risk factors nor any specific individual risk factors and risk of disease complications in the 265 patients with UC included. DISCUSSION: We found a significant association between the number of AGA risk factors and the risk of disease complication in CD; this association was not significant in UC. The presence of ≥ 3 risk factors in CD leads to the highest risk of complications. The AGA care pathway is a useful tool to stratify patients who are at higher risk of disease complications in patients with CD.

Use of the Esophageal Sponge in Directing Food Reintroduction in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Dietary therapy is successful in eosinophilic esophagitis (EoE) but requires multiple upper endoscopies. The aim of this study was to determine if food reintroduction in EoE can be directed by minimally-invasive esophageal sponge cytology. METHODS: In this prospective non-blinded trial, 22 responders to 6-food elimination diets underwent sequential food reintroduction guided by esophageal sponge cytology. Foods were reintroduced followed by unsedated esophageal sponge cytology assessment. A food trigger was defined by sponge cytology peak eosinophil count of ≥15 eos/high-powered field (hpf). Symptoms (EoE symptom activity index [EEsAI]), endoscopic score (EoE endoscopic reference score [EREFS]), and biopsy histology (peak eosinophil count) were collected pre-dietary therapy and post-dietary therapy, and then 4 weeks post food reintroduction. RESULTS: The EEsAI and EREFS were similar post-dietary therapy to post-food reintroduction: 12.0 (interquartile range [IQR], 0.0-27.0) vs 16.5 (IQR, 9.0-28.8) (P = .265) and 1.5 (IQR, 0.2-3.0) vs 1.0 (IQR, 0.0-2.0) (P = .185). However, the peak eosinophil count was increased post-food reintroduction compared with post-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 2.0 (IQR, 1.0-4.0) (P < .001), suggesting a failure of identification of all food triggers. The peak eosinophil count was lower post-food reintroduction compared with pre-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 52.0 (IQR, 30.8-76.2) (P = .008). At the post food reintroduction evaluation, sponge cytology and biopsy histology were in agreement in 59% (13/22) of cases using a cutoff of <15 eos/hpf and 68% (15/22) of cases using a cutoff of <6 eos/hpf. CONCLUSIONS: In the first study to evaluate a non-endoscopic technique in the clinical management of EoE, the esophageal sponge was moderately successful at guiding food reintroduction in EoE dietary responders in the outpatient setting. CLINICALTRIALS: gov, Number NCT02599558.

Neuropathologic evaluation of cerebrovascular disease in patients with rheumatoid arthritis.

OBJECTIVES: Active RA has been associated with an increased risk of both cardiovascular and peripheral vascular disease. We aimed to compare cerebrovascular changes in patients with and without RA, both with and without a neuropathologic diagnosis of neurodegenerative disease. METHODS: Patients with RA (n = 32) who died and underwent autopsy between 1994 and 2021 were matched to non-RA controls (n = 32) on age, sex and level of neurodegenerative proteinopathy. Routine neuropathologic examination was performed at the time of autopsy. Cerebrovascular disease severity was evaluated using modified Kalaria and Strozyk scales. Clinical dementia diagnoses were manually collected from patients' medical records. RESULTS: Prior to death, 15 (47%) RA patients and 14 (44%) controls were diagnosed with dementia; 9 patients in each group (60% and 64%, respectively) had Alzheimer's disease. The prevalence of cerebral amyloid angiopathy, microinfarcts, infarcts or strokes was found to be similar between groups. Patients with RA were more likely to have more severe vascular changes in the basal ganglia by Kalaria scale (P = 0.04), but not in other brain areas. There were no significant differences in the presence of large infarcts, lacunar infarcts or leukoencephalopathy by Strozyk scale. Among patients with RA and no clinical diagnosis of dementia, the majority had mild-moderate cerebrovascular abnormalities, and a subset of patients had Alzheimer's disease neuropathologic changes. CONCLUSION: In this small series of autopsies, patients with and without RA had largely similar cerebrovascular pathology when controlling for neurodegenerative proteinopathies, although patients with RA exhibited more pronounced cerebrovascular disease in the basal ganglia.

