IU Indianapolis ScholarWorks :: Browsing by Author "Gardner, Timothy B."

Browsing by Author "Gardner, Timothy B."

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Acute pancreatitis precedes chronic pancreatitis in the majority of patients: Results from the NAPS2 consortium
(Elsevier, 2022-12) Singh, Vikesh K.; Whitcomb, David C.; Banks, Peter A.; AlKaade, Samer; Anderson, Michelle A.; Amann, Stephen T.; Brand, Randall E.; Conwel, Darwin L.; Cote, Gregory A.; Gardner, Timothy B.; Gelrud, Andres; Guda, Nalini; Forsmark, Christopher E.; Lewis, Michele; Sherman, Stuart; Muniraj, Thiruvengadam; Romagnuolo, Joseph; Tan, Xiaoqing; Tang, Gong; Sandhu, Bimaljit S.; Slivka, Adam; Wilcox, C. Mel; Yadav, Dhiraj; Medicine, School of Medicine
Introduction: The mechanistic definition of chronic pancreatitis (CP) identifies acute pancreatitis (AP) as a precursor stage. We hypothesized that clinical AP frequently precedes the diagnosis of CP and is associated with patient- and disease-related factors. We describe the prevalence, temporal relationship and associations of AP in a well-defined North American cohort. Methods: We evaluated data from 883 patients with CP prospectively enrolled in the North American Pancreatitis Studies across 27 US centers between 2000 and 2014. We determined how often patients had one or more episodes of AP and its occurrence in relationship to the diagnosis of CP. We used multivariable logistic regression to determine associations for prior AP. Results: There were 624/883 (70.7%) patients with prior AP, among whom 161 (25.8%) had AP within 2 years, 115 (18.4%) within 3–5 years, and 348 (55.8%) >5 years prior to CP diagnosis. Among 504 AP patients with available information, 436 (86.5%) had >1 episode. On multivariable analyses, factors associated with increased odds of having prior AP were a younger age at CP diagnosis, white race, abdominal pain, pseudocyst(s) and pancreatic duct dilatation/stricture, while factors associated with a lower odds of having prior AP were exocrine insufficiency and pancreatic atrophy. When compared with patients with 1 episode, those with >1 AP episode were diagnosed with CP an average of 5 years earlier. Conclusions: Nearly three-quarters of patients were diagnosed with AP prior to CP diagnosis. Identifying which AP patients are at-risk for future progression to CP may provide opportunities for primary and secondary prevention.
Chronic pancreatitis: Pediatric and adult cohorts show similarities in disease progress despite different risk factors
(Lippincott, Williams & Wilkins, 2020-04) Schwarzenberg, Sarah J.; Uc, Aliye; Zimmerman, Bridget; Wilschanski, Michael; Wilcox, C. Mel; Whitcomb, David C.; Werlin, Steven L.; Troendle, David; Tang, Gong; Slivka, Adam; Singh, Vikesh K.; Sherman, Stuart; Shah, Uzma; Sandhu, Bimaljit S.; Romagnuolo, Joseph; Rhee, Sue; Pohl, John F.; Perito, Emily R.; Ooi, Chee Y.; Nathan, Jaimie D.; Muniraj, Thiruvengadam; Morinville, Veronique D.; McFerron, Brian; Mascarenhas, Maria; Maqbool, Asim; Liu, Quin; Lin, Tom K.; Lewis, Michele; Husain, Sohail Z.; Himes, Ryan; Heyman, Melvin B.; Guda, Nalini; Gonska, Tanja; Giefer, Matthew J.; Gelrud, Andres; Gariepy, Cheryl E.; Gardner, Timothy B.; Freedman, Steven D.; Forsmark, Christopher E.; Fishman, Douglas S.; Cote, Gregory A.; Conwell, Darwin; Brand, Randall E.; Bellin, Melena; Barth, Bradley; Banks, Peter A.; Anderson, Michelle A.; Amann, Stephen T.; Alkaade, Samer; Abu-El-Haija, Maisam; Abberbock, Judah N.; Lowe, Mark E.; Yadav, Dhiraj; Medicine, School of Medicine
Objectives: To investigate the natural history of chronic pancreatitis (CP), patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared. Methods: Demographics, risk factors, disease duration, management and outcomes of 224 children and 1,063 adults were compared using appropriate statistical tests for categorical and continuous variables. Results: Alcohol was a risk in 53% of adults and 1% of children (p<0.0001); tobacco in 50% of adults and 7% of children (p<0.0001). Obstructive factors were more common in children (29% vs 19% in adults, p=0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, p=0.107). Diabetes was more common in adults than children (36% vs 4% respectively, p<0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2-CO) were compared to INSPPIRE subjects. These two cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2-CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2-CO vs 1% INSPPIRE cohorts, p=0.011). Conclusions: Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.
