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BACKGROUND: Low procedural complication rates, barriers to access, and patient preference have encouraged the development of percutaneous coronary intervention (PCI) programs at centers that are often closer to home but without on-site cardiac surgical capability. OBJECTIVES: We compared clinical and economic outcomes associated with performing low-risk elective PCI at a community hospital without on-site cardiac surgery with those obtained at a more remote tertiary care center with on-site cardiac surgery. DESIGN AND MEASURES: We matched 257 patients undergoing low-risk, elective PCI at a community hospital (Immanuel St. Joseph's Hospital [ISJ] between January 27, 2000, and July 31, 2002) to 514 PCI patients treated at a tertiary care hospital (Saint Marys Hospital [SMH] between January 27, 2000, and April 30, 2002) based on clinical and lesion criteria. Clinical outcomes (in-hospital procedural success and target vessel failure during long-term follow up) and economic outcomes (direct medical costs, billed charges, and hospital length of stay [LOS]) were compared between groups. The Mayo Clinic PCI Registry (containing clinical, angiographic, and follow-up data) and administrative data were used in matching and outcomes assessment. RESULTS: Procedural success was achieved more often among ISJ-treated patients (99% vs. 95%; P = 0.02); however, no difference in target vessel failure rates was observed during a median follow-up time of 3.1 years (estimated 1-year event rate: 15.2% vs. 14.8%; P = 0.46). ISJ-treated patients incurred, on average, $3024 more in estimated total costs ($13,771 vs. $10,746; P < 0.001) and $6084 more in billed charges (P < 0.001), but incurred similar LOS post procedure (1.53 days). CONCLUSIONS: Similar clinical outcomes were achieved at a community hospital without on-site cardiac surgery but at significantly increased direct medical cost. Patients, providers, hospitals, payers, and policymakers should consider whether the benefits associated with locally provided specialized cardiovascular services warrant this additional cost. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the short-term and long-term outcomes of patients with coronary artery disease and peripheral arterial disease (PAD) who underwent intracoronary (IC) stent Implantation during percutaneous coronary intervention (PCI) with the outcomes of patients with isolated coronary artery disease but without PAD who underwent IC stent implantation. PATIENTS AND METHODS: We analyzed the outcomes of 7696 patients who underwent IC stent implantation during PCI at the Mayo Clinic in Rochester, Minn, between January 1996 and December 2002. Outcomes of 6299 patients (82%) with Isolated coronary artery disease and without PAD who underwent IC stent implantation (group 1) were compared with outcomes of 1397 patients (18%) with coronary artery disease and PAD (group 2) who underwent PCI with IC stent implantation. RESULTS: Patients in group 2 were older (71.1+/-10.2 years vs 65.0+/-12.0 years; P<.001) and had a higher prevalence of hypertension (79% vs 61%; P<.001), diabetes mellitus (33% vs 20%; P<.001), hyperlipidemia (76% vs 70%; P<.001), and history of smoking (70% vs 63%; P<.001) compared with group 1. Prevalence of multivessel disease was higher in group 2 (79% vs 68%; P<.001). Procedural success was significantly lower In group 2 (95% vs 97%; P<.001). In-hospital complications were higher in group 2: death (3% vs 1%; P<.001), any myocardial Infarction (MI) (8% vs 5%; P<.001), death/MI/coronary artery bypass grafting (CABG)/target vessel revascularization (11% vs 7%; P<.001), and blood loss requiring transfusion (11% vs 5.8%; P<.001). After adjustment for other risk factors, the odds ratio for in-hospital death was 1.84 (95% confidence interval [CI], 1.16-2.90; P=.009), and for death/MI/CABG/target vessel revascularization, the odds ratio was 1.25 (95% CI, 1.00-1.55; P=.048) in patients with PAD treated with IC stents. Median follow-up was 3.1 years. Six-month, 1-year, and 2-year Kaplan-Meier estimates of survival free of death/MI/CABG/target vessel revascularization were 84%, 77%, and 69%, respectively, for group 2 and were significantly worse compared with group 1 (89%, 85%, and 80%, respectively; P<.001). This effect remained after adjustment for other risk factors (hazard ratio, 1.36; 95% CI, 1.22-1.51). CONCLUSIONS: Compared with patients who had isolated coronary artery disease but no PAD, patients with coronary artery disease and PAD had lower procedural success and higher in-hospital major cardiovascular complications, including higher blood loss requiring transfusion, after PCI with stent Implantation. On follow-up, the short-term and long-term outcomes of patients with PAD were worse, with higher mortality, MI, and need for repeated target vessel revascularization. [ABSTRACT FROM AUTHOR]

Frailty is a geriatric syndrome characterized by functional impairments and is associated with poor outcomes; however, the prevalence of frailty and its association with health status in patients treated with percutaneous coronary intervention (PCI) are unknown. To assess the prevalence of frailty and its association with health status in PCI-treated patients, we studied 629 patients ≥65 years old undergoing PCI from October 2005 through September 2008. Frailty was characterized using the Fried criteria: weight loss >10 lbs. in previous 1 year, exhaustion, low physical activity, poor gait speed, and poor grip strength (3 features = frail; 1 feature to 2 features = intermediate frailty; 0 feature = not frail). Health status was assessed using the Short-Form 36 and the Seattle Angina Questionnaire (SAQ). Multivariable linear regression models were used to estimate the independent association between frailty and health status. Complete data on 545 patients demonstrated that 19% (n = 117) were frail, 47% (n = 298) had intermediate frailty, and 21% (n = 130) were not frail. Frail patients had more co-morbidities and more frequent left main coronary artery or multivessel disease after adjusting for age and gender (p <0.05 across groups). Multivariable linear regression demonstrated poorer health status in frail patients compared to nonfrail patients as evidenced by lower Short-Form 36 scores, lower SAQ scores for physical limitation, and lower SAQ scores for quality of life (p <0.001 for each health status domain). In conclusion, 1/5 of older patients are frail at the time of PCI and have greater comorbid burden, angiographic disease severity, and poorer health status than nonfrail adults. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To derive risk models for percutaneous coronary intervention (PCI) outcomes from clinical and laboratory variables available before the procedure so they can be used for preprocedure risk stratification. PATIENTS AND METHODS: Using the Mayo Clinic registry, we analyzed 9035 PCIs on 7640 unique patients from January 1, 2000, through April 30, 2005. We included only the first PCI per patient (n=7457). Logistic regression was used to model the calculated risk score and major procedural complications. Separate risk models were made for mortality and major adverse cardiovascular events (MACE) derived solely from baseline and laboratory characteristics. Final risk scores for procedural death, defined as any death during the index hospitalization, and MACE contained the same 7 variables (age, myocardial infarction less than or equal to 24 hours, preprocedural shock, serum creatinine level, left ventricular ejection fraction, congestive heart failure, and peripheral artery disease). RESULTS: Models had adequate goodness of fit, and areas under the receiver operating characteristic curve were 0.74 and 0.89 for MACE and procedural death, respectively, indicating excellent overall discrimination. The model was robust across many subgroups, including those undergoing elective PCI, those having diabetes mellitus, and elderly patients. Bootstrap analysis indicated that the model was not overfit to the available data set. CONCLUSION: Before coronary angiography is performed, a risk-scoring system based on 7 variables can be used conveniently to predict cardiovascular complications after PCI. This model may be useful for providing patients with individualized, evidence-based estimates of procedural risk as part of the informed consent process. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether either of the gene variants associated with age-related macular degeneration is associated with coronary artery disease (CAD). PATIENTS AND METHODS: This study consisted of 493 patients who underwent clinically indicated coronary angiography between June 1, 1998, and January 1, 1999. The Y402H variant of the complement factor H (CFH) gene and the A69S variant of the LOC387715 gene locus were examined by restriction fragment length polymorphism. Multiple logistic regression models were used to assess the association of CFH and LOC gene variants with CAD. Covariates with well-established associations with CAD were also evaluated. RESULTS: Seventy patients (14%) were homozygous for the histidine variant (HH) of CFH, 237 (48%) were heterozygous for the histidine variant (HY), and 186 (38%) were homozygous for the tyrosine variant (YY). Three hundred eight patients (62%) were homozygous for the alanine allele of LOC387715, 170 (34%) were heterozygous for Ala and Ser alleles, and 15 (3%) were homozygous for the serine variant. The overall association of the CFH genotype with CAD was not statistically significant (P=.08). However, some evidence (P=-.046) suggested that CAD was increased for the HH genotype compared to the homozygous wild-type YY genotype (odds ratio, 1.95; 95% confidence interval, 1.01-3.76). Male sex, hypertension, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and age were other variables that demonstrated significant associations with CAD. The overall effect of the LOC genotype was not statistically significant (P=-.06). Heterozygosity for the serine variant was (P=-.02) associated with the absence of CAD vs the AS genotype (odds ratio, 0.59; confidence interval, 0.38-0.91; P=-.02). CONCLUSION: The CFH genotype may have an independent association with CAD, although our evidence did not show statistical significance. Controlling for known risk factors, the age-related macular degeneration-associated HH variant appears to be associated with CAD. The LOC387715 gene may also play a role in CAD. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the difference in endothelial function between premenopausal and postmenopausal women and to determine whether hormone replacement therapy (HRT) is associated with an improvement in coronary endothelial function. PATIENTS AND METHODS: Women undergoing coronary physiology studies for chest pain at the Mayo Clinic In Rochester, Minn, between December 1992 and April 2002 underwent assessment of coronary endothelium-independent and -dependent function with intracoronary administration of adenosine and acetylcholine, respectively. The coronary diameters, coronary blood flows, and coronary velocity reserves were measured. RESULTS: A total of 270 women (89 premenopausal and 181 postmenopausal) participated in the study. Endothelium-dependent coronary blood flow change (baseline to peak flow) in response to acetylcholine (10(-4), 10(-5), and 10(-4) mol/L) was lower in postmenopausal women compared with premenopausal women (39.7% vs 72.9%, P = .03). There was no significant difference between the postmenopausal women receiving and not receiving HRT with regard to percent change in coronary diameter (-21.8% vs -13.9%, P = .15), percent change in coronary blood flow (37.3% vs 42.7%, P = .74), or coronary velocity reserve (2.7 vs 2.7, P = .82). CONCLUSION: This study shows that the postmenopausal state is associated with a greater abnormality in coronary endothelial function at the level of the microcirculation. Moreover, HRT status was not associated with an improvement in coronary endothelial function in postmenopausal women. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to examine the rate of adverse cardiac events in patients undergoing magnetic resonance imaging (MRI) <8 weeks after coronary stent placement.Background: The risk of coronary stent thrombosis from dislodgement due to MRI early after stent placement is not well defined. Manufacturers recommend postponing MRI studies until eight weeks after coronary stent placement.Methods: We analyzed the Mayo Clinic Rochester Percutaneous Coronary Intervention Database and examined records of 111 patients who underwent MRI <8 weeks after coronary stent placement treated with aspirin and a thienopyridine. Occurrence of death, myocardial infarction (MI), and repeat revascularization within 30 days of MRI were recorded.Results: Magnetic resonance imaging (1.5 tesla) was performed within a median of 18 days (range, 0 to 54 days) after coronary stent placement. Four noncardiac deaths occurred, and three patients had repeat revascularization procedures. Stent thrombosis did not occur (95% confidence interval, 0% to 3.3%).Conclusions: Magnetic resonance imaging <8 weeks after coronary stent placement appears to be safe, and the risk of cardiac death or MI due to stent thrombosis is low. Postponing MRI does not appear to be necessary. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To study clinical outcomes in patients given glycoprotein (GP) IIb/IIIa inhibitors with concomitant clopidogrel at the time of ad hoc percutaneous coronary interventions (PCI). PATIENTS AND METHODS: We studied 30-day and long-term outcomes of patients undergoing elective or urgent PCI from March 1, 1998, to December 31, 2006, stratified by administration of GP IIb/IIIa inhibitors with concomitant clopidogrel treatment at the time of ad hoc PCI. RESULTS: The mean+/-SD age was 66.3+/-11.9 years in 5196 patients receiving compared with 67.8+/-11.8 years in 4681 patients not receiving a GP IIb/IIIa inhibitor (P<.001). Overall, 30-day unadjusted mortality was lower in patients who received a GP IIb/IIIa inhibitor (1.0% vs 1.2%; P=.22). Long-term mortality was significantly lower (P<.001) in patients receiving GP IIb/IIIa inhibitors at the time of PCI. After propensity analysis to adjust for the likelihood of receiving GP IIb/IIIa inhibitors on the basis of clinical, angiographic, and procedural characteristics, a significant reduction in 30-day mortality with GP IIb/IIIa inhibitor use was identified (hazard ratio, 0.56; 95% confidence interval, 0.36-0.87; P=.01). Kaplan-Meier analysis (median follow-up, 48 months) revealed a significant improvement in long-term survival in patients receiving a GP IIb/IIIa inhibitor at the time of ad hoc PCI that persisted after propensity adjustments (hazard ratio, 0.88; 95% confidence interval, 0.79-0.98; P=.021). Patients treated with drug-eluting stents showed a significant improvement in adjusted long-term mortality. CONCLUSION: In patients undergoing elective or urgent ad hoc PCI, coadministration of a GP IIb/IIIa inhibitor and dual antiplatelet therapy is associated with reduced risk-adjusted 30-day and long-term mortality. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to examine whether gender-based differences in mortality after percutaneous coronary interventions (PCIs) have changed in the past 25 years.Background: Women with coronary artery disease have a higher risk of adverse outcomes after PCIs than do men. Recent temporal trends in short-term and long-term mortality in women after PCIs are unknown.Methods: We performed a retrospective cohort study of 18,885 consecutive, unique patients who underwent PCIs between 1979 and 1995 (early group, n = 7,904, 28% women) and between 1996 and 2004 (recent group, n = 10,981, 31% women). Thirty-day and long-term mortality were compared by gender.Results: Compared with men, women undergoing PCIs were older and more likely to have diabetes mellitus, hypertension, or hypercholesterolemia. Overall, PCI was successful in 89% of women and 90% of men. In the recent group, 30-day mortality was significantly reduced compared with that in the early group in women (2.9% vs. 4.4%, p = 0.002) and men (2.2% vs. 2.8%, p = 0.04). However, long-term survival was similar between the early and recent groups among both men and women. After adjustment for risk factors, there was no difference between men and women from 1994 onward for either 30-day or long-term outcomes.Conclusions: The 30-day mortality after PCI in men and women has decreased in the past 25 years. After accounting for baseline risks, no differences in short-term or long-term mortality were observed between men and women. [ABSTRACT FROM AUTHOR]

Objective: To compare outcomes among patients receiving eptifibatide or abciximab during primary percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) with ST elevation or new left bundle branch block.Patients and Methods: From January 1999 through January 2004, 576 patients underwent primary PCI and received adjunctive glycoprotein IIb/IIIa receptor antagonists. Propensity scores were used to adjust for baseline differences between groups. Logistic regression and Cox proportional hazards were used to model the association between choice of glycoprotein IIlb/IIIa receptor antagonist and adverse events.Results: Abciximab was given to 327 patients (57%) and eptifibatide to 249 (43%). Observed rates of in-hospital death or MI did not differ between groups (eptifibatide, 6%; abciximab, 5%; P = .95). This result persisted with adjustment for various patient characteristics (adjusted odds ratio, 1.03; 95% confidence interval, 0.40-2.65; P = .95). Kaplan-Meier estimated rates of death, MI, or target vessel revascularization at 1-year follow-up were 20.9% with eptifibatide and 22.3% with abciximab. The adjusted hazard ratio for the composite end point during a median follow-up of 12 months was 1.36 (95% confidence interval, 0.89-2.07; P = -.16).Conclusion: In this observational analysis, outcomes were similar with use of either abciximab or eptifibatide among patients undergoing primary PCI for acute MI. Additional comparative research is warranted to confirm these results. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the safety and efficacy of percutaneous coronary intervention (PCI) for acute myocardial infarction performed at a hospital without cardiac surgical capability with PCI performed for acute myocardial infarction at a center with on-site surgery. PATIENTS AND METHODS: We included patients with acute myocardial infarction in whom PCI was performed from March 1, 2000, through May 31, 2002, at a community hospital (Immanuel St Joseph's) without on-site surgery. The procedural success, in-hospital adverse cardiac events, and 6-month follow-up were compared with those of PCI performed for acute myocardial infarction in matched controls from January 1, 2000, through February 28, 2002, at a center with cardiac surgery (Saint Marys Hospital). RESULTS: One hundred sixty patients (and 160 matched controls) underwent PCI for acute myocardial infarction. The procedural success rate was high and similar for the 2 groups (96% vs 95%; P=.79). In-hospital mortality, Q-wave myocardial infarction, and target vessel revascularization were low and similar for the 2 groups. No patient was referred for emergency coronary artery bypass graft surgery for failed PCI. Six-month survival from all-cause mortality was 96% for the Immanuel St Joseph's group and 94% for the Saint Marys Hospital group (P=.92). Subgroup analysis of patients with primary PCI for ST-segment elevation acute myocardial infarction revealed high procedural success and low and similar rates of major cardiac adverse events in the 2 groups. CONCLUSION: This study shows that PCI for acute myocardial infarction can be performed safely and effectively in a community hospital without on-site cardiac surgery. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine the frequency and timing of complications at our institution when surgery was performed within two months of coronary stent placement.Background: The optimal delay following coronary stent placement prior to non-cardiac surgery is unknown.Methods: We analyzed the Mayo Clinic Percutaneous Coronary Intervention and Surgical databases between 1990 and 2000 and identified 207 patients who underwent surgery in the two months following successful coronary stent placement.Results: Eight patients (4.0%) died or suffered a myocardial infarction or stent thrombosis. All 8 patients were among the 168 patients (4.8%, 95% confidence interval [CI] 2.1 to 9.2) undergoing surgery six weeks after stent placement; the frequency of these events ranged from 3.8% to 7.1% per week during each of the six weeks. No events occurred in the 39 patients undergoing surgery seven to nine weeks after stent placement (0%, 95% CI 0.0 to 9.0).Conclusions: These data suggest that, whenever possible, non-cardiac surgery should be delayed six weeks after stent placement, by which time stents are generally endothelialized, and a course of antiplatelet therapy to prevent stent thrombosis has been completed. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between a comprehensive list of morbidities and serious infection (SI) in patients with rheumatoid arthritis (RA)., Methods: This study evaluated SI risk associated with 55 comorbidities using a population-based inception cohort including all adult patients with incident RA from 1999 through 2014 with follow up through 2021. Morbidities and SI were ascertained using previously validated international classification of disease (ICD)-9 and ICD-10 codes. Conditional frailty models were utilized to analyze the association between each morbidity and SI: Model 1 adjusted for age, sex, and calendar year; Model 2 adjusted for factors in Model 1 and the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) Risk Score of Infections; and Model 3 adjusted for factors in Model 1 and the Mayo SI Risk Score., Results: 911 patients (70 % female, mean age 56 years, 66 % seropositive) were included. There were 293 SI among 155 patients (17 %), corresponding to an incidence of 3.9 SI per 100 person-years. Eighteen SI were fatal. Risk of SI was significantly increased in 27 of 55 morbidities in Model 1, 11 morbidities in Model 2, and 23 morbidities in Model 3. Additionally, several morbidities included in the RABBIT and Mayo risk scores continued to have large effect sizes despite adjustment. Serious infection risk increased by 11-16 % per morbidity in the three models., Conclusions: Several morbidities are associated with an increased risk for SI. Future risk scores may include morbidities identified in this study for improved SI risk assessment., Competing Interests: Declaration of competing interest Dr. Davis declares research funding from Pfizer and has submitted a provisional U.S. patent application no. 63/243,933 entitled, “Methods and Materials for Assessing and Treating Arthritis.” These are unrelated to the current study. There are no other potential conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To examine the association of multimorbidity phenotypes at baseline with disease activity and functional status over time in ankylosing spondylitis (AS)., Methods: Patient-reported AS morbidities (comorbidities, N = 28 and extra-musculoskeletal manifestations, EMMs, N = 3) within 3 years of enrollment with a prevalence ≥1 %, were included from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) cohort. We defined multimorbidity as ≥2 morbidities (MM2+) and substantial multimorbidity as ≥5 morbidities (MM5+). Multimorbidity clusters or phenotypes were identified using K-median clustering. Disease activity (ASDAS-CRP) and functional status (BASFI) measures were collected every 6 months. Generalized estimating equation method was used to examine the associations of multimorbidity counts and multimorbidity clusters with measures of disease activity and functional status over time., Results: Among 1,270 AS patients (9,885 visits) with a median follow-up of 2.9 years (IQ range: 1.0-6.8 years), the prevalence of MM2+ and MM5+ was 49 % and 9 % respectively. We identified five multimorbidity clusters: depression (n = 321, 25 %), hypertension (n = 284, 22 %), uveitis (n = 274, 22 %), no morbidities (n = 238, 19 %), and miscellaneous (n = 153, 12 %). Patients in the depression cluster were more likely to be female and had significantly more morbidities and worse disease activity and functional status compared to those with no morbidities., Conclusion: Approximately 49 % of AS patients in the PSOAS cohort had multimorbidity and five distinct multimorbidity phenotypes were identified. In addition to the number of morbidities, the type of morbidity appears to be important to longitudinal outcomes in AS. The depression cluster was associated with worse disease activity and function., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Davis has received consulting fees and/or honoraria from Sanofi-Genzyme (less than $10,000 each), Girihlet (Rights to royalties for licensed technology; none received to date), and research support from Pfizer. Dr. Ogdie has received grant/research support from Amgen (to Forward), Novartis (to Penn) and Pfizer (to Penn) Inc, has been a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Gilead, Janssen, Novartis, Pfizer Inc and UCB. Dr. Reveille has received consulting fees from Eli Lilly and Company (less than $5000). Dr. Weisman has received consulting fees from Eli Lilly and Company, UCB, and Novartis (less than $10,000 each). Dr. Gensler has received consulting fees from AbbVie, Acelyrin, Eli Lilly and Company, Fresenius Kabi, Janssen, Novartis, Pfizer, and UCB (less than $10,000 each) and has received grant support from UCB, Novartis, and Pfizer. Rest of the authors have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Background and study aims Adequacy of endoscope disinfection in resource-limited settings is unknown. Adenosine triphosphate (ATP) testing is useful for evaluation of endoscope reprocessing, and ATP <200 relative light units (RLUs) after manual endoscope cleaning has been associated with adequacy of endoscope disinfection. Methods Consecutive endoscopes undergoing reprocessing at five World Gastroenterology Organisation (WGO) training centers underwent ATP testing before and after an on-site educational intervention designed to optimize reprocessing practices. Results A total of 343 reprocessing cycles of 65 endoscopes were studied. Mean endoscope age was 5.3 years (range 1-13 years). Educational interventions, based on direct observation of endoscope reprocessing practices at each site, included refinements in pre-cleaning, manual cleaning, high-level disinfection, and endoscope drying and storage. The percentage of reprocessing cycles with post-manual cleaning ATP ≧200 decreased from 21.4% prior to educational intervention to 14.8% post-intervention ( P =0.11). In multivariable logistic modelling, gastroscopes were significantly less likely (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.01-0.19; P <0.001) than colonoscopes to achieve post-manual cleaning ATP < 200. No other factor (educational intervention, study site, endoscope age) was significantly associated with improved outcomes. Endoscope ID was not significantly associated with ATP values, and sites that performed manual versus automated HLD did not have significantly different