Interobserver agreement of the modified Paris classification and histology prediction of colorectal lesions in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: SCENIC (International Consensus Statement on Surveillance and Management of Dysplasia in IBD) guidelines recommend that visible dysplasia in patients with longstanding inflammatory bowel disease (IBD) should be endoscopically characterized using a modified Paris classification. This study aimed to determine the interobserver agreement (IOA) of the modified Paris classification and endoscopists' accuracy for pathology prediction of IBD visible lesions. METHODS: One hundred deidentified endoscopic still images and 30 videos of IBD visible colorectal lesions were graded by 10 senior and 4 trainee endoscopists from 5 tertiary care centers. Endoscopists were asked to assign 4 classifications for each image: the standard Paris classification, modified Paris classification, pathology prediction, and lesion border. Agreement was measured using Light's kappa coefficient. Consensus of ratings was assessed according to strict majority. RESULTS: The overall Light's kappa for all study endpoints was between .32 and .49. In a subgroup analysis between junior and senior endoscopists, Light's kappa continued to be less than .6 with a slightly higher agreement among juniors. Lesions with the lowest agreement and no consensus were mostly classified as Is, IIa, and mixed Paris classification and sessile and superficial elevated for modified Paris classification. Endoscopist accuracy for prediction of dysplastic, nondysplastic, and serrated pathology was 77%, 56%, and 30%, respectively. There was a strong association (P < .001) between the given morphology classification and the predicted pathology with Ip lesions carrying a much lower expectation of dysplasia than Is/IIc/III and mixed lesions. The agreement for border prediction was .5 for junior and .3 for senior endoscopists. CONCLUSIONS: This study demonstrates very low IOA for Paris and modified Paris classifications and low accuracy and IOA for lesion histopathology prediction. Revisions of these classifications are required to create a clinically useful risk stratification tool and enable eventual application of augmented intelligence tools.

Eosinophilic Esophagitis Histologic Scoring System: Correlation with Histologic, Endoscopic, and Symptomatic Disease and Clinical Use.

BACKGROUND: The eosinophilic esophagitis histologic scoring system (EoEHSS) was developed to enhance the diagnostic standard of peak eosinophil count (PEC) in evaluating disease activity in EoE. AIMS: (1) Correlate the EoEHSS and PEC to measures of symptomatic and endoscopic disease activity, (2) Correlate EoEHSS grade and stage subcomponents to clinical, radiology, and endoscopic markers of fibrotic disease, (3) Evaluate EoEHSS remission in asymptomatic patients with PEC < 15 eosinophils per high powered field (eos/hpf). METHODS: Secondary analysis of prospective cohort data of 22 patients with EoE that underwent dietary therapy and endoscopy at 3 time points. Active disease was defined by EoEHSS grade or stage > 0.125, symptomatic disease by EoE symptom activity index > 20, endoscopic disease by endoscopic reference score > 2, and histologic disease by PEC ≥ 15 eos/hpf. EoEHSS remission was defined by esophageal inflammation (EI) grade of 0-1, EI stage of 0, total grade ≤ 3, and total stage ≤ 3. RESULTS: EoEHSS grade and stage did not correlate with symptomatic disease but did with endoscopic and histologic disease. PEC showed similar correlation pattern. Abnormal grade and stage had strong sensitivity (87-100%) but poor specificity (11-36%) to detect symptomatic, endoscopic, and histologic disease activity. Lamina propria fibrosis was evaluated in 36% of biopsies and did not correlate with minimum esophageal diameter. Out of 14 patients who were in complete symptomatic, endoscopic, and histologic remission, 8 met criteria for EoEHSS remission. CONCLUSION: The positive and negative correlations of EoEHSS to specific measures of symptomatic, histologic, and endoscopic activity suggest that it provides complementary information in EoE.

Digital Tool-Assisted Hospitalization Detection in the Tailored Antiplatelet Initiation to Lessen Outcomes due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention Study Compared to Traditional Site-Coordinator Ascertainment: Intervention Study.

