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21/01/2025

Parastomal hernia (PSH) repair at Mayo Clinic: Helping patients live their life

21/01/2025

In a pilot study of 165 people, Mayo Clinic researchers looked at the effectiveness of two different approaches to weight loss: a standard lifestyle intervention and individualized therapy. The standard lifestyle intervention included a reduced diet, exercise and behavior therapy. The individualized approach was based on phenotypes and included different interventions depending on the person's predominant underlying cause of obesity. A diet based on phenotypes considers a person's genetic and phenotypic characteristics to create a tailored eating plan meant to optimize health and well-being.
The researchers compared whether diet and lifestyle interventions tailored to obesity phenotypes would work better than standard lifestyle interventions on weight loss, cardiometabolic risk factors and physical variables contributing to obesity. Cardiometabolic health describes the connection between the heart and blood vessels and the body's energy and chemical processes. It covers a wide range of disorders and risk factors that contribute to heart disease and metabolic syndrome.
In adults with obesity, the phenotype-tailored lifestyle interventions resulted in more weight loss than the standard lifestyle interventions of a reduced-calorie diet, exercise and behavior therapy.

21/01/2025

Although frequently associated with diabetes, the majority of gastroparesis cases remain idiopathic. About a decade ago, researchers noted that the loss of interstitial cells of Cajal (ICCs) might be linked to the cellular pathophysiology underlying gastroparesis. More recently, researchers have begun examining the role of the immune system and its dysregulation in gastroparesis. Observations in animal models suggested that immune cells play a critical role in maintaining and protecting enteric neuronal and ICC function, which can affect motility in the gastrointestinal tract.
In a study conducted by Madhusudan (Madhu) Grover, M.B.B.S., Mayo Clinic colleagues and others from the National Institutes of Health Gastroparesis Clinical Research Consortium (NIH GpCRC), the researchers profiled the human gastric muscle immunome in patients with idiopathic gastroparesis (IG). The results of that study were published in iScience in 2024, with Dr. Grover, a gastroenterologist and researcher at Mayo Clinic in Minnesota, serving as corresponding author.
"The aim of our study was to characterize the immune cell populations in human gastric muscle and determine changes in patients with idiopathic gastroparesis. We sought to create an atlas of the types of macrophages and other immune cells in the muscularis propria of the human stomach."
— Madhusudan (Madhu) Grover, M.B.B.S.
Study methods
Dr. Grover notes that prior research efforts using bulk RNA-sequencing analysis as well as proteomics of gastric muscle tissue revealed evidence of macrophage-based immune dysregulation in patients with IG.
"Multiple studies have suggested that muscularis macrophages have an important role in maintaining peristaltic motility and in preventing neuronal loss in response to pathogen-mediated injury," explains Dr. Grover. "The aim of our study was to characterize the immune cell populations in human gastric muscle and determine changes in patients with idiopathic gastroparesis. We sought to create an atlas of the types of macrophages and other immune cells in the muscularis propria of the human stomach."
In this study funded by the NIH GpCRC, the researchers performed single-cell sequencing on 26,000 CD45-positive cells from gastric muscle tissue obtained from 20 study participants — seven individuals with IG (the IG group) and 13 individuals without IG (the control group).
Results
Dr. Grover and co-authors note that the study yielded multiple findings that broaden the understanding about the immune system in the gastric muscle layers as well as changes in IG.
The researchers identified 11 clusters of immune cells in gastric muscle tissue, with T cells (~ 45% of overall cells) and myeloid cells (~ 27%) constituting the largest compartments.
The proportions of cells belonging to the 11 clusters were similar in participants from the IG and control groups. However, differential expression analysis showed cell subsets containing from 578 to 11,429 differentially expressed genes in nine of the 11 clusters.
IG group participants had muscularis macrophages (MMs) with decreased expression of tissue-protective and microglial genes and increased expression of monocyte trafficking and stromal activating genes.
IG group participants had enriched cell signaling pathways, including interleukin-12-mediated Janus kinase signal transducer and activator of transcription signaling, involved in the activation of tissue-resident macrophages, and Eph-ephrin signaling, involved in monocyte chemotaxis.
IG group participants had a greater abundance of monocyte-like cells in the tissue, suggesting increased trafficking.
"Overall, these data advance the understanding of IG," explains Dr. Grover. "The atlas created will be helpful for other researchers and will allow additional studies of other immune cells as well as understanding of signaling between immune and nonimmune cells in the gastric muscle layers. Until now, the immune cell compartment within the muscle layers of human stomach was not characterized. The study expands our understanding of canonical gene markers for various immune cell types, which acts as a resource for the research community. From the standpoint of IG, this study paves the way for therapeutic targets."
Next steps
Dr. Grover notes that additional research is needed to address study size and other limitations, and to explore the implications of these findings more fully. "Future efforts will need to understand the protein expression and distribution of various cell types, as well as in vitro experiments to examine interactions between immune cells and cells like ICC and enteric nerves that directly regulate the gastric motor function," says Dr. Grover.

