Inflammation and aging-related disease: A transdisciplinary inflammaging framework.

Inflammaging, a state of chronic, progressive low-grade inflammation during aging, is associated with several adverse clinical outcomes, including frailty, disability, and death. Chronic inflammation is a hallmark of aging and is linked to the pathogenesis of many aging-related diseases. Anti-inflammatory therapies are also increasingly being studied as potential anti-aging treatments, and clinical trials have shown benefits in selected aging-related diseases. Despite promising advances, significant gaps remain in defining, measuring, treating, and integrating inflammaging into clinical geroscience research. The Clin-STAR Inflammation Research Interest Group was formed by a group of transdisciplinary clinician-scientists with the goal of advancing inflammaging-related clinical research and improving patient-centered care for older adults. Here, we integrate insights from nine medical subspecialties to illustrate the widespread impact of inflammaging on diseases linked to aging, highlighting the extensive opportunities for targeted interventions. We then propose a transdisciplinary approach to enhance understanding and treatment of inflammaging that aims to improve comprehensive care for our aging patients.

Sarcopenia Is a Risk Factor for Postoperative Complications Among Older Adults With Inflammatory Bowel Disease.

BACKGROUND: Sarcopenia has been associated with adverse postoperative outcomes in older age cohorts, but has not been assessed in older adults with inflammatory bowel disease (IBD). Further, current assessments of sarcopenia among all aged individuals with IBD have used various measures of muscle mass as well as cutoffs to define its presence, leading to heterogeneous findings. METHODS: In this single-institution, multihospital retrospective study, we identified all patients aged 60 years and older with IBD who underwent disease-related intestinal resection between 2012 and 2022. Skeletal Muscle Index (SMI) and Total Psoas Index (TPI) were measured at the superior L3 endplate on preoperative computed tomography scans and compared through receiver operating characteristic curve. We then performed multivariable logistic regression to assess risk factors associated with an adverse 30-day postoperative outcome. Our primary outcome included a 30-day composite of postoperative mortality and complications, including infection, bleeding, cardiac event, cerebrovascular accident, acute kidney injury, venous thromboembolism, reoperation, all-cause rehospitalization, and need for intensive care unit-level care. RESULTS: A total of 120 individuals were included. Overall, 52% were female, 40% had ulcerative colitis, 60% had Crohn's disease, and median age at time of surgery was 70 years (interquartile range: 65-75). Forty percent of older adults had an adverse 30-day postoperative outcome, including infection (23%), readmission (17%), acute kidney injury (13%), bleeding (13%), intensive care unit admission (10%), cardiac event (8%), venous thromboembolism (7%), reoperation (6%), mortality (5%), and cerebrovascular accident (2%). When evaluating the predictive performance of SMI vs TPI for an adverse 30-day postoperative event, SMI had a significantly higher area under the curve of 0.66 (95% CI, 0.56-0.76) as compared to 0.58 (95% CI, 0.48-0.69) for TPI (P = .02). On multivariable logistic regression, prior IBD-related surgery (adjusted odds ratio [adjOR] 6.46, 95% CI, 1.85-22.51) and preoperative sepsis (adjOR 5.74, 95% CI, 1.36-24.17) significantly increased the odds of adverse postoperative outcomes, whereas increasing SMI was associated with a decreased risk of an adverse postoperative outcome (adjOR 0.88, 95% CI, 0.82-0.94). CONCLUSIONS: Sarcopenia, as measured by SMI, is associated with an increased risk of postoperative complications among older adults with IBD. Measurement of SMI from preoperative imaging can help risk stratify older adults with IBD undergoing intestinal resection.

Sarcopenia has been associated with adverse postoperative outcomes in older adult populations but data among older adults with inflammatory bowel disease are limited. In our study, sarcopenia was significantly associated with adverse postoperative outcomes in older adults undergoing disease-related intestinal resection.

Severe Polypharmacy Increases Risk of Hospitalization Among Older Adults With Inflammatory Bowel Disease.