likelihood of post-manual cleaning ATP <200 (OR 1.18, 95% CI 0.56-2.50; P =0.67). Conclusions In resource-limited settings, approximately 20% of endoscope reprocessing cycles may result in inadequate disinfection. This was not significantly improved by a comprehensive educational intervention. Alternative approaches to endoscope reprocessing are needed., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: The Sepsis-3 guidelines have incorporated serum lactate levels of >2 mmol/L in septic shock definition to account for higher observed mortality. Further evidence is needed to support this threshold in cirrhosis, as well as target mean arterial pressure (MAP) during resuscitation., Methods: This observational cohort study investigated the association between initial serum lactate and resuscitation MAP levels on in-hospital mortality in patients with and without cirrhosis. Patients admitted to the intensive care unit for the treatment of septic shock between 2006 and 2021 in a quaternary academic center were included. Patients with cirrhosis documented on imaging and International Classification of Disease codes (n=595) were compared to patients without cirrhosis (n=575). The association of intensive care unit admission lactate levels and median 2-hour MAP with in-hospital mortality and the need for continuous renal replacement therapy was assessed. The association between median 24-hour MAP and in-hospital mortality was analyzed post hoc., Results: Within the cirrhosis group, admission lactate levels of 2-4 and >4 mmol/L were associated with increased in-hospital mortality compared to lactate <2 mmol/L [adjusted odds ratio (aOR): 1.69, CI: 1.03-2.81, aOR: 4.02, CI: 2.53-6.52]. Median 24-hour MAP 60-65 and <60 mm Hg were also associated with increased in-hospital mortality compared with MAP >65 mm Hg (aOR: 2.84, CI: 1.64-4.92 and aOR: 7.34, CI: 3.17-18.76). In the noncirrhosis group, associations with in-hospital mortality were weaker for lactate 2-4 and >4 mmol/L (aOR: 1.32, CI: 0.77-2.27 and aOR: 2.25, CI: 1.40-3.67) and median 24-hour MAP 60-65 and <60 mm Hg (aOR: 1.70, CI: 0.65-4.14 and aOR: 4.41, CI: 0.79-29.38)., Conclusions: These findings support utilizing lactate >2 mmol/L in the definition of septic shock, as well as a target MAP of >65 mm Hg during resuscitation in patients with cirrhosis., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

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., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can give rise to pancreatic cancer (PC). Limited population data exist on their prevalence, natural history, or risk of malignant transformation (IPMN-PC)., Objective: To fill knowledge gaps in epidemiology of IPMNs and associated PC risk by estimating population prevalence of IPMNs, associated PC risk, and proportion of IPMN-PC., Design, Setting, and Participants: : This retrospective cohort study was conducted in Olmsted County, Minnesota. Using the Rochester Epidemiology Project (REP), patients aged 50 years and older with abdominal computed tomography (CT) scans between 2000 and 2015 were randomly selected (CT cohort). All patients from the REP with PC between 2000 and 2019 were also selected (PC cohort). Data were analyzed from November 2021 through August 2023., Main Outcomes and Measures: CIs for PC incidence estimates were calculated using exact methods with the Poisson distribution. Cox models were used to estimate age, sex, and stage-adjusted hazard ratios for time-to-event end points., Results: The CT cohort included 2114 patients (1140 females [53.9%]; mean [SD] age, 68.6 [12.1] years). IPMNs were identified in 231 patients (10.9%; 95% CI, 9.7%-12.3%), most of which were branch duct (210 branch-duct [90.9%], 16 main-duct [6.9%], and 5 mixed [2.2%] IPMNs). There were 5 Fukuoka high-risk (F-HR) IPMNs (2.2%), 39 worrisome (F-W) IPMNs (16.9%), and 187 negative (F-N) IPMNs (81.0%). After a median (IQR) follow-up of 12.0 (8.1-15.3) years, 4 patients developed PC (2 patients in F-HR and 2 patients in F-N groups). The PC incidence rate per 100 person years for F-HR IPMNs was 34.06 incidents (95% CI, 4.12-123.02 incidents) and not significantly different for patients with F-N IPMNs compared with patients without IPMNs (0.16 patients; 95% CI, 0.02-0.57 patients vs 0.11 patients; 95% CI, 0.06-0.17 patients; P = .62). The PC cohort included 320 patients (155 females [48.4%]; mean [SD] age, 72.0 [12.3] years), and 9.8% (95% CI, 7.0%-13.7%) had IPMN-PC. Compared with 284 patients with non-IPMN PC, 31 patients with IPMN-PC were older (mean [SD] age, 76.9 [9.2] vs 71.3 [12.5] years; P = .02) and more likely to undergo surgical resection (14 patients [45.2%] vs 60 patients [21.1%]; P = .003) and more-frequently had nonmetastatic PC at diagnosis (20 patients [64.5%] vs 130 patients [46.8%]; P = .047). Patients with IPMN-PC had better survival (adjusted hazard ratio, 0.62; 95% CI, 0.40-0.94; P = .03) than patients with non-IPMN PC., Conclusions and Relevance: In this study, CTs identified IPMNs in approximately 10% of patients aged 50 years or older. PC risk in patients with F-N IPMNs was low and not different compared with patients without IPMNs; approximately 10% of patients with PC had IPMN-PC, and they had better survival compared with patients with non-IPMN PC.

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Non-lethal infections are common in free-living animals and the associated sickness behaviours can impact crucial life-history trade-offs. However, little is known about the duration and extent of such sickness behaviours in free-living animals, and consequently how they affect life-history decisions. Here, free-living Eurasian blackbirds, Turdus merula , were immune-challenged with lipopolysaccharide (LPS) to mimic a bacterial infection and their behaviour was monitored for up to 48 days using accelerometers. As expected, immune-challenged birds were less active than controls within the first 24 h. Unexpectedly, this reduced activity remained detectable for 20 days, before both groups returned to similar activity levels. Furthermore, activity was positively correlated with a pre-experimental index of complement activity, but only in immune-challenged birds, suggesting that sickness behaviours are modulated by constitutive immune function. Differences in daily activity levels stemmed from immune-challenged birds resting earlier at dusk than control birds, while activity levels between groups were similar during core daytime hours. Overall, activity was reduced by 19% in immune-challenged birds and they were on average almost 1 h less active per day for 20 days. This unexpected longevity in sickness behaviour may have severe implications during energy-intense annual-cycle stages (e.g. breeding, migration, winter). Thus, our data help to understand the consequences of non-lethal infections on free-living animals.