Constant-Severe Pain in Chronic Pancreatitis is Associated with Genetic Loci for Major Depression in the NAPS2 Cohort
(Springer, 2020) Dunbar, Ellyn; Greer, Phil J.; Melhem, Nadine; Alkaade, Samer; Amann, Stephen T.; Brand, Randall; Coté, Gregory A.; Forsmark, Christopher E.; Gardner, Timothy B.; Gelrud, Andres; Guda, Nalini M.; LaRusch, Jessica; Lewis, Michele D.; Machicado, Jorge D.; Muniraj, Thiruvengadam; Papachristou, Georgios I.; Romagnuolo, Joseph; Sandhu, Bimaljit S.; Sherman, Stuart; Wilcox, Charles M.; Singh, Vikesh K.; Yadav, Dhiraj; Whitcomb, David C.; NAPS2 study group; Medicine, School of Medicine
Background: Pain is the most debilitating symptom of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) and often requires chronic opioids or total pancreatectomy with islet autotransplantation to manage. Pain is a complex experience that can be exacerbated by depression and vice versa. Our aim was to test the hypothesis that depression-associated genes are associated with a constant-severe pain experience in RAP/CP patients. Study: A retrospective study was done using North American Pancreatitis Study II (NAPS2) genotyped RAP and CP patients with completed case report forms (n = 1,357). Subjects were divided based on pattern of pain and pain severity as constant-severe pain (n = 787) versus not constant-severe pain (n = 570) to conduct a nested genome-wide association study. The association between reported antidepressant medication use and depression gene loci was tested. Results: Constant-severe pain was reported in 58% (n = 787) of pancreatitis patients. No differences in sex or alcohol consumption were found based on pain severity. Antidepressant use was reported in 28% (n = 223), and they had lower SF-12 mental quality of life (MCS, p < 2.2 × 10- 16). Fifteen loci associated with constant-severe pain (p < 0.00001) were found to be in or near depression-associated genes including ROBO2, CTNND2, SGCZ, CNTN5 and BAIAP2. Three of these genes respond to antidepressant use (SGCZ, ROBO2, and CTNND2). Conclusion: Depression is a major co-factor in the pain experience. This genetic predisposition to depression may have utility in counseling patients and in instituting early antidepressant therapy for pain management of pancreatitis patients. Prospective randomized trials are warranted.
Development and Validation of a Machine Learning-based, Point-of-Care Risk Calculator for Post-ERCP Pancreatitis and Prophylaxis Selection
(Elsevier, 2024) Brenner, Todd; Kuo, Albert; Sperna Weiland, Christina J.; Kamal, Ayesha; Elmunzer, B. Joseph; Luo, Hui; Buxbaum, James; Gardner, Timothy B.; Mok, Shaffer S.; Fogel, Evan S.; Phillip, Veit; Choi, Jun-Ho; Lua, Guan W.; Lin, Ching-Chung; Reddy, D. Nageshwar; Lakhtakia, Sundeep; Goenka, Mahesh K.; Kochhar, Rakesh; Khashab, Mouen A.; van Geenen, Erwin J. M.; Singh, Vikesh K.; Tomasetti, Cristian; Akshintala, Venkata S.; Medicine, School of Medicine
Background and Aims A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning–based tool for PEP risk prediction to aid in clinical decision making related to periprocedural prophylaxis selection and postprocedural monitoring. Methods Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk, and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a 1-month period. Results A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on 20 PEP risk factors and 5 prophylactic interventions (rectal nonsteroidal anti-inflammatory drugs [NSAIDs], aggressive hydration, combined rectal NSAIDs and aggressive hydration, pancreatic duct stenting, and combined rectal NSAIDs and pancreatic duct stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, and 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74. Conclusions This study demonstrates the feasibility and utility of a novel machine learning–based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended postprocedure monitoring.