INTRODUCTION: As the inflammatory bowel disease (IBD) patient population is aging, the prevalence of polypharmacy is rising. However, data exploring the prevalence, risk factors, and clinical outcomes associated with polypharmacy among older adults with IBD are limited. The aim of the study is to determine (i) prevalence of polypharmacy (≥5 medications) and potentially inappropriate medication (PIM) utilization in older adults with IBD, (ii) changes in medications over time, (iii) predictors of polypharmacy, and (iv) the impact of polypharmacy/PIMs on 1-year hospitalization rates. METHODS: We conducted a retrospective single-center study of older adults with IBD from September 1, 2011, to December 31, 2022. Wilcoxon-signed rank and McNemar tests were used to assess changes in polypharmacy between visits, with ordinal logistic regression and Cox proportional hazards models used to determine risk factors for polypharmacy and time to hospitalization, respectively. RESULTS: Among 512 older adults with IBD, 74.0% experienced polypharmacy at the initial visit, with 42.6% receiving at least one PIM. In addition, severe polypharmacy (≥10 medications) was present among 28.6% individuals at the index visit and increased to 38.6% by the last visit ( P < 0.01). Multivariable analysis revealed that age ≥70 years, body mass index ≥30.0 kg/m 2 , previous IBD-related surgery, and the presence of comorbidities were associated with polypharmacy. Moreover, severe polypharmacy ( adj hazard ratio 1.95, 95% confidence interval 1.29-2.92), as well as PIM use ( adj hazard ratio 2.16, 95% confidence interval 1.37-3.43) among those with polypharmacy, was significantly associated with all-cause hospitalization within a year of the index visit. DISCUSSION: Severe polypharmacy was initially present in more than 25% of older adults with IBD and increased to 34% within 4 years of the index visit. Severe polypharmacy, as well as PIM utilization among those with polypharmacy, were also associated with an increased risk of hospitalization at 1 year, highlighting the need for deprescribing efforts in this population.

Sarcopenia as a Preoperative Risk Stratification Tool among Older Adults with Inflammatory Bowel Disease.

Sarcopenia, defined as a loss of muscle mass and function, is a physiologic factor that has been implicated as a predictor of adverse postoperative outcomes in many older adult populations. However, data related to sarcopenia in older adults with inflammatory bowel disease (IBD) remain limited. Older adults with IBD are particularly vulnerable to adverse postoperative outcomes, in part, due to muscle depletion from systemic inflammation, malnutrition, and reduced physical activity. However, few patients undergo routine muscle evaluation as a part of preoperative assessment. Moreover, cut-off values for measures of sarcopenia in the literature are modeled after non-IBD populations. The lack of standardized measures and values for sarcopenia in the IBD patient population has led to heterogenous findings and a paucity of preoperative risk stratification tools. Therefore, we aim to explore the scope of sarcopenia as a preoperative risk stratification tool among older adults with IBD.

Risk of Kidney Failure in Patients With Inflammatory Bowel Disease Undergoing Colectomy: A Nationwide Cohort Study.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is frequently accompanied by kidney complications. Potential triggers or subpopulations at high-risk of kidney problems are not well-elucidated. We hypothesized that surgical interventions, specifically colectomy, might in part explain this risk. METHODS: This study was a nationwide Swedish cohort study comprising 82,051 individuals with biopsy-proven IBD diagnosed during 1965 to 2017, with follow-up until 2019. We investigated the association between incident colectomy (time-varying exposure) and future risk of acute kidney injury (AKI) and kidney failure (diagnosis of end-stage kidney disease or death due to chronic kidney disease) using Cox proportional hazard models. We also examined the impact of partial vs total colectomy and the presence/duration of a stoma. Covariates included demographics, education level, and selected comorbidities. RESULTS: Over a median follow-up of 14 years, 16,479 individuals underwent colectomy, and 2556 AKI and 1146 kidney failure events occurred. Colectomy was associated with an increased relative risk of both AKI (adjusted hazard ratio, 2.37; 95% confidence interval, 2.17-2.58) and kidney failure (adjusted hazard ratio, 1.54; 95% confidence interval, 1.34-1.76). Compared with pre-colectomy periods, undergoing total colectomy and colectomy with prolonged stoma showed higher risks of both kidney outcomes versus partial colectomy or colectomy with a temporary stoma, respectively. Subgroup analyses suggested higher risks in patients with ulcerative colitis. CONCLUSIONS: In people with IBD, rates of AKI and kidney failure are higher among those undergoing colectomy, particularly among those following total colectomy, or colectomy with a prolonged stoma. This study identifies a high-risk population that may benefit from established protocols for kidney function monitoring/surveillance and referral to nephrologist care.