Background: Genetic-guided P2Y 12 inhibitor selection has been proposed to reduce ischemic events by identifying CYP2C19 loss-of-function (LOF) carriers at increased risk with clopidogrel treatment after percutaneous coronary intervention (PCI). A prespecified analysis of TAILOR-PCI (Tailored Antiplatelet Therapy Following PCI) evaluated the effect of genetic-guided P2Y 12 inhibitor therapy on cumulative ischemic and bleeding events., Objectives: Here, the authors detail a prespecified analysis of cumulative endpoints. The primary endpoint was cumulative incidence rate of ischemic events at 12 months. Cumulative incidence of major and minor bleeding was a secondary endpoint. Cox proportional hazards models as adapted by Wei, Lin, and Weissfeld were used to estimate the effect of this strategy on all observed events., Methods: The TAILOR-PCI trial was a prospective trial including 5,302 post-PCI patients with acute and stable coronary artery disease (CAD) who were randomized to genetic-guided P2Y 12 inhibitor or conventional clopidogrel therapy. In the genetic-guided group, LOF carriers were prescribed ticagrelor, whereas noncarriers received clopidogrel. TAILOR-PCI's primary analysis was time to first event in LOF carriers., Results: Among 5,276 patients (median age 62 years; 25% women; 82% acute CAD; 18% stable CAD), 1,849 were LOF carriers (903 genetic-guided; 946 conventional therapy). The cumulative primary endpoint was significantly reduced in the genetic-guided group compared with the conventional therapy (HR: 0.61; 95% CI: 0.41-0.89; P = 0.011) with no significant difference in cumulative incidence of major or minor bleeding (HR: 1.36; 95% CI: 0.67-2.76; P = 0.39)., Conclusions: Among CYP2C19 LOF carriers undergoing PCI, a genetic-guided strategy resulted in a statistically significant reduction in cumulative ischemic events without a significant difference in bleeding. (Tailored Antiplatelet Therapy Following PCI [TAILOR-PCI]; NCT01742117)., Competing Interests: Funding Support and Author Disclosures Funding for this research was provided by the National Institutes of Health (NIH) grants U01HL128606 to Drs Pereira and Farkouh and U01HL128626 to Dr Bailey. The content of this manuscript is solely the responsibility of the authors and does not necessarily reflect the views of the National Heart, Lung, and Blood Institute (NHLBI) or the National Institutes of Health. Dr Farkouh has received grants from NHLBI, Amgen, Novartis, and Novo Nordisk. Mr Lennon has received grants from the National Institutes of Health (NIH)/NHLBI and receiving nonfinancial support from Spartan Biosciences. Dr So has received grants from Eli Lilly Canada, Spartan Biosciences, Roche Diagnostics, and Aggredyne Inc; and has received personal fees from AstraZeneca Canada, Bayer Canada, and Servier Canada. Dr Goodman has received research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, and Valeo Pharma; and has received salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, and the TIMI Study Group (Brigham Health). Dr Lerman has received personal fees from Itamar Medical, Phillips/Volcano, Shahal, and Wei Jian RC Inc. Dr Tanguay has received personal fees from Mayo Clinic, AstraZeneca, Bayer, Daiichi Sankyo, Servier, Novartis, and BMS-Pfizer Alliance. Dr Welsh has received grants and/or personal fees from AstraZeneca, Pfizer, Bayer, Canadian Cardiac Society, Mayo Clinic, Boehringer Ingelheim, and Novartis. Dr Bailey has received grants from NIH. Dr Pereira has received grants from the NHLBI. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

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., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. All rights reserved.)

Background: Lifestyle interventions for weight loss are currently not individualised to underlying pathophysiology and behavioral traits in obesity. We aim to compare the outcome of a standard lifestyle intervention (SLI) to phenotype-tailored lifestyle interventions (PLI) on weight loss, cardiometabolic risk factors and physiologic variables contributing to obesity., Methods: This 12-week, single-centre non-randomised proof-of-concept clinical trial including men and women aged 18-65 years with a body mass index (BMI) greater than 30 without history of any bariatric procedure, and current use of any medication known to affect weight. Participants lived anywhere in the United States, and underwent in-person testing in Rochester, MN at a teaching hospital. All participants completed in-person phenotype testing at baseline and after 12 weeks. Participants were assigned to their intervention based on their period of enrollment. In the first phase, participants were assigned to SLI with a low-calorie diet (LCD), moderate physical activity, and weekly behavioral therapy sessions. In the second phase, other participants were assigned to PLI according to phenotype: abnormal satiation (time-restricted volumetric LCD); abnormal postprandial satiety (LCD with pre-meal protein supplementation); emotional eating (LCD with intensive behavioral therapy); and abnormal resting energy expenditure (LCD with post-workout protein supplementation and high-intensity interval training). The primary outcome was total body weight loss in kg at 12 weeks using multiple imputation for missing data. Linear models estimated the association of study group allocation and study endpoints adjusting for age, sex, and baseline weight. This study was registered with ClinicalTrials.gov, NCT04073394., Findings: Between July 2020 and August 2021, 211 participants were screened, and 165 were assigned to one of the two treatments in the two phases: 81 SLI (mean [SD] age 42.9 [12] years; 79% women; BMI 38.0 [6.0]) and 84 PLI (age 44.8 [12.2] years; 83% women; BMI 38.7 [6.9]); 146 completed the 12-week programs. The weight loss was -7.4 kg (95%CI, -8.8, -6.0) with PLI vs. -4.3 kg (95%CI, -5.8, -2.7) with SLI (difference, -3.1 kg [95%CI, -5.1 to -1.1]; P = 0.004). No adverse events were reported in any group., Interpretation: Phenotype-tailored lifestyle interventions may result in significant weight loss, but a randomised controlled trial is required to confirm causality., Funding: Mayo Clinic; NIH (K23-DK114460)., Competing Interests: AA is a stockholder in Gila Therapeutics and Phenomix Sciences; he served as a consultant for Rhythm Pharmaceuticals, General Mills, Amgen, Bausch Health, RareStone; has contracts with Vivus Inc, Satiogen Pharmaceutical, and Rhythm pharmaceutical; and has a patent submitted for biomarkers of phenotype tailored diet. MC is a stockholder in Phenomix Sciences. No other disclosure to be reported. DHD receives royalties from the book, The Mayo Clinic Diet and consulting fees from the app that includes the Mayo Clinic Diet. All other authors declare no competing interests., (© 2023 The Author(s).)