Differences in Age at Onset of Symptoms, and Effects of Genetic Variants, in Patients With Early- vs Late-Onset Idiopathic Chronic Pancreatitis in a North American Cohort
(Elsevier, 2020) Lewis, Michele D.; Talluri, Jyothsna; Wilcox, C. Mel; Abberbock, Judah N.; Tang, Gong; Conwell, Darwin L.; Banks, Peter A.; Cote, Gregory A.; Sherman, Stuart; Alkaade, Samer; Gardner, Timothy B.; Anderson, Michelle A.; Sandhu, Bimaljit S.; Muniraj, Thiruvengadam; Forsmark, Chris E.; Guda, Nalini; Gelrud, Andres; Romagnuolo, Joseph; Brand, Randall; LaRusch, Jessica; Amann, Stephen T.; Slivka, Adam; Whitcomb, David C.; Yadav, Dhiraj; Medicine, School of Medicine
Background & Aims Idiopathic chronic pancreatitis (ICP) is the second most common subtype of CP. In 1994, researchers reported the bimodal age at onset of ICP symptoms: early-onset ICP (EO-ICP; median age, 19.2 years) and late-onset ICP (LO-ICP; median age, 56.2 years). Ages of onset and clinical features of ICP differed from those of alcohol-related CP (ACP). However, variants in PRSS1 had not yet been associated with ICP. We reexamined ages of onset of ICP in a large, North American cohort of patients, and investigated the effects of genetic factors and alcohol use in patients with EO-ICP, LO-ICP, or ACP. Methods We performed a cross-sectional analysis of patients with CP of European ancestry enrolled in the North American Pancreatitis Study 2 studies, a prospective study of 1195 patients with CP from 26 centers in the United States from August 2000 through December 2014. We compared age at onset of symptoms for 130 patients with CP who were lifetime abstainers from alcohol (61 patients with early onset and 69 patients with late onset), 308 light to moderate alcohol drinkers with CP, and 225 patients with ACP and heavy to very heavy alcohol use. DNA from available patients was analyzed for variants associated with CP in SPINK1, CFTR, and CTRC. The Kruskal-Wallis test was used to compare continuous variables across groups and based on genetic variants. Results Median ages at onset of symptoms were 20 years for patients with EO-ICP and no alcohol use, 58 years for patients with LO-ICP and no alcohol use, 47 years for light to moderate alcohol drinkers with CP, and 44 years for patients with ACP. A higher proportion of patients with EO-ICP had constant pain (65%) than patients with LO-ICP (31%) (P=.04). A higher proportion of patients with ACP had pseudocysts (43%) than patients with EO-ICP (11%) (P=.001). A higher proportion of patients with EO-ICP had pathogenic variants in SPINK1, CFTR, or CTRC (49%) than patients with LO-ICP (23%), light to moderate alcohol drinking with CP (26%), or ACP (23%) (P=.001). Among patients with variants in SPINK1, those with EO-ICP had onset of symptoms at a median age of 12 years, and light to moderate alcohol drinkers with CP had an age at onset of 24 years. Among patients with variants in CFTR, light to moderate alcohol drinkers had an age at onset of symptoms of 41 years, but this variant did not affect age at onset of EO-ICP or ACP. Conclusions We confirmed previously reported ages at onset of symptoms for EO-ICP and LO-ICP in a North American cohort. We found differences in clinical features among patients with EO-ICP, LO-ICP, and ACP. Almost half of patients with EO-ICP have genetic variants associated with CP, compared to about one-quarter of patients with LO-CP or ACP. Genetic variants affect ages at onset of symptoms in some groups.