Optimal Management of Refractory Crohn's Disease: Current Landscape and Future Direction.

Refractory Crohn's disease, defined as ongoing inflammation despite the trial of multiple advanced therapies, impacts a number of individuals with Crohn's disease, and leads to significant burden in quality of life and cost. Interventions such as early implementation of advanced therapies, optimization of current therapies prior to switching to an alternative, as well as understanding the overlapping pathophysiology between immune-mediated disorders, however, can help shift the current landscape and reduce the number of patients with refractory disease. As such, in this review we summarize the key takeaways of the latest research in the management of moderate-to-severe Crohn's disease, focusing on maximization of our currently available medications, while also exploring topics such as combination advanced therapies. We also describe evidence for emerging and alternative therapeutic modalities, including fecal microbiota transplant, exclusive enteral feeding, hyperbaric oxygen, stem cell therapy, bone marrow transplant, and posaconazole, with a focus on both the potential impact and specific indications for each.

Subtypes of Venous Thromboembolism in Inflammatory Bowel Disease: A Nationwide Assessment.

Background: Data detailing the risk of Venous Thromboembolism (VTE) subtypes among individuals with Inflammatory bowel disease (IBD) remain limited.Aims: We looked to assess the odds of VTE subtypes among hospitalized individuals with IBD as compared to those without IBD. Materials & Methods: Using the Nationwide Inpatient Sample database, we applied a multivariable regression analysis to compare the odds of primary VTE-related hospitalizations among individuals with and without IBD from 2016 to 2020, including deep venous thrombosis (DVT), pulmonary embolism (PE), portal vein thrombosis (PVT), Budd Chiari syndrome (BCS), renal vein thrombosis (RVT), and cerebral venous sinus thrombosis (CVST). Results: Overall, there were 15,565 primary VTE-related hospitalizations among individuals with IBD, as compared to 1,449,164 among individuals without IBD. Having IBD increased the odds for DVT (aOR = 1.34, 95%CI: 1.25-1.43), PVT (aOR = 3.16, 95%CI: 2.65-3.76), and CVST (aOR=1.45, 95%CI: 1.05-2.00), without significant increase in the odds of a PE, BCS, or RVT. Further, individuals with ulcerative colitis (UC) were at a higher risk for the majority of VTE-subtypes as compared to those with Crohn's disease (CD). Among individuals with a VTE-related hospitalization, the presence of IBD was not associated with increased mortality (aOR = 0.77, 95%CI: 0.40-1.50), but was associated with an increased length of stay (CD - 4.8 days, UC - 5.3 days, without IBD - 4.3 days, p<0.01). Conclusions: Clinicians should retain a high index of suspicion when evaluating VTE-related symptoms among individuals with IBD, as the presence of IBD confers a higher risk of DVT, PVT and CVST related-hospitalizations, and longer stays as compared to individuals without IBD.

Older Adults With Inflammatory Bowel Disease Are at Higher Risk of Developing Antibodies to Infliximab.

Although older age is thought to confer immunosenescence, we found that older adults with inflammatory bowel disease are independently at higher risk to develop antibodies to infliximab. Additionally, older adults are less likely to receive escalated doses of infliximab.

Atherosclerosis as a Risk Factor of Inflammatory Bowel Disease: A Population-Based Case-Control Study.