BACKGROUND: Accurate, timely ascertainment of clinical end points, particularly hospitalizations, is crucial for clinical trials. The Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention (TAILOR-PCI) Digital Study extended the main TAILOR-PCI trial's follow-up to 2 years, using a smartphone-based research app featuring geofencing-triggered surveys and routine monthly mobile phone surveys to detect cardiovascular (CV) hospitalizations. This pilot study compared these digital tools to conventional site-coordinator ascertainment of CV hospitalizations. OBJECTIVE: The objectives were to evaluate geofencing-triggered notifications and routine monthly mobile phone surveys' performance in detecting CV hospitalizations compared to telephone visits and health record reviews by study coordinators at each site. METHODS: US and Canadian participants from the TAILOR-PCI Digital Follow-Up Study were invited to download the Eureka Research Platform mobile app, opting in for location tracking using geofencing, triggering a smartphone-based survey if near a hospital for ≥4 hours. Participants were sent monthly notifications for CV hospitalization surveys. RESULTS: From 85 participants who consented to the Digital Study, downloaded the mobile app, and had not previously completed their final follow-up visit, 73 (85.8%) initially opted in and consented to geofencing. There were 9 CV hospitalizations ascertained by study coordinators among 5 patients, whereas 8 out of 9 (88.9%) were detected by routine monthly hospitalization surveys. One CV hospitalization went undetected by the survey as it occurred within two weeks of the previous event, and the survey only allowed reporting of a single hospitalization. Among these, 3 were also detected by the geofencing algorithm, but 6 out of 9 (66.7%) were missed by geofencing: 1 occurred in a participant who never consented to geofencing, while 5 hospitalizations occurred among participants who had subsequently turned off geofencing prior to their hospitalization. Geofencing-detected hospitalizations were ascertained within a median of 2 (IQR 1-3) days, monthly surveys within 11 (IQR 6.5-25) days, and site coordinator methods within 38 (IQR 9-105) days. The geofencing algorithm triggered 245 notifications among 39 participants, with 128 (52.2%) from true hospital presence and 117 (47.8%) from nonhospital health care facility visits. Additional geofencing iterative improvements to reduce hospital misidentification were made to the algorithm at months 7 and 12, elevating the rate of true alerts from 35.4% (55 true alerts/155 total alerts before month 7) to 78.7% (59 true alerts/75 total alerts in months 7-12) and ultimately to 93.3% (14 true alerts/5 total alerts in months 13-21), respectively. CONCLUSIONS: The monthly digital survey detected most CV hospitalizations, while the geofencing survey enabled earlier detection but did not offer incremental value beyond traditional tools. Digital tools could potentially reduce the burden on study coordinators in ascertaining CV hospitalizations. The advantages of timely reporting via geofencing should be weighed against the issue of false notifications, which can be mitigated through algorithmic refinements.

Primary Sclerosing Cholangitis-Associated Pouchitis: A Distinct Clinical Phenotype.

BACKGROUND & AIMS: Patients with primary sclerosing cholangitis (PSC) commonly undergo ileal pouch-anal anastomosis (IPAA) for medically-refractory ulcerative colitis (UC) or colorectal dysplasia. Pouchitis develops more frequently in patients with PSC, potentially leading to increased morbidity. We aimed to assess clinical characteristics and treatment outcomes for pouchitis in patients with PSC compared to a matched, non-PSC cohort. METHODS: All patients with PSC who underwent IPAA and were diagnosed with pouchitis (PSC-pouchitis) were identified. A matched cohort composed of non-PSC patients who underwent IPAA for UC and subsequently developed pouchitis (UC-pouchitis) was developed. Relevant demographic, clinical, endoscopic, histologic, and treatment data were collected and compared between groups. RESULTS: Of those with PSC-pouchitis (n=182), 53.9% and 46.1% underwent IPAA for medically-refractory disease and dysplasia, respectively, compared to 88.7% and 11.3% in the UC-pouchitis group (P < .001). Patients with PSC-pouchitis were more likely to develop chronic pouchitis (68.1% vs 34.1%; P < .001), have moderate-to-severe pouch inflammation (54.9% vs 32.4%; P < .001), and prepouch ileitis (34.1% vs 11.5%; P < .001) compared to UC-pouchitis. Of those with PSC-pouchitis, 50.6% and 17.6% developed chronic antibiotic-dependent or antibiotic-refractory pouchitis, respectively, compared to 25.8% and 7.7% with UC-pouchitis. There was no difference in treatment response between the two groups with use of thiopurines, anti-tumor necrosis factor agents, and newer biologics. CONCLUSIONS: PSC-associated pouchitis presents with a unique clinical phenotype, characterized by increased risk of chronic pouchitis, moderate-to-severe pouch inflammation, prepouch ileitis, and less response to conventional antimicrobial therapy.

Microscopic Colitis and Risk of Colon Adenomas: A Multicenter Retrospective Cohort Study.