EUS pancreatic function testing and dynamic pancreatic duct evaluation for the diagnosis of exocrine pancreatic insufficiency and chronic pancreatitis
(Elsevier, 2020) DeWitt, John M.; Al-Haddad, Mohammad A.; Easler, Jeffrey J.; Sherman, Stuart; Slaven, James; Gardner, Timothy B.; Medicine, School of Medicine
Background and Aims EUS and endoscopic pancreatic function tests (ePFTs) may be used to diagnose minimal- change chronic pancreatitis (MCCP). The impact of evaluation for exocrine pancreatic insufficiency (EPI) and real-time assessment of EUS changes after intravenous secretin on the clinical diagnosis of MCCP is unknown. Methods Patients with suspected MCCP underwent baseline EUS assessment of the pancreatic parenchyma and measurement of the main pancreatic duct (B-MPD) in the head, body, and tail. Human secretin 0.2 μg/kg IV was given followed 4, 8, and 12 minutes later by repeat MPD (S-MPD) measurements. Duodenal samples at 15, 30, and 45 minutes were aspirated for bicarbonate concentration. Endoscopists rated the percent clinical likelihood of CP: (1) before secretin; (2) after secretin but before aspiration; and (3) after bicarbonate results. Results 145 consecutive patients (mean age 44±13 years; 98F) were diagnosed with EPI (n=32; 22%). S-MPD/B-MPD ratios in the tail 4 and 8 minutes after secretin were higher in the group with normal exocrine function. Ratios at other times, locations and duodenal fluid volumes were similar between the 2 groups. A statistically significant change in the median percent likelihood of CP was noted after secretin in all groups. The sensitivity and specificity of EPI for the EUS diagnosis of CP (≥5 criteria) were 23.4% (95% CI, 12.3-38.0) and 78.6% (95% CI, 69.1-86.2), respectively. Conclusion Real-time EUS findings and ePFTs have a significant impact on the clinical assessment of MCCP. The diagnosis of EPI shows poor correlation with the EUS diagnosis of MCCP.
Multicenter evaluation of the clinical utility of laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass
(Elsevier, 2017) Abbas, Ali M.; Strong, Andrew T.; Diehl, David L.; Brauer, Brian C.; Lee, Iris H.; Burbridge, Rebecca; Zivny, Jaroslav; Higa, Jennifer T.; Falcão, Marcelo; El Hajj, Ihab I.; Tarnasky, Paul; Enestvedt, Brintha K.; Ende, Alexander R.; Thaker, Adarsh M.; Pawa, Rishi; Jamidar, Priya; Sampath, Kartik; de Moura, Eduardo Guimarães Hourneaux; Kwon, Richard S.; Suarez, Alejandro L.; Aburajab, Murad; Wang, Andrew Y.; Shakhatreh, Mohammad H.; Kaul, Vivek; Kang, Lorna; Kowalski, Thomas E.; Pannala, Rahul; Tokar, Jeffrey; Aadam, A. Aziz; Tzimas, Demetrios; Wagh, Mihir S.; Draganov, Peter V.; Ponsky, Jeffrey; Greenwald, Bruce D.; Uradomo, Lance T.; McGhan, Alyson A.; Hakimian, Shahrad; Ross, Andrew; Sherman, Stuart; Bick, Benjamin L.; Forsmark, Christopher E.; Yang, Dennis; Gupte, Anand; Chauhan, Shailendra; Hughes, Steven J.; Saks, Karen; Bakis, Gennadiy; Templeton, Adam W.; Saunders, Michael; Sedarat, Alireza; Evans, John A.; Muniraj, Thiruvengadam; Gardner, Timothy B.; Ramos, Almino C.; Santo, Marco Aurelio; Nett, Andrew; Coté, Gregory A.; Elmunzer, Joseph; Dua, Kulwinder S.; Nosler, Michael J.; Strand, Daniel S.; Yeaton, Paul; Kothari, Shivangi; Ullah, Asad; Taunk, Pushpak; Brady, Patrick; Pinkas, Haim; Faulx, Ashley L.; Shahid, Haroon; Holmes, Jordan; Pannu, Davinderbir; Komanduri, Srinadh; Bucobo, Juan Carlos; Dhaliwal, Harry; Rostom, Alaa; Acker, Brent W.; Medicine, School of Medicine