Objective: To study the incidence of complications when undergoing right heart catheterization (RHC) and right ventricular biopsy (RVB)., Methods: Complications following RHC and RVB are not well reported. We studied the incidence of death, myocardial infarction, stroke, unplanned bypass, pneumothorax, hemorrhage, hemoptysis, heart valve repair/replacement, pulmonary artery perforation, ventricular arrhythmias, pericardiocentesis, complete heart block, and deep vein thrombosis (primary endpoint) following these procedures. We also adjudicated the severity of tricuspid regurgitation and causes of in-hospital death following RHC. Diagnostic RHC procedures, RVB, multiple right heart procedures alone or combined with left heart catheterization, and complications from January 1, 2002, through December 31, 2013, were identified using the clinical scheduling system and electronic records at Mayo Clinic, Rochester, Minnesota. International Classification of Diseases, Ninth Revision billing codes were used. Registration was queried to identify all-cause mortality. All clinical events and echocardiograms for worsening tricuspid regurgitation were reviewed and adjudicated., Results: A total of 17,696 procedures were identified. Procedures were categorized into those undergoing RHC (n=5556), RVB (n=3846), multiple right heart catheterization (n=776), and combined right and left heart catheterization procedures (n=7518). Primary endpoint was seen in 21.6 and 20.8 of 10,000 procedures for RHC and RVB, respectively. There were 190 (1.1%) deaths during hospital admission and none was related to the procedure., Conclusion: Complications following diagnostic RHC and RVB are seen in 21.6 and 20.8 procedures, respectively, of 10,000 procedures and all deaths were secondary to acute illness., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose: Survivors of coronary artery disease (CAD) events are at risk for repeat events. Although evidence supports cardiac rehabilitation (CR) after an initial CAD event, it is unclear whether a repeat course of CR (CR × 2) is beneficial after a recurrent CAD event. The purpose of this study was to determine the association of CR × 2 with clinical outcomes in persons undergoing repeat percutaneous coronary intervention (PCI)., Methods: We assessed the prevalence of CR × 2 and its impact on cardiovascular outcomes in individuals who experienced a repeat PCI at the Mayo Clinic hospitals between January 1, 1998, and December 31, 2013. Landmark analyses were used to calculate unadjusted and propensity score adjusted mortality rates and cardiovascular (CV) events rates for patients who underwent CR × 2 compared with those who did not., Results: Among 240 individuals who had a repeat PCI and who had participated in CR after their first PCI, 97 (40%) participated in CR × 2. Outcomes were assessed for a mean follow-up time of 7.8 yr (IQR 7.1-9.0 yr). Propensity score-based inverse probability weighting analysis revealed that CR × 2 was associated with significantly lower target lesion revascularization (HR = 0.47: 95% CI, 0.26-0.86; P = .014), lower combined end point of CV death, myocardial infarction, and target lesion revascularization (HR = 0.57: 95% CI, 0.36-0.89; P = .014), and lower CV hospitalization (HR = 0.60; 95% CI, 0.43-0.84; P = .003)., Conclusion: A second course of CR following repeat PCI is associated with a lower risk of adverse clinical outcomes. These findings support current policies that allow for repeat courses of CR following recurrent CV events., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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)., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Restoring touch perception for individuals with upper extremity limb loss is an ambitious task. It is important to understand how persons with upper limb loss think this would be best achieved., Methods: An anonymous online survey was developed to obtain data from prosthetic users. Participants ranked the perceived acceptability and effectiveness of noninvasive sensory feedback to areas of intact sensation not typically involved in sensory feedback (i.e., the arm). The focus was on 4 main types of haptic information-object contact, proprioception, surface texture, and grasp force-as well as how best to convey those senses with various stimuli. The users were asked to grade themselves in certain tasks and then analyze which tasks would be improved with sensory feedback. Associations were explored between demographic characteristics and interest in sensory feedback., Results: Nationally, prostheses providers sent more than 2000 email invitations to the online survey and received 142 unique responses. Responses indicated interest in sensory feedback through prosthetic limbs by individuals with upper limb loss. The most popular pairing of haptic information with sensory substitution was grasp force paired with gentle vibration. Tasks that most persons taking the survey agreed would benefit from sensory feedback were zipping a jacket, tying shoes, buttoning a shirt, and using a cup. No difference was observed in interest between sex and employment status, but a significant decrease (P = .004) was seen in interest among participants with more years of prosthetic use., Discussion: The results from this national survey of upper extremity prosthetic users can be used to help guide the development of noninvasive sensory feedback options., (Copyright © 2022 International Society for Prosthetics and Orthotics.)