Microscopic colitis (MC) is a common cause of chronic watery diarrhea, with the highest incidence in women over age 50.1 Cross-sectional studies have suggested that patients with MC have a lower incidence of adenomatous colon polyps compared with those without MC.2-4 The existing literature is limited by cross-sectional design, small sample sizes, lack of longitudinal follow-up, and the use of average-risk patients, rather than those with chronic diarrhea, as controls. We aimed to explore the association between MC and colon adenomas.

High-Dimensional Clustering of 4000 Irritable Bowel Syndrome Patients Reveals Seven Distinct Disease Subsets.

BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) is a pain disorder classified by bowel habits, disregarding other factors that may influence the clinical course. The aim of this study was to determine if IBS patients can be clustered based on clinical, dietary, lifestyle, and psychosocial factors. METHODS: Between 2013 and 2020, the Mayo Clinic Biobank surveyed and received 40,291 responses to a questionnaire incorporating Rome III criteria. Factors associated with IBS were determined and latent class analysis, a model-based clustering, was performed on IBS cases. RESULTS: We identified 4021 IBS patients (mean 64 years; 75% women) and 12,063 controls. Using 26 variables separating cases from controls, the optimal clustering revealed 7 latent clusters. These were characterized by perceived health impairment (moderate or severe), psychoneurological factors, and bowel dysfunction (diarrhea or constipation predominance). Health impairment clusters demonstrated more pain, with the severe cluster also having more psychiatric comorbidities. The next 3 clusters had unique enrichment of psychiatric, neurological, or both comorbidities. The bowel dysfunction clusters demonstrated less abdominal pain, with diarrhea cluster most likely to report pain improvement with defecation. The constipation cluster had the highest exercise score and consumption of fruits, vegetables, and alcohol. The distribution of clusters remained similar when Rome IV criteria were applied. Physiologic tests were available on a limited subset (6%), and there were no significant differences between clusters. CONCLUSIONS: In this cohort of older IBS patients, 7 distinct clusters were identified demonstrating varying degrees of gastrointestinal symptoms, comorbidities, dietary, and lifestyle factors. Further research is required to assess whether these unique clusters could be used to direct clinical trials and individualize patient management.

Prospective Study Assessing Impact of Ethylene Oxide Sterilization on Endoscopic Ultrasound Image Quality.

BACKGROUND & AIMS: Duodenoscope-associated transmission of infections has raised questions about efficacy of endoscope reprocessing using high-level disinfection (HLD). Although ethylene oxide (ETO) gas sterilization is effective in eradicating microbes, the impact of ETO on endoscopic ultrasound (EUS) imaging equipment remains unknown. In this study, we aimed to compare the changes in EUS image quality associated with HLD vs HLD followed by ETO sterilization. METHODS: Four new EUS instruments were assigned to 2 groups: Group 1 (HLD) and Group 2 (HLD + ETO). The echoendoscopes were assessed at baseline, monthly for 6 months, and once every 3 to 4 months thereafter, for a total of 12 time points. At each time point, review of EUS video and still image quality was performed by an expert panel of reviewers along with phantom-based objective testing. Linear mixed effects models were used to assess whether the modality of reprocessing impacted image and video quality. RESULTS: For clinical testing, mixed linear models showed minimal quantitative differences in linear analog score (P = .04; estimated change, 3.12; scale, 0-100) and overall image quality value (P = .007; estimated change, -0.12; scale, 1-5) favoring ETO but not for rank value (P = .06). On phantom testing, maximum depth of penetration was lower for ETO endoscopes (P < .001; change in depth, 0.49 cm). CONCLUSIONS: In this prospective study, expert review and phantom-based testing demonstrated minimal differences in image quality between echoendoscopes reprocessed using HLD vs ETO + HLD over 2 years of clinical use. Further studies are warranted to assess the long-term clinical impact of these findings. In the interim, these results support use of ETO sterilization of EUS instruments if deemed clinically necessary.

Point of care CYP2C19 genotyping after percutaneous coronary intervention.