INTRODUCTION: Data suggest atherosclerotic-related inflammation may play a role in the pathogenesis of inflammatory bowel disease (IBD), but large-scale studies are missing. METHODS: In this nationwide case-control study, we used the Swedish Patient Register and the Epidemiology Strengthened by histoPathology Reports in Sweden cohort to identify adult cases of incident IBD between 2002 and 2021, with each case matched to up to 10 general population controls. We used conditional logistic regression to calculate odds ratios (OR) for exposure to an atherosclerotic-related condition (myocardial infarction, thromboembolic stroke, or atherosclerosis itself) before being diagnosed with IBD. RESULTS: There were a total of 56,212 individuals with IBD and 531,014 controls. Of them, 2,334 (4.2%) cases and 18,222 (3.4%) controls had a prior diagnosis of an atherosclerotic-related condition, corresponding to an OR of 1.30 (95% confidence interval [CI] 1.24-1.37). Results were statistically significant for both Crohn's disease (OR 1.37, 95% CI 1.26-1.48) and ulcerative colitis (OR 1.27, 95% CI 1.20-1.35) and for individuals who developed IBD at 40-59 years of age and 60 years or older. In addition, associations persisted when adjusting for underlying comorbidities, including the presence of immune-mediated diseases and prior aspirin and/or statin use. The highest odds of an atherosclerotic-related condition were seen in the 6-12 months before IBD diagnosis, though odds were increased even ≥5 years before. A higher magnitude of odds was also observed when having 2 or more atherosclerotic-related conditions when compared with having only 1 condition. DISCUSSION: A history of an atherosclerotic-related condition is associated with increased odds of developing IBD, particularly among older adults. Future studies should investigate whether drugs targeting atherosclerotic-related inflammation may prevent IBD in higher-risk individuals.

Preoperative Risk Factors for Adverse Events in Adults Undergoing Bowel Resection for Inflammatory Bowel Disease: 15-Year Assessment of the American College of Surgeons National Surgical Quality Improvement Program.

INTRODUCTION: Older adults with inflammatory bowel disease (IBD) are at higher risk for postoperative complications as compared to their younger counterparts; however, factors contributing to this are unknown. We assessed risk factors associated with adverse IBD-related surgical outcomes, evaluated trends in emergency surgery, and explored differential risks by age. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified adults ≥18 years of age who underwent an IBD-related intestinal resection from 2005 to 2019. Our primary outcome included a 30-day composite of mortality, readmission, reoperation, and/or major postoperative complication. RESULTS: Overall, 49,746 intestinal resections were performed with 9,390 (18.8%) occurring among older adults with IBD. Nearly 37% of older adults experienced an adverse outcome as compared to 28.1% among younger adults with IBD ( P < 0.01). Among all adults with IBD, the presence of preoperative sepsis (adjusted odds ratio [aOR], 2.08; 95% confidence interval [CI] 1.94-2.24), malnutrition (aOR, 1.22; 95% CI 1.14-1.31), dependent functional status (aOR, 6.92; 95% CI 4.36-11.57), and requiring emergency surgery (aOR, 1.50; 95% CI 1.38-1.64) increased the odds of an adverse postoperative outcome, with similar results observed when stratifying by age. Furthermore, 8.8% of surgeries among older adults were emergent, with no change observed over time ( P = 0.16). DISCUSSION: Preoperative factors contributing to the risk of an adverse surgical outcome are similar between younger and older individuals with IBD, and include elements such as malnutrition and functional status. Incorporating these measures into surgical decision-making can reduce surgical delays in older individuals at low risk and help target interventions in those at high risk, transforming care for thousands of older adults with IBD.

Managing the older adult with inflammatory bowel disease: is age just a number?

PURPOSE OF REVIEW: This review summarizes the most recent literature on older adults with inflammatory bowel diseases (IBD). Additionally, we review geriatric syndromes that may be pertinent to the management of older adults with IBD. RECENT FINDINGS: Traditionally chronological age has been used to risk stratify older adults with IBD, however physiologic status, including comorbidities, frailty, and sarcopenia, are more closely associated with clinical outcomes for older adults. Delaying care for and undertreating older adults with IBD based upon advanced chronologic age alone is associated with worse outcomes, including increased mortality. Treatment decisions should be made considering physiologic status, with an understanding of the differential risks associated with both ongoing disease and treatment. As such, there is an increasing recognition of the impact geriatric syndromes have on older adults with IBD, which need to be further explored. SUMMARY: Older adults with IBD are less likely to receive advanced therapies and timely surgery. They are also more likely to have adverse outcomes despite having similar disease courses to younger adults with IBD. Focusing on biological age as opposed to chronological age can shift this trajectory and improve quality of care for this growing population of patients with IBD.