Objective: We aimed to determine the association of physical activity and dietary factors on RA risk., Methods: This case-control study within the Mayo Clinic Biobank matched incident RA cases (two codes plus disease-modifying anti-rheumatic drug, PPV 95%) to controls 1:3 on age, sex, and recruitment year/location. A baseline questionnaire assessed activity and dietary exposures. Logistic regression models calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI) of RA for each of 45 activity/dietary exposures., Results: We identified 212 incident RA cases and 636 controls (mean age 64, 70% female). Active work physical activity was associated with elevated risk of RA (aOR 3.00, 95% CI 1.58-5.69 vs. sedentary); leisure activity was not (aOR 0.96, 95% CI 0.64-1.42 sedentary vs. active). Three or more servings high-fat food and 5+ servings fruits/vegetables daily showed non-significant associations with RA (aOR 1.22, 95% CI 0.74-2.00 vs. 0-1 time; aOR 0.75, 95% CI 0.51-1.11 vs. 0-3 times), especially in sensitivity analyses with at least five years between questionnaire and RA (aOR 1.80, 95% CI 0.69-4.71; aOR 0.54, 95% CI 0.27-1.08). Alcohol binging was not associated with RA risk (aOR 1.28, 95% CI 0.56-2.96). Finally, sensitivity (versus primary) analyses showed a nonsignificant increase in RA risk for most vitamins and supplements., Conclusion: Active work physical activity and some nutritional profiles (increased high-fat, reduced fruit/vegetable consumption) may be associated with increased risk of RA. Confirmatory studies are needed., Competing Interests: Declaration of Competing Interest Dr. Sparks has received research support from Bristol Myers Squibb and performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer unrelated to this work., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Chronic pancreatitis (CP) is a chronic fibroinflammatory condition of the pancreas difficult to diagnose in early stages. Novel biomarkers useful to facilitate early diagnosis or treatment responses may be found in biofluids. Although saliva can be easily and noninvasively collected from patients, useful salivary biomarkers from CP patients have not yet been identified., Methods: Here, we analyzed the proteome by quantitative proteomics, cytokine/chemokine levels by Luminex analysis, prostaglandin E2 (PGE2) levels by a mass spectrometry-based assay, and bacterial species diversity by 16S ribosomal ribonucleic acid sequencing in saliva samples from confirmed CP patients and healthy controls., Results: Our results indicate the presence of various differentially expressed proteins, cytokines/chemokines, and a loss of oral bacterial diversity in the saliva of CP patients. The PGE2 levels trend toward elevation in CP patients. Area under the receiver operating characteristic curve models for proteomic, cytokine, and PGE2 assays ranged from 0.59 to 0.90., Conclusions: Collectively, our studies identify a range of putative CP biomarkers and alterations in human saliva requiring further validation. The biomarker discovery approaches we used might lead to identification of biomarkers useful for CP diagnosis and monitoring., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Management of intraductal papillary mucinous neoplasms (IPMNs) relies on clinical and imaging features to select patients for either pancreatectomy or periodic image-based surveillance. We aimed to compare outcomes in patients with IPMNs who underwent surgery at diagnosis with those who underwent surgery after a period of surveillance and identify preoperative clinical and imaging features associated with advanced neoplasia., Methods: Patients with surgically resected IPMN (n = 450) were divided into 2 groups: "immediate surgery": resection within 6 months of IPMN detection, and "surveillance surgery": resection after surveillance >6 months. Survival was analyzed with Kaplan-Meier estimates and Cox proportional hazard models., Results: Pancreatic cancers in the surveillance surgery group (n = 135) was more frequently stage I compared with the immediate surgery group (9/13, 69.2% vs 41/110, 37.3%; P  = .027). Among Fukuoka "worrisome features," only main pancreatic duct dilation 5-9 mm (odds ratio [OR] = 3.12, 95% confidence interval [CI]: 1.72-5.68; P < .001) and serum CA 19-9≥ 35 U/mL (OR = 2.82, 95% CI: 1.31-6.06; P  = .008) were significantly associated with advanced neoplasia. In addition, smoking history was associated with increased risk of advanced neoplasia (OR = 2.05, 95% CI: 1.23-3.43). Occurrence of future cancer was 16-fold higher in IPMN with high-grade dysplasia when compared with low-grade dysplasia (hazard ratio: 16.5; 95% CI: 4.19-64.7)., Conclusion: Surveillance-detected pancreatic cancers in patients with IPMNs are more frequently stage I, and IPMN-HGD on surgical pathology is associated with significant risk of future pancreatic cancer. In addition to known "high-risk" features, main pancreatic duct dilation 5-9 mm, CA 19-9 elevation, and smoking history are significantly associated with advanced neoplasia., (© 2022 The Authors.)

Objective: To investigate the prevalence of rotator cuff and long head of the biceps pathologies in manual wheelchair (MWC) users with spinal cord injury (SCI). Design: Cross-sectional study. Setting: Outpatient clinic at a tertiary medical center. Participants: Forty-four adult MWC users with SCI (36 men and 8 women) with an average age (SD) of 42 (13) years. SCI levels ranged from C6 to L1; complete and incomplete SCI. Outcome Measures: Participants' demographic and anthropometric information, presence of shoulder pain, Wheelchair User's Pain Index (WUSPI) scores, and magnetic resonance imaging findings of shoulder pathologies including tendinopathy, tendon tears, and muscle atrophy. Results: Fifty-nine percent of the participants reported some shoulder pain. The prevalence of any tendinopathy across the rotator cuff and the long head of biceps tendon was 98%. The prevalence of tendinopathy in the supraspinatus was 86%, infraspinatus was 91%, subscapularis was 75%, and biceps was 57%. The majority of tendinopathies had mild or moderate severity. The prevalence of any tears was 68% . The prevalence of tendon tears in the supraspinatus was 48%, infraspinatus was 36%, subscapularis was 43%, and biceps was 12%. The majority of the tears were partial-thickness tears. Participants without tendon tears were significantly younger (P < 0.001) and had been wheelchair user for a significantly shorter time (P = 0.005) than those with tendon tears. Conclusion: Mild and moderate shoulder tendinopathy and partial-thickness tendon tears were highly prevalent in MWC users with SCI. Additionally, the findings of this study suggest that strategies for monitoring shoulder pathologies in this population should not be overly reliant on patient-reported pain, but perhaps more concerned with years of wheelchair use and age.

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/m 2 ) compared to normal BMI (OR = 0.41; 95% CI, 0.20 to 0.83; P = 0.014). Similarly, overweight (BMI 25-29.9 kg/m 2 ) 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.

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., (Copyright © 2022. Published by Elsevier Inc.)