Background and Aims The obesity epidemic has led to increased use of Roux-en-Y gastric bypass (RYGB). These patients have an increased incidence of pancreaticobiliary diseases yet standard ERCP is not possible due to surgically altered gastroduodenal anatomy. Laparoscopic-ERCP (LA-ERCP) has been proposed as an option but supporting data are derived from single center small case-series. Therefore, we conducted a large multicenter study to evaluate the feasibility, safety, and outcomes of LA-ERCP. Methods This is retrospective cohort study of adult patients with RYGB who underwent LA-ERCP in 34 centers. Data on demographics, indications, procedure success, and adverse events were collected. Procedure success was defined when all of the following were achieved: reaching the papilla, cannulating the desired duct and providing endoscopic therapy as clinically indicated. Results A total of 579 patients (median age 51, 84% women) were included. Indication for LA-ERCP was biliary in 89%, pancreatic in 8%, and both in 3%. Procedure success was achieved in 98%. Median total procedure time was 152 minutes (IQR 109-210) with median ERCP time 40 minutes (IQR 28-56). Median hospital stay was 2 days (IQR 1-3). Adverse events were 18% (laparoscopy-related 10%, ERCP-related 7%, both 1%) with the clear majority (92%) classified as mild/moderate whereas 8% were severe and 1 death occurred. Conclusion Our large multicenter study indicates that LA-ERCP in patients with RYGB is feasible with a high procedure success rate comparable with that of standard ERCP in patients with normal anatomy. ERCP-related adverse events rate is comparable with conventional ERCP, but the overall adverse event rate was higher due to the added laparoscopy-related events.
Pain Experience in Pancreatitis: Strong Association of Genetic Risk Loci for Anxiety and PTSD in Patients With Severe, Constant, and Constant-Severe Pain
(Wolters Kluwer, 2021) Dunbar, Ellyn K.; Greer, Phil J.; Amann, Stephen T.; Alkaade, Samer; Banks, Peter; Brand, Randall; Conwell, Darwin L.; Forsmark, Christopher E.; Gardner, Timothy B.; Guda, Nalini M.; Lewis, Michele D.; Machicado, Jorge D.; Muniraj, Thiruvengadam; Papachristou, Georgios I.; Romagnuolo, Joseph; Sandhu, Bimaljit S.; Sherman, Stuart; Slivka, Adam; Wilcox, C. Mel; Yadav, Dhiraj; Whitcomb, David C.; NAPS2 Consortium; Medicine, School of Medicine
Introduction: Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are progressive inflammatory syndromes with variable features. Pain is the primary feature that contributes to low physical and mental quality of life with a third of patients reporting severe pain. Pain experience is worsened by depression. Here, we tested the hypothesis that genetic risk of the psychiatric conditions of anxiety and post-traumatic stress disorder (PTSD) is associated with pain in CP and RAP + CP subjects. Methods: The study cohort included phenotyped and genotyped RAP and CP patients from the North American Pancreatitis Study II of European Ancestry. Candidate genetic association studies were based on the absence of pain vs pain that is constant, constant-severe, or severe. Twenty-eight candidate genetic loci for anxiety and PTSD risk were identified in the literature and were the focus of this study. Results: We identified 24 significant pain-associated single nucleotide polymorphisms within 13 loci across the 3 pain patterns in CP and RAP + CP (P < 0.002). Thirteen anxiety or PTSD genes were within these pain loci indicating nonrandom associations (P < 4.885 × 10-23). CTNND2 was associated with all pain categories and all pancreatitis etiologies. Implicated systems include neuronal signaling (HTR2A, DRD3, NPY, and BDNF), hypothalamic-pituitary-adrenal axis (NR3C1 and FKBP5), and cell-cell interaction (CTNND2 and THBS2). Discussion: A component of constant and severe pain in patients with RAP and CP is associated with genetic predisposition to anxiety and PTSD. Identification of patients at risk eligible for trials of targeted treatment as a component of a multidisciplinary pain management strategy should be formally evaluated.