21/01/2025

Pancreatic cancer (PC) is the third-leading cause of cancer deaths in the United States, with an extremely low five-year survival rate of 13%. According to Mayo Clinic gastroenterologist and pancreatologist Shounak Majumder, M.D., this poor prognosis is largely attributed to the fact that most patients are diagnosed at a stage when the malignancy is either locally advanced or has distant metastasis. Dr. Majumder directs the High-Risk Pancreas Clinic, which conducts PC screening in individuals with certain familial and genetic risk factors at Mayo Clinic in Rochester, Minnesota.
Detecting PC at an early, asymptomatic stage can positively impact survival rates, but currently there is no population-based screening strategy for this disease. Dr. Majumder and colleagues are actively engaged in research exploring new ways to address these challenges. Noting that accurate assessment of risk factor status requires manual review of the electronic health record (EHR) by experts, Dr. Majumder and colleagues studied the use of natural language processing (NLP) for automated extraction of PC risk factors from unstructured clinical notes in the EHR. The results of this study were published in Pancreatology in 2024.
In a systematic review published in the American Journal of Gastroenterology in 2024, Dr. Majumder and colleagues extracted and reviewed data from 30 studies to discern ML methods for predicting PC risk and identifying novel risk factors from EHR data.
In this Q&A, Dr. Majumder discusses this vein of research and what the recent findings say about a potential role for AI in the creation of tools designed to accurately identify pancreatic cancer risk and novel risk factors using EHR data.
Why is this an important area of research?
Based on expert consensus, PC screening is currently considered in individuals with extensive family history of the disease and germline variants in PC susceptibility genes. Identifying these high-risk individuals using data within the EHR and connecting them to appropriate screening programs requires time and expertise that is not widely available. While this approach of risk-based screening has helped shift diagnosis to an earlier stage and prolong survival, 80% to 85% of PC cases are sporadic, occurring in individuals without known familial or genetic risk. These issues pose a significant barrier to the paradigm of risk-based PC screening. Therefore, there is a critical need to automate the identification of individuals with familial and genetic risk of PC and to identify novel risk factors for sporadic PC.
AI- and ML-based applications are poised to transform health data summarization and visualization capabilities. This presents an opportunity to leverage advances in AI and ML capabilities to develop EHR-based applications that accurately identify both known and novel risk factors for PC.
What is the significance of the findings presented in your most recent publications, and how might they guide clinical practice?
In the two Mayo Clinic research publications highlighted here, we developed NLP algorithms that identify familial and genetic risk of PC from unstructured clinical notes within the EHR. We also performed a systematic review to gain insight into the current state of EHR-based AI-ML approaches for estimating patient-level risk of PC.
In our NLP algorithm study, we concluded that rule-based NLP algorithms applied to unstructured clinical notes within the EHR are highly sensitive for automated identification of PC risk factors. These findings are a first step toward automated detection of the high-risk patient population that would benefit from risk-based PC screening. This is especially relevant in the context of PC, which is a lethal cancer for which there is no population-level screening.
In our systematic review, we found that several groups have aimed to develop ML models using EHR data to predict PC risk with variable success. Most studies relied on a curated set of known predictors to develop their models instead of utilizing unbiased approaches using the full spectrum of EHR data, such as combining structured data with unstructured data from clinical notes. Moreover, missing data were underreported, and explainable-AI techniques underutilized. To address these issues, and based on our interpretation of published studies, we have summarized a list of best practices and recommendations for consideration in future studies focusing on EHR-based AI-ML model development for PC.
"In the two Mayo Clinic research publications highlighted here, we developed natural language processing algorithms that identify familial and genetic risk of PC from unstructured clinical notes within the EHR. We also performed a systematic review to gain insight into the current state of EHR-based AI-ML approaches for estimating patient-level risk of PC."
— Shounak Majumder, M.D.
Can you elaborate on how additional research might further advance the field?
The performance of rule-based NLP algorithms for identification of familial and genetic risk of PC can be further enhanced by incorporating emerging tools such as large language models with subsequent validation in a real-world primary care cohort. In ongoing studies, we are exploring pathways to clinical implementation of this digital risk phenotyping tool as we seek to understand the impact on both patient- and healthcare professional-level outcomes.
Additional research will also need to focus on developing EHR-based AI-ML models for identification of novel risk factors for sporadic PC within diverse real-world population cohorts leveraging longitudinal data. While the focus is on the development of the most accurate AI-ML models for estimating PC risk, it will be equally important to minimize the risk of inaccurate biased estimates that lack explainability.