Early Ileocecal Resection for Crohn's Disease Is Associated With Improved Long-term Outcomes Compared With Anti-Tumor Necrosis Factor Therapy: A Population-Based Cohort Study.

BACKGROUND & AIMS: Early Crohn's disease (CD) treatment involves anti-tumor necrosis factor (TNF) agents, whereas ileocecal resection (ICR) is reserved for complicated CD or treatment failure. We compared long-term outcomes of primary ICR and anti-TNF therapy for ileocecal CD. METHODS: Using cross-linked nationwide registers, we identified all individuals diagnosed with ileal or ileocecal CD between 2003 and 2018 and treated with ICR or anti-TNF agents within 1 year of diagnosis. The primary outcome was a composite of ≥1 of the following: CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD. We conducted adjusted Cox's proportional hazards regression analyses and determined the cumulative risk of different treatments after primary ICR or anti-TNF therapy. RESULTS: Of 16,443 individuals diagnosed with CD, 1279 individuals fulfilled the inclusion criteria. Of these, 45.4% underwent ICR and 54.6% received anti-TNF. The composite outcome occurred in 273 individuals (incidence rate, 110/1000 person-years) in the ICR group and in 318 individuals (incidence rate, 202/1000 person-years) in the anti-TNF group. The risk of the composite outcome was 33% lower with ICR compared with anti-TNF (adjusted hazard ratio, 0.67; 95% confidence interval, 0.54-0.83). ICR was associated with reduced risk of systemic corticosteroid exposure and CD-related surgery, but not other secondary outcomes. The proportion of individuals on immunomodulator, anti-TNF, who underwent subsequent resection, or were on no therapy 5 years post-ICR was 46.3%, 16.8%, 1.8%, and 49.7%, respectively. CONCLUSION: These data suggest that ICR may have a role as first-line therapy in CD management and challenge the current paradigm of reserving surgery for complicated CD refractory or intolerant to medications. Yet, given inherent biases associated with observational data, our findings should be interpreted and applied cautiously in clinical decision making.

Risk factors for incomplete telehealth appointments among patients with inflammatory bowel disease.

Background: The COVID-19 pandemic led to the urgent implementation of telehealth visits in inflammatory bowel disease (IBD) care; however, data assessing feasibility remain limited. Objectives: We looked to determine the completion rate of telehealth appointments for adults with IBD, as well as to evaluate demographic, clinical, and social predictors of incomplete appointments. Design: We conducted a retrospective analysis of all patients with IBD who had at least one scheduled telehealth visit at the NYU IBD Center between 1 March 2020 and 31 August 2021, with only the first scheduled telehealth appointment considered. Methods: Medical records were parsed for relevant covariables, and multivariable logistic regression was used to estimate the adjusted association between demographic factors and an incomplete telehealth appointment. Results: From 1 March 2020 to 31 August 2021, there were 2508 patients with IBD who had at least one telehealth appointment, with 1088 (43%) having Crohn's disease (CD), 1037 (41%) having ulcerative colitis (UC), and 383 (15%) having indeterminate colitis. Of the initial telehealth visits, 519 (21%) were not completed, including 435 (20%) among patients <60 years as compared to 84 (23%) among patients ⩾60 years (p = 0.22). After adjustment, patients with CD had higher odds of an incomplete appointment as compared to patients with UC [adjusted odds ratio (adjOR): 1.37, 95% confidence interval (CI): 1.10-1.69], as did females (adjOR: 1.26, 95% CI: 1.04-1.54), and patients who had a non-first-degree relative listed as an emergency contact (adjOR: 1.69, 95% CI: 1.16-2.44). While age ⩾60 years was not associated with appointment completion status, we did find that age >80 years was an independent predictor of missed telehealth appointments (adjOR: 2.92, 95% CI: 1.12-7.63) when compared to individuals aged 60-70 years. Conclusion: Patients with CD, females, and those with less social support were at higher risk for missed telehealth appointments, as were adults >80 years. Engaging older adults via telehealth, particularly those aged 60-80 years, may therefore provide an additional venue to complement in-person care.