Preventive Measures and Risk Factors for Post-ERCP Pancreatitis: A Systematic Review and Individual Patient Data Meta-Analysis
(Springer, 2024) Sperna Weiland, Christina J.; Akshintala, Venkata S.; Singh, Anmol; Buxbaum, James; Choi, Jun-Ho; Elmunzer, Badih J.; Fogel, Evan S.; Lai, Jian-Han; Levenick, John M.; Gardner, Timothy B.; Lua, Guan W.; Luo, Hui; de Jong, Mike; Mok, Shaffer R. S.; Phillip, Veit; Singh, Vikesh; Siersema, Peter D.; Drenth, Joost P. H.; van Geenen, Erwin J. M.; Medicine, School of Medicine
Background: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP, with limited studies comparing combined prophylactic measures and their efficacy relative to individual patient risk profiles. This study aims to perform an individual patient data meta-analysis (IPDMA) to evaluate the contribution of patient and ERCP-related risk factors to PEP development and to identify the best prophylaxis strategies according to the patient's risk profile. Methods: We systematically searched MEDLINE, Embase, and Cochrane databases until November 2022 for randomized controlled PEP prophylaxis trials. We invited authors to share individual patient data, including PEP risk profile and prophylaxes used. PEP incidence rates for different prophylaxis were calculated. Efficacy was compared using multilevel logistic regression and expressed as relative risk (RR). Subgroup analysis evaluated the role of patient and ERCP-related risk factors in developing PEP. Results: Data from 11 studies, including 6430 patients, were analyzed. After adjusting for risk factors, rectal NSAIDs (RR 0.69, 95%CI 0.54-0.88) and peri-procedural high-volume intravenous fluid (IVF) (RR 0.40, 95%CI 0.21-0.79) were effective in reducing PEP incidence, while no benefit was noted with pancreatic duct (PD) stents (RR 1.25, 95%CI 0.91-1.73). In patients receiving rectal NSAIDs (n = 2617), difficult cannulation (RR 1.99, 1.45-2.73), contrast injection into the pancreatic duct (PD) (RR2.37, 1.68-3.32), and prior history of PEP (RR 1.90, 1.06-3.41) were associated with increased PEP risk. Conclusion: This IPDMA confirms that rectal NSAIDs and peri-procedural IVF are effective PEP prophylactic strategies. Further studies focusing on combination therapy or the development of personalized PEP risk calculators are needed to improve prophylactic strategies.
Serum biomarkers for chronic pancreatitis pain patterns
(Elsevier, 2021) Saloman, Jami L.; Tang, Gong; Stello, Kimberly M.; Hall, Kristen E.; Wang, Xianling; AlKaade, Samer; Banks, Peter A.; Brand, Randall E.; Conwell, Darwin L.; Coté, Gregory A.; Forsmark, Christopher E.; Gardner, Timothy B.; Gelrud, Andres; Lewis, Michele D.; Sherman, Stuart; Slivka, Adam; Whitcomb, David C.; Yadav, Dhiraj; NAPS consortium; Medicine, School of Medicine
Objectives: Chronic pancreatitis (CP) is associated with debilitating refractory pain. Distinct subtypes of CP pain have been previously characterized based on severity (none, mild-moderate, severe) and temporal (none, intermittent, constant) nature of pain, but no mechanism-based tools are available to guide pain management. This exploratory study was designed to determine if potential pain biomarkers could be detected in patient serum and whether they associate with specific pain patterns. Methods: Cytokines, chemokines, and peptides associated with nociception and pain were measured in legacy serum samples from CP patients (N = 99) enrolled in the North American Pancreatitis Studies. The unsupervised hierarchical cluster analysis was applied to cluster CP patients based on their biomarker profile. Classification and regression tree was used to assess whether these biomarkers can predict pain outcomes. Results: The hierarchical cluster analysis revealed a subset of patients with predominantly constant, mild-moderate pain exhibited elevated interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor alpha (TNFα), and monocyte chemoattractant protein-1 (MCP1) whereas patients with higher interleukin-4 (IL-4), interleukin-8 (IL-8) and calcitonin gene related peptide (CGRP) were more likely to have severe pain. Interestingly, analyses of each individual biomarker revealed that patients with constant pain had reduced circulating TNFα and fractalkine. Patients with severe pain exhibited a significant reduction in TNFα as well as trends towards lower levels of IL-6 and substance P. Discussion: The observations from this study indicate that unique pain experiences within the chronic pancreatitis population can be associated with distinct biochemical signatures. These data indicate that further hypothesis-driven analyses combining biochemical measurements and detailed pain phenotyping could be used to develop precision approaches for pain management in patients with chronic pancreatitis.

Browsing by Author "Gardner, Timothy B."

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