21/01/2025

Individuals diagnosed with inflammatory bowel disease (IBD) have an increased risk of developing herpes zoster (HZ) and HZ-related complications. Several studies, including work conducted by Mayo Clinic researchers, have shown that patients with IBD have a higher incidence of HZ compared with individuals without IBD.
"This risk is related, in part, to the underlying immune dysregulation associated with IBD, and to the use of certain commonly used therapies," explains Francis A. Farraye, M.D., M.S. "For example, prednisone, thiopurines, anti-TNFs and JAK inhibitors are associated with a significantly increased risk of shingles in patients with IBD." Dr. Farraye is a gastroenterologist and director of the Inflammatory Bowel Disease Center at Mayo Clinic in Jacksonville, Florida.
Recombinant zoster vaccine (RZV), an inactive vaccine that can be given to all patients regardless of immune suppression, reduces the short-term risk of HZ in patients with IBD. However, there is lack of data demonstrating the long-term effectiveness in this population. To address this knowledge gap, Dr. Farraye and colleagues conducted a retrospective cohort study examining the effectiveness of RZV in patients with IBD. Secondary aims of this study included identifying the risk of HZ complications among patients who developed HZ, the impact of IBD medications on the efficacy of RZV, and the risk of HZ in patients with diabetes mellitus and chronic lower respiratory diseases. The results of this study were published in the Journal of Crohn's and Colitis in 2024.
"In an earlier study that our group conducted and published in Alimentary Pharmacology and Therapeutics in 2023, we demonstrated that RZV was cost-effective for all patients with IBD. Based on this study and the new data demonstrating RZV effectiveness that we shared in our cohort study publication, and the recommendations by the Advisory Committee on Immunization Practices, I now offer RZV to all patients with IBD who are 19 and older."
— Francis A. Farraye, M.D., M.S.
Methods
This cohort study involved 5,489 adults age 50 years and older diagnosed with IBD (Crohn's disease and ulcerative colitis) who received two doses of RZV (the IBD-RZV cohort) and 5,265 adults with IBD who did not receive RZV (the IBD control cohort). The primary outcome was risk of incident HZ. The researchers performed a subgroup analysis for age, comorbid conditions and use of immunosuppressive therapy. Using propensity score matching (PSM), the researchers balanced the following covariates between cohorts: age, gender, race, diabetes mellitus, chronic lower respiratory disease, human immunodeficiency virus (HIV), chronic kidney disease, other autoimmune diseases and patients after transplantation. The patients were followed for a mean of over 900 days.
Results
"Overall, we demonstrated that vaccinated patients had a significantly lower risk of developing herpes zoster compared with the nonvaccinated IBD control cohort," explains Dr. Farraye.
The IBD-RZV cohort had a lower risk of HZ when compared with the IBD control cohort, with an adjusted odds ratio of 0.44, and a confidence interval of 95% (0.32-0.62). After PSM, 52 patients (1.09%) in the IBD-RZV cohort and 123 patients (2.4%) in the IBD control cohort developed HZ. The incidence rate of HZ was 10.9 per 1,000 person-years in the IBD-RZV cohort and 24.2 per 1,000 person-years in the IBD control cohort.
The risk of HZ was lower in patients age 50 to 65 years as well as in patients older than age 65 years in the IBD-RZV cohort compared with the IBD control cohort.
After PSM, among patients who developed HZ, the two cohorts had no significant difference in the risk of severe HZ complications and no significant difference in the risk of postherpetic neuralgia.
After PSM, patients in the IBD-RZV cohort on immunosuppressive therapy were at a lower risk of HZ compared with the IBD control cohort. Subgroup analysis of immunosuppressive therapy classes suggests that patients with chronic steroid use in the IBD-RZV cohort also were at lower risk of HZ compared with the IBD control cohort.
Dr. Farraye and co-authors recommend that all patients with IBD age 50 years and older receive the two-dose RZV 2 to 6 months apart. Although the authors acknowledge that their study did not assess the effectiveness of RZV in patients ages 18 to 49 years, they note that RZV is licensed for use in immunosuppressed populations in the United States and Europe.
"In an earlier study that our group conducted and published in Alimentary Pharmacology and Therapeutics in 2023, we demonstrated that RZV was cost-effective for all patients with IBD," explains Dr. Farraye. "Based on this study and the new data demonstrating RZV effectiveness that we shared in our cohort study publication, and the recommendations by the Advisory Committee on Immunization Practices, I now offer RZV to all patients with IBD who are 19 and older."