Loss-of-function CYP2C19 variants are associated with increased cumulative ischemic outcomes warranting CYP2C19 genotyping prior to clopidogrel administration. TAILOR-PCI was an international, multicenter (40 sites), prospective, randomized trial comparing rapid point of care (POC) genotype-guided vs. conventional anti-platelet therapy. The performance of buccal-based rapid CYP2C19 genotyping performed by non-laboratory-trained staff in TAILOR-PCI was assessed. Pre-trial training and evaluation involved rapid genotyping of 373 oral samples, with 99.5% (371/373) concordance with Sanger sequencing. During TAILOR-PCI, 5302 patients undergoing PCI were randomized to POC rapid CYP2C19 *2, *3, and *17 genotyping versus no genotyping. At 12 months post-PCI, TaqMan genotyping determined 99.1% (2,364/2,385) concordance with the POC results, with 90.7-98.8% sensitivity and 99.2-99.6% specificity. In conclusion, non-laboratory personnel can be successfully trained for on-site instrument operation and POC rapid genotyping with analytical accuracy and precision across multiple international centers, thereby supporting POC genotyping in patient-care settings, such as the cardiac catheterization laboratory.Clinical Trial Registration: https://www.clinicalTrials.gov (Identifier: NCT01742117).

Outcomes of idiopathic versus secondary nodular regenerative hyperplasia of the liver: A longitudinal study of 167 cases.

BACKGROUND: Nodular regenerative hyperplasia (NRH) is a rare condition characterized clinically by the development of non-cirrhotic portal hypertension. NRH is the histopathological result in the liver of various systemic disease processes including autoimmune disorders, haematological malignancies and medications. However, natural history of this condition has been limited to small case series while patient outcomes pertaining to different aetiologies of NRH are largely unknown. METHODS: A retrospective cohort of consecutive patients diagnosed with pathology-confirmed NRH at Mayo Clinic between 2002 and 2017 was identified. The histological diagnosis of NRH was determined by expert liver pathologists. Patients with metastatic liver disease, history of liver transplantation or younger than 18 were excluded. Potential aetiologies of NRH were classified as haematological, rheumatological, drug-associated, miscellaneous or idiopathic. Long-term mortality was analysed using Kaplan-Meier estimation and Cox regression models. RESULTS: One hundred and sixty-seven consecutive patients with pathology-confirmed NRH were analysed over a 15-year period and followed for a median time of 50 months (1-306 months). The mean age at diagnosis was 53 years. No aetiology or risk factor for NRH was identified in the majority of patients (94, 56.3%), whereas an associated, possibly causal, condition was found in 73 patients (secondary NRH). The most common presenting feature was elevated liver tests (80%), but no significant differences in laboratory tests were seen based on aetiology of NRH. Compared to idiopathic NRH, those with an identified cause had a higher rate of splenomegaly at presentation (54% vs. 27%, p = 0.002). Portal hypertension-related complications at diagnosis were common, with ascites present in one-third of patients. Overall transplant-free survival was 63% at 5 years. Median survival in idiopathic NRH was 9.4 years compared to 7.3 years in secondary NRH. Age, renal function and volume status at presentation were significantly associated with survival; however, MELD score was not. CONCLUSIONS: The rates of liver-related complications and mortality in NRH are low, and only a small number of patients ultimately require liver transplantation. Most patients do not have an identified risk factor or aetiology for NRH, and liver-related outcomes do not appear to differ based on associated, possibly causal, conditions.

Safety and Efficacy of CYP2C19 Genotype-Guided Escalation of P2Y12 Inhibitor Therapy After Percutaneous Coronary Intervention in Chronic Kidney Disease: a Post Hoc Analysis of the TAILOR-PCI Study.

PURPOSE: Chronic kidney disease (CKD) is a risk factor for ischemic and bleeding events with dual antiplatelet therapy after percutaneous coronary intervention (PCI). Whether the presence of CYP2C19 loss of function (LOF) alleles modifies this risk, and whether a genotype-guided (GG) escalation of P2Y12 inhibitor therapy post PCI is safe in this population is unclear. METHODS: This was a post hoc analysis of randomized patients in TAILOR PCI. Patients were divided into two groups based on estimated glomerular filtration rate (eGFR) threshold of < 60 ml/min/1.73 m2 for CKD (n = 539) and non-CKD (n = 4276). The aggregate of cardiovascular death, stroke, myocardial infarction, stent thrombosis, and severe recurrent coronary ischemia at 12-months post-PCI was assessed as the primary endpoint. Secondary endpoint was major or minor bleeding. RESULTS: Mean (standard deviation) eGFR among patients with CKD was 49.5 (8.4) ml/min/1.72 m2. Among all patients, there was no significant interaction between randomized strategy and CKD status for any endpoint. Among LOF carriers, the interaction between randomized strategy and CKD status on composite ischemic outcome was not significant (p = 0.2). GG strategy was not associated with an increased risk of bleeding in either CKD group. CONCLUSIONS: In this exploratory analysis, escalation of P2Y12 inhibitor therapy following a GG strategy did not reduce the primary outcome in CKD. However, P2Y12 inhibitor escalation following a GG strategy was not associated with increased bleeding risk in CKD. Larger studies in CKD are needed. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01742117?term=TAILOR-PCI&draw=2&rank=1 . NCT01742117.