Antibiotic use as a risk factor for inflammatory bowel disease across the ages: a population-based cohort study.

BACKGROUND: There is an increasing incidence of inflammatory bowel disease (IBD) for which environmental factors are suspected. Antibiotics have been associated with development of IBD in earlier generations, but their influence on IBD risk in adults is uncertain. OBJECTIVE: To assess the impact of antibiotic exposure, including dose-response, timing and antibiotic class, on the risk of IBD in all individuals aged ≥10 years. DESIGN: Using Denmark nationwide registries, a population-based cohort of residents aged ≥10 years was established between 2000 and 2018. Incidence rate ratios (IRRs) for IBD following antibiotic exposure were calculated using Poisson regression. RESULTS: There were a total of 6 104 245 individuals, resulting in 87 112 328 person-years of follow-up, and 52 898 new cases of IBD. Antibiotic exposure was associated with an increased risk of IBD as compared with no antibiotic exposure for all age groups, although was greatest among individuals aged 40-60 years and ≥60 years (age 10-40 years, IRR 1.28, 95% CI 1.25 to 1.32; age 40-60 years, IRR 1.48, 95% CI 1.43 to 1.54; age ≥60 years, IRR 1.47, 95% CI 1.42 to 1.53). For all age groups a positive dose-response was observed, with similar results seen for both ulcerative colitis and Crohn's disease. The highest risk of developing IBD was seen 1-2 years after antibiotic exposure, and after use of antibiotic classes often prescribed to treat gastrointestinal pathogens. CONCLUSION: Antibiotic exposure is associated with an increased risk of IBD, and was highest among individuals aged 40 years and older. This risk increased with cumulative antibiotic exposure, with antibiotics targeting gastrointestinal pathogens and within 1-2 years after antibiotic exposure.

Management Considerations for the Older Adult With Inflammatory Bowel Disease.

As the prevalence of older adults with inflammatory bowel disease (IBD) is rising, understanding the unique challenges in both diagnosis and management is becoming increasingly important. Knowledge of phenotypic differences as well as overlapping symptoms with other medical conditions is critical to obtaining a timely diagnosis of IBD in older adults. Although older adults with IBD are at higher risk for adverse events compared with younger adults with IBD, recent data have suggested that ongoing disease activity may be a significant driver of adverse clinical outcomes rather than use of current treatment modalities. Ultimately, earlier and effective treatments can improve outcomes and quality of life for older adults with IBD. However, to help improve medical decision-making, clinicians must move away from the use of chronological age alone and begin to integrate measures of biological age, such as frailty and sarcopenia, into risk stratification tools. This article reviews the management considerations for older adults with IBD and provides the rationale for incorporating measures of biological age into current practice.

Sarcopenia in Inflammatory Bowel Diseases: Reviewing Past Work to Pave the Path for the Future.

Purpose of the Review: Sarcopenia is the loss of muscle quantity and strength. It is highly prevalent in patients with inflammatory bowel disease (IBD) and is associated with periods of ongoing inflammation. This review will summarize the prior work in the field and highlight areas for future research. Recent Findings: The presence of sarcopenia has been associated with adverse outcomes in different populations. Most recently, sarcopenia has been associated with adverse postoperative outcomes and an increased likelihood of surgery in IBD. Despite this, significant heterogeneity among these studies limits the ability to draw definitive conclusions. Summary: The importance of sarcopenia in inflammatory bowel disease (IBD) is only beginning to be recognized. Future studies assessing it utility both as a risk stratification tool and a modifiable factor in IBD are needed.

Post-operative prevention and monitoring of Crohn's disease recurrence.

Crohn's disease (CD) and ulcerative colitis (UC) are relapsing and remitting chronic inflammatory diseases of the gastrointestinal tract. Although surgery for UC can provide a cure, surgery for CD is rarely curative. In the past few decades, research has identified risk factors for postsurgical CD recurrence, enabling patient risk stratification to guide monitoring and prophylactic treatment to prevent CD recurrence. A MEDLINE literature review identified articles regarding post-operative monitoring of CD recurrence after resection surgery. In this review, we discuss the evidence on risk factors for post-operative CD recurrence as well as suggestions on post-operative management.