21/01/2025

Obesity is rising among individuals diagnosed with inflammatory bowel disease (IBD), a trend that has led researchers to question how it may impact the natural history of IBD.
To shed light on this topic, Mayo Clinic researchers conducted a population-based study in a cohort of individuals with newly diagnosed Crohn's disease (CD). The results of that study were published in the Journal of Clinical Gastroenterology in 2024.
"Recently published data suggest that obesity, particularly increased visceral adiposity, may negatively impact IBD-specific outcomes such that patients experience an increased risk of penetrating or fibrostenotic disease, a reduced response to biologic therapies, and a higher risk of postoperative Crohn's recurrence. But the full extent of these impacts is not well understood," explains Amanda M. Johnson, M.D., lead author on the study publication. Dr. Johnson is a gastroenterologist at Mayo Clinic in Rochester, Minnesota.
Dr. Johnson and co-authors sought to describe the prevalence of obesity in the study population and the impact obesity has on disease phenotype and outcomes, including corticosteroid use, hospitalization, intestinal resection, and development of fistulizing or penetrating disease.
Study methods
The researchers performed a chart review of Olmsted County, Minnesota, residents diagnosed with CD between 1970 and 2010 whose medical records included body mass index (BMI) data within six months of their diagnosis. They analyzed the proportion of individuals considered obese at the time of CD diagnosis and how that changed over time. Using Kaplan-Meier survival analysis, they assessed any CD-associated complications that occurred within that cohort, including hospitalizations, corticosteroid use and intestinal resection.
Results
Among 334 individuals diagnosed with CD, 156 (46.7%) were classified as overweight (27.8%) or obese (18.9%) at the time of diagnosis.
Participants classified as overweight or obese tended to be older at the time of their CD diagnosis (42.3 and 44.3 years, respectively) as compared with those who were considered underweight or normal weight (31.6 and 35.8 years, respectively).
Over the course of the 40-year study period, the proportion of patients classified as obese at the time of CD diagnosis increased two- to threefold. During the 1970s, approximately 9% of individuals diagnosed with CD had comorbid obesity, though this proportion rose to more than 20% of individuals diagnosed between 2000 and 2010.
Obesity at the time of CD diagnosis did not appear to significantly impact future risk of corticosteroid use, hospitalization, intestinal resection, or the development of penetrating and stricturing complications.
"Our findings demonstrate that obesity is increasingly common in patients with Crohn's disease, with rates having more than doubled in recent decades," explains Dr. Johnson. "It is important to note that the presence of obesity was captured at the time of Crohn's disease diagnosis, and thus should not have been impacted by weight gain from factors like corticosteroid use or smoking cessation."
Dr. Johnson and co-authors acknowledge that this study had a few limitations. Patients diagnosed with CD in 1970s did not have access to the same advanced therapies available today. This creates a more heterogenous population, leading to the possibility that associations between obesity and CD-related outcomes may have been overlooked or skewed. Additionally, although BMI is widely used as a measure of obesity, the researchers note that it is not the most accurate surrogate measure. Dr. Johnson notes that prospective studies including measures such as visceral adipose tissue assessment may help researchers paint a clearer picture of how obesity affects CD outcomes.
Overall, Dr. Johnson notes that this study provides some useful takeaways for clinicians.
"It is important for us as care providers to be mindful that many patients with IBD are struggling with comorbid obesity," says Dr. Johnson. "This fact may have negative implications for our patients' general health outcomes as well as potentially their IBD outcomes. Additional research is needed to better understand how to provide the most effective and safest weight-loss therapies to patients with IBD, as these individuals are typically excluded from clinical trials of these interventions."
"It is important for us as care providers to be mindful that many patients with IBD are struggling with comorbid obesity. This fact may have negative implications for our patients' general health outcomes as well as potentially their IBD outcomes."
— Amanda M. Johnson, M.D.
Additional related research
The 2024 study publication is a part of a larger research effort that Dr. Johnson and co-investigators are conducting. "The ultimate goal of these studies is to augment our ability to provide more evidence-based approaches and personalized care to patients struggling with both obesity and IBD," says Dr. Johnson.
In a 2023 publication in The American Journal of Gastroenterology, Dr. Johnson and colleagues shared the results from a single-center experience with the use of anti-obesity medications in patients with IBD. They also affirmed the safety and efficacy of endoscopic bariatric therapies in a cohort of seven patients with IBD and published those results in Obesity Surgery in 2023.

19/08/2024