Relationship Between Body Mass Index and Survival Among Critically Ill Patients With Cirrhosis.

BACKGROUND: Obesity paradox is a phenomenon in which obesity increases the risk of obesity-related chronic diseases but paradoxically is associated with improved survival among obese patients with these diagnoses. OBJECTIVES: The aim of this study was to explore the obesity paradox among critically ill patients with cirrhosis admitted to the Intensive Care Unit. METHODS: A retrospective cohort of 1,143 consecutive patients with cirrhosis admitted to the ICU between January of 2006 and December of 2015 was analyzed. Primary outcome of interest was in-hospital mortality with secondary end points including ICU and short-term mortality at 30 days post ICU admission. RESULTS: Logistic regression with generalized additive models was used, controlling for clinically relevant and statistically significant factors to determine the adjusted relationship between body mass index (BMI) and ICU, post-ICU in-hospital, and 30 day mortality following ICU discharge. ICU and hospital length of stay was similar across all BMI classes. Adjusted ICU mortality was also similar when stratified by BMI. However, a significant reduction in post-ICU hospital mortality was observed in class I and II obese patients with cirrhosis (BMI 30-39.9 kg/m2) compared to normal BMI (OR = 0.41; 95% CI, 0.20 to 0.83; P = 0.014). Similarly, overweight (BMI 25-29.9 kg/m2) and class I and II obese patients with cirrhosis had significantly lower 30-day mortality following ICU discharge (OR = 0.52, 95% CI 0.31 to 0.87; P = 0.014; OR = 0.50, 95% CI 0.29 to 0.86; P = 0.012, respectively) compared to those with normal BMI. CONCLUSION: The signal of obesity paradox is suggested among critically ill patients with cirrhosis.

Histologic response to steroids in eosinophilic esophagitis is dependent on delivery compound.

Topical steroids are commonly used in treatment of eosinophilic esophagitis (EoE), but currently there is lack of data to clarify most effective regimen. We aimed to study the achievement of histologic remission using the same dose of budesonide in two different delivery formulations. Patients with established EoE treated with pharmacy compounded budesonide capsule or budesonide Rincinol gel (both 3 mg twice daily) were studied retrospectively. Those with pre-treatment and post-treatment histologic assessment were included with main endpoint being histologic remission. 103 patients (62 gel, 41 capsule) were included, with higher rate of histologic remission with gel (84 vs. 59%, P=0.004). A subset of patients in both groups had lack of steroid response (<50% drop in eosinophils) (15% for gel, 32% for capsule). Formulation/delivery vehicle of steroid treatments to esophageal mucosa in EoE appears important for treatment efficacy, with budesonide gel having higher likelihood of histologic remission compared to budesonide capsules in our population. A truly steroid refractory group appears likely in our population. Larger, prospective studies may help clarify best regimen of topical steroids in EoE and may work to identify patients likely to benefit from alternative therapies.

Incidence, Trends, and Outcomes of Type 2 Myocardial Infarction in a Community Cohort.

BACKGROUND: Type 2 myocardial infarction (T2MI) occurs because of an acute imbalance in myocardial oxygen supply and demand in the absence of atherothrombosis. Despite being frequently encountered in clinical practice, the population-based incidence and trends remain unknown, and the long-term outcomes are incompletely characterized. METHODS: We prospectively recruited residents of Olmsted County, Minnesota, who experienced an event associated with a cardiac troponin T >99th percentile of a normal reference population (≥0.01 ng/mL) between January 1, 2003, and December 31, 2012. Events were retrospectively classified into type 1 myocardial infarction (T1MI, atherothombotic event), T2MI, or myocardial injury (troponin rise not meeting criteria for myocardial infarction [MI]) using the universal definition. Outcomes were long-term all-cause and cardiovascular mortality and recurrent MI. T2MI was further subclassified by the inciting event for supply/demand mismatch. RESULTS: A total of 5460 patients had at least one cardiac troponin T ≥0.01 ng/mL; 1365 of these patients were classified as index T1MI (age, 68.5±14.8 years; 63% male) and 1054 were classified as T2MI (age, 73.7±15.8 years; 46% male). The annual incidence of T1MI decreased markedly from 202 to 84 per 100 000 persons between 2003 and 2012 (P<0.001), whereas the incidence of T2MI declined from 130 to 78 per 100 000 persons (P=0.02). In comparison with patients with T1MI, patients with T2MI had higher long-term all-cause mortality after adjustment for age and sex, driven by early and noncardiovascular death. Rates of cardiovascular death were similar after either type of MI (hazard ratio, 0.8 [95% CI, 0.7-1.0], P=0.11). Subclassification of T2MI by cause demonstrated a more favorable prognosis when the principal provoking mechanism was arrhythmia, in comparison with postoperative status, hypotension, anemia, and hypoxia. After index T2MI, the most common MI during follow-up was a recurrent T2MI, whereas the occurrence of a new T1MI was relatively rare (estimated rates at 5 years, 9.7% and 1.7%). CONCLUSIONS: There has been an evolution in the type of MI occurring in the community over a decade, with the incidence of T2MI now being similar to T1MI. Mortality after T2MI is higher and driven by early and noncardiovascular death. The provoking mechanism of supply/demand mismatch affects long-term survival. These findings underscore the healthcare burden of T2MI and provide benchmarks for clinical trial design.

Clostridioides difficile Whole-genome Sequencing Differentiates Relapse With the Same Strain From Reinfection With a New Strain.

BACKGROUND: Current approaches in tracking Clostridioides difficile infection (CDI) and individualizing patient management are incompletely defined. METHODS: We recruited 468 subjects with CDI at Mayo Clinic Rochester between May and December 2016 and performed whole-genome sequencing (WGS) on C. difficile isolates from 397. WGS was also performed on isolates from a subset of the subjects at the time of a recurrence of infection. The sequence data were analyzed by determining core genome multilocus sequence type (cgMLST), with isolates grouped by allelic differences and the predicted ribotype. RESULTS: There were no correlations between C. difficile isolates based either on cgMLST or ribotype groupings and CDI outcome. An epidemiologic assessment of hospitalized subjects harboring C. difficile isolates with ≤2 allelic differences, based on standard infection prevention and control assessment, revealed no evidence of person-to-person transmission. Interestingly, community-acquired CDI subjects in 40% of groups with ≤2 allelic differences resided within the same zip code. Among 18 subjects clinically classified as having recurrent CDI, WGS revealed 14 with initial and subsequent isolates differing by ≤2 allelic differences, suggesting a relapse of infection with the same initial strain, and 4 with isolates differing by >50 allelic differences, suggesting reinfection. Among the 5 subjects classified as having a reinfection based on the timing of recurrence, 3 had isolates with ≤2 allelic differences between them, suggesting a relapse, and 2 had isolates differing by >50 allelic differences, suggesting reinfection. CONCLUSIONS: Our findings point to potential transmission of C. difficile in the community. WGS better differentiates relapse from reinfection than do definitions based on the timing of recurrence.

Characteristics and Risk Factors of Post-Infection Irritable Bowel Syndrome After Campylobacter Enteritis.

BACKGROUND & AIMS: Campylobacter is the leading cause of bacterial gastroenteritis in the United States. We investigated the prevalence of postinfection irritable bowel syndrome (PI-IBS) in a cohort with culture-confirmed Campylobacter cases; risk factors for PI-IBS based on clinical factors; and shifts in IBS patterns postinfection in patients with pre-existing IBS. METHODS: The Minnesota Department of Health collects data on symptoms and exposures upon notification of Campylobacter cases. From 2011 through 2019, we sent surveys (the Rome III and IBS symptom severity surveys) to 3586 patients 6 to 9 months after Campylobacter infection. The prevalence of PI-IBS was estimated and risk factors were assessed using multivariable logistic regression. RESULTS: There were 1667 responders to the survey, 249 of whom had pre-existing IBS. Of the 1418 responders without pre-existing IBS, 301 (21%) subsequently developed IBS. Most of these individuals had IBS-mixed (54%), followed by IBS-diarrhea (38%), and IBS-constipation (6%). The mean IBS symptom severity score was 218 (indicating moderate severity). Female sex, younger age, bloody stools, abdominal cramps, and hospitalization during acute enteritis were associated with increased risk, whereas fever was protective for the development of PI-IBS. Antibiotic use and exposure patterns were similar between PI-IBS and control groups. Among patients with IBS-mixed or IBS-diarrhea before infection, 78% retained their subtypes after infection. In contrast, only 50% of patients with IBS-constipation retained that subtype after infection, whereas 40% transitioned to IBS-mixed. Of patients with pre-existing IBS, 38% had increased frequency of abdominal pain after Campylobacter infection. CONCLUSIONS: In a cohort of patients with Campylobacter infection in Minnesota, 21% developed PI-IBS; most cases reported mixed IBS or diarrhea of moderate severity. Demographic and clinical factors during acute enterocolitis are associated with PI-IBS development. Campylobacter infection also can result in a switch of a pre-existing IBS phenotype.

Rationale and design of the TAILOR-PCI digital study: Transitioning a randomized controlled trial to a digital registry.

BACKGROUND: Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention (TAILOR-PCI) is the largest cardiovascular genotype-based randomized pragmatic trial (NCT#01742117) to evaluate the role of genotype-guided selection of oral P2Y12 inhibitor therapy in improving ischemic outcomes after PCI. The trial has been extended from the original 12- to 24-month follow-up, using study coordinator-initiated telephone visits. TAILOR-PCI Digital Study tests the feasibility of extending the trial follow-up in a subset of patients for up to 24 months using state-of-the-art digital solutions. The rationale, design, and approach of extended digital study of patients recruited into a large, international, multi-center clinical trial has not been previously described. METHODS: A total of 930 patients from U.S. and Canadian sites previously enrolled in the 5,302 patient TAILOR-PCI trial within 23 months of randomization are invited by mail to the Digital Study website (http://tailorpci.eurekaplatform.org) and by up to 2 recruiting telephone calls. Eureka, a direct-to-participant digital research platform, is used to consent and collect prospective data on patients for the digital study. Patients are asked to answer health-related surveys at fixed intervals using the Eureka mobile app and or desktop platform. The likelihood of patients enrolled in a randomized clinical trial transitioning to a registry using digital technology, the reasons for nonparticipation and engagement rates are evaluated. To capture hospitalizations, patients may optionally enable geofencing, a process that allows background location tracking and triggering of surveys if a hospital visit greater than 4 hours is detected. In addition, patients answer digital hospitalization surveys every month. Hospitalization data received from the Digital Study will be compared to data collected from study coordinator telephone visits during the same time frame. CONCLUSIONS: The TAILOR-PCI Digital Study evaluates the feasibility of transitioning a large multicenter randomized clinical trial to a digital registry. The study could provide evidence for the ability of digital technology to follow clinical trial patients and to ascertain trial-related events thus also building the foundation for conducting digital clinical trials. Such a digital approach may be especially pertinent in the era of COVID-19.

Clinical impact of celiac ganglia metastasis upon pancreatic ductal adenocarcinoma.

BACKGROUND: Pre-operative staging of pancreatic adenocarcinoma guides clinical decision making. Limited data indicate that metastasis to celiac ganglia (CG) correlates with poor prognosis. We investigated feasibility and safety of endoscopic ultrasound fine needle aspiration (EUS-FNA) detection of CG metastasis and its impact upon tumor stage, resectability, and survival in pancreatic ductal adenocarcinoma (PDAC). PATIENTS: We reviewed our prospectively maintained EUS and cytopathology databases to identify patients with FNA proven CG metastasis in patients with PDAC from 2004 to 2017. Clinical demographics, EUS, CT, MRI, cytopathology, cancer stage, and resectability data were analyzed. Survival of PDAC patients with CG metastasis was compared to the expected survival of PDAC patients of similar stage as reported by the United States National Cancer Database. RESULTS: Twenty-one patients with PDAC [median age 73 (IQR63-78); 14 (67%) female)], had CG metastasis confirmed by cytopathologic assessment. CG metastasis resulted in tumor upstaging relative to other EUS findings and cross sectional imaging findings in 12 (57%) and 15 (71%) patients, and converted cancers from resectable to unresectable relative to EUS and cross sectional imaging in 7 (37%) and 7 (37%) patients, respectively. In patients with PDAC, the survival of patients with CG metastasis was not significantly different from the overall survival (hazard ratio 0.71; 95% confidence interval 0.44, 1.13; p = 0.15). CONCLUSIONS: EUS-FNA may safely identify CG metastases. While CG metastasis upstaged and altered the resectability status among this cohort of patients with PDAC, the survival data with regard to PDAC suggest that this may